A malignant mixed Müllerian tumor, also known as malignant mixed mesodermal tumor (MMMT) is a

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 ...

found in the

uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...

, the ovaries, the fallopian tubes and other parts of the body that contains both

carcinoma Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal ...

tous (

epithelial tissue Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...

) and

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 ...

tous (

connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...

) components. It is divided into two types, homologous (in which the sarcomatous component is made of tissues found in the uterus such as

endometrial The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional layer ...

fibrous 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/or

smooth muscle Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...

tissues) and a heterologous type (made up of tissues not found in the uterus, such as

cartilage Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...

skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

and/or

bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...

). MMMT account for between two and five percent of all tumors derived from the body of the uterus, and are found predominantly in

postmenopausal 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 ...

women with an average age of 66 years. Risk factors are similar to those of

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 ...

s and include

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 ...

exogenous In a variety of contexts, exogeny or exogeneity () is the fact of an action or object originating externally. It contrasts with endogeneity or endogeny, the fact of being influenced within a system. Economics In an economic model, an exogeno ...

estrogen therapies, and

nulliparity In biology and human medicine, gravidity and parity are the number of times a woman is or has been pregnant (gravidity) and carried the pregnancies to a viable gestational age (parity). These terms are usually coupled, sometimes with additional te ...

. Less well-understood but potential risk factors 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 ...

therapy and pelvic irradiation.

Classification

There is debate over the naming of MMMT; the term

carcinosarcoma Carcinosarcomas are malignant tumors that consist of a mixture of carcinoma (or epithelial cancer) and sarcoma (or mesenchymal/connective tissue cancer). Carcinosarcomas are rare tumors, and can arise in diverse organs, such as the skin, salivary g ...

was formerly used to describe lesions with homologous tumors, and "malignant mixed Müllerian tumor" or "mixed mesodermal tumor" was used to describe heterologous tumors. While "carcinosarcoma" now considered standard, "malignant mixed Müllerian tumor" has a lengthy history within gynecological literature and is expected to continue to be used. The naming issue to a certain extent reflects

histological 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 ...

characteristics and development of the tumors, in which the different types of tissues are believed to either develop separately and join into a single mass (the "collision" theory), that an adenocarcinoma stimulates the stroma to create a tumor (the "composition" theory), or that the tumor is the result of a

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 ...

that differentiates into different cell types (the "combination" theory). "Collision" tumors are normally easily recognized and not considered true MMMTs; the "combination" theory is most widely held, and is due to evidence that the tumors develop from a single line of cells, developing in a fashion similar to the

fundus of the uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uteru ...

from the

Müllerian duct Paramesonephric ducts (or Müllerian ducts) are paired ducts of the embryo that run down the lateral sides of the genital ridge and terminate at the sinus tubercle in the primitive urogenital sinus. In the female, they will develop to form the fal ...

– first from a stem cell into a population of cells, that then differentiates into epithelial and stromal components. There is evidence that some tumors are better explained by the composition theory, due to the aggressive nature of the epithelial cells involved which tend to

metastasize 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, ...

much more readily than the sarcomal component. The behavior of MMMT overall is more related to the type and grade of the epithelium than the sarcoma, which suggests the sarcomal portion is an atypical "bystander" than primary driver of the tumor. Despite this, when purely endometrial tumors are compared to MMMTs, the MMMT tumor tends to have a worse prognosis.

Morphology

In gross appearance, MMMTs are fleshier than

s, may be bulky and polypoid, and sometimes protrude through the

cervical os The cervical canal is the spindle-shaped, flattened canal of the cervix, the neck of the uterus. Anatomy The cervical canal communicates with the uterine cavity via the internal orifice of the uterus (or internal os) and with the vagina via the ...

. On

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 ...

, the tumors consist of adenocarcinoma (endometrioid, serous or clear cell) mixed with the malignant mesenchymal (

) elements; alternatively, the tumor may contain two distinct and separate epithelial and mesenchymal components. Sarcomatous components may also mimic extrauterine tissues (e.g., striated muscle, cartilage, adipose tissue, and bone). Metastases usually contain only epithelial components.

Prognosis

Outcome of MMMTs is determined primarily by depth of invasion and stage. As with endometrial carcinomas, the prognosis is influenced by the grade and type of the adenocarcinoma, being poorest with serous differentiation. MMMTs are highly malignant; a stage I tumor has an expected five-year survival rate of 50%, while the overall five-year survival rate is less than 20%. Staging of uterine MMMTs is as follows: *Stage I. Carcinoma is confined to the

corpus uteri The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ut ...

itself. *Stage II. Carcinoma involves the corpus and the

cervix The cervix or cervix uteri (Latin, 'neck of the uterus') is the lower part of the uterus (womb) in the human female reproductive system. The cervix is usually 2 to 3 cm long (~1 inch) and roughly cylindrical in shape, which changes during ...

. *Stage III. Carcinoma extends outside the uterus but not outside the

lesser pelvis The pelvic cavity is a body cavity that is bounded by the bones of the pelvis. Its oblique roof is the pelvic inlet (the superior opening of the pelvis). Its lower boundary is the pelvic floor. The pelvic cavity primarily contains the reproducti ...

. *Stage IV. Carcinoma extends outside the true pelvis or involves the mucosa of the bladder or the rectum. A Cochrane review indicates women with high stage uterine carcinosarcoma (stage 3 or 4) who were treated with combination chemotherapy including Ifosfamide, were at lower risk of disease progression and death than those women treated with Ifosfamide alone. However, more women experienced side effects with combination therapy than with ifosamide alone. Radiotherapy to the abdomen was not associated with improved survival.

References

External links

{{DEFAULTSORT:Mixed Mullerian Tumor Gynaecological neoplasia