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

cancer 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. Po ...

found in the

uterus The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...

, 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, mesoder ...

tous (

epithelial tissue Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

) and

sarcoma A sarcoma is a rare type of cancer that arises from cells of mesenchymal origin. Originating from mesenchymal cells means that sarcomas are cancers of connective tissues such as bone, cartilage, muscle, fat, or vascular tissues. Sarcom ...

tous (

connective tissue Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...

) 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 epithelium, 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 funct ...

fibrous Fiber (spelled fibre in British English; from ) 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 inco ...

and/or

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

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. Semi-transparent and non-porous, it is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints ...

skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

and/or

bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...

). 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 when menstrual periods permanently stop, marking the end of the reproductive stage for the female human. It typically occurs between the ages of 45 and 55, although the exact timing can ...

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, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

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

estrogen therapies, and

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

. 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 men. It is also being studied for other types of cancer. It has been used for Albright syndrome ...

therapy and pelvic irradiation.

Classification

There is debate over the naming of MMMT; the term

carcinosarcoma Carcinosarcomas are malignant tumors that consist of a Mixed tumor, 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 ski ...

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 that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...

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 change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...

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 from the

Müllerian duct The paramesonephric ducts (or Müllerian ducts) are paired ducts of the embryo in the reproductive system of humans and other mammals that run down the lateral sides of the genital ridge and terminate at the sinus tubercle in the primitive uroge ...

– 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 spreading 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, ...

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. On

histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...

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

cervix The cervix (: cervices) or cervix uteri is a dynamic fibromuscular sexual organ of the female reproductive system that connects the vagina with the uterine cavity. The human female cervix has been documented anatomically since at least the time ...

. *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 reproduc ...

. *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 Connective and soft tissue neoplasms