Germ cell tumor (GCT) is a

neoplasm 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 ...

derived from

germ cell 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 ...

s. Germ-cell tumors can be

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

ous or

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 in that a malignancy is not s ...

. Germ cells normally occur inside the

gonads A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sper ...

(

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. ...

and

testis A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testostero ...

). GCTs that originate outside the gonads may be

birth defect 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 ca ...

s resulting from errors during

development Development or developing may refer to: Arts *Development hell, when a project is stuck in development *Filmmaking, development phase, including finance and budgeting *Development (music), the process thematic material is reshaped * Photograph ...

of the

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 ...

Classification

Relative incidences of testicular tumors

GCTs are classified by their

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 v ...

, regardless of location in the body. However, as more information about the genetics of these tumors become available, they may be classified based on specific gene mutations that characterize specific tumors. They are broadly divided in two classes: * The germinomatous or seminomatous germ-cell tumors (GGCT, SGCT) include only germinoma and its synonyms

dysgerminoma A dysgerminoma is a type of germ cell tumor; it usually is malignant and usually occurs in the ovary. A tumor of the identical histology but not occurring in the ovary may be described by an alternate name: seminoma in the testis or germinoma in ...

and

seminoma A seminoma is a germ cell tumor of the testicle or, more rarely, the mediastinum or other extra-gonadal locations. It is a malignant neoplasm and is one of the most treatable and curable cancers, with a survival rate above 95% if discovered in ...

. * The nongerminomatous or nonseminomatous germ-cell tumors (NGGCT, NSGCT) include all other germ-cell tumors, pure and mixed. The two classes reflect an important clinical difference. Compared with germinomatous tumors, nongerminomatous tumors tend to grow faster, have an earlier mean age at time of diagnosis (around 25 years versus 35 years, in the case of

testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle, or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include a ...

s), and have a lower five-year survival rate. The survival rate for germinomatous tumors is higher in part because these tumors are very sensitive to radiation, and they also respond well to chemotherapy. The prognosis for nongerminomatous tumours has improved dramatically, however, due to the use of platinum-based chemotherapy regimens.

Germinomatous

Nongerminomatous

Mixed

Mixed germ cell tumors occur in many forms. Among these, a common form is teratoma with endodermal sinus tumor. Teratocarcinoma refers to a germ cell tumor that is a mixture of

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 ter ...

with

embryonal carcinoma Embryonal carcinoma is a relatively uncommon type of germ cell tumour that occurs in the ovaries and testes. Signs and symptoms The presenting features may be a palpable testicular mass or asymmetric testicular enlargement in some cases. The tu ...

, or with

choriocarcinoma 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 c ...

, or with both. This kind of mixed germ cell tumor may be known simply as a teratoma with elements of embryonal carcinoma or choriocarcinoma, or simply by ignoring the teratoma component and referring only to its malignant component: embryonal carcinoma and/or choriocarcinoma. They can present in the

anterior mediastinum The mediastinum (from ) is the central compartment of the thoracic cavity. Surrounded by loose connective tissue, it is an undelineated region that contains a group of structures within the thorax, namely the heart and its vessels, the esophagu ...

Cause

Some investigators suggest that this distribution arises as a consequence of abnormal migration of germ cells during embryogenesis. Others hypothesize a widespread distribution of germ cells to multiple sites during normal embryogenesis, with these cells conveying genetic information or providing regulatory functions at somatic sites. Extragonadal GCTs were thought initially to be isolated

metastases 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, the ...

from an undetected primary tumor in a

gonad A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sp ...

, but many germ cell tumors are now known to be

congenital 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 ...

and originate outside the gonads. The most notable of these is

sacrococcygeal teratoma Sacrococcygeal teratoma (SCT) is a type of tumor known as a teratoma that develops at the base of the coccyx (tailbone) and is thought to be primarily derived from remnants of the primitive streak. Sacrococcygeal teratomas are benign 75% of the t ...

, the single most common tumor diagnosed in babies at birth. Of all anterior mediastinal tumors, 15–20% are GCTs of which about 50% are benign teratomas. Ovarian teratomas may be associated with anti-NMDA receptor encephalitis.

Location

Despite their name, GCTs occur both within and outside the

and

. They are found in:} *

head A head is the part of an organism which usually includes the ears, brain, forehead, cheeks, chin, eyes, nose, and mouth, each of which aid in various sensory functions such as sight, hearing, smell, and taste. Some very simple animals ...

** inside the

cranium The skull is a bone protective cavity for the brain. The skull is composed of four types of bone i.e., cranial bones, facial bones, ear ossicles and hyoid bone. However two parts are more prominent: the cranium and the mandible. In humans, th ...

—

pineal The pineal gland, conarium, or epiphysis cerebri, is a small endocrine gland in the brain of most vertebrates. The pineal gland produces melatonin, a serotonin-derived hormone which modulates sleep patterns in both circadian and seasonal cycl ...

and suprasellar locations are most commonly reported ** inside the

mouth In animal anatomy, the mouth, also known as the oral cavity, or in Latin cavum oris, is the opening through which many animals take in food and issue vocal sounds. It is also the cavity lying at the upper end of the alimentary canal, bounded on ...

— a fairly common location for

neck The neck is the part of the body on many vertebrates that connects the head with the torso. The neck supports the weight of the head and protects the nerves that carry sensory and motor information from the brain down to the rest of the body. In ...

mediastinum The mediastinum (from ) is the central compartment of the thoracic cavity. Surrounded by loose connective tissue, it is an undelineated region that contains a group of structures within the thorax, namely the heart and its vessels, the esopha ...

— account for 1% to 5% of all germ cell neoplasms *

pelvis 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 ...

, particularly

In females, GCTs account for 30% of ovarian tumors, but only 1 to 3% of

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different ...

s in

North America North America is a continent in the Northern Hemisphere and almost entirely within the Western Hemisphere. It is bordered to the north by the Arctic Ocean, to the east by the Atlantic Ocean, to the southeast by South America and th ...

. In younger women, they are more common, thus in patients under the age of 21, 60% of ovarian tumors are of the germ-cell type, and up to one-third are

malignant 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 in that a malignancy is not s ...

. In males, GCTs of the testis occur typically after puberty and are malignant (

). In

neonates An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...

infants An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used ...

, and

children A child ( : children) is a human being between the stages of birth and puberty, or between the developmental period of infancy and puberty. The legal definition of ''child'' generally refers to a minor, otherwise known as a person younger ...

younger than 4 years, most are

s. Males with

Klinefelter syndrome Klinefelter syndrome (KS), also known as 47,XXY, is an aneuploid genetic condition where a male has an additional copy of the X chromosome. The primary features are infertility and small, poorly functioning testicles. Usually, symptoms are sub ...

have a 50 times greater risk of GSTs. In these persons, GSTs usually contain nonseminomatous elements, present at an earlier age, and seldom are gonadal in location.

Treatment

Women with benign GCTs such as mature teratomas (dermoid cysts) are cured by ovarian cystectomy or

oophorectomy Oophorectomy (; from Greek , , 'egg-bearing' and , , 'a cutting out of'), historically also called ''ovariotomy'' is the surgical removal of an ovary or ovaries. The surgery is also called ovariectomy, but this term is mostly used in reference ...

. In general, all patients with malignant GCTs have the same staging surgery that is done for epithelial ovarian cancer. If the patient is in her reproductive years, an alternative is unilateral

salpingoophorectomy 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 tumor ...

, while the uterus, the ovary, and the fallopian tube on the opposite side can be left behind. This is not an option when the cancer is in both ovaries. If the patient has finished having children, the surgery involves complete staging, including salpingoophorectomy on both sides, as well as

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 ...

. Patients with germ-cell cancer often need to be treated with combination

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. Chemother ...

for at least three cycles, but female patients with early-stage disease may not require this treatment. The

chemotherapy regimen A chemotherapy regimen is a regimen for chemotherapy, defining the drugs to be used, their dosage, the frequency and duration of treatments, and other considerations. In modern oncology, many regimens combine several chemotherapy drugs in combina ...

most commonly used in GCTs is called PEB (or BEP), and consists 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 a

platinum-based antineoplastic Platinum-based antineoplastic drugs (informally called platins) are chemotherapeutic agents used to treat cancer. They are coordination complexes of platinum. These drugs are used to treat almost half of people receiving chemotherapy for 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, ...

). Targeted treatments, such as immunotherapy, hormonal therapy and kinase inhibitors, are being evaluated for tumors that do not respond to chemotherapy.

Prognosis

The 1997 International Germ Cell Consensus Classification is a tool for estimating the risk of relapse after treatment of malignant germ-cell tumor. A small study of ovarian tumors in girls reports a correlation between

cyst A cyst is a closed sac, having a distinct envelope and division compared with the nearby tissue. Hence, it is a cluster of cells that have grouped together to form a sac (like the manner in which water molecules group together to form a bubble) ...

ic and benign tumors, and conversely, solid and malignant tumors. Because the cystic extent of a tumor can be estimated by ultrasound, MRI, or CT scan before surgery, this permits selection of the most appropriate surgical plan to minimize risk of spillage of a malignant tumor. Access to appropriate treatment has a large effect on outcome. A 1993 study of outcomes in Scotland found that for 454 men with nonseminomatous (nongerminomatous) GCTs diagnosed between 1975 and 1989, five-year survival increased over time and with earlier diagnosis. Adjusting for these and other factors, survival was 60% higher for men treated in a cancer unit that treated the majority of these men, though the unit treated more men with the worst prognosis.

Choriocarcinoma 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 c ...

of the testicles has the worst prognosis of all germ-cell cancers.