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Ovarian cancer is a
cancerous Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Poss ...
tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
of an
ovary The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. ...
. It may originate from the ovary itself or more commonly from communicating nearby structures such as
fallopian tube The fallopian tubes, also known as uterine tubes, oviducts or salpinges (singular salpinx), are paired tubes in the human female that stretch from the uterus to the ovaries. The fallopian tubes are part of the female reproductive system. In ot ...
s or the inner lining of the abdomen. The ovary is made up of three different cell types including epithelial cells, germ cells, and stromal cells. When these cells become abnormal, they have the ability to divide and form tumors. These cells can also invade or
spread Spread may refer to: Places * Spread, West Virginia Arts, entertainment, and media * ''Spread'' (film), a 2009 film. * ''$pread'', a quarterly magazine by and for sex workers * "Spread", a song by OutKast from their 2003 album ''Speakerboxxx/T ...
to other parts of the body. When this process begins, there may be no or only vague symptoms. Symptoms become more noticeable as the cancer progresses. These symptoms may include
bloating Abdominal bloating (or simply bloating) is a short-term disease that affects the gastrointestinal tract. Bloating is generally characterized by an excess buildup of gas, air or fluids in the stomach. A person may have feelings of tightness, press ...
, vaginal bleeding,
pelvic pain Pelvic pain is pain in the area of the pelvis. Acute pain is more common than chronic pain. If the pain lasts for more than six months, it is deemed to be chronic pelvic pain. It can affect both the male and female pelvis. Common causes in include ...
, abdominal swelling,
constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
, and
loss of appetite Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others i ...
, among others. Common areas to which the cancer may spread include the lining of the abdomen,
lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s,
lungs The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of th ...
, and
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
. The risk of ovarian cancer increases with age. Most cases of ovarian cancer develop after menopause. It is also more common in women who have
ovulate Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilized ...
d more over their lifetime. This includes those who have never had children, those who began ovulation at a younger age and those who reach menopause at an older age. Other risk factors include
hormone therapy Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are oncologic horm ...
after
menopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
,
fertility medication Fertility medications, also known as fertility drugs, are medications which enhance reproductive fertility. For women, fertility medication is used to stimulate follicle development of the ovary. There are very few fertility medication options a ...
, and
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
. Factors that decrease risk include
hormonal birth control Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original ...
,
tubal ligation Tubal ligation (commonly known as having one's "tubes tied") is a surgical procedure for female sterilization in which the fallopian tubes are permanently blocked, clipped or removed. This prevents the fertilization of eggs by sperm and thus th ...
, pregnancy, and
breast feeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that brea ...
. About 10% of cases are related to inherited genetic risk; women with mutations in the genes ''
BRCA1 Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a h ...
'' or ''
BRCA2 ''BRCA2'' and BRCA2 () are a human gene and its protein product, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (originally breast cancer 2; currently BRCA2, DNA repair associated) ...
'' have about a 50% chance of developing the disease. Some family cancer syndromes such as hereditary nonpolyposis colon cancer and Peutz-Jeghers syndrome also increase the risk of developing ovarian cancer. Epithelial ovarian carcinoma is the most common type of ovarian cancer, comprising more than 95% of cases. There are five main subtypes of ovarian carcinoma, of which high-grade serous carcinoma (HGSC) is the most common. Less common types of ovarian cancer include germ cell tumors and
sex cord stromal tumor Sex is the phenotypic trait, trait that determines whether a sexual reproduction, sexually reproducing animal or plant produces male or female gametes. Male plants and animals produce smaller mobile gametes (spermatozoa, sperm, pollen), while ...
s. A diagnosis of ovarian cancer is confirmed through a
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
of tissue, usually removed during surgery.
Screening Screening may refer to: * Screening cultures, a type a medical test that is done to find an infection * Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees) * Screening (environmental), a ...
is not recommended in women who are at average risk, as evidence does not support a reduction in death and the high rate of false positive tests may lead to unneeded surgery, which is accompanied by its own risks. Those at very high risk may have their ovaries removed as a preventive measure. If caught and treated in an early stage, ovarian cancer is often curable. Treatment usually includes some combination of surgery,
radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
, and
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
. Outcomes depend on the extent of the disease, the subtype of cancer present, and other medical conditions. The overall
five-year survival rate The five-year survival rate is a type of survival rate for estimating the prognosis of a particular disease, normally calculated from the point of diagnosis. Lead time bias from earlier diagnosis can affect interpretation of the five-year surviva ...
in the United States is 49%. Outcomes are worse in the developing world. In 2020, new cases occurred in approximately 313,000 women. In 2019 it resulted in 13,445 deaths in the United States. Death from ovarian cancer increased globally between 1990 to 2017 by 84.2%.Zhou Z, Wang X, Ren X, Zhou L, Wang N, Kang H. Disease Burden and Attributable Risk Factors of Ovarian Cancer From 1990 to 2017: Findings From the Global Burden of Disease Study 2017. Front Public Health. 2021 Sep 17;9:619581. doi: 10.3389/fpubh.2021.619581. PMID 34604147; PMCID: PMC8484795. Ovarian cancer is the second-most common gynecologic cancer in the United States. It causes more deaths than any other cancer of the female reproductive system. Among women it ranks fifth in cancer-related deaths. The typical age of diagnosis is 63. Death from ovarian cancer is more common in North America and Europe than in Africa and Asia. In the United States, it is more common in White and Hispanic women than Black or American Indian women.


Signs and symptoms


Early symptoms

Early signs and
symptoms Signs and symptoms are the observed or detectable signs, and experienced symptoms of an disease, illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormali ...
of ovarian cancer may be absent or subtle. In most cases, symptoms exist for several months before being recognized and diagnosed. Symptoms can often be misdiagnosed as
irritable bowel syndrome Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or abdominal bloating and changes in the consistency of bowel movements. These symptoms may ...
. The early stages of ovarian cancer tend to be painless which makes it difficult to detect it early on. Symptoms can vary based on the subtype. Ovarian
borderline tumor A borderline tumor, sometimes called low malignant potential (LMP) tumor, is a distinct but yet heterogeneous group of tumors defined by their histopathology as atypical epithelial proliferation without stromal invasion. This topic last updated: Fe ...
s, also known as low malignant potential (LMP) ovarian tumors, do not cause an increase in CA125 levels and are not identifiable with an ultrasound. The typical symptoms of an LMP tumor can include
abdominal distension Abdominal distension occurs when substances, such as air (gas) or fluid, accumulate in the abdomen causing its expansion. It is typically a symptom of an underlying disease or dysfunction in the body, rather than an illness in its own right. Pe ...
or pelvic pain. Particularly large masses tend to be benign or borderline. The most typical symptoms of ovarian cancer include
bloating Abdominal bloating (or simply bloating) is a short-term disease that affects the gastrointestinal tract. Bloating is generally characterized by an excess buildup of gas, air or fluids in the stomach. A person may have feelings of tightness, press ...
, abdominal or pelvic pain or discomfort, back pain,
irregular menstruation Irregular menstruation is a menstrual disorder whose manifestations include irregular cycle lengths as well as metrorrhagia (vaginal bleeding between expected periods). The possible causes of irregular menstruation may vary. The common factors of ...
or postmenopausal vaginal bleeding, pain or bleeding after or during
sexual intercourse Sexual intercourse (or coitus or copulation) is a sexual activity typically involving the insertion and thrusting of the penis into the vagina for sexual pleasure or reproduction.Sexual intercourse most commonly means penile–vaginal penetrat ...
,
loss of appetite Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others i ...
,
fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
,
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
,
indigestion Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier t ...
,
heartburn Heartburn, also known as pyrosis, cardialgia or acid indigestion, is a burning sensation in the central chest or upper central abdomen. Heartburn is usually due to regurgitation of gastric acid (gastric reflux) into the esophagus. It is the m ...
,
constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
,
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
, feeling full, and possibly urinary symptoms (including
frequent urination Frequent urination, or urinary frequency (sometimes called pollakiuria), is the need to urinate more often than usual. Diuretics are medications that increase urinary frequency. Nocturia is the need of frequent urination at night. The most common c ...
and urgent urination).


Later symptoms

Later symptoms of ovarian cancer are due to the growing mass causing pain by pressing on other abdominopelvic organs or from metastases. Because of the anatomic location of the ovaries deep in the pelvis, most masses are large and advanced at the time of diagnosis. The growing mass may cause pain if
ovarian torsion Ovarian torsion (OT) or adnexal torsion is an abnormal condition where an ovary twists on its attachment to other structures, such that blood flow is decreased. Symptoms typically include pelvic pain on one side. While classically the pain is su ...
develops. If these symptoms start to occur more often or more severely than usual, especially after no significant history of such symptoms, ovarian cancer is considered. Metastases may cause a Sister Mary Joseph nodule. Rarely,
teratoma A teratoma is a tumor made up of several different types of tissue, such as hair, muscle, teeth, or bone. Teratomata typically form in the ovary, testicle, or coccyx. Symptoms Symptoms may be minimal if the tumor is small. A testicular terato ...
s can cause growing teratoma syndrome or
peritoneal gliomatosis The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of meso ...
. Some experience menometrorrhagia and
abnormal vaginal bleeding Vaginal bleeding is any expulsion of blood from the vagina. This bleeding may originate from the uterus, vaginal wall, or cervix. Generally, it is either part of a normal menstrual cycle or is caused by hormonal or other problems of the reprod ...
after menopause in most cases. Other common symptoms include
hirsutism Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin ''hirsutus'' meaning "hairy". It usually refers to a "male" pattern of hair growth in a female that ...
, abdominal pain,
virilization Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens. Virilization is most commonly used in three medical and biology ...
, and an
adnexal mass In anatomy, adnexa (plural) refers to the appendage An appendage (or outgrowth) is an external body part, or natural prolongation, that protrudes from an organism's body. In arthropods, an appendage refers to any of the homologous body parts ...
.


Children

In adolescents or children with ovarian tumors, symptoms can include severe abdominal pain, irritation of the
peritoneum The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesoth ...
, or
bleeding Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
. Sex cord stromal tumors produce hormones which can lead to the premature development of secondary sex characteristics. Sex cord-stromal tumors in prepubertal children may be manifested by signs of
early puberty In medicine, precocious puberty is puberty occurring at an unusually early age. In most cases, the process is normal in every aspect except the unusually early age and simply represents a variation of normal development. In a minority of childr ...
; abdominal pain and distension are also common. Adolescents with sex cord-stromal tumors may experience
amenorrhea Amenorrhea is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen, most commonly, during pregnancy and lactation (breastfeeding). Outside the reproductive years, there is absence of menses ...
. As the cancer becomes more advanced, it can cause an accumulation of fluid in the abdomen and lead to distension. If the malignancy has not been diagnosed by the time it causes ascites, it is typically diagnosed shortly thereafter. Advanced cancers can also cause abdominal masses, lymph node masses, or
pleural effusion A pleural effusion is accumulation of excessive fluid in the pleural space, the potential space that surrounds each lung. Under normal conditions, pleural fluid is secreted by the parietal pleural capillaries at a rate of 0.6 millilitre per kilog ...
.


Risk factors

There are many known risk factors that may increase a women's risk of developing ovarian cancer. The risk of developing ovarian cancer is related to the amount of time a woman spends ovulating. Factors that increase the number of ovulatory cycles a women undergoes may increase the risk of developing ovarian cancer. During ovulation, cells are stimulated to divide. If this division is abnormally regulated, tumors may form which can be malignant. Early menarche and late menopause increase the number of ovulatory cycles a woman undergoes in her lifetime and so increases the risk of developing ovarian cancer. Since ovulation is suppressed during pregnancy, not having children also increases the risk of ovarian cancer. Therefore, women who have not borne children are at twice the risk of ovarian cancer than those who have. Both obesity and hormone replacement therapy also raise the risk. The risk of developing ovarian cancer is less for women who have fewer menstrual cycles, no menstrual cycles,
breast feeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that brea ...
, take oral contraceptives, have multiple pregnancies, and have a pregnancy at an early age. The risk of developing ovarian cancer is reduced in women who have had
tubal ligation Tubal ligation (commonly known as having one's "tubes tied") is a surgical procedure for female sterilization in which the fallopian tubes are permanently blocked, clipped or removed. This prevents the fertilization of eggs by sperm and thus th ...
(colloquially known as having one's "tubes tied"), both ovaries removed, or
hysterectomy Hysterectomy is the surgical removal of the uterus. It may also involve removal of the cervix, ovaries (oophorectomy), Fallopian tubes (salpingectomy), and other surrounding structures. Usually performed by a gynecologist, a hysterectomy may b ...
(an operation in which the uterus is removed). Age is also a risk factor. Non-genetic factors such as diabetes mellitus, high body mass index, tobacco, and alcohol use are also risk factors for ovarian cancer.


Hormones

The use of fertility medication may contribute to ovarian
borderline tumor A borderline tumor, sometimes called low malignant potential (LMP) tumor, is a distinct but yet heterogeneous group of tumors defined by their histopathology as atypical epithelial proliferation without stromal invasion. This topic last updated: Fe ...
formation, but the link between the two is disputed and difficult to study. Fertility drugs may be associated with a higher risk of borderline tumors. Those who have been treated for infertility but remain nulliparous are at higher risk for epithelial ovarian cancer due to hormonal exposure that may lead to proliferation of cells. However, those who are successfully treated for infertility and subsequently give birth are at no higher risk. This may be due to shedding of precancerous cells during pregnancy, but the cause remains unclear. The risk factor may instead be infertility itself, not the treatment. Hormonal conditions such as
polycystic ovary syndrome Polycystic ovary syndrome, or PCOS, is the most common endocrine disorder in women of reproductive age. The syndrome is named after the characteristic cysts which may form on the ovaries, though it is important to note that this is a sign and no ...
and
endometriosis Endometriosis is a disease of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Most often this is on the ovaries, f ...
are associated with ovarian cancer, but the link is not completely confirmed. Postmenopausal hormone replacement therapy (HRT) with estrogen likely increases the risk of ovarian cancer. The association has not been confirmed in a large-scale study, but notable studies including the
Million Women Study The Million Women Study is a study of women’s health analysing data from more than one million women aged 50 and over, led by Dame Valerie Beral and a team of researchers at the Cancer Epidemiology Unit, University of Oxford. It is a collabo ...
have supported this link. Postmenopausal HRT with combined estrogen and progesterone may increase contemporaneous risk if used for over 5 years, but this risk returns to normal after cessation of therapy. Estrogen HRT with or without progestins increases the risk of endometrioid and serous tumors but lowers the risk of mucinous tumors. Higher doses of estrogen increase this risk. Endometriosis is another risk factor for ovarian cancer, as is pain with menstruation. Endometriosis is associated with clear-cell and endometrioid subtypes, low-grade serous tumors, stage I and II tumors, grade 1 tumors, and lower mortality. Before menopause, obesity can increase a person's risk of ovarian cancer, but this risk is not present after menopause. This risk is also relevant in those who are both obese and have never used HRT. A similar association with ovarian cancer appears in taller women.


Genetics

A family history of ovarian cancer is a risk factor for ovarian cancer. Women with
hereditary nonpolyposis colon cancer Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal dominant genetic condition that is associated with a high risk of colon cancer as well as other cancers including endometrial cancer (second most common), ova ...
(Lynch syndrome), and those with BRCA-1 and BRCA-2 genetic abnormalities are at increased risk. The major genetic risk factor for ovarian cancer is a mutation in ''BRCA1'' or ''BRCA2'' genes, or in
DNA mismatch repair DNA mismatch repair (MMR) is a system for recognizing and repairing erroneous insertion, deletion, and mis-incorporation of nucleobase, bases that can arise during DNA replication and Genetic recombination, recombination, as well as DNA repair, r ...
genes, which is present in 10% of ovarian cancer cases. Only one
allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...
needs to be mutated to place a person at high risk. The gene can be inherited through either the maternal or paternal line, but has variable
penetrance Penetrance in genetics is the proportion of individuals carrying a particular variant (or allele) of a gene (the genotype) that also express an associated trait (the phenotype). In medical genetics, the penetrance of a disease-causing mutation is t ...
. Though mutations in these genes are usually associated with increased risk of breast cancer, they also carry a substantial lifetime risk of ovarian cancer, a risk that peaks in a person's 40s and 50s. The lowest risk cited is 30% and the highest 60%. Mutations in BRCA1 have a lifetime risk of developing ovarian cancer of 15–45%. Mutations in ''BRCA2'' are less risky than those with ''BRCA1'', with a lifetime risk of 10% (lowest risk cited) to 40% (highest risk cited). On average, BRCA-associated cancers develop 15 years before their sporadic counterparts because people who inherit the mutations on one copy of their gene only need one mutation to start the process of carcinogenesis, whereas people with two normal genes would need to acquire two mutations. In the United States, five of 100 women with a
first-degree relative A first-degree relative (FDR) is a person's parent (father or mother), full sibling (brother or sister) or child. It constitutes a category of family members that largely overlaps with the term nuclear family, but without spouses. If the persons ...
with ovarian cancer will eventually get ovarian cancer themselves, placing those with affected family members at triple the risk of women with unaffected family members. Seven of 100 women with two or more relatives with ovarian cancer will eventually get ovarian cancer. In general, 5–10% of ovarian cancer cases have a genetic cause. BRCA mutations are associated with high-grade serous nonmucinous epithelial ovarian cancer. A strong family history of
endometrial cancer Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most o ...
,
colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...
, or other gastrointestinal cancers may indicate the presence of a syndrome known as
hereditary nonpolyposis colorectal cancer Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal dominant genetic condition that is associated with a high risk of colon cancer as well as other cancers including endometrial cancer (second most common), ovary, ...
(also known as Lynch syndrome), which confers a higher risk for developing a number of cancers, including ovarian cancer. Lynch syndrome is caused by mutations in mismatch repair genes, including ''
MSH2 DNA mismatch repair protein Msh2 also known as MutS homolog 2 or MSH2 is a protein that in humans is encoded by the ''MSH2'' gene, which is located on chromosome 2. MSH2 is a tumor suppressor gene and more specifically a caretaker gene that codes ...
,
MLH1 DNA mismatch repair protein Mlh1 or MutL protein homolog 1 is a protein that in humans is encoded by the MLH1 gene located on chromosome 3. It is a gene commonly associated with hereditary nonpolyposis colorectal cancer. Orthologs of human MLH1 h ...
, MLH6,
PMS1 PMS1 protein homolog 1 is a protein that in humans is encoded by the ''PMS1'' gene. Function The protein encoded by this gene was identified by its homology to a yeast protein involved in DNA mismatch repair. A role for this protein in mismatch ...
'', and ''
PMS2 Mismatch repair endonuclease PMS2 is an enzyme that in humans is encoded by the ''PMS2'' gene. Function This gene is one of the PMS2 gene family members which are found in clusters on chromosome 7. Human PMS2 related genes are located at bands ...
''. The risk of ovarian cancer for an individual with Lynch syndrome is between 10 and 12 percent. Women of Icelandic descent, European Jewish descent/ Ashkenazi Jewish descent, and Hungarian descent are at higher risk for epithelial ovarian cancer. Estrogen receptor beta gene ( ESR2) seems to be a key to pathogenesis and response to therapy. Other genes that have been associated with ovarian cancer are ''
BRIP1 Fanconi anemia group J protein is a protein that in humans is encoded by the ''BRCA1-interacting protein 1'' (''BRIP1'') gene. Function The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT r ...
'', ''
MSH6 MSH6 or mutS homolog 6 is a gene that codes for DNA mismatch repair protein Msh6 in the budding yeast ''Saccharomyces cerevisiae''. It is the homologue of the human "G/T binding protein," (GTBP) also called p160 or hMSH6 (human MSH6). The MSH6 prot ...
'', ''
RAD51C RAD51 homolog C (S. cerevisiae), also known as RAD51C, is a protein which in humans is encoded by the ''RAD51C'' gene. Function The RAD51C protein is one of five paralogs of RAD51, including RAD51B ( RAD51L1), RAD51C (RAD51L2), RAD51D ( RAD51 ...
'' and ''
RAD51D DNA repair protein RAD51 homolog 4 is a protein that in humans is encoded by the ''RAD51L3'' gene. Function The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are highly similar to bacterial RecA and ...
''. '' CDH1'', ''
CHEK2 CHEK2 (Checkpoint kinase 2) is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. CHK2 is involved in DNA repair, cell cycle arrest or apoptosis in response to DNA damage. Mutations to the CHEK2 gene have been linked ...
'', ''
PALB2 Partner and localizer of BRCA2, also known as PALB2 or FANCN, is a protein which in humans is encoded by the ''PALB2'' gene. Function This gene encodes a protein that functions in genome maintenance ( double strand break repair). This prote ...
'' and ''
RAD50 DNA repair protein RAD50, also known as RAD50, is a protein that in humans is encoded by the ''RAD50'' gene. Function The protein encoded by this gene is highly similar to ''Saccharomyces cerevisiae'' Rad50, a protein involved in DNA double- ...
'' have also been associated with ovarian cancer. Several rare genetic disorders are associated with specific subtypes of ovarian cancer.
Peutz–Jeghers syndrome Peutz–Jeghers syndrome (often abbreviated PJS) is an autosomal dominant genetic disorder characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa (melanos ...
, a rare genetic disorder, also predisposes women to sex cord tumour with annular tubules.
Ollier disease Ollier disease is a rare sporadic nonhereditary skeletal disorder in which typically benign cartilaginous tumors (enchondromas) develop near the growth plate cartilage. This is caused by cartilage rests that grow and reside within the metaphysis o ...
and
Maffucci syndrome Maffucci syndrome is a very rare disorder in which multiple benign tumors of cartilage develop within the bones (such tumors are known as enchondromas). The tumors most commonly appear in the bones of the hands, feet, and limbs, causing bone deform ...
are associated with
granulosa cell tumor Granulosa cell tumours are tumours that arise from granulosa cells. They are estrogen secreting tumours and present as large, complex, ovarian masses. These tumours are part of the sex cord-gonadal stromal tumour or non-epithelial group of tumours ...
s in children and may also be associated with Sertoli-Leydig tumors. Benign fibromas are associated with
nevoid basal cell carcinoma syndrome Nevoid basal-cell carcinoma syndrome (NBCCS) is an inherited medical condition involving defects within multiple body systems such as the skin, nervous system, eyes, endocrine system, and bones. People with this syndrome are particularly prone to ...
.


Diet

Alcohol consumption does not appear to be related to ovarian cancer. The American Cancer Society recommends a healthy eating pattern that includes plenty of fruits, vegetables,
whole grain A whole grain is a grain of any cereal and pseudocereal that contains the endosperm, germ, and bran, in contrast to refined grains, which retain only the endosperm. As part of a general healthy diet, consumption of whole grains is associated w ...
s, and a diet that avoids or limits red and
processed meat Processed meat is considered to be any meat which has been modified in order to either improve its taste or to extend its shelf life. Methods of meat processing include salting, curing, fermentation, smoking, and/or the addition of chemical pre ...
s and processed sugar. High consumption of total, saturated and trans-fats increases ovarian cancer risk. A 2021 umbrella review found that coffee, egg, and fat intake significantly increases the risk of ovarian cancer. There is mixed evidence from studies on ovarian cancer risk and consumption of
dairy product Dairy products or milk products, also known as lacticinia, are food products made from (or containing) milk. The most common dairy animals are cow, water buffalo, nanny goat, and ewe. Dairy products include common grocery store food items in th ...
s.


Environmental factors

Industrialized nations, with the exception of Japan, have high rates of epithelial ovarian cancer, which may be due to diet in those countries. White women are at a 30–40% higher risk for ovarian cancer when compared to Black women and Hispanic women, likely due to socioeconomic factors; white women tend to have fewer children and different rates of gynecologic surgeries that affect risk for ovarian cancer. Tentative evidence suggests that
talc Talc, or talcum, is a Clay minerals, clay mineral, composed of hydrated magnesium silicate with the chemical formula Mg3Si4O10(OH)2. Talc in powdered form, often combined with corn starch, is used as baby powder. This mineral is used as a thi ...
,
pesticides Pesticides are substances that are meant to control pests. This includes herbicide, insecticide, nematicide, molluscicide, piscicide, avicide, rodenticide, bactericide, insect repellent, animal repellent, microbicide, fungicide, and lampric ...
, and
herbicides Herbicides (, ), also commonly known as weedkillers, are substances used to control undesired plants, also known as weeds.EPA. February 201Pesticides Industry. Sales and Usage 2006 and 2007: Market Estimates. Summary in press releasMain page fo ...
increase the risk of ovarian cancer. The American Cancer Society notes that as of now, no study has been able to accurately link any single chemical in the environment, or in the human diet, directly to mutations that cause ovarian cancer.


Other

Other factors that have been investigated, such as
smoking Smoking is a practice in which a substance is burned and the resulting smoke is typically breathed in to be tasted and absorbed into the bloodstream. Most commonly, the substance used is the dried leaves of the tobacco plant, which have bee ...
, low levels of
vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
in the blood, presence of inclusion
ovarian cysts An ovarian cyst is a fluid-filled sac within the ovary. Often they cause no symptoms. Occasionally they may produce bloating, lower abdominal pain, or lower back pain. The majority of cysts are harmless. If the cyst either breaks open or causes ...
, and infection with
human papilloma virus Human papillomavirus infection (HPV infection) is caused by a DNA virus from the '' Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and r ...
(the cause of some cases of
cervical cancer Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal ...
), have been disproven as risk factors for ovarian cancer. The carcinogenicity of perineal
talc Talc, or talcum, is a Clay minerals, clay mineral, composed of hydrated magnesium silicate with the chemical formula Mg3Si4O10(OH)2. Talc in powdered form, often combined with corn starch, is used as baby powder. This mineral is used as a thi ...
is controversial, because it can act as an irritant if it travels through the reproductive tract to the ovaries. Case-control studies have shown that use of perineal talc does increase the risk of ovarian cancer, but using talc more often does not create a greater risk. Use of
talc Talc, or talcum, is a Clay minerals, clay mineral, composed of hydrated magnesium silicate with the chemical formula Mg3Si4O10(OH)2. Talc in powdered form, often combined with corn starch, is used as baby powder. This mineral is used as a thi ...
elsewhere on the body is unrelated to ovarian cancer.
Sitting Sitting is a List of human positions, basic action and resting position in which the body weight is supported primarily by the bony ischial tuberosities with the buttocks in contact with the ground or a horizontal surface such as a chair seat, in ...
regularly for prolonged periods is associated with higher mortality from epithelial ovarian cancer. The risk is not negated by regular exercise, though it is lowered. Increased age (up to the 70s) is a risk factor for epithelial ovarian cancer because more mutations in cells can accumulate and eventually cause cancer. Those over 80 are at slightly lower risk.
Smoking Smoking is a practice in which a substance is burned and the resulting smoke is typically breathed in to be tasted and absorbed into the bloodstream. Most commonly, the substance used is the dried leaves of the tobacco plant, which have bee ...
tobacco is associated with a higher risk of mucinous ovarian cancer; after
smoking cessation Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is addictive and can cause dependence. As a result, nicotine withdrawal often make ...
, the risk eventually returns to normal. Higher levels of
C-reactive protein C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin-6 ...
are associated with a higher risk of developing ovarian cancer.


Protective factors

Suppression of ovulation, which would otherwise cause damage to the
ovarian epithelium The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...
and, consequently,
inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
, is generally protective. This effect can be achieved by having children, taking
combined oral contraceptive The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: progesti ...
s, and
breast feeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that brea ...
, all of which are protective factors. A longer period of breastfeeding correlates with a larger decrease in the risk of ovarian cancer. Each birth decreases risk of ovarian cancer more, and this effect is seen with up to five births. Combined oral contraceptives reduce the risk of ovarian cancer by up to 50%, and the protective effect of combined oral contraceptives can last 25–30 years after they are discontinued. Regular use of
aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
or
acetaminophen Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...
(paracetamol) may be associated with a lower risk of ovarian cancer; other NSAIDs do not seem to have a similar protective effect.
Tubal ligation Tubal ligation (commonly known as having one's "tubes tied") is a surgical procedure for female sterilization in which the fallopian tubes are permanently blocked, clipped or removed. This prevents the fertilization of eggs by sperm and thus th ...
is protective because
carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...
s are unable to reach the ovary and fimbriae via the vagina, uterus, and Fallopian tubes. Tubal ligation is also protective in women with the BRCA1 mutation, but not the BRCA2 mutation.
Hysterectomy Hysterectomy is the surgical removal of the uterus. It may also involve removal of the cervix, ovaries (oophorectomy), Fallopian tubes (salpingectomy), and other surrounding structures. Usually performed by a gynecologist, a hysterectomy may b ...
reduces the risk, and removal of both Fallopian tubes and ovaries (bilateral
salpingo-oophorectomy In medicine, salpingo-oophorectomy is the removal of an ovary and its Fallopian tube. This procedure is most frequently associated with prophylactic surgery in response to the discovery of a BRCA mutation, particularly those of the normally tumo ...
) dramatically reduces the risk of not only ovarian cancer but breast cancer as well. This is still a topic of research, as the link between hysterectomy and lower ovarian cancer risk is controversial. The reasons that hysterectomy may be protective have not been elucidated as of 2015. A diet that includes large amounts of
carotene The term carotene (also carotin, from the Latin ''carota'', "carrot") is used for many related unsaturated hydrocarbon substances having the formula C40Hx, which are synthesized by plants but in general cannot be made by animals (with the exc ...
,
fiber Fiber or fibre (from la, fibra, links=no) is a natural or artificial substance that is significantly longer than it is wide. Fibers are often used in the manufacture of other materials. The strongest engineering materials often incorporate ...
, and
vitamin A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an Nutrient#Essential nutrients, essential micronutrient that an organism needs in small quantities for the proper functioning of its ...
s with low amounts of fat—specifically, a diet with non-starchy vegetables (e.g.
broccoli Broccoli (''Brassica oleracea'' var. ''italica'') is an edible green plant in the cabbage family (family Brassicaceae, genus ''Brassica'') whose large flowering head, stalk and small associated leaves are eaten as a vegetable. Broccoli is cl ...
and
onion An onion (''Allium cepa'' L., from Latin ''cepa'' meaning "onion"), also known as the bulb onion or common onion, is a vegetable that is the most widely cultivated species of the genus ''Allium''. The shallot is a botanical variety of the onion ...
s) may be protective. Dietary fiber is associated with a significant reduced risk of ovarian cancer. A 2021 review found that green leafy vegetables, allium vegetables, fiber,
flavanoid Flavonoids (or bioflavonoids; from the Latin word ''flavus'', meaning yellow, their color in nature) are a class of polyphenolic secondary metabolites found in plants, and thus commonly consumed in the diets of humans. Chemically, flavonoids ...
s and
green tea Green tea is a type of tea that is made from '' Camellia sinensis'' leaves and buds that have not undergone the same withering and oxidation process which is used to make oolong teas and black teas. Green tea originated in China, and since the ...
intake can significantly reduce ovarian cancer risk.


Pathophysiology

Ovarian cancer forms when errors in normal ovarian
cell growth Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater than ...
occur. Usually, when cells grow old or get damaged, they
die Die, as a verb, refers to death, the cessation of life. Die may also refer to: Games * Die, singular of dice, small throwable objects used for producing random numbers Manufacturing * Die (integrated circuit), a rectangular piece of a semicondu ...
, and new cells take their place. Cancer starts when new cells form unneeded, and old or damaged cells do not die as they should. The buildup of extra cells often forms a mass of tissue called an
ovarian tumor Ovarian tumors, or ovarian neoplasms, are tumors arising from the ovary. They can be benign or malignant (ovarian cancer). They consist of mainly solid tissue, while ovarian cysts contain fluid. Histopathologic classification Ovarian tumors are ...
or growth. These abnormal cancer cells have many
genetic abnormalities A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
that cause them to grow excessively. When an ovary releases an egg, the egg follicle bursts open and becomes the
corpus luteum The corpus luteum (Latin for "yellow body"; plural corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is t ...
. This structure needs to be repaired by dividing cells in the ovary. Continuous ovulation for a long time means more repair of the ovary by dividing cells, which can acquire mutations in each division. Overall, the most common gene mutations in ovarian cancer occur in '' NF1, BRCA1, BRCA2, ''and '' CDK12''. Type I ovarian cancers, which tend to be less aggressive, tend to have
microsatellite instability Microsatellite instability (MSI) is the condition of genetic hypermutability (predisposition to mutation) that results from impaired DNA mismatch repair (MMR). The presence of MSI represents phenotypic evidence that MMR is not functioning normal ...
in several genes, including both oncogenes (most notably '' BRAF'' and ''
KRAS ''KRAS'' (Kirsten rat sarcoma virus) is a gene that provides instructions for making a protein called K-Ras, a part of the RAS/MAPK pathway. The protein relays signals from outside the cell to the cell's nucleus. These signals instruct the cell ...
'') and tumor suppressors (most notably '' PTEN''). The most common mutations in Type I cancers are ''KRAS, BRAF, ERBB2, PTEN, PIK3CA,'' and ''ARID1A.'' Type II cancers, the more aggressive type, have different genes mutated, including ''
p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
, BRCA1'', and ''BRCA2''. Low-grade cancers tend to have mutations in KRAS, whereas cancers of any grade that develop from low malignant potential tumors tend to have mutations in p53. Type I cancers tend to develop from precursor lesions, whereas Type II cancers can develop from a
serous tubal intraepithelial carcinoma In physiology, serous fluid or serosal fluid (originating from the Medieval Latin word ''serosus'', from Latin ''serum'') is any of various body fluids resembling serum, that are typically pale yellow or transparent and of a benign nature. The fl ...
. Serous cancers that have BRCA mutations also inevitably have p53 mutations, indicating that the removal of both functional genes is important for cancer to develop. In 50% of high-grade serous cancers, homologous recombination DNA repair is dysfunctional, as are the notch and
FOXM1 Forkhead box protein M1 is a protein that in humans is encoded by the ''FOXM1'' gene. The protein encoded by this gene is a member of the FOX family of transcription factors. Its potential as a target for future cancer treatments led to it being ...
signaling pathways. They also almost always have p53 mutations. Other than this, mutations in high-grade serous carcinoma are hard to characterize beyond their high degree of
genomic instability Genome instability (also genetic instability or genomic instability) refers to a high frequency of mutations within the genome of a cellular lineage. These mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneu ...
. ''BRCA1'' and ''BRCA2'' are essential for homologous recombination DNA repair, and
germline mutation A germline mutation, or germinal mutation, is any detectable variation within germ cells (cells that, when fully developed, become sperm and ova). Mutations in these cells are the only mutations that can be passed on to offspring, when either a mu ...
s in these genes are found in about 15% of women with ovarian cancer. The most common mutations in BRCA1 and BRCA2 are the frameshift mutations that originated in a small founding population of Ashkenazi Jews. Almost 100% of rare mucinous carcinomas have mutations in ''KRAS'' and amplifications of ''ERBB2'' (also known as ''Her2/neu''). Overall, 20% of ovarian cancers have mutations in ''Her2/neu''. Serous carcinomas may develop from
serous tubal intraepithelial carcinoma In physiology, serous fluid or serosal fluid (originating from the Medieval Latin word ''serosus'', from Latin ''serum'') is any of various body fluids resembling serum, that are typically pale yellow or transparent and of a benign nature. The fl ...
, rather than developing spontaneously from ovarian tissue. Other carcinomas develop from cortical inclusion cysts, which are groups of epithelial ovarian cells inside the stroma.


Diagnosis


Examination

Diagnosis of ovarian cancer starts with a physical examination (including a
pelvic examination A pelvic examination is the physical examination of the external and internal female pelvic organs. It is frequently used in gynecology for the evaluation of symptoms affecting the female reproductive and urinary tract, such as pain, bleeding, dis ...
), a blood test (for
CA-125 Mucin-16 (MUC-16) also known as Ovarian cancer-related tumor marker CA125 is a protein that in humans is encoded by the ''MUC16'' gene. MUC-16 is a member of the mucin family glycoproteins. MUC-16 has found application as a tumor marker or biom ...
and sometimes other markers), and
transvaginal ultrasound Vaginal ultrasonography is a medical ultrasonography that applies an ultrasound transducer (or "probe") in the vagina to visualize organs within the pelvic cavity. It is also called transvaginal ultrasonography because the ultrasound waves go ''a ...
. Sometimes a
rectovaginal examination A rectovaginal examination is a type of gynecological examination used to supplement a pelvic examination. In the rectovaginal examination, a doctor or other health care provider places one finger in the vagina and another in the rectum to assess ...
is used to help plan a surgery. The diagnosis must be confirmed with surgery to inspect the
abdominal cavity The abdominal cavity is a large body cavity in humans and many other animals that contains many organs. It is a part of the abdominopelvic cavity. It is located below the thoracic cavity, and above the pelvic cavity. Its dome-shaped roof is the th ...
, take
biopsies A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
(tissue samples for microscopic analysis), and look for cancer cells in the abdominal fluid. This helps to determine if an ovarian mass is
benign Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malign ...
or malignant. Ovarian cancer's early stages (I/II) are difficult to diagnose because most symptoms are nonspecific and thus of little use in diagnosis; as a result, it is rarely diagnosed until it spreads and advances to later stages (III/IV). Additionally, symptoms of ovarian cancer may appear similar to
irritable bowel syndrome Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or abdominal bloating and changes in the consistency of bowel movements. These symptoms may ...
. In women in whom pregnancy is a possibility,
BHCG Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantation ...
level can be measured during the diagnosis process. Serum
alpha-fetoprotein Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the ''AFP'' gene. The ''AFP'' gene is located on the ''q'' arm of chromosome 4 ...
, neuron-specific enolase, and
lactate dehydrogenase Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of lactate to pyruvate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that transfers a hydride from on ...
can be measured in young girls and adolescents with suspected
ovarian tumor Ovarian tumors, or ovarian neoplasms, are tumors arising from the ovary. They can be benign or malignant (ovarian cancer). They consist of mainly solid tissue, while ovarian cysts contain fluid. Histopathologic classification Ovarian tumors are ...
s as younger women with ovarian cancer are more likely to have malignant germ cell tumors. A physical examination, including a pelvic examination, and a pelvic ultrasound (transvaginal or otherwise) are both essential for diagnosis: physical examination may reveal increased abdominal girth and/or
ascites Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, ab ...
(fluid within the abdominal cavity), while pelvic examination may reveal an ovarian or abdominal mass. An adnexal mass is a significant finding that often indicates ovarian cancer, especially if it is fixed, nodular, irregular, solid, and/or bilateral. 13–21% of adnexal masses are caused by malignancy; however, there are other benign causes of adnexal masses, including ovarian follicular cyst,
leiomyoma A leiomyoma, also known as a fibroid, is a benign smooth muscle tumor that very rarely becomes cancer (0.1%). They can occur in any organ, but the most common forms occur in the uterus, small bowel, and the esophagus. Polycythemia may occur due to ...
,
endometriosis Endometriosis is a disease of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Most often this is on the ovaries, f ...
,
ectopic pregnancy Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. Signs and symptoms classically include abdominal pain and vaginal bleeding, but fewer than 50 percent of affected women have both of these symptoms. ...
,
hydrosalpinx A hydrosalpinx is a condition that occurs when a Fallopian tube is blocked and fills with serous or clear fluid near the ovary (distal to the uterus). The blocked tube may become substantially distended giving the tube a characteristic sausage-li ...
, tuboovarian abscess,
ovarian torsion Ovarian torsion (OT) or adnexal torsion is an abnormal condition where an ovary twists on its attachment to other structures, such that blood flow is decreased. Symptoms typically include pelvic pain on one side. While classically the pain is su ...
,
dermoid cyst A dermoid cyst is a teratoma of a cystic nature that contains an array of developmentally mature, solid tissues. It frequently consists of skin, hair follicles, and sweat glands, while other commonly found components include clumps of long hair ...
,
cystadenoma Cystadenoma (or "cystoma") is a type of cystic adenoma. When malignant, it is called cystadenocarcinoma. Classification When not otherwise specified, the ICD-O coding is 8440/0. However, the following classifications also exist: By form * sero ...
(serous or mucinous), diverticular or appendiceal abscess,
nerve sheath tumor A nerve sheath tumor is a type of tumor of the nervous system (nervous system neoplasm) which is made up primarily of the myelin surrounding nerves. From benign tumors like schwannoma to high grade malignant neoplasms known as malignant peripheral ...
,
pelvic kidney A pelvic kidney, also known as an ectopic kidney, is a normal kidney located in the pelvis, instead of the abdomen. This occurs when a kidney does not ascend from its original location in the pelvis to its final location during prenatal developmen ...
,
ureteral The ureters are tubes made of smooth muscle that propel urine from the kidneys to the urinary bladder. In a human adult, the ureters are usually long and around in diameter. The ureter is lined by urothelial cells, a type of transitional epit ...
or bladder diverticulum, benign cystic mesothelioma of the peritoneum, peritoneal tuberculosis, or
paraovarian cyst Paraovarian cysts or paratubal cysts are epithelium-lined fluid-filled cysts in the adnexa adjacent to the fallopian tube and ovary. The terms are used interchangeably, and depend on the location of the cyst. Topic Completed: 1 July 2013. Minor c ...
. Ovaries that can be felt are also a sign of ovarian cancer in postmenopausal women. Other parts of a physical examination for suspected ovarian cancer can include a
breast examination Breast examination, also known as clinical breast examination, is a physical examination performed by a medical professional on an individual presenting with signs and symptoms in a breast, periodically on some people with a family history of breas ...
and a
digital rectal exam Digital rectal examination (DRE; la, palpatio per anum, PPA) is an internal examination of the rectum, performed by a healthcare provider. Prior to a 2018 report from the U.S. Preventive Services Task Force, the DRE was a common and "dreaded" ...
. Palpation of the
supraclavicular The supraclavicular nerves (descending branches) arise from the third and fourth cervical nerves. They emerge beneath the posterior border of the sternocleidomastoideus (sternocleidomastoid muscle), and descend in the posterior triangle of the neck ...
, axillary, and inguinal
lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s may reveal
lymphadenopathy Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cli ...
, which can be indicative of metastasis. Another indicator may be the presence of a
pleural effusion A pleural effusion is accumulation of excessive fluid in the pleural space, the potential space that surrounds each lung. Under normal conditions, pleural fluid is secreted by the parietal pleural capillaries at a rate of 0.6 millilitre per kilog ...
, which can be noted on
auscultation Auscultation (based on the Latin verb ''auscultare'' "to listen") is listening to the internal sounds of the body, usually using a stethoscope. Auscultation is performed for the purposes of examining the circulatory and respiratory systems (hea ...
. When an ovarian malignancy is included in a list of diagnostic possibilities, a limited number of laboratory tests are indicated. A complete blood count and serum electrolyte test is usually obtained; when an ovarian cancer is present, these tests often show a high number of platelets (20–25% of patients) and low blood sodium levels due to chemical signals secreted by the tumor. A positive test for
inhibin A Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Identified in 1986, activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual ...
and inhibin B can indicate a granulosa cell tumor. A blood test for a marker molecule called CA-125 is useful in differential diagnosis and in follow up of the disease, but it by itself has not been shown to be an effective method to screen for early-stage ovarian cancer due to its unacceptable low sensitivity and specificity. CA-125 levels in premenopausal women over 200 U/mL may indicate ovarian cancer, as may any elevation in CA-125 above 35 U/mL in post-menopausal women. CA-125 levels are not accurate in early stage ovarian cancer, as half of stage I ovarian cancer patients have a normal CA-125 level. CA-125 may also be elevated in benign (non-cancerous) conditions, including
endometriosis Endometriosis is a disease of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Most often this is on the ovaries, f ...
,
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
,
uterine fibroids Uterine fibroids, also known as uterine leiomyomas or fibroids, are benign smooth muscle tumors of the uterus. Most women with fibroids have no symptoms while others may have painful or heavy periods. If large enough, they may push on the bl ...
,
menstruation Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of hor ...
,
ovarian cysts An ovarian cyst is a fluid-filled sac within the ovary. Often they cause no symptoms. Occasionally they may produce bloating, lower abdominal pain, or lower back pain. The majority of cysts are harmless. If the cyst either breaks open or causes ...
,
systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...
,
liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the sig ...
,
inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammation, inflammatory conditions of the colon (anatomy), colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine a ...
,
pelvic inflammatory disease Pelvic inflammatory disease, also known as pelvic inflammatory disorder (PID), is an infection of the upper part of the female reproductive system, namely the uterus, fallopian tubes, and ovaries, and inside of the pelvis. Often, there may be no ...
, and
leiomyoma A leiomyoma, also known as a fibroid, is a benign smooth muscle tumor that very rarely becomes cancer (0.1%). They can occur in any organ, but the most common forms occur in the uterus, small bowel, and the esophagus. Polycythemia may occur due to ...
.
HE4 WAP four-disulfide core domain protein 2 - also known as Human Epididymis Protein 4 (HE4) - is a protein that in humans is encoded by the ''WFDC2'' gene. HE4 is a tumor marker of ovarian cancer, with 80% sensitivity at a cut-off A cut-off ...
is another candidate for ovarian cancer testing, though it has not been extensively tested. Other tumor markers for ovarian cancer include
CA19-9 Carbohydrate antigen 19-9 (CA19-9), also known as sialyl-LewisA, is a tetrasaccharide which is usually attached to O- glycans on the surface of cells. It is known to play a role in cell-to-cell recognition processes. It is also a tumor marker used ...
, CA72-4,
CA15-3 CA 15-3, for Carcinoma Antigen 15-3, is a tumor marker for many types of cancer, most notably breast cancer. It is derived from MUC1. CA 15-3 and associated CA 27-29 are different epitopes on the same protein antigen product of the breast cancer ...
,
immunosuppressive acidic protein Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reacti ...
, haptoglobin-alpha, OVX1, mesothelin,
lysophosphatidic acid Lysophosphatidic acid (LPA) is a phospholipid derivative that can act as a signaling molecule. Function LPA acts as a potent mitogen due to its activation of three high-affinity G-protein-coupled receptors called LPAR1, LPAR2, and LPAR3 (a ...
,
osteopontin Osteopontin (OPN), also known as bone /sialoprotein I (BSP-1 or BNSP), early T-lymphocyte activation (ETA-1), secreted phosphoprotein 1 (SPP1), 2ar and Rickettsia resistance (Ric), is a protein that in humans is encoded by the ''SPP1'' gene (secr ...
, and
fibroblast growth factor 23 Fibroblast growth factor 23 (FGF23) is a protein and member of the fibroblast growth factor (FGF) family which participates in the regulation of phosphate in plasma and vitamin D metabolism. In humans it is encoded by the gene. FGF23 decreases rea ...
. Use of blood test panels may help in diagnosis. The OVA1 panel includes CA-125,
beta-2 microglobulin β2 microglobulin (B2M) is a component of MHC class I molecules. MHC class I molecules have α1, α2, and α3 proteins which are present on all nucleated cells (excluding red blood cells). In humans, the β2 microglobulin protein is encoded by th ...
,
transferrin Transferrins are glycoproteins found in vertebrates which bind to and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encode ...
,
apolipoprotein A1 Apolipoprotein AI (ApoA-I) is a protein that in humans is encoded by the ''APOA1'' gene. As the major component of HDL particles, it has a specific role in lipid metabolism. Structure ''APOA1'' is located on chromosome 11, with its specific lo ...
, and
transthyretin Transthyretin (TTR or TBPA) is a transport protein in the plasma and cerebrospinal fluid that transports the thyroid hormone thyroxine (T4) and retinol to the liver. This is how transthyretin gained its name: ''transports thyroxine and retinol'' ...
. OVA1 above 5.0 in premenopausal women and 4.4 in postmenopausal women indicates a high risk for cancer. A different set of laboratory tests is used for detecting sex cord-stromal tumors. High levels of
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
or
dehydroepiandrosterone sulfate Dehydroepiandrosterone sulfate, abbreviated as DHEA sulfate or DHEA-S, also known as androstenolone sulfate, is an endogenous androstane steroid that is produced by the adrenal cortex. It is the 3β-sulfate ester and a metabolite of dehydroepi ...
, combined with other symptoms and high levels of
inhibin A Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Identified in 1986, activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual ...
and inhibin B can be indicative of an SCST of any type. Current research is looking at ways to consider tumor marker
proteomics Proteomics is the large-scale study of proteins. Proteins are vital parts of living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replication of DNA. In ...
in combination with other indicators of disease (i.e. radiology and/or symptoms) to improve diagnostic accuracy. The challenge in such an approach is that the disparate prevalence of ovarian cancer means that even testing with very high sensitivity and specificity will still lead to a number of false positive results, which in turn may lead to issues such as performing surgical procedures in which cancer is not found intraoperatively.
Genomics Genomics is an interdisciplinary field of biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, three-dim ...
approaches have not yet been developed for ovarian cancer. CT scanning is preferred to assess the extent of the tumor in the abdominopelvic cavity, though
magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
can also be used. CT scanning can also be useful for finding
omental caking Omentum (Latin for 'apron') is a medical term referring to layers of peritoneum that surround abdominal organs. The term may refer to: * Greater omentum * Lesser omentum The lesser omentum (small omentum or gastrohepatic omentum) is the double l ...
or differentiating fluid from solid tumor in the abdomen, especially in low malignant potential tumors. However, it may not detect smaller tumors. Sometimes, a
chest x-ray A chest radiograph, called a chest X-ray (CXR), or chest film, is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common film taken in med ...
is used to detect metastases in the chest or
pleural effusion A pleural effusion is accumulation of excessive fluid in the pleural space, the potential space that surrounds each lung. Under normal conditions, pleural fluid is secreted by the parietal pleural capillaries at a rate of 0.6 millilitre per kilog ...
. Another test for metastatic disease, though it is infrequently used, is a
barium enema A lower gastrointestinal series is a medical procedure used to examine and diagnose problems with the human colon of the large intestine. Radiographs (X-ray pictures) are taken while barium sulfate, a radiocontrast agent, fills the colon via an ...
, which can show if the rectosigmoid colon is involved in the disease.
Positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...
,
bone scan A bone scan or bone scintigraphy is a nuclear medicine imaging technique of the bone. It can help diagnose a number of bone conditions, including cancer of the bone or metastasis, location of bone inflammation and fractures (that may not be vi ...
s, and
paracentesis Paracentesis (from Greek κεντάω, "to pierce") is a form of body fluid sampling procedure, generally referring to peritoneocentesis (also called laparocentesis or abdominal paracentesis) in which the peritoneal cavity is punctured by a needl ...
are of limited use; in fact, paracentesis can cause metastases to form at the needle insertion site and may not provide useful results. However, paracentesis can be used in cases where there is no pelvic mass and ascites is still present. A physician suspecting ovarian cancer may also perform
mammography Mammography (also called mastography) is the process of using low-energy X-rays (usually around 30 kVp) to examine the human breast for diagnosis and screening. The goal of mammography is the early detection of breast cancer, typically through d ...
or an
endometrial biopsy The endometrial biopsy is a medical procedure that involves taking a tissue sample of the lining of the uterus. The tissue subsequently undergoes a histologic evaluation which aids the physician in forming a diagnosis. Medical uses There are a ...
(in the case of abnormal bleeding) to assess the possibility of breast malignancies and endometrial malignancy, respectively.
Vaginal ultrasonography Vaginal ultrasonography is a medical ultrasonography that applies an ultrasound transducer (or "probe") in the vagina to visualize organs within the pelvic cavity. It is also called transvaginal ultrasonography because the ultrasound waves go ''a ...
is often the first-line imaging study performed when an adnexal mass is found. Several characteristics of an adnexal mass indicate ovarian malignancy; they usually are solid, irregular, multilocular, and/or large; and they typically have papillary features, central vessels, and/or irregular internal septations. However, SCST has no definitive characteristics on radiographic study. To definitively diagnose ovarian cancer, a surgical procedure to inspect the abdomen is required. This can be an open procedure (
laparotomy A laparotomy is a surgical procedure involving a surgical incision through the abdominal wall to gain access into the abdominal cavity. It is also known as a celiotomy. Origins and history The first successful laparotomy was performed without ane ...
, incision through the
abdominal wall In anatomy, the abdominal wall represents the boundaries of the abdominal cavity. The abdominal wall is split into the anterolateral and posterior walls. There is a common set of layers covering and forming all the walls: the deepest being the v ...
) or
keyhole surgery Laparoscopy () is an operation performed in the abdomen or pelvis using small incisions (usually 0.5–1.5 cm) with the aid of a camera. The laparoscope aids diagnosis or therapeutic interventions with a few small cuts in the abdomen.Medl ...
(
laparoscopy Laparoscopy () is an operation performed in the abdomen or pelvis using small incisions (usually 0.5–1.5 cm) with the aid of a camera. The laparoscope aids diagnosis or therapeutic interventions with a few small cuts in the abdomen.Medli ...
). During this procedure, suspicious tissue is removed and sent for microscopic analysis. Usually, this includes a unilateral
salpingo-oophorectomy In medicine, salpingo-oophorectomy is the removal of an ovary and its Fallopian tube. This procedure is most frequently associated with prophylactic surgery in response to the discovery of a BRCA mutation, particularly those of the normally tumo ...
, removal of a single affected ovary and Fallopian tube. Fluid from the abdominal cavity can also be analyzed for cancerous cells. If cancer is found, this procedure can also be used to determine the extent of its spread (which is a form of
tumor staging Cancer staging is the process of determining the extent to which a cancer has developed by growing and spreading. Contemporary practice is to assign a number from I to IV to a cancer, with I being an isolated cancer and IV being a cancer that ha ...
).
Pafolacianine Pafolacianine, sold under the brand name Cytalux, is an optical imaging agent used in fluorescence-guided surgery. The most common side effects of pafolacianine include infusion-related reactions, including nausea, vomiting, abdominal pain ...
is
indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...
for use in adults with ovarian cancer to help identify cancerous lesions during surgery. It is a diagnostic agent that is administered in the form of an intravenous injection prior to surgery.


Risk scoring

A widely recognized method of estimating the risk of malignant ovarian cancer is the risk of malignancy index (RMI), calculated based on an initial workup. An RMI score of over 200 or 250 is generally felt to indicate high risk for ovarian cancer. The RMI is calculated as: :RMI = ultrasound score × menopausal score x CA-125 level in U/ml. Two methods can be used to determine the ultrasound score and menopausal score, with the resultant scores being referred to as RMI 1 and RMI 2, respectively, depending on what method is used. Another method for quantifying risk of ovarian cancer is the Risk of Ovarian Cancer Algorithm (ROCA), which observes levels over time and determines if they are increasing rapidly enough to warrant transvaginal ultrasound. The Risk of Ovarian Malignancy algorithm uses CA-125 levels and
HE4 WAP four-disulfide core domain protein 2 - also known as Human Epididymis Protein 4 (HE4) - is a protein that in humans is encoded by the ''WFDC2'' gene. HE4 is a tumor marker of ovarian cancer, with 80% sensitivity at a cut-off A cut-off ...
levels to calculate the risk of ovarian cancer; it may be more effective than RMI. The IOTA models can be used to estimate the probability that an adnexal tumor is malignant. They include LR2 risk model, The Simple Rules risk (SRrisk) calculation and Assessment of Different Neoplasias in the Adnexa (ADNEX) model that can be used to assess risk of malignancy in an adnexal mass, based on its characteristics and risk factors. The QCancer (Ovary) algorithm is used to predict likelihood of ovarian cancer from risk factors.


Pathology

Ovarian cancers are classified according to the microscopic appearance of their structures (
histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
or
histopathology Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία '' -logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spe ...
). Histology dictates many aspects of clinical treatment, management, and
prognosis Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stabl ...
. The gross pathology of ovarian cancers is very similar regardless of histologic type: ovarian tumors have solid and cystic masses. According to
SEER In the United States, the efficiency of air conditioners is often rated by the seasonal energy efficiency ratio (SEER) which is defined by the Air Conditioning, Heating, and Refrigeration Institute, a trade association, in its 2008 standard AHR ...
, the types of ovarian cancers in women age 20 and over are: Ovarian cancers are histologically and genetically divided into type I or type II. Type I cancers are of low histological grade and include endometrioid, mucinous, and clear-cell carcinomas. Type II cancers are of higher histological grade and include serous carcinoma and carcinosarcoma.


Epithelial carcinoma

Epithelial ovarian cancer typically presents at an advanced stage and is derived from the malignant transformation of the epithelium of the ovarian surface, peritoneum, or fallopian tube. It is the most common cause of gynecologic cancer death. There are various types of epithelial ovarian cancer, including serous tumor, endometrioid tumor, clear cell tumor, mucinous tumor, and undifferentiated or unclassified tumors. Annually worldwide, 230,000 women will be diagnosed and 150,000 will die. It has a 46% 5 year survival rate after diagnosis because of the advanced stage of the disease at the time of diagnosis. Typically, around 75% of patients are diagnosed as having an advanced stage of the disease because of the asymptomatic nature of its presentation. There is a genomic predisposition to epithelial ovarian cancer and the BRCA1 and BRCA2 genes have been found to be the causative genes in 65-75% of hereditary epithelial ovarian cancer.


= Serous carcinoma

= Serous ovarian cancer is the most common type of epithelial ovarian cancer and it accounts for about two-thirds of cases of epithelial ovarian cancer. Low-grade serous carcinoma is less aggressive than high-grade serous carcinomas, though it does not typically respond well to chemotherapy or hormonal treatments. Serous carcinomas are thought to begin in the
Fallopian tube The fallopian tubes, also known as uterine tubes, oviducts or salpinges (singular salpinx), are paired tubes in the human female that stretch from the uterus to the ovaries. The fallopian tubes are part of the female reproductive system. In ot ...
. High grade serous carcinoma accounts for 75% of all epithelial ovarian cancer. About 15-20% of high grade serous carcinoma have germline BRCA1 and BRCA2 mutations. Histologically, the growth pattern of high grade serous carcinoma is heterogenous and has some papillary or solid growth patterns. The tumor cells are atypical with large, irregular nuclei. It has a high proliferation rate. 50% of the time, serous carcinomas are bilateral, and in 85% of cases, they have spread beyond the ovary at the time of diagnosis. Serous Tubal Intraepithelial Carcinoma (STIC) is now recognized to be the precursor lesion of most so-called ovarian high-grade serous carcinomas. STIC is characterised by #Abnormal p53 staining #Ki67 proliferation index in excess of 10% #Positive WT1 (to exclude metastases)


= Small-cell carcinoma

= Small-cell ovarian carcinoma is rare and aggressive, with two main subtypes: hypercalcemic and pulmonary. This rare malignancy most commonly affects young women under the age of 40 years old with a range between 14 months to 58 years. The mean age of diagnosis of 24 years. Approximately two-thirds of patients will present with paraneoplastic hypercalcemia meaning they have high blood calcium levels for an unknown reason. The tumor secretes Parathyroid hormone related protein which acts similarly to PTH and binds PTH receptors in the bone and kidney causing hypercalcemia. Recent research has found an inactivating germline and somatic mutation of ''SMARCA4'' gene. The hypercalcemic subtype is very aggressive and has a overall survival rate of 16% with a recurrence rate of 65% in patients who receive treatment. Patients who have spread of the disease to other parts of the body tend to die 2 years after the diagnosis. Extra-ovarian spread is involved in 50% of cases and lymph node spread is present in 55% of cases. The most common initial presentation is a rapidly growing unilateral pelvic mass with a mean size of 15 cm. Histologically, it is characterized by many sheets of small, round, tightly packed cells with clusters, nests, and cords. Immunohistochemistry is typically positive for vimentin, cytokeratin, CD10, p53, and WT-1. Small cell ovarian carcinoma of the pulmonary subtype presents differently from the hypercalcemic subtype. Typically, pulmonary small cell ovarian cancer usually affects both ovaries of older women and looks like oat-cell carcinoma of the lung. The average age of disease onset is 59 years old and approximately 45% of cases are bilateral for the pulmonary subtype. Additionally, several hormones can be elevated in the pulmonary subtype including serotonin, somatostatin, insulin, gastrin, and calcitonin.


Primary peritoneal carcinoma

Primary peritoneal carcinomas develop from the
peritoneum The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesoth ...
, a membrane that covers the
abdominal cavity The abdominal cavity is a large body cavity in humans and many other animals that contains many organs. It is a part of the abdominopelvic cavity. It is located below the thoracic cavity, and above the pelvic cavity. Its dome-shaped roof is the th ...
that has the same embryonic origin as the ovary. They are often discussed and classified with ovarian cancers when they affect the ovary. They can develop even after the ovaries have been removed and may appear similar to
mesothelioma Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The most common area affected is the lining of the lungs and chest wall. Less commonly the lining ...
.


= Clear-cell carcinoma

= Clear cell ovarian carcinoma is a rare subtype of epithelial ovarian cancer. Those diagnosed with clear cell ovarian carcinoma are typically younger at the age of diagnosis and diagnosed at earlier stages than other subtypes of epithelial ovarian cancer. The highest incidence of clear cell carcinoma of the ovary have been observed among young Asian women, especially those of Korean, Taiwanese, and Japanese background. Endometriosis has been linked to being the main risk factor for the development of clear cell carcinoma of the ovary and has been found to be present in 50% of women diagnosed with clear cell carcinoma of the ovary. The development of clots in the legs such as deep vein thromboembolism or in the lungs with pulmonary embolism is reported to be 40% higher in patients with clear cell carcinoma than other epithelial ovarian cancer subtypes. Mutations in molecular pathways such as ARID1A, PIK3, and PIK3CA have been found to be linked to clear cell carcinoma. They typically present as a large, unilateral mass, with a mean size between 13–15 cm. 90% of cases are unilateral. Clear-cell ovarian carcinomas do not typically respond well to chemotherapy due to intrinsic chemoresistance therefore treatment is typically with aggressive cytoreductive surgery and platinum-based chemotherapy.


= Clear-cell adenocarcinoma

= Clear-cell adenocarcinomas are histopathologically similar to other clear cell carcinomas, with
clear cell In histology, a clear cell is a cell that shows a clear cytoplasm when stained with hematoxylin and eosin (H&E). Normal histology In the skin, some secretory cells in the epithelium appear as clear cells, and are one of the components of eccrine ...
s and hobnail cells. They represent approximately 5–10% of epithelial ovarian cancers and are associated with endometriosis in the pelvic cavity. They are typically early-stage and therefore curable by surgery, but advanced clear-cell adenocarcinomas (approximately 20%) have a poor prognosis and are often resistant to platinum chemotherapy.


= Endometrioid

= Endometrioid adenocarcinomas make up approximately 13-15% of all ovarian cancers. Because they are typically low-grade, endometrioid adenocarcinomas have a good prognosis. The median age of diagnosis is around 53 years of age. These tumors frequently co-occur with
endometriosis Endometriosis is a disease of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Most often this is on the ovaries, f ...
or endometrial cancer. Cancer antigen 125 levels are typically elevated and a family history of a first degree relative with endometrioid ovarian cancer is associated with increased risk of developing endometrioid ovarian cancer. The average tumor size is larger than 10 cm.


Malignant mixed müllerian tumor (carcinosarcoma)

Mixed müllerian tumors make up less than 1% of ovarian cancer. They have epithelial and mesenchymal cells visible and tend to have a poor prognosis.


= Mucinous

= Mucinous tumors include mucinous adenocarcinoma and mucinous cystadenocarcinoma.


Mucinous adenocarcinoma

Mucinous adenocarcinomas make up 5–10% of epithelial ovarian cancers. Histologically, they are similar to intestinal or cervical adenocarcinomas and are often actually metastases of appendiceal or
colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...
s. Advanced mucinous adenocarcinomas have a poor prognosis, generally worse than serous tumors, and are often resistant to platinum chemotherapy, though they are rare.


Pseudomyxoma peritonei

''Pseudomyxoma peritonei'' refers to a collection of encapsulated mucous or gelatinous material in the abdominopelvic cavity, which is very rarely caused by a primary mucinous ovarian tumor. More commonly, it is associated with ovarian metastases of intestinal cancer.


= Undifferentiated epithelial

= Undifferentiated cancers - those where the cell type cannot be determined - make up about 10% of epithelial ovarian cancers and have a comparatively poor prognosis. When examined under the microscope, these tumors have very abnormal cells that are arranged in clumps or sheets. Usually there are recognizable clumps of serous cells inside the tumor.


Malignant Brenner tumor

Malignant Brenner tumors are rare. Histologically, they have dense fibrous stroma with areas of transitional epithelium and some squamous differentiation. To be classified as a malignant Brenner tumor, it must have Brenner tumor foci and transitional cell carcinoma. The transitional cell carcinoma component is typically poorly differentiated and resembles urinary tract cancer.


Transitional cell carcinoma

Transitional cell carcinomas represent less than 5% of ovarian cancers. Histologically, they appear similar to
bladder carcinoma Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become mali ...
. The prognosis is intermediate - better than most epithelial cancers but worse than malignant Brenner tumors.


Sex cord-stromal tumor

Sex cord-stromal tumor, including
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
-producing
granulosa cell tumor Granulosa cell tumours are tumours that arise from granulosa cells. They are estrogen secreting tumours and present as large, complex, ovarian masses. These tumours are part of the sex cord-gonadal stromal tumour or non-epithelial group of tumours ...
, the benign
thecoma Thecomas or theca cell tumors are benign Ovarian cancer, ovarian neoplasms composed only of theca cells. Histogenetically they are classified as sex cord-stromal tumours. They are typically estrogen-producing and they occur in older women (mean a ...
, and virilizing Sertoli-Leydig cell tumor or arrhenoblastoma, accounts for 7% of ovarian cancers. They occur most frequently in women between 50 and 69 years of age but can occur in women of any age, including young girls. They are not typically aggressive and are usually unilateral; they are therefore usually treated with surgery alone. Sex cord-stromal tumors are the main hormone-producing ovarian tumors. Several different cells from the
mesenchyme Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every o ...
can give rise to sex-cord or stromal tumors. These include
fibroblast A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...
s and endocrine cells. The symptoms of a sex-cord or stromal ovarian tumor can differ from other types of ovarian cancer. Common signs and symptoms include
ovarian torsion Ovarian torsion (OT) or adnexal torsion is an abnormal condition where an ovary twists on its attachment to other structures, such that blood flow is decreased. Symptoms typically include pelvic pain on one side. While classically the pain is su ...
,
hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
from or rupture of the tumor, an abdominal mass, and hormonal disruption. In children, isosexual precocious pseudopuberty may occur with granulosa cell tumors since they produce estrogen. These tumors cause abnormalities in menstruation ( excessive bleeding, infrequent menstruation, or no menstruation) or postmenopausal bleeding. Because these tumors produce estrogen, they can cause or occur at the same time as
endometrial cancer Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most o ...
or
breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...
. Other sex-cord/stromal tumors present with distinct symptoms. Sertoli-Leydig cell tumors cause
virilization Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens. Virilization is most commonly used in three medical and biology ...
and excessive hair growth due to the production of
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
and
androstenedione Androstenedione, or 4-androstenedione (abbreviated as A4 or Δ4-dione), also known as androst-4-ene-3,17-dione, is an endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehydroepia ...
, which can also cause
Cushing's syndrome Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a ...
in rare cases. Also, sex-cord stromal tumors occur that do not cause a hormonal imbalance, including benign fibromas, which cause ascites and
hydrothorax Hydrothorax is a type of pleural effusion in which transudate accumulates in the pleural cavity. This condition is most likely to develop secondary to congestive heart failure, following an increase in hydrostatic pressure within the lungs. More ...
. With germ cell tumors, sex cord-stromal tumors are the most common ovarian cancer diagnosed in women under 20.


= Granulosa cell tumor

= Granulosa cell tumors are the most common sex-cord stromal tumors, making up 70% of cases, and are divided into two histologic subtypes: adult granulosa cell tumors, which develop in women over 50, and juvenile granulosa tumors, which develop before puberty or before the age of 30. Both develop in the
ovarian follicle An ovarian follicle is a roughly spheroid cellular aggregation set found in the ovaries. It secretes hormones that influence stages of the menstrual cycle. At the time of puberty, women have approximately 200,000 to 300,000 follicles, each with th ...
from a population of cells that surrounds
germinal cell Germinal may refer to: *Germinal (French Republican Calendar), the seventh month of the calendar, approximately March 21 - April 19 Émile Zola * ''Germinal'' (novel), an 1885 novel by Émile Zola ** ''Germinal'' (1913 film), a French silent film ...
s.


Adult granulosa cell tumor

Adult granulosa cell tumors are characterized by later onset (30+ years, 50 on average). These tumors produce high levels of estrogen, which causes its characteristic symptoms: menometrorrhagia;
endometrial hyperplasia Endometrial hyperplasia is a condition of excessive proliferation of the cells of the endometrium, or inner lining of the uterus. Most cases of endometrial hyperplasia result from high levels of estrogens, combined with insufficient levels of t ...
; tender, enlarged breasts; postmenopausal bleeding; and
secondary amenorrhea Amenorrhea is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen, most commonly, during pregnancy and lactation (breastfeeding). Outside the reproductive years, there is absence of menses ...
. The mass of the tumor can cause other symptoms, including abdominal pain and distension, or symptoms similar to an
ectopic pregnancy Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. Signs and symptoms classically include abdominal pain and vaginal bleeding, but fewer than 50 percent of affected women have both of these symptoms. ...
if the tumor bleeds and ruptures.


Juvenile granulosa cell tumor


= Sertoli-Leydig cell tumor

= Sertoli-Leydig tumors are most common in women before the age of 30, and particularly common before puberty.


= Sclerosing stromal tumors

= Sclerosing stromal tumors typically occur in girls before puberty or women before the age of 30.


Germ cell tumor

Germ cell tumors of the ovary develop from the ovarian
germ cells Germ or germs may refer to: Science * Germ (microorganism), an informal word for a pathogen * Germ cell, cell that gives rise to the gametes of an organism that reproduces sexually * Germ layer, a primary layer of cells that forms during embr ...
. Germ cell tumor accounts for about 30% of ovarian tumors, but only 5% of ovarian cancers, because most germ-cell tumors are
teratoma A teratoma is a tumor made up of several different types of tissue, such as hair, muscle, teeth, or bone. Teratomata typically form in the ovary, testicle, or coccyx. Symptoms Symptoms may be minimal if the tumor is small. A testicular terato ...
s and most teratomas are benign. Malignant teratomas tend to occur in older women, when one of the germ layers in the tumor develops into a
squamous cell carcinoma Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
. Germ-cell tumors tend to occur in young women (20s–30s) and girls, making up 70% of the ovarian cancer seen in that age group. Germ-cell tumors can include dysgerminomas, teratomas, yolk sac tumors/endodermal sinus tumors, and choriocarcinomas, when they arise in the ovary. Some germ-cell tumors have an
isochromosome An isochromosome is an unbalanced structural abnormality in which the arms of the chromosome are mirror images of each other. The chromosome consists of two copies of either the long (q) arm or the short (p) arm because isochromosome formation ...
12, where one arm of chromosome 12 is deleted and replaced with a duplicate of the other. Most germ-cell cancers have a better prognosis than other subtypes and are more sensitive to chemotherapy. They are more likely to be stage I at diagnosis. Overall, they metastasize more frequently than epithelial ovarian cancers. In addition, the cancer markers used vary with tumor type:
choriocarcinomas Choriocarcinoma is a malignant, trophoblastic cancer, usually of the placenta. It is characterized by early hematogenous spread to the lungs. It belongs to the malignant end of the spectrum in gestational trophoblastic disease (GTD). It is also cl ...
are monitored with
beta-HCG Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantatio ...
and endodermal sinus tumors with
alpha-fetoprotein Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the ''AFP'' gene. The ''AFP'' gene is located on the ''q'' arm of chromosome 4 ...
. Germ-cell tumors are typically discovered when they become large, palpable masses. However, like sex cord tumors, they can cause ovarian torsion or hemorrhage and, in children, isosexual precocious puberty. They frequently metastasize to nearby lymph nodes, especially para-aortic and pelvic lymph nodes. The most common symptom of germ cell tumors is subacute abdominal pain caused by the tumor bleeding,
necrotizing Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
, or stretching the ovarian capsule. If the tumor ruptures, causes significant bleeding, or torses the ovary, it can cause acute abdominal pain, which occurs in less than 10% of those with germ-cell tumors. They can also secrete hormones which change the
menstrual cycle The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...
. In 25% of germ-cell tumors, the cancer is discovered during a routine examination and does not cause symptoms. Diagnosing germ cell tumors may be difficult because the normal menstrual cycle and
puberty Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a boy. ...
can cause pain and pelvic symptoms, and a young woman may even believe these symptoms to be those of pregnancy, and not seek treatment due to the stigma of
teen pregnancy Teenage pregnancy, also known as adolescent pregnancy, is pregnancy in a female adolescent or young adult under the age of 20. This includes those who are Legal adult, legally considered adults in their country. The WHO defines adolescence as the ...
. Blood tests for alpha-fetoprotein,
karyotype A karyotype is the general appearance of the complete set of metaphase chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is disce ...
, human chorionic gonadotropin, and liver function are used to diagnose germ cell tumor and potential co-occurring gonadal dysgenesis. A germ cell tumor may be initially mistaken for a benign
ovarian cyst An ovarian cyst is a fluid-filled sac within the ovary. Often they cause no symptoms. Occasionally they may produce bloating, lower abdominal pain, or lower back pain. The majority of cysts are harmless. If the cyst either breaks open or causes ...
.


= Dysgerminoma

= Dysgerminoma accounts for 35% of ovarian cancer in young women and is the most likely germ cell tumor to metastasize to the lymph nodes; nodal metastases occur in 25–30% of cases. These tumors may have mutations in the ''KIT'' gene, a mutation known for its role in
gastrointestinal stromal tumor Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs arise in the smooth muscle pacemaker interstitial cell of Cajal, or similar cells. They are defined as tumors whose behavior is ...
. People with an XY karyotype and ovaries (
gonadal dysgenesis Gonadal dysgenesis is classified as any congenital developmental disorder of the reproductive system in the male or female. It is the atypical development of the gonads in an embryo, with reproductive tissue replaced with functionless, fibrous ti ...
) or an X,0 karyotype and ovaries (
Turner syndrome Turner syndrome (TS), also known as 45,X, or 45,X0, is a genetic condition in which a female is partially or completely missing an X chromosome. Signs and symptoms vary among those affected. Often, a short and webbed neck, low-set ears, low hair ...
) who develop a unilateral dysgerminoma are at risk for a
gonadoblastoma A gonadoblastoma is a complex neoplasm composed of a mixture of gonadal elements, such as large primordial germ cells, immature Sertoli cells or granulosa cells of the sex cord, and gonadal stromal cells. Gonadoblastomas are by definition benign, ...
in the other ovary, and in this case, both ovaries are usually removed when a unilateral dysgerminoma is discovered to avoid the risk of another malignant tumor. Gonadoblastomas in people with Swyer or Turner syndrome become malignant in approximately 40% of cases. However, in general, dysgerminomas are bilateral 10–20% of the time. They are composed of cells that cannot differentiate further and develop directly from germ cells or from gonadoblastomas. Dysgerminomas contain
syncytiotrophoblast Syncytiotrophoblast (from the Greek 'syn'- "together"; 'cytio'- "of cells"; 'tropho'- "nutrition"; 'blast'- "bud") is the epithelial covering of the highly vascular embryonic placental villi, which invades the wall of the uterus to establish nut ...
s in approximately 5% of cases, and can therefore cause elevated hCG levels. On gross appearance, dysgerminomas are typically pink to tan-colored, have multiple lobes, and are solid. Microscopically, they appear identical to
seminoma A seminoma is a germ cell tumor of the testicle or, more rarely, the mediastinum or other extra-gonadal locations. It is a Malignancy, malignant neoplasm and is one of the most treatable and curable cancers, with a survival rate above 95% if dis ...
s and very close to embryonic primordial germ cells, having large, polyhedral, rounded
clear cell In histology, a clear cell is a cell that shows a clear cytoplasm when stained with hematoxylin and eosin (H&E). Normal histology In the skin, some secretory cells in the epithelium appear as clear cells, and are one of the components of eccrine ...
s. The nuclei are uniform and round or square with prominent
nucleoli The nucleolus (, plural: nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of s ...
and the
cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
has high levels of
glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one o ...
. Inflammation is another prominent histologic feature of dysgerminomas.


= Choriocarcinoma

= Choriocarcinoma can occur as a primary ovarian tumor developing from a germ cell, though it is usually a gestational disease that metastasizes to the ovary. Primary ovarian choriocarcinoma has a poor prognosis and can occur without a pregnancy. They produce high levels of hCG and can cause
early puberty In medicine, precocious puberty is puberty occurring at an unusually early age. In most cases, the process is normal in every aspect except the unusually early age and simply represents a variation of normal development. In a minority of childr ...
in children or menometrorrhagia (irregular, heavy menstruation) after menarche.


= Immature (solid) teratoma

= Immature, or solid, teratomas are the most common type of ovarian germ cell tumor, making up 40–50% of cases. Teratomas are characterized by the presence of disorganized tissues arising from all three embryonic
germ layer A germ layer is a primary layer of cells that forms during embryonic development. The three germ layers in vertebrates are particularly pronounced; however, all eumetazoans (animals that are sister taxa to the sponges) produce two or three pr ...
s:
ectoderm The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from t ...
,
mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical E ...
, and
endoderm Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gast ...
; immature teratomas also have undifferentiated
stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
s that make them more malignant than mature teratomas (dermoid cysts). The different tissues are visible on gross pathology and often include bone, cartilage, hair,
mucus Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It is ...
, or
sebum A sebaceous gland is a microscopic exocrine gland in the skin that opens into a hair follicle to secrete an oily or waxy matter, called sebum, which lubricates the hair and skin of mammals. In humans, sebaceous glands occur in the greatest nu ...
, but these tissues are not visible from the outside, which appears to be a solid mass with lobes and cysts. Histologically, they have large amounts of
neuroectoderm Neuroectoderm (or neural ectoderm or neural tube epithelium) consists of cells derived from ectoderm. Formation of the neuroectoderm is first step in the development of the nervous system. The neuroectoderm receives bone morphogenetic protein-inh ...
organized into sheets and tubules along with
glia Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form mye ...
; the amount of neural tissue determines the histologic grade. Immature teratomas usually only affect one ovary (10% co-occur with dermoid cysts) and usually metastasize throughout the peritoneum. They can also cause mature teratoma implants to grow throughout the abdomen in a disease called growing teratoma syndrome; these are usually benign but will continue to grow during chemotherapy, and often necessitate further surgery. Unlike mature teratomas, immature teratomas form many
adhesions Adhesions are fibrous bands that form between tissues and organs, often as a result of injury during surgery. They may be thought of as internal scar tissue that connects tissues not normally connected. Pathophysiology Adhesions form as a natural ...
, making them less likely to cause ovarian torsion. There is no specific marker for immature teratomas, but
carcinoembryonic antigen Carcinoembryonic antigen (CEA) describes a set of highly related glycoproteins involved in cell adhesion. CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birth. Consequently, CEA is ...
(CEA), CA-125, CA19-9, or AFP can sometimes indicate an immature teratoma. Stage I teratomas make up the majority (75%) of cases and have the best prognosis, with 98% of patients surviving 5 years; if a Stage I tumor is also grade 1, it can be treated with unilateral surgery only. Stage II though IV tumors make up the remaining quarter of cases and have a worse prognosis, with 73–88% of patients surviving 5 years.


= Mature teratoma (dermoid cyst)

= Mature teratomas, or dermoid cysts, are rare tumors consisting of mostly benign tissue that develop after menopause. The tumors consist of disorganized tissue with nodules of malignant tissue, which can be of various types. The most common malignancy is
squamous cell carcinoma Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
, but
adenocarcinoma Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ) (AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or ...
,
basal-cell carcinoma Basal-cell carcinoma (BCC), also known as basal-cell cancer, is the most common type of skin cancer. It often appears as a painless raised area of skin, which may be shiny with small blood vessels running over it. It may also present as a raise ...
,
carcinoid tumor A carcinoid (also carcinoid tumor) is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut (jejunum, ileum, appendix, and cecum) ...
,
neuroectodermal tumor A neuroectodermal neoplasm is a neoplasm or tumor of the neuroectoderm.Neuroectodermal tumor
entry in the public ...
,
malignant melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the Biological pigment, pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, i ...
,
sarcoma A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal (connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sarcom ...
, sebaceous tumor, and
struma ovarii A struma ovarii (literally: goitre of the ovary) is a rare disease, rare form of monodermal teratoma that contains mostly thyroid tissue, which may cause hyperthyroidism. Despite its name, struma ovarii is not restricted to the ovary. The vast ma ...
can also be part of the dermoid cyst. They are treated with surgery and adjuvant platinum chemotherapy or radiation.


= Yolk sac tumor/endodermal sinus tumor

=
Yolk sac The yolk sac is a membranous sac attached to an embryo, formed by cells of the hypoblast layer of the bilaminar embryonic disc. This is alternatively called the umbilical vesicle by the Terminologia Embryologica (TE), though ''yolk sac'' is far ...
tumors, formerly called endodermal sinus tumors, make up approximately 10–20% of ovarian germ cell malignancies, and have the worst prognosis of all ovarian germ cell tumors. They occur both before menarche (in one-third of cases) and after menarche (the remaining two-thirds of cases). Half of the people with yolk sac tumors are diagnosed in stage I. Typically, they are unilateral until metastasis, which occurs within the peritoneal cavity and via the bloodstream to the lungs. Yolk sac tumors grow quickly and recur easily, and are not easily treatable once they have recurred. Stage I yolk sac tumors are highly treatable, with a 5-year disease-free survival rate of 93%, but stage II-IV tumors are less treatable, with survival rates of 64–91%. Their gross appearance is solid, friable, and yellow, with necrotic and hemorrhagic areas. They also often contain cysts that can degenerate or rupture. Histologically, yolk sac tumors are characterized by the presence of Schiller-Duval bodies (which are pathognomonic for yolk sac tumors) and a reticular pattern. Yolk sac tumors commonly secrete
alpha-fetoprotein Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the ''AFP'' gene. The ''AFP'' gene is located on the ''q'' arm of chromosome 4 ...
and can be immunohistochemically stained for its presence; the level of alpha-fetoprotein in the blood is a useful marker of recurrence.


= Embryonal carcinoma

= Embryonal carcinomas, a rare tumor type usually found in mixed tumors, develop directly from germ cells but are not terminally differentiated; in rare cases, they may develop in dysgenetic gonads. They can develop further into a variety of other neoplasms, including choriocarcinoma, yolk sac tumor, and teratoma. They occur in younger people, with an average age at diagnosis of 14, and secrete both alpha-fetoprotein (in 75% of cases) and hCG. Histologically, embryonal carcinoma appears similar to the embryonic disc, made up of epithelial,
anaplastic Anaplasia (from grc, ἀνά ''ana'', "backward" + πλάσις ''plasis'', "formation") is a condition of cells with poor cellular differentiation, losing the morphological characteristics of mature cells and their orientation with respect to ...
cells in disorganized sheets, with gland-like spaces and papillary structures.


= Polyembryoma

= Polyembryomas, the most immature form of teratoma and very rare ovarian tumors, are histologically characterized by having several
embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
-like bodies with structures resembling a germ disk,
yolk sac The yolk sac is a membranous sac attached to an embryo, formed by cells of the hypoblast layer of the bilaminar embryonic disc. This is alternatively called the umbilical vesicle by the Terminologia Embryologica (TE), though ''yolk sac'' is far ...
, and
amniotic sac The amniotic sac, also called the bag of waters or the membranes, is the sac in which the embryo and later fetus develops in amniotes. It is a thin but tough transparent pair of membranes that hold a developing embryo (and later fetus) until shor ...
. Syncytiotrophoblast giant cells also occur in polyembryomas.


Squamous cell carcinoma

Primary ovarian squamous cell carcinomas are rare and have a poor prognosis when advanced. More typically, ovarian squamous cell carcinomas are cervical metastases, areas of differentiation in an endometrioid tumor, or derived from a mature teratoma.


Mixed tumors

Mixed tumors contain elements of more than one of the above classes of tumor histology. To be classed as a mixed tumor, the minor type must make up more than 10% of the tumor. Though mixed carcinomas can have any combination of cell types, mixed ovarian cancers are typically serous/endometrioid or clear cell/endometrioid. Mixed germ cell tumors make up approximately 25–30% of all germ cell ovarian cancers, with combinations of dysgerminoma, yolk sac tumor, and/or immature teratoma. The prognosis and treatment vary based on the component cell types.


Secondary ovarian cancer

Ovarian cancer can also be a secondary cancer, the result of
metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
from a primary cancer elsewhere in the body. About 5-30% of ovarian cancers are due to metastases, while the rest are primary cancers. Common primary cancers are
breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...
,
colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...
,
appendiceal cancer Appendix cancer are very rare cancers of the vermiform appendix. Gastrointestinal stromal tumors are rare tumors with malignant potential. Primary lymphomas can occur in the appendix. Breast cancer, colon cancer, and tumors of the female genital ...
, and
stomach cancer Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lymph ...
(primary gastric cancers that metastasize to the ovary are called Krukenberg tumors). Krukenberg tumors have signet ring cells and mucinous cells. Endometrial cancer and lymphomas can also metastasize to the ovary.


Borderline tumors

Ovarian
borderline tumor A borderline tumor, sometimes called low malignant potential (LMP) tumor, is a distinct but yet heterogeneous group of tumors defined by their histopathology as atypical epithelial proliferation without stromal invasion. This topic last updated: Fe ...
s, sometimes called low malignant potential (LMP) ovarian tumors, have some benign and some malignant features. LMP tumors make up approximately 10%-15% of all ovarian tumors. They develop earlier than epithelial ovarian cancer, around the age of 40–49. They typically do not have extensive invasion; 10% of LMP tumors have areas of stromal microinvasion (<3mm, <5% of tumor). LMP tumors have other abnormal features, including increased mitosis, changes in cell size or nucleus size, abnormal nuclei, cell stratification, and small projections on cells (papillary projections). Serous and/or mucinous characteristics can be seen on histological examination, and serous histology makes up the overwhelming majority of advanced LMP tumors. More than 80% of LMP tumors are Stage I; 15% are stage II and III and less than 5% are stage IV. Implants of LMP tumors are often non-invasive.


Staging

Ovarian cancer is staged using the FIGO staging system and uses information obtained after surgery, which can include a total
abdominal hysterectomy Hysterectomy is the surgical removal of the uterus. It may also involve removal of the cervix, ovary, ovaries (oophorectomy), Fallopian tubes (salpingectomy), and other surrounding structures. Usually performed by a gynaecology, gynecologist, a ...
via midline laparotomy, removal of (usually) both ovaries and Fallopian tubes, (usually) the omentum, pelvic (peritoneal) washings, assessment of retroperitoneal lymph nodes (including the
pelvic The pelvis (plural pelves or pelvises) is the lower part of the trunk, between the abdomen and the thighs (sometimes also called pelvic region), together with its embedded skeleton (sometimes also called bony pelvis, or pelvic skeleton). The ...
and para-aortic lymph nodes),
appendectomy An appendectomy, also termed appendicectomy, is a Surgery, surgical operation in which the vermiform appendix (a portion of the intestine) is removed. Appendectomy is normally performed as an urgent or emergency procedure to treat complicated acu ...
in suspected mucinous tumors, and pelvic/peritoneal biopsies for
cytopathology Cytopathology (from Greek , ''kytos'', "a hollow"; , ''pathos'', "fate, harm"; and , '' -logia'') is a branch of pathology that studies and diagnoses diseases on the cellular level. The discipline was founded by George Nicolas Papanicolaou in 1 ...
. Around 30% of ovarian cancers that appear confined to the ovary have metastasized microscopically, which is why even stage-I cancers must be staged completely. 22% of cancers presumed to be stage I are observed to have lymphatic metastases. The AJCC stage is the same as the FIGO stage. The AJCC staging system describes the extent of the primary tumor (T), the absence or presence of
metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
to nearby
lymph nodes A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
(N), and the absence or presence of distant metastasis (M). The most common stage at diagnosis is stage IIIc, with over 70% of diagnoses.


FIGO

File:Diagram showing stage 1 ovarian cancer CRUK 193.svg, Stage 1 ovarian cancer File:Diagram showing stage 2A to 2C ovarian cancer CRUK 214.svg, Stage 2 ovarian cancer File:Diagram showing stage 3A to 3C ovarian cancer CRUK 225.svg, Stage 3 ovarian cancer File:Diagram showing stage 4 ovarian cancer CRUK 233.svg, Stage 4 ovarian cancer


AJCC/TNM

The AJCC/TNM staging system indicates where the tumor has developed, spread to lymph nodes, and metastasis. The AJCC/TNM stages can be correlated with the FIGO stages:


Grading

Grade 1 tumors have well differentiated cells (look very similar to the normal tissue) and are the ones with the best prognosis. Grade 2 tumors are also called moderately well-differentiated and they are made up of cells that resemble the normal tissue. Grade 3 tumors have the worst prognosis and their cells are abnormal, referred to as poorly differentiated. Metastasis in ovarian cancer is very common in the abdomen and occurs via exfoliation, where cancer cells burst through the ovarian capsule and are able to move freely throughout the peritoneal cavity. Ovarian cancer metastases usually grow on the surface of organs rather than the inside; they are also common on the omentum and the peritoneal lining. Cancer cells can also travel through the
lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid o ...
and metastasize to lymph nodes connected to the ovaries via blood vessels; i.e. the lymph nodes along the
infundibulopelvic ligament The suspensory ligament of the ovary, also infundibulopelvic ligament (commonly abbreviated IP ligament or simply IP), is a fold of peritoneum that extends out from the ovary to the wall of the pelvis. Some sources consider it a part of the broa ...
, the
broad ligament The broad ligament of the uterus is the wide fold of peritoneum that connects the sides of the uterus to the walls and floor of the pelvis. Structure Subdivisions Contents The contents of the broad ligament include the following: * Reproduc ...
, and the round ligament. The most commonly affected groups include the paraaortic, hypogastric,
external iliac The external iliac arteries are two major arteries which bifurcate off the common iliac arteries anterior to the sacroiliac joint of the pelvis. Structure The external iliac artery arises from the bifurcation of the common iliac artery. The ...
, obturator, and
inguinal lymph node Inguinal lymph nodes are lymph nodes in the human groin. Located in the femoral triangle of the inguinal region, they are grouped into superficial and deep lymph nodes. The superficial have three divisions: the superomedial, superolateral, and inf ...
s. Usually, ovarian cancer does not metastasize to the liver, lung, brain, or kidneys unless it is a recurrent disease; this differentiates ovarian cancer from many other forms of cancer.


Prevention

Women with strong genetic risk for ovarian cancer may consider the surgical removal of their ovaries as a preventive measure. This is often done after completion of childbearing years. This reduces the chances of developing both breast cancer (by around 50%) and ovarian cancer (by about 96%) in women at high risk. Women with ''BRCA'' gene mutations usually also have their Fallopian tubes removed at the same time (salpingo-oophorectomy), since they also have an increased risk of
Fallopian tube cancer Primary fallopian tube cancer (PFTC), often just tubal cancer, is a malignant neoplasm that originates from the fallopian tube. Signs and symptoms The internal location of the fallopian tubes makes it difficult to reach an early diagnosis. Sympto ...
. However, these statistics may overestimate the risk reduction because of how they have been studied. Women with a significant family history for ovarian cancer are often referred to a
genetic counselor Genetic counseling is the process of investigating individuals and families affected by or at risk of genetic disorders to help them understand and adapt to the medical, psychological and familial implications of genetic contributions to disease; t ...
to see if testing for BRCA mutations would be beneficial. The use of oral contraceptives, the absence of 'periods' during the menstrual cycle, and tubal ligation reduce the risk. There may an association of developing ovarian cancer and ovarian stimulation during infertility treatments. Endometriosis has been linked to ovarian cancers.
Human papillomavirus infection Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...
, smoking, and
talc Talc, or talcum, is a Clay minerals, clay mineral, composed of hydrated magnesium silicate with the chemical formula Mg3Si4O10(OH)2. Talc in powdered form, often combined with corn starch, is used as baby powder. This mineral is used as a thi ...
have not been identified as increasing the risk for developing ovarian cancer.


Screening

There is no simple and reliable way to test for ovarian cancer in women who do not have any signs or symptoms. Screening is not recommended in women who are at average risk, as evidence does not support a reduction in death and the high rate of false positive tests may lead to unneeded surgery, which is accompanied by its own risks. Women with high risk of ovarian cancer that are currently identified based on family history and genetic testing may benefit from screening. The
Pap test The Papanicolaou test (abbreviated as Pap test, also known as Pap smear (AE), cervical smear (BE), cervical screening (BE), or smear test (BE)) is a method of cervical screening used to detect potentially precancerous and cancerous processes in t ...
does not screen for ovarian cancer. Ovarian cancer is usually only palpable in advanced stages. Screening is not recommended using
CA-125 Mucin-16 (MUC-16) also known as Ovarian cancer-related tumor marker CA125 is a protein that in humans is encoded by the ''MUC16'' gene. MUC-16 is a member of the mucin family glycoproteins. MUC-16 has found application as a tumor marker or biom ...
measurements,
HE4 WAP four-disulfide core domain protein 2 - also known as Human Epididymis Protein 4 (HE4) - is a protein that in humans is encoded by the ''WFDC2'' gene. HE4 is a tumor marker of ovarian cancer, with 80% sensitivity at a cut-off A cut-off ...
levels, ultrasound, or adnexal palpation in women who are at average risk. This high risk group has benefited with earlier detection. Ovarian cancer has low prevalence, even in the high-risk group of women from the ages of 50 to 60 (about one in 2000), and screening of women with average risk is more likely to give ambiguous results than detect a problem that requires treatment. Because ambiguous results are more likely than detection of a treatable problem, and because the usual response to ambiguous results is invasive interventions, in women of average risk, the potential harms of having screening without an indication outweigh the potential benefits. The purpose of screening is to diagnose ovarian cancer at an early stage when it is more likely to be treated successfully. Screening with
transvaginal ultrasound Vaginal ultrasonography is a medical ultrasonography that applies an ultrasound transducer (or "probe") in the vagina to visualize organs within the pelvic cavity. It is also called transvaginal ultrasonography because the ultrasound waves go ''a ...
, pelvic examination, and CA-125 levels can be used instead of preventive surgery in women who have BRCA1 or BRCA2 mutations. This strategy has shown some success. Screening for CA125, a chemical released by ovarian tumours, with follow-up using ultrasound, was shown to be ineffective in reducing mortality in a large-scale UK study. There have been some screening trials that have used age, family history of ovarian cancer, and mutation status to identify target populations for screening.


Management

Once it is determined that ovarian, fallopian tube or primary peritoneal cancer is present, treatment is scheduled by a gynecologic oncologist (a physician trained to treat cancers of a woman's reproductive system). Gynecologic oncologists can perform surgery on and give chemotherapy to women with ovarian cancer. A treatment plan is developed. Treatment usually involves
surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...
and
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
, and sometimes
radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
, regardless of the subtype of ovarian cancer. Surgical treatment may be sufficient for well-differentiated malignant tumors and confined to the ovary. Addition of chemotherapy may be required for more aggressive tumors confined to the ovary. For patients with advanced disease, a combination of surgical reduction with a combination chemotherapy regimen is standard. Since 1980, platinum-based drugs have had an important role in treating ovarian cancer.
Borderline tumor A borderline tumor, sometimes called low malignant potential (LMP) tumor, is a distinct but yet heterogeneous group of tumors defined by their histopathology as atypical epithelial proliferation without stromal invasion. This topic last updated: Fe ...
s, even following spread outside of the ovary, are managed well with surgery, and chemotherapy is not seen as useful. Second-look surgery and
maintenance chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
have not been shown to provide benefit.


Surgery

Surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...
has been the standard of care for decades and may be necessary for obtaining a specimen for
diagnosis Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine " cause and effect". In systems engin ...
. The surgery depends upon the extent of nearby invasion of other tissues by the cancer when it is diagnosed. This extent of the cancer is described by assigning it a stage, the presumed type, and the grade of cancer. The gynecological surgeon may remove one (unilateral oophorectomy) or both ovaries (bilateral oophorectomy). The Fallopian tubes (salpingectomy), uterus (hysterectomy), and the omentum (omentectomy) may also be removed. Typically, all of these organs are removed. For those who test positive for faulty BRCA1 or BRCA2 genes having a risk-reducing surgery is an option. An increasing number of women choose this. At the same time the average waiting time for undergoing the procedure is two-years which is much longer than recommended. For low-grade, unilateral stage-IA cancers, only the involved ovary (which must be unruptured) and Fallopian tube will be removed. This can be done especially in young people who wish to preserve their fertility. However, a risk of microscopic metastases exists and staging must be completed. If any metastases are found, a second surgery to remove the remaining ovary and uterus is needed.
Tranexamic acid Tranexamic acid (TXA) is a medication used to treat or prevent excessive blood loss from major trauma, postpartum bleeding, surgery, tooth removal, nosebleeds, and heavy menstruation. It is also used for hereditary angioedema. It is taken eith ...
can be administered prior to surgery to reduce the need for blood transfusions due to blood loss during the surgery. If a tumor in a premenopausal woman is determined to be a low malignant potential tumor during surgery, and it is clearly stage I cancer, only the affected ovary is removed. For postmenopausal women with low malignant potential tumors, hysterectomy with bilateral salpingo-oophorectomy is still the preferred option. During staging, the appendix can be examined or removed. This is particularly important with mucinous tumors. In children or adolescents with ovarian cancer, surgeons typically attempt to preserve one ovary to allow for the completion of
puberty Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a boy. ...
, but if the cancer has spread, this is not always possible. Dysgerminomas, in particular, tend to affect both ovaries: 8–15% of dysgerminomas are present in both ovaries. People with low-grade (well-differentiated) tumors are typically treated only with surgery, which is often curative. In general, germ cell tumors can be treated with unilateral surgery unless the cancer is widespread or fertility is not a factor. In women with surgically staged advanced epithelial ovarian cancer (stages III and IV), studies suggest all attempts should be made to reach complete cytoreduction (surgical efforts to remove the bulk of the tumor). In advanced cancers, where complete removal is not an option, as much tumor as possible is removed in a procedure called
debulking Debulking is the reduction of as much of the bulk (volume) of a tumour without the intention of a complete eradication. It is usually achieved by surgical removal. When performed for curative intent, it is a different procedure, which is called sur ...
surgery. This surgery is not always successful, and is less likely to be successful in women with extensive metastases in the peritoneum, stage- IV disease, cancer in the transverse fissure of the liver,
mesentery The mesentery is an organ that attaches the intestines to the posterior abdominal wall in humans and is formed by the double fold of peritoneum. It helps in storing fat and allowing blood vessels, lymphatics, and nerves to supply the intestines ...
, or diaphragm, and large areas of ascites. Debulking surgery has usually only been done once but a recent study has shown a longer overall survival in recurrent ovarian cancer when surgery combined with chemotherapy was performed compared to treatment with chemotherapy alone. Computed tomography (abdominal CT) is often used to assess if primary debulking surgery is possible, but low certainty evidence also suggests fluorodeoxyglucose‐18 (FDG) PET/CT and MRI may be useful as an addition for assessing macroscopic incomplete debulking. More complete debulking is associated with better outcomes: women with no macroscopic evidence of disease after debulking have a median survival of 39 months, as opposed to 17 months with less complete surgery. By removing metastases, many cells that are resistant to chemotherapy are removed, and any clumps of cells that have died are also removed. This allows chemotherapy to better reach the remaining cancer cells, which are more likely to be fast-growing and therefore chemosensitive. Interval debulking surgery is another protocol used, where neoadjuvant chemotherapy is given, debulking surgery is performed, and chemotherapy is finished after debulking. Though no definitive studies have been completed, it is shown to be approximately equivalent to primary debulking surgery in terms of survival and shows slightly lower morbidity. Previous studies have shown different results from primary debulking versus interval debulking. Hopefully the ongoing TRUST study will clarify selection criterias for each surgical approach. There are several different surgical procedures that can be employed to treat ovarian cancer. For stage I and II cancer, laparoscopic (keyhole) surgery can be used, but metastases may not be found. For advanced cancer, laparoscopy is not used, since debulking metastases requires access to the entire peritoneal cavity. Depending on the extent of the cancer, procedures may include a bilateral salpingo-oophorectomy, biopsies throughout the peritoneum and abdominal lymphatic system,
omentectomy The greater omentum (also the great omentum, omentum majus, gastrocolic omentum, epiploon, or, especially in animals, caul) is a large apron-like fold of Peritoneum#Layers, visceral peritoneum that hangs down from the stomach. It extends from the ...
,
splenectomy A splenectomy is the surgical procedure that partially or completely removes the spleen. The spleen is an important organ in regard to immunological function due to its ability to efficiently destroy encapsulated bacteria. Therefore, removal of ...
,
bowel resection A bowel resection or enterectomy ('' enter-'' + '' -ectomy'') is a surgical procedure in which a part of an intestine (bowel) is removed, from either the small intestine or large intestine. Often the word ''enterectomy'' is reserved for the sense ...
, diaphragm stripping or resection,
appendectomy An appendectomy, also termed appendicectomy, is a Surgery, surgical operation in which the vermiform appendix (a portion of the intestine) is removed. Appendectomy is normally performed as an urgent or emergency procedure to treat complicated acu ...
, or even a posterior
pelvic exenteration Pelvic exenteration (or pelvic evisceration) is a radical surgical treatment that removes all organs from a person's pelvic cavity. It is used to treat certain advanced or recurrent cancers. The urinary bladder, urethra, rectum, and anus are r ...
. To fully stage ovarian cancer,
lymphadenectomy Lymphadenectomy or lymph node dissection is the surgical removal of one or more groups of lymph nodes. It is almost always performed as part of the surgical management of cancer. In a regional lymph node dissection, some of the lymph nodes in the ...
can be included in the surgery, but a significant survival benefit to this practice may not happen. This is particularly important in germ cell tumors because they frequently metastasize to nearby lymph nodes. If ovarian cancer recurs, secondary surgery is sometimes a treatment option. This depends on how easily the tumor can be removed, how much fluid has accumulated in the abdomen, and overall health. Effectivenes of this surgery depends on surgical technique, completeness of cytoreduction, and extent of disease. It also can be helpful in people who had their first surgery done by a generalist and in epithelial ovarian cancer. Secondary surgery can be effective in dysgerminomas and immature teratomas. Evidence suggests surgery in recurrent epithelial ovarian cancer may be associated with prolonging life in some women with platinum-sensitive disease. The major side effect of oophorectomy in younger women is early
menopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
, which can cause
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
. After surgery, hormone replacement therapy can be considered, especially in younger women. This therapy can consist of a combination of estrogen and progesterone, or estrogen alone. Estrogen alone is safe after hysterectomy; when the uterus is still present, unopposed estrogen dramatically raises the risk of
endometrial cancer Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most o ...
. Estrogen therapy after surgery does not change survival rates. People having ovarian cancer surgery are typically hospitalized afterwards for 3–4 days and spend around a month recovering at home. Surgery outcomes are best at hospitals that do a large number of ovarian cancer surgeries. It is unclear if
laparoscopy Laparoscopy () is an operation performed in the abdomen or pelvis using small incisions (usually 0.5–1.5 cm) with the aid of a camera. The laparoscope aids diagnosis or therapeutic interventions with a few small cuts in the abdomen.Medli ...
or
laparotomy A laparotomy is a surgical procedure involving a surgical incision through the abdominal wall to gain access into the abdominal cavity. It is also known as a celiotomy. Origins and history The first successful laparotomy was performed without ane ...
is better or worse for FIGO stage I ovarian cancer. There is also no apparent difference between total abdominal hysterectomy and supracervical hysterectomy for advanced cancers. Approximately 2.8% of people having a first surgery for advanced ovarian cancer die within two weeks of the surgery (2.8%
perioperative mortality Perioperative mortality has been defined as any death, regardless of cause, occurring within 30 days after surgery in or out of the hospital. Globally, 4.2 million people are estimated to die within 30 days of surgery each year. An important consid ...
rate). More aggressive surgeries are associated with better outcomes in advanced (stage III or IV) ovarian cancer.


Chemotherapy

Chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
has been a general
standard of care In tort law, the standard of care is the only degree of prudence and caution required of an individual who is under a duty of care. The requirements of the standard are closely dependent on circumstances. Whether the standard of care has been b ...
for ovarian cancer for decades, although with variable protocols. Chemotherapy is used after surgery to treat any residual disease, if appropriate. In some cases, there may be reason to perform chemotherapy first, followed by surgery. This is called "neoadjuvant chemotherapy", and is common when a tumor cannot be completely removed or optimally debulked via surgery. Though it has not been shown to increase survival, it can reduce the risk of complications after surgery. If a unilateral salpingo-oophorectomy or other surgery is performed, additional chemotherapy, called "adjuvant chemotherapy", can be given. Adjuvant chemotherapy is used in stage 1 cancer typically if the tumor is of a high histologic grade (grade 3) or the highest substage (stage 1c), provided the cancer has been optimally staged during surgery.
Bevacizumab Bevacizumab, sold under the brand name Avastin among others, is a medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, l ...
may be used as an adjuvant chemotherapy if the tumor is not completely removed during surgery or if the cancer is stage IV; it can extend progression-free survival but has not been shown to extend overall survival. Chemotherapy is curative in approximately 20% of advanced ovarian cancers; it is more often curative with malignant germ cell tumors than epithelial tumors. Adjuvant chemotherapy has been found to improve survival and reduce the risk of ovarian cancer recurring compared to no adjuvant therapy in women with early stage epithelial ovarian cancer. Chemotherapy in ovarian cancer typically consists of platins, a group of
platinum Platinum is a chemical element with the symbol Pt and atomic number 78. It is a dense, malleable, ductile, highly unreactive, precious, silverish-white transition metal. Its name originates from Spanish , a diminutive of "silver". Platinu ...
-based drugs, combined with non-platins. Platinum-based drugs have been used since 1980. Common therapies can include
paclitaxel Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer ...
,
cisplatin Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, br ...
,
topotecan Topotecan, sold under the brand name Hycamtin among others, is a chemotherapeutic agent medication that is a topoisomerase inhibitor. It is a synthetic, water-soluble analog of the natural chemical compound camptothecin. It is used in the form o ...
, doxorubicin,
epirubicin Epirubicin is an anthracycline drug used for chemotherapy. It can be used in combination with other medications to treat breast cancer in patients who have had surgery to remove the tumor. It is marketed by Pfizer under the trade name Ellence in ...
, and
gemcitabine Gemcitabine, with brand names including Gemzar, is a chemotherapy medication. It treats cancers including testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer. It is administered by ...
.
Carboplatin Carboplatin, sold under the trade name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is used b ...
is typically given in combination with either
paclitaxel Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer ...
or
docetaxel Docetaxel (DTX or DXL), sold under the brand name Taxotere among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-ce ...
; the typical combination is carboplatin with paclitaxel. Carboplatin is superior to cisplatin in that it is less toxic and has fewer side effects, generally allowing for an improved quality of life in comparison, though both are similarly effective. Three-drug regimens have not been found to be more effective, and platins alone or nonplatins alone are less effective than platins and nonplatins in combination. There is a small benefit in platinum‐based chemotherapy compared with non‐platinum therapy. Platinum combinations can offer improved survival over single platinum. In people with relapsed ovarian cancer, evidence suggests topotecan has a similar effect on overall survival as paclitaxel and topotecan plus thalidomide, whilst it is superior to treosulfan and not as effective as pegylated liposomal doxorubicin in platinum-sensitive people. Chemotherapy can be given
intravenously Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
or in the peritoneal cavity. Though intraperitoneal chemotherapy is associated with longer progression-free survival and overall survival, it also causes more adverse side effects than intravenous chemotherapy. It is mainly used when the cancer has been optimally debulked. Intraperitoneal chemotherapy can be highly effective because ovarian cancer mainly spreads inside the peritoneal cavity, and higher doses of the drugs can reach the tumors this way. Chemotherapy can cause
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
; intravenous iron has been found to be more effective than oral
iron supplement Iron supplements, also known as iron salts and iron pills, are a number of iron formulations used to treat and prevent iron deficiency including iron deficiency anemia. For prevention they are only recommended in those with poor absorption, h ...
s in reducing the need for
blood transfusion Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...
s. Typical cycles of treatment involve one treatment every 3 weeks, repeated for 6 weeks or more. Fewer than 6 weeks (cycles) of treatment is less effective than 6 weeks or more. Germ-cell malignancies are treated differently than other ovarian cancers — a regimen of
bleomycin -13- (1''H''-imidazol-5-yl)methyl9-hydroxy-5- 1''R'')-1-hydroxyethyl8,10-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazapentadec-1-yl}-2,4'-bi-1,3-thiazol-4-yl)carbonyl]amino}propyl)(dimethyl)sulfonium , chemical_formula = , C=55 , H=84 , N=1 ...
,
etoposide Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is ...
, and cisplatin (BEP) is used with 5 days of chemotherapy administered every 3 weeks for 3 to 4 cycles. Chemotherapy for germ cell tumors has not been shown to cause
amenorrhea Amenorrhea is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen, most commonly, during pregnancy and lactation (breastfeeding). Outside the reproductive years, there is absence of menses ...
, infertility,
birth defects A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
, or
miscarriage Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...
.
Maintenance chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
has not been shown to be effective. In people with ''BRCA'' mutations, platinum chemotherapy is more effective. Germ-cell tumors and malignant sex-cord/stromal tumors are treated with chemotherapy, though dysgerminomas and sex-cord tumors are not typically very responsive.


Platinum-sensitive or platinum-resistant

If ovarian cancer recurs, it is considered partially platinum-sensitive or platinum-resistant, based on the time since the last recurrence treated with platins: partially platinum-sensitive cancers recurred 6–12 months after last treatment, and platinum-resistant cancers have an interval of less than 6 months. Second-line chemotherapy can be given after the cancer becomes symptomatic because no difference in survival is seen between treating asymptomatic (elevated CA-125) and symptomatic recurrences. For platinum-sensitive tumors, platins are the drugs of choice for second-line chemotherapy, in combination with other cytotoxic agents. Regimens include carboplatin combined with pegylated liposomal doxorubicin,
gemcitabine Gemcitabine, with brand names including Gemzar, is a chemotherapy medication. It treats cancers including testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer. It is administered by ...
, or
paclitaxel Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer ...
. Carboplatin-doublet therapy can be combined with paclitaxel for increased efficacy in some cases. Another potential adjuvant therapy for platinum-sensitive recurrences is
olaparib Olaparib, sold under the brand name Lynparza, is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair ...
, which may improve
progression-free survival Progression-free survival (PFS) is "the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse". In oncology, PFS usually refers to situations in which a tumor is p ...
but has not been shown to improve
overall survival Survival rate is a part of survival analysis. It is the proportion of people in a study or treatment group still alive at a given period of time after diagnosis. It is a method of describing prognosis in certain disease conditions, and can be use ...
. (
Olaparib Olaparib, sold under the brand name Lynparza, is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair ...
, a
PARP inhibitor PARP inhibitors are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP). They are developed for multiple indications, including the treatment of heritable cancers. Several forms of cancer are more dependent on ...
, was approved by the
US FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...
for use in BRCA-associated ovarian cancer that had previously been treated with chemotherapy.) For recurrent germ cell tumors, an additional 4 cycles of BEP chemotherapy is the first-line treatment for those tho have been treated with surgery or platins. If the tumor is determined to be platinum-resistant,
vincristine Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's ...
,
dactinomycin Dactinomycin, also known as actinomycin D, is a chemotherapy medication used to treat a number of types of cancer. This includes Wilms tumor, rhabdomyosarcoma, Ewing's sarcoma, trophoblastic neoplasm, testicular cancer, and certain types of ovari ...
, and
cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
(VAC) or some combination of paclitaxel, gemcitabine, and oxaliplatin may be used as a second-line therapy. For platinum-resistant tumors, there are no high-efficacy chemotherapy options. Single-drug regimens (doxorubicin or
topotecan Topotecan, sold under the brand name Hycamtin among others, is a chemotherapeutic agent medication that is a topoisomerase inhibitor. It is a synthetic, water-soluble analog of the natural chemical compound camptothecin. It is used in the form o ...
) do not have high response rates, but single-drug regimens of topotecan, pegylated liposomal doxorubicin, or gemcitabine are used in some cases. Topotecan cannot be used in people with an intestinal blockage. Paclitaxel used alone is another possible regimen, or it may be combined with liposomal doxorubicin, gemcitabine, cisplatin, topotecan,
etoposide Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is ...
, or
cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
. ( See also Palliative care below.) Novel agents are being developed to inhibit the development of new blood vessels (angiogenesis) for women with ovarian cancer who develop resistance to chemotherapy drugs. As of 2011 only preliminary results are available. Novocure sponsored a phase-2 trial proving efficacy of
tumor treating fields Alternating electric field therapy, sometimes called tumor treating fields (TTFields), is a type of electromagnetic field therapy using low-intensity, intermediate frequency electrical fields to treat cancer. A TTField-generating device manufact ...
in recurrent platinum-resistant ovarian carcinoma, in conjunction with weekly paclitaxel chemotherapy.


Radiation therapy

Dysgerminomas are most effectively treated with radiation, though this can cause infertility and is being phased out in favor of chemotherapy. Radiation therapy does not improve survival in people with well-differentiated tumors. In stage 1c and 2 cancers, radiation therapy is used after surgery if there is the possibility of residual disease in the pelvis but the abdomen is cancer-free. Radiotherapy can also be used in palliative care of advanced cancers. A typical course of radiotherapy for ovarian cancer is 5 days a week for 3–4 weeks. Common side effects of radiotherapy include diarrhea, constipation, and frequent urination.


Hormonal therapy

Despite the fact that 60% of ovarian tumors have
estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen ( 17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the ...
s, ovarian cancer is only rarely responsive to hormonal treatments. A Cochrane review found a lack of evidence about the effects of tamoxifen in people with relapsed ovarian cancer. Estrogen alone does not have an effect on the cancer, and
tamoxifen Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men. It is also being studied for other types of cancer. It has b ...
and
letrozole Letrozole, sold under the brand name Femara among others, is an aromatase inhibitor medication that is used in the treatment of breast cancer. It was patented in 1986 and approved for medical use in 1996. In 2020, it was the 257th most common ...
are rarely effective. "Some women with borderline malignancy ovarian cancer and stromal ovarian cancer may receive hormonal therapy."


Immunotherapy

Immunotherapy is a topic of current research in ovarian cancer. In some cases, the antibody drug
bevacizumab Bevacizumab, sold under the brand name Avastin among others, is a medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, l ...
, though still a topic of active research, is used to treat advanced cancer along with chemotherapy. It has been approved for this use in the European Union.


Follow-up

Specific follow-up depends on, for example, the type and stage of ovarian cancer, the treatment, and the presence of any symptoms. Usually, a check-up appointment is made about every 2 to 3 months initially, followed by twice per year for up to 5 years. For epithelial ovarian cancers, the most common test upon follow-up is CA-125 level. However, treatment based only on elevated CA-125 levels and not any symptoms can increase side effects without any prolongation of life, so the implication of the outcome of a CA-125 test can be discussed before taking it.Follow-up care
from
American Cancer Society The American Cancer Society (ACS) is a nationwide voluntary health organization dedicated to eliminating cancer. Established in 1913, the society is organized into six geographical regions of both medical and lay volunteers operating in more than ...
. Last Medical Review: 03/21/2013. Last Revised: 02/06/2014
The recommendation as of 2014 is recurrent cancer may be present if the CA-125 level is twice normal. Treating a recurrence detected by CA-125 does not improve survival. For women with germ-cell tumors, follow-up tests generally include
alpha-fetoprotein Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the ''AFP'' gene. The ''AFP'' gene is located on the ''q'' arm of chromosome 4 ...
(AFP) and/or
human chorionic gonadotropin Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantation ...
. For women with
stromal cancer Gastrointestinal stromal tumors (GISTs) form in the soft mesenchymal tissue of the gastrointestinal tract and form from the rapid growth of interstitial cells of Cajal (ICCs). GISTs are the most common type of tumor found in the gastrointestinal ...
s, tests for hormones like estrogen, testosterone, and
inhibin Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Identified in 1986, activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual ...
are sometimes helpful. Inhibin can also be useful for monitoring the progress of sex-cord tumors, along with mullerian inhibiting substance. AFP can also be used to monitor Sertoli-Leydig tumors. In dysgerminomas,
lactate dehydrogenase Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of lactate to pyruvate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that transfers a hydride from on ...
and its two
isozyme In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. dif ...
s ( LDH-1 and LDH-2) are used to test for recurrence. Women with ovarian cancer may not need routine surveillance imaging to monitor the cancer unless new symptoms appear or
tumor markers A tumor marker is a biomarker found in blood, urine, or body tissues that can be elevated by the presence of one or more types of cancer. There are many different tumor markers, each indicative of a particular disease process, and they are used ...
begin rising., which cites * Imaging without these indications is discouraged because it is unlikely to detect a recurrence, improve survival, and because it has its own costs and side effects. However, CT imaging can be used if desired, though this is not common. If a tumor is easily imaged, imaging may be used to monitor the progress of treatment.


Palliative care

Palliative care Palliative care (derived from the Latin root , or 'to cloak') is an interdisciplinary medical caregiving approach aimed at optimizing quality of life and mitigating suffering among people with serious, complex, and often terminal illnesses. Wit ...
focuses on relieving symptoms and increasing or maintaining quality of life. This type of treatment's purpose is not to cure the cancer but to make the woman more comfortable while living with cancer that can not be cured. It has been recommended as part of the treatment plan for any person with advanced ovarian cancer or patients with significant symptoms. In platinum-refractory and platinum-resistant cases, other palliative chemotherapy is the main treatment. Palliative care can entail treatment of symptoms and complications of the cancer, including pain, nausea, constipation, ascites,
bowel obstruction Bowel obstruction, also known as intestinal obstruction, is a mechanical or Ileus, functional obstruction of the Gastrointestinal tract#Lower gastrointestinal tract, intestines which prevents the normal movement of the products of digestion. Eith ...
,
edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...
,
pleural effusion A pleural effusion is accumulation of excessive fluid in the pleural space, the potential space that surrounds each lung. Under normal conditions, pleural fluid is secreted by the parietal pleural capillaries at a rate of 0.6 millilitre per kilog ...
, and
mucositis Mucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tract, usually as an adverse effect of chemotherapy and radiotherapy treatment for cancer. Mucositis can occur anywhere along the gastrointestinal ( ...
. Especially if the cancer advances and becomes incurable, treatment of symptoms becomes one of the main goals of therapy. Palliative care can also entail helping with decision-making such as if or when
hospice care Hospice care is a type of health care that focuses on the palliation of a terminally ill patient's pain and symptoms and attending to their emotional and spiritual needs at the end of life. Hospice care prioritizes comfort and quality of life by ...
is appropriate, and the preferred place for the patient at end of life care. Bowel obstruction can be treated with
palliative surgery Palliative surgery is surgical intervention targeted to make a patient’s symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower ...
(
colostomy A colostomy is an opening ( stoma) in the large intestine (colon), or the surgical procedure that creates one. The opening is formed by drawing the healthy end of the colon through an incision in the anterior abdominal wall and suturing it int ...
,
ileostomy Ileostomy is a stoma (surgical opening) constructed by bringing the end or loop of small intestine (the ileum) out onto the surface of the skin, or the surgical procedure which creates this opening. Intestinal waste passes out of the ileostomy an ...
, or internal bypass) or medicine, but surgery has been shown to increase survival time. Palliative surgery may result in
short bowel syndrome Short bowel syndrome (SBS, or simply short gut) is a rare malabsorption disorder caused by a lack of functional small intestine. The primary symptom is diarrhea, which can result in dehydration, malnutrition, and weight loss. Other symptoms may in ...
,
enterocutaneous fistula An enterocutaneous fistula (ECF) is an abnormal communication between the small or large bowel and the skin that allows the contents of the stomach or intestines to leak through an opening in the skin. Causes The mnemonic HIS FRIENDS can be used ...
, or re-obstruction; or may not be possible due to the extent of obstruction. Other treatments of complications can include
total parenteral nutrition Parenteral nutrition (PN) is the feeding of nutritional products to a person intravenously, bypassing the usual process of eating and digestion. The products are made by pharmaceutical compounding companies. The person receives a nutritional mix ...
, a low-residue diet, palliative
gastrostomy Gastrostomy is the creation of an artificial external opening into the stomach for nutritional support or gastric decompression. Typically this would include an incision in the patient's epigastrium as part of a formal operation. It can be perfor ...
, and adequate pain control. Bowel obstruction can also be treated with
octreotide Octreotide, sold under the brand name Sandostatin among others, is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone. It was ...
when palliative surgery is not an option. Cancer can also block the
ureters The ureters are tubes made of smooth muscle that propel urine from the kidneys to the urinary bladder. In a human adult, the ureters are usually long and around in diameter. The ureter is lined by urothelial cells, a type of transitional epit ...
, which can be relieved by a
nephrostomy A nephrostomy is an artificial opening created between the kidney and the skin which allows for the urinary diversion directly from the upper part of the urinary system (renal pelvis). An urostomy is a related procedure performed more distally a ...
or a
ureteric stent A ureteral stent (pronounced you-REE-ter-ul), or ureteric stent, is a thin tube inserted into the ureter to prevent or treat obstruction of the urine flow from the kidney. The length of the stents used in adult patients varies between 24 and 30&nb ...
. Ascites can be relieved by repeated
paracentesis Paracentesis (from Greek κεντάω, "to pierce") is a form of body fluid sampling procedure, generally referring to peritoneocentesis (also called laparocentesis or abdominal paracentesis) in which the peritoneal cavity is punctured by a needl ...
or placement of a
drain Drain may refer to: Objects and processes * Drain (plumbing), a fixture that provides an exit-point for waste water or for water that is to be re-circulated on the side of a road * Drain (surgery), a tube used to remove pus or other fluids from ...
to increase comfort. Pleural effusions can be treated in a similar manner, with repeated
thoracentesis Thoracentesis , also known as thoracocentesis (from Greek ''thōrax'' 'chest, thorax'—GEN ''thōrakos''—and ''kentēsis'' 'pricking, puncture'), pleural tap, needle thoracostomy, or needle decompression (often used term), is an invasive med ...
,
pleurodesis Pleurodesis is a medical procedure in which part of the pleural space is artificially obliterated. It involves the adhesion of the visceral and the costal pleura. The mediastinal pleura is spared. Uses Pleurodesis is performed to prevent recurre ...
, or placement of a drain. Radiation therapy can be used as part of the palliative care of advanced ovarian cancer, since it can help to shrink tumors that are causing symptoms. Palliative radiotherapy typically lasts for only a few treatments, a much shorter course of therapy than non-palliative radiotherapy. It is also used for palliation of chemotherapy-resistant germ cell tumors.


Psychosocial care

Ovarian cancer has a significant effect on
quality of life Quality of life (QOL) is defined by the World Health Organization as "an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards ...
, psychological health and well-being. Interventions are available to help with the needs and social support. Many ovarian cancer survivors report a good quality of life and
optimism Optimism is an attitude reflecting a belief or hope that the outcome of some specific endeavor, or outcomes in general, will be positive, favorable, and desirable. A common idiom used to illustrate optimism versus pessimism is a glass filled wi ...
. Others reported a "spiritual change" that helped them find meaning during their experience. Others have described their loss of faith after their diagnosis with ovarian cancer. Those who have gone through treatment sometimes experience
social isolation Social isolation is a state of complete or near-complete lack of contact between an individual and society. It differs from loneliness, which reflects temporary and involuntary lack of contact with other humans in the world. Social isolation c ...
but benefit from having relationships with other survivors.
Frustration In psychology, frustration is a common emotional response to opposition, related to anger, annoyance and disappointment. Frustration arises from the perceived resistance to the fulfillment of an individual's will or goal and is likely to inc ...
and
guilt Guilt may refer to: *Guilt (emotion), an emotion that occurs when a person feels that they have violated a moral standard *Culpability, a legal term *Guilt (law), a legal term Music *Guilt (album), ''Guilt'' (album), a 2009 album by Mims *Guilt ( ...
have been described by some who have expressed their inability to care for their family.
Self-esteem Self-esteem is confidence in one's own worth or abilities. Self-esteem encompasses beliefs about oneself (for example, "I am loved", "I am worthy") as well as emotional states, such as triumph, despair, pride, and shame. Smith and Mackie (2007) d ...
and
body image Body image is a person's thoughts, feelings and perception of the aesthetics or sexual attractiveness of their own body. The concept of body image is used in a number of disciplines, including neuroscience, psychology, medicine, psychiatry, ps ...
changes can occur due to
hair loss Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarri ...
, removal of ovaries and other reproductive structures, and
scar A scar (or scar tissue) is an area of fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other organs, and tissues of the body. Thus, scarring is a na ...
s. There is some improvement after hair grows in. Sexual issues can develop. The removal of ovaries results in surgically induced
menopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
that can result in painful intercourse, vaginal dryness, loss of
sexual desire Sexual desire is an emotion and motivational state characterized by an interest in sexual objects or activities, or by a drive to seek out sexual objects or to engage in sexual activities. It is an aspect of sexuality, which varies significantly ...
and being tired. Though prognosis is better for younger survivors, the impact on sexuality can still be substantial.
Anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
, depression and distress is present in those surviving ovarian cancer at higher rates than in the general population. The same psychosocial problems can develop in family members. Emotional effects can include a
fear of death Death anxiety is anxiety caused by thoughts of one's own death, and is also referred to as thanatophobia (fear of death). Death anxiety differs from necrophobia, which is the fear of others who are dead or dying. Psychotherapist Robert Lang ...
,
sadness Sadness is an emotional pain associated with, or characterized by, feelings of disadvantage, loss, despair, grief, helplessness, disappointment and sorrow. An individual experiencing sadness may become quiet or lethargic, and withdraw thems ...
, memory problems and difficulty in concentrating. When optimism was adopted by those at the beginning of their treatment, they were less likely to develop distress. Those who have fear of the cancer recurring may have difficulty in expressing
joy The word joy refers to the emotion evoked by well-being, success, or good fortune, and is typically associated with feelings of intense, long lasting happiness. Dictionary definitions Dictionary definitions of joy typically include a sense of ...
even when disease-free. The more treatments that a woman undergoes, the more likely the loss of
hope Hope is an optimistic state of mind that is based on an expectation of positive outcomes with respect to events and circumstances in one's life or the world at large. As a verb, its definitions include: "expect with confidence" and "to cherish ...
is expressed. Women often can cope and reduce negative psychosocial effects by a number of strategies. Activities such as traveling, spending additional time with family and friends, ignoring
statistics Statistics (from German language, German: ''wikt:Statistik#German, Statistik'', "description of a State (polity), state, a country") is the discipline that concerns the collection, organization, analysis, interpretation, and presentation of ...
, journaling and increasing involvement in spiritually-based events are adaptive. Women with ovarian cancer may also experience difficulties with their diet and are at risk of malnutrition.


Prognosis

Ovarian cancer usually has a relatively poor
prognosis Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stabl ...
. It is disproportionately deadly because it lacks any clear early detection or screening test, meaning most cases are not diagnosed until they have reached advanced stages. Ovarian cancer metastasizes early in its development, often before it has been diagnosed. High-grade tumors metastasize more readily than low-grade tumors. Typically, tumor cells begin to metastasize by growing in the peritoneal cavity. More than 60% of women presenting with ovarian cancer have stage-III or stage-IV cancer, when it has already spread beyond the ovaries. Ovarian cancers shed cells into the naturally occurring fluid within the abdominal cavity. These cells can then implant on other abdominal (peritoneal) structures, including the uterus,
urinary bladder The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...
,
bowel The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
, lining of the bowel wall, and omentum, forming new tumor growths before cancer is even suspected. The five-year survival rate for all stages of ovarian cancer is 46%; the one-year survival rate is 72% and the ten-year survival rate is 35%. For cases where a diagnosis is made early in the disease, when the cancer is still confined to the primary site, the five-year survival rate is 92.7%.Survival rates based on SEER incidence and NCHS mortality statistics, as cited by the National Cancer Institute i
SEER Stat Fact Sheets — Cancer of the Ovary
About 70% of women with advanced disease respond to initial treatment, most of whom attain complete remission, but half of these women experience a recurrence 1–4 years after treatment.
Brain metastasis A brain metastasis is a cancer that has metastasized (spread) to the brain from another location in the body and is therefore considered a secondary brain tumor. The metastasis typically shares a cancer cell type with the original site of the c ...
is more common in stage III/IV cancer but can still occur in cancers staged at I/II. People with brain metastases survive a median of 8.2 months, though surgery, chemotherapy, and whole brain radiation therapy can improve survival. Ovarian cancer survival varies significantly with subtype. Dysgerminomas have a very favorable prognosis. In early stages, they have a five-year survival rate of 96.9%. Around two-thirds of dysgerminomas are diagnosed at stage I. Stage-III dysgerminomas have a five-year survival of 61%; when treated with BEP chemotherapy after incomplete surgical removal, dysgerminomas have a 95% two-year survival rate. Sex-cord-stromal malignancies also have a favorable prognosis; because they are slow-growing, even those with metastatic disease can survive a decade or more. Low malignant potential tumors usually only have a bad prognosis when there are invasive tumor implants found in the peritoneal cavity. Complications of ovarian cancer can include spread of the cancer to other organs, progressive function loss of various organs, ascites, and intestinal obstructions, which can be fatal. Intestinal obstructions in multiple sites are the most common proximate cause of death. Intestinal obstruction in ovarian cancer can either be a true obstruction, where tumor blocks the
intestinal lumen The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...
, or a pseudo-obstruction, when tumor prevents normal
peristalsis Peristalsis ( , ) is a radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an anterograde direction. Peristalsis is progression of coordinated contraction of involuntary circular muscles, which ...
. Continuous accumulation of ascites can be treated by placing a drain that can be self-drained.


Prognostic factors

There are a number of
prognostic factor Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stable ...
s in ovarian cancer. Positive prognostic factors – those indicating better chances of survival – include no residual disease after surgery (stage III/IV), complete macroscopic resection (stage IV), BRCA2 mutations, young age (under 45 years), nonserous type, low histologic grade, early stage, co-occurrence with endometrial cancer, and low CA-125 levels. There is conflicting evidence for BRCA1 as a prognostic factor. Conversely, negative prognostic factors – those that indicate a worse chance of survival – include rupture of the ovarian capsule during surgery, older age (over 45 years), mucinous type, stage IV, high histologic grade, clear cell type, upper abdominal involvement, high CA-125 levels, the presence of tumor cells in the blood, and elevated
cyclooxygenase-2 Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (The HUGO official symbol is PTGS2; HGNC ID, HGNC:9605), also known as cyclooxygenase-2 or COX-2, is an enzyme that in humans is encoded by the ''PTGS2'' ge ...
. Expression of various mRNAs can also be prognostic for ovarian cancer. High levels of
Drosha Drosha is a Class 2 ribonuclease III enzyme that in humans is encoded by the ''DROSHA'' (formerly ''RNASEN'') gene. It is the primary nuclease that executes the initiation step of miRNA processing in the nucleus. It works closely with DGCR8 and ...
and
Dicer Dicer, also known as endoribonuclease Dicer or helicase with RNase motif, is an enzyme that in humans is encoded by the gene. Being part of the RNase III family, Dicer cleaves double-stranded RNA (dsRNA) and pre-microRNA (pre-miRNA) into short d ...
are associated with improved survival, whereas high levels of let-7b,
HIF1A Hypoxia-inducible factor 1-alpha, also known as HIF-1-alpha, is a subunit of a heterodimeric transcription factor hypoxia-inducible factor 1 ( HIF-1) that is encoded by the ''HIF1A'' gene. The Nobel Prize in Physiology or Medicine 2019 was awarde ...
,
EphA1 EPH receptor A1 (ephrin type-A receptor 1) is a protein that in humans is encoded by the ''EPHA1'' gene. This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated ...
, and poly(ADP-ribose) polymerase are associated with worse survival. Cancers that are positive for
WT1 Wilms tumor protein (WT33) is a protein that in humans is encoded by the ''WT1'' gene on chromosome 11p. Function This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-ric ...
carry a worse prognosis; estrogen-receptor positive cancers have a better prognosis.


Survival rates

Overall five-year survival rates for all types of ovarian cancer are presented below by stage and histologic grade: The survival rates given below are for the different types of ovarian cancer, according to
American Cancer Society The American Cancer Society (ACS) is a nationwide voluntary health organization dedicated to eliminating cancer. Established in 1913, the society is organized into six geographical regions of both medical and lay volunteers operating in more than ...
. They come from the
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
, SEER, and are based on patients diagnosed from 2004 to 2010.


Recurrence rates

Ovarian cancer frequently recurs after treatment. Overall, in a 5-year period, 20% of stage I and II cancers recur. Most recurrences are in the abdomen. If a recurrence occurs in advanced disease, it typically occurs within 18 months of initial treatment (18 months
progression-free survival Progression-free survival (PFS) is "the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse". In oncology, PFS usually refers to situations in which a tumor is p ...
). Recurrences can be treated, but the disease-free interval tends to shorten and chemoresistance increases with each recurrence. When a dysgerminoma recurs, it is most likely to recur within a year of diagnosis, and other malignant germ cell tumors recur within 2 years 90% of the time. Germ cell tumors other than dysgerminomas have a poor prognosis when they relapse, with a 10% long-term survival rate. Low malignant potential tumors rarely relapse, even when fertility-sparing surgery is the treatment of choice. 15% of LMP tumors relapse after unilateral surgery in the previously unaffected ovary, and they are typically easily treated with surgery. More advanced tumors may take up to 20 years to relapse, if they relapse at all, and are only treated with surgery unless the tumor has changed its histological characteristics or grown very quickly. In these cases, and when there is significant ascites, chemotherapy may also be used. Relapse is usually indicated by rising CA-125 levels and then progresses to symptomatic relapse within 2–6 months. Recurrent sex cord-stromal tumors are typically unresponsive to treatment but not aggressive. It is the most deadly gynecologic cancer.


Epidemiology

Globally, in 2018, the incidence of ovarian cancer was 6.6 per 100,000 and mortality was 3.9. Globally, about 160,000 people died from ovarian cancer in 2010. This was an increase from 113,000 in 1990. The number of new cases per year in Europe is approximately 5–15 per 100,000 women. In Europe,
Lithuania Lithuania (; lt, Lietuva ), officially the Republic of Lithuania ( lt, Lietuvos Respublika, links=no ), is a country in the Baltic region of Europe. It is one of three Baltic states and lies on the eastern shore of the Baltic Sea. Lithuania ...
,
Latvia Latvia ( or ; lv, Latvija ; ltg, Latveja; liv, Leţmō), officially the Republic of Latvia ( lv, Latvijas Republika, links=no, ltg, Latvejas Republika, links=no, liv, Leţmō Vabāmō, links=no), is a country in the Baltic region of ...
,
Ireland Ireland ( ; ga, Éire ; Ulster Scots dialect, Ulster-Scots: ) is an island in the Atlantic Ocean, North Atlantic Ocean, in Northwestern Europe, north-western Europe. It is separated from Great Britain to its east by the North Channel (Grea ...
,
Slovakia Slovakia (; sk, Slovensko ), officially the Slovak Republic ( sk, Slovenská republika, links=no ), is a landlocked country in Central Europe. It is bordered by Poland to the north, Ukraine to the east, Hungary to the south, Austria to the s ...
, and the
Czech Republic The Czech Republic, or simply Czechia, is a landlocked country in Central Europe. Historically known as Bohemia, it is bordered by Austria to the south, Germany to the west, Poland to the northeast, and Slovakia to the southeast. The ...
have the highest incidences of ovarian cancer, whereas
Portugal Portugal, officially the Portuguese Republic ( pt, República Portuguesa, links=yes ), is a country whose mainland is located on the Iberian Peninsula of Southwestern Europe, and whose territory also includes the Atlantic archipelagos of ...
and
Cyprus Cyprus ; tr, Kıbrıs (), officially the Republic of Cyprus,, , lit: Republic of Cyprus is an island country located south of the Anatolian Peninsula in the eastern Mediterranean Sea. Its continental position is disputed; while it is geo ...
have the lowest incidences. In 2008, the five-year survival rate was 44%. This has increased since 1977 when the survival rate was 36%.


United States

In 2022, in the United States, an estimated 19,880 new cases were diagnosed and 12,810 women died of ovarian cancer. The 5-year relative survival rate is 49.7%. Around 57% cases have metastasized at the time of diagnosis. In 2014, over 220,000 diagnoses of epithelial ovarian cancer were made yearly. The overall lifetime risk in the US is around 1.6% In the US, ovarian cancer affects 1.3–1.4% and is the cause of death of about 1% of women. In the United States, it is also the fifth-most common cancer in women but the fourth-most common cause of cancer death. This decrease made it the ninth-most common cancer in women. The risks from developing specific types of ovarian cancer varies. Germ cell tumors and sex cord-stromal tumors are less common than epithelial tumors. The number of new cases a year in the US is 0.4 per 100,000 women and 0.2 per 100,000 women, respectively. In young people, sex-cord stromal tumors and germ cell tumors total 1% of overall ovarian cancer. Ovarian cancer represents approximately 4% of cancers diagnosed in women.


United Kingdom

It is the 5th-most common cancer in UK women (around 7,100 were diagnosed in 2011) and the 5th-most common cause of cancer death in women (around 4,300 died in 2012). The incidence rate over the whole UK population is 21.6 per 100,000. As of 2014, the UK saw approximately 7,000–7,100 yearly diagnoses with 4,200 deaths. A 2022 article from ''The Times'' put the estimate at 7,500 new cases yearly in Britain. Early symptoms are often mistaken for common conditions such as cystitis or irritable bowel syndrome, and about 40 per cent of UK women wrongly believe that cervical screening detects ovarian cancer, an increase from 30 per cent in 2016.
Ashkenazi Jew Ashkenazi Jews ( ; he, יְהוּדֵי אַשְׁכְּנַז, translit=Yehudei Ashkenaz, ; yi, אַשכּנזישע ייִדן, Ashkenazishe Yidn), also known as Ashkenazic Jews or ''Ashkenazim'',, Ashkenazi Hebrew pronunciation: , singu ...
ish women carry mutated ''BRCA'' alleles five times more often than the rest of the population, giving them a higher risk developing ovarian cancer.


Ethnicity

Black women have twice the risk for sex cord-stromal tumors compared to non-Black women. The highest prevalence is in Caucasian and Hispanic women, followed by African-American and Asian women. The highest mortality from ovarian cancer is in African-American women.


Older women

In the US, the incidence rate in women over 50 is approximately 33 per 100,000. The rate of ovarian cancer between 1993 and 2008 decreased in women of the 40–49 age cohort and in the 50–64 age cohort. Ovarian cancer is most commonly diagnosed after menopause, between the ages of 60 and 64. Ninety percent of ovarian cancer occurs in women over the age of 45 and 80% in women over 50. Older women are more likely to present with advanced ovarian cancer.


In pregnancy

Malignant germ cell tumors are the type of ovarian cancer most likely to occur during
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
. They are typically diagnosed when an adnexal mass is found on examination (in 1–2% of all pregnancies), a tumor is seen on ultrasound, or the parent's level of alpha-fetoprotein is elevated. Dermoid cysts and dysgerminomas are the most common germ cell tumors during pregnancy. Germ cell tumors diagnosed during pregnancy are unlikely to have metastasized and can be treated by surgery and, in some cases, chemotherapy, which carries the risk of birth defects. Yolk sac tumors and immature teratomas grow particularly quickly and are usually treated with chemotherapy even during pregnancy; however, dysgerminomas that have been optimally debulked may be treated after childbirth.


Other animals

Ovarian tumors have been reported in
equine Equinae is a subfamily of the family Equidae, which have lived worldwide (except Indonesia and Australia) from the Hemingfordian stage of the Early Miocene (16 million years ago) onwards. They are thought to be a monophyletic grouping.B. J. MacFa ...
mare A mare is an adult female horse or other equine. In most cases, a mare is a female horse over the age of three, and a filly is a female horse three and younger. In Thoroughbred horse racing, a mare is defined as a female horse more than four ...
s. Reported tumor types include teratoma,
cystadenocarcinoma Cystadenocarcinoma is a malignant form of a cystadenoma and is a cancer derived from glandular epithelium, in which cystic accumulations of retained secretions are formed. The neoplastic cells manifest varying degrees of anaplasia and invasivenes ...
, and particularly
granulosa cell tumor Granulosa cell tumours are tumours that arise from granulosa cells. They are estrogen secreting tumours and present as large, complex, ovarian masses. These tumours are part of the sex cord-gonadal stromal tumour or non-epithelial group of tumours ...
.


Research


Screening

Screening by hysteroscopy to obtain cell samples obtained for histological examination is being developed. This is similar to the current pap smear that is used to detect cervical cancer. subscription required The UK Collaborative Trial of Ovarian Cancer Screening is testing a screening technique that combines CA-125 blood tests with transvaginal ultrasound. Other studies suggest that this screening procedure may be effective. Although results published in 2015 were not conclusive, there was some evidence that screening may save lives in the long-term. As a result, the trial has been extended and will publish definitive results at the end of 2019. One major problem with screening is no clear progression of the disease from stage I (noninvasive) to stage III (invasive) is seen, and it may not be possible to find cancers before they reach stage III. Another problem is that screening methods tend to find too many suspicious lesions, most of which are not cancer, but malignancy can only be assessed with surgery. The ROCA method combined with transvaginal ultrasonography is being researched in high-risk women to determine if it is a viable screening method. It is also being investigated in normal-risk women as it has shown promise in the wider population. Studies are also in progress to determine if screening helps detect cancer earlier in people with BRCA mutations.


Prognosis research

Research into various
prognostic factor Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stable ...
s for ovarian cancer is also going on. Recent research shows that
thrombocytosis Thrombocythemia is a condition of high platelet (thrombocyte) count in the blood. Normal count is in the range of 150x109 to 450x109 platelets per liter of blood, but investigation is typically only considered if the upper limit exceeds 750x109/L. ...
predicts lower survival and higher stage cancer. Ongoing research is also investigating the benefits of surgery for recurrent ovarian cancer.


Immunotherapy

While an active area of research, as of 2018 there is no good evidence that
immunotherapy Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
is effective for ovarian cancer. However, trials of the antibody and
VEGF Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, ...
inhibitor
bevacizumab Bevacizumab, sold under the brand name Avastin among others, is a medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, l ...
, which can slow the growth of new blood vessels in the cancer, have shown promising results, especially in combination with
pazopanib Pazopanib, sold under the brand name Votrient, is an anti-cancer medication marketed worldwide by Novartis. It is a potent and selective multi-targeted receptor tyrosine kinase inhibitor that blocks tumour growth and inhibits angiogenesis. It ha ...
, which also slows the process of blood vessel growth. Bevacizumab has been particularly effective in preliminary studies on stage-III and -IV cancer and has been cited as having at least a 15% response rate. It is being investigated particularly in mucinous ovarian cancers.


Pharmacology

mTOR inhibitor mTOR inhibitors are a class of drugs that inhibit the mechanistic target of rapamycin (mTOR), which is a serine/threonine-specific protein kinase that belongs to the family of phosphatidylinositol-3 kinase (PI3K) related kinases (PIKKs). mTOR re ...
s were a highly investigated potential treatment in the 2000s and 2010s, but the side effects of these drugs (particularly
hyperglycemia Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200  mg/dL), but symptoms may not start to become noticeable until even ...
and
hyperlipidemia Hyperlipidemia is abnormally elevated levels of any or all lipids (fats, cholesterol, or triglycerides) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also used as an umbre ...
) were not well tolerated and the survival benefit not confirmed. PI3 kinase inhibitors have been of interest, but they tend to be highly toxic and cause
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
. Another investigated drug is
selumetinib Selumetinib ( ), sold under the brand name Koselugo, is a medication for the treatment of children, two years of age and older, with neurofibromatosis type I (NF-1), a genetic disorder of the nervous system causing tumors to grow on nerves. It ...
, a
MAPK A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase). MAPKs are involved in directing cellular responses to ...
inhibitor. It improved survival, but did not correlate with any mutations found in tumors. Bevacizumab can also be combined with platinum chemotherapy, a combination that has had positive preliminary results in PFS, but equivocal results regarding overall survival. One disadvantage to these treatments is the side effect profile, which includes
high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
and
proteinuria Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy (although this symptom ma ...
. The drug can also exacerbate bowel disease, leading to
fistula A fistula (plural: fistulas or fistulae ; from Latin ''fistula'', "tube, pipe") in anatomy is an abnormal connection between two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other hollow or ...
e or
bowel perforation Gastrointestinal perforation, also known as ruptured bowel, is a hole in the wall of part of the gastrointestinal tract. The gastrointestinal tract includes the esophagus, stomach, small intestine, and large intestine. Symptoms include severe abd ...
.
Vintafolide Vintafolide is an investigational targeted cancer therapeutic currently under development by Endocyte and Merck & Co. It is a small molecule drug conjugate consisting of a small molecule targeting the folate receptor, which is overexpressed on ...
, which consists of an
antifolate Antifolates are a class of antimetabolite medications that antagonise (that is, block) the actions of folic acid (vitamin B9). Folic acid's primary function in the body is as a cofactor to various methyltransferases involved in serine, methionin ...
conjugated with
vinblastine Vinblastine (VBL), sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small cell lung cancer, bladder ca ...
, is also in clinical trials; it may prove beneficial because
folate receptor Folate receptors bind folate and reduced folic acid derivatives and mediates delivery of tetrahydrofolate to the interior of cells. It is then converted from monoglutamate to polyglutamate forms - such as 5-methyltetrahydrofolate - as only monog ...
s are overexpressed in many ovarian cancers. Another potential immunotherapy is
trastuzumab Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together wit ...
, which is active against tumors positive for Her2/neu mutations. Other angiogenesis inhibitors are also being investigated as potential ovarian cancer treatments.
Combretastatin Combretastatin is a dihydrostilbenoid found in '' Combretum caffrum''. As a class Combretastatins are a class of natural phenols. A variety of different natural combretastatin molecules are present in the bark of '' Combretum caffrum'', commonly ...
and
pazopanib Pazopanib, sold under the brand name Votrient, is an anti-cancer medication marketed worldwide by Novartis. It is a potent and selective multi-targeted receptor tyrosine kinase inhibitor that blocks tumour growth and inhibits angiogenesis. It ha ...
are being researched in combination for recurrent ovarian cancer. Trebananib and tasquinimod are other angiogenesis inhibitors being investigated. The
monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...
farletuzumab Farletuzumab (MORAb-003) is a humanized monoclonal antibody of IgG1/κ which is being investigated for the treatment of ovarian cancer. This drug was developed by Morphotek, Inc. It is targeted at folate receptor alpha (FRα) which is overexpre ...
is being researched as an adjuvant to traditional chemotherapy. Another type of immunotherapy involves
vaccines A vaccine is a biological preparation that provides active acquired immunity The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and pro ...
, including
TroVax TroVax is a cancer vaccine that was developed by Oxford BioMedica. No cancer vaccines have been proven to cure cancer or extend life yet, TroVax has been studied in a number of trials for colon cancer. TroVax uses a tumor-associated antigen, 5T ...
. An alternative to BEP chemotherapy, a regimen of 3 cycles of
carboplatin Carboplatin, sold under the trade name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is used b ...
and
etoposide Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is ...
, is a current topic of research for germ cell malignancies. Intraperitoneal chemotherapy has also been under investigation during the 2000s and 2010s for its potential to deliver higher doses of cytotoxic agent to tumors. Preliminary trials with cisplatin and paclitaxel have shown it is not well tolerated, but does improve survival, and more tolerable regimens are being researched. Cisplatin and paclitaxel are both being researched as intraperitoneal chemotherapy agents. A specific chemotherapy regimen for rare clear-cell cancers is also under investigation:
irinotecan Irinotecan, sold under the brand name Camptosar among others, is a medication used to treat colon cancer, and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is used with cisp ...
combined with cisplatin.
PARP inhibitor PARP inhibitors are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP). They are developed for multiple indications, including the treatment of heritable cancers. Several forms of cancer are more dependent on ...
s have also shown promise in early trials, particularly in people with ''BRCA'' gene mutations, since the BRCA protein interacts with the PARP pathway. It is also being studied in recurrent ovarian cancer in general, where preliminary studies have shown longer PFS. Specifically,
olaparib Olaparib, sold under the brand name Lynparza, is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair ...
has shown greater survival compared to doxorubicin, though this treatment is still being investigated. It is not clear yet which
biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...
s are predictive of responsiveness to PARP inhibitors.
Rucaparib Rucaparib, sold under the brand name Rubraca, is a PARP inhibitor used as an anti-cancer agent. Rucaparib is a first-in-class pharmaceutical drug targeting the DNA repair enzyme poly-ADP ribose polymerase-1 (PARP-1). It is taken by mouth. The ...
is another PARP inhibitor being researched in BRCA-positive and BRCA-negative recurrent advanced ovarian cancer.
Niraparib Niraparib, sold under the brand name Zejula, is an anti-cancer medication used for the treatment of epithelial ovarian, fallopian tube, or primary peritoneal cancer. It is taken Oral administration, by mouth. It is a PARP inhibitor. The most co ...
is a PARP inhibitor being tested in BRCA-positive recurrent ovarian cancer.
Tyrosine kinase inhibitors A tyrosine kinase inhibitor (TKI) is a pharmaceutical drug that inhibits tyrosine kinases. Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. The proteins are activated by adding a phosph ...
are another investigational drug class that may have applications in ovarian cancer. Angiogenesis inhibitors in the
receptor tyrosine kinase Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase ...
inhibitor group, including
pazopanib Pazopanib, sold under the brand name Votrient, is an anti-cancer medication marketed worldwide by Novartis. It is a potent and selective multi-targeted receptor tyrosine kinase inhibitor that blocks tumour growth and inhibits angiogenesis. It ha ...
, cediranib, and
nintedanib Nintedanib, sold under the brand names Ofev and Vargatef, is an oral medication used for the treatment of idiopathic pulmonary fibrosis and along with other medications for some types of non-small-cell lung cancer. In March 2020, it was appro ...
, have also been shown to increase progression free survival (PFS), but their benefit for overall survival has not been investigated as of 2015. Preliminary research showed that cediranib combined with platins in recurrent ovarian cancer increased the time to second recurrence by 3–4 months and increased survival by 3 months. MK-1775 is a tyrosine kinase inhibitor that is being used in combination with paclitaxel and carboplatin in platinum-sensitive cancers with p53 mutations.
Nintedanib Nintedanib, sold under the brand names Ofev and Vargatef, is an oral medication used for the treatment of idiopathic pulmonary fibrosis and along with other medications for some types of non-small-cell lung cancer. In March 2020, it was appro ...
is being researched as a potential therapy in combination with cyclophosphamide for people with recurrences.
Histone deacetylase inhibitor Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that inhibit histone deacetylases. HDIs have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics. More recently they are bei ...
s (HDACi) are another area of research.


Hormones and radiation

Hormone therapies are a topic of current research in ovarian cancer, particularly, the value of certain medications used to treat breast cancer. These include
tamoxifen Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men. It is also being studied for other types of cancer. It has b ...
,
letrozole Letrozole, sold under the brand name Femara among others, is an aromatase inhibitor medication that is used in the treatment of breast cancer. It was patented in 1986 and approved for medical use in 1996. In 2020, it was the 257th most common ...
, and
anastrozole Anastrozole, sold under the brand name Arimidex among others, is a medication used in addition to other treatments for breast cancer. Specifically it is used for hormone receptor-positive breast cancer. It has also been used to prevent breast ca ...
. Preliminary studies have showed a benefit for tamoxifen in a small number of people with advanced ovarian cancer. Letrozole may help to slow or stop growth of
estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen ( 17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the ...
positive ovarian cancer. Anastrozole is being investigated in postmenopausal people with estrogen receptor-positive cancer. Research into mitigating side effects of ovarian cancer treatment is also ongoing. Radiation fibrosis, the formation of scar tissue in an area treated with radiation, may be relieved with
hyperbaric oxygen therapy Hyperbaric medicine is medical treatment in which an ambient pressure greater than sea level atmospheric pressure is a necessary component. The treatment comprises hyperbaric oxygen therapy (HBOT), the medical use of oxygen at an ambient pressure ...
, but research has not been completed in this area. Treatment of ovarian cancer may also cause people to experience psychiatric difficulties, including depression. Research is ongoing to determine how counseling and psychotherapy can help people who have ovarian cancer during treatment.


Inflammation

There are some indications that pelvic inflammatory disease may be associated with ovarian cancer, especially in non-western countries. It may be due to the inflammatory process present with pelvic inflammatory disease.


Clinical trials

Clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
s are monitored and funded by US governmental organizations to test treatment options to see if they are safe and effective. These include NIH Clinical Research Trials and You (
National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
), Learn About Clinical Trials (
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
), Search for Clinical Trials (National Cancer Institute), ClinicalTrials.gov (National Institutes of Health). Clinical trials are also conducted in Canada.


References


Further reading

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External links

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What is Ovarian Cancer Infographic, information on ovarian cancer
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Mount Sinai Hospital, New York Mount Sinai Hospital, founded in 1852, is one of the oldest and largest teaching hospitals in the United States. It is located in East Harlem in the New York City borough of Manhattan, on the eastern border of Central Park stretching along Madis ...
{{DEFAULTSORT:Ovarian Cancer Gynaecological cancer Gynaecology Oncology Wikipedia medicine articles ready to translate