Tumor of the uterus containing a mixture of epithelial and mesenchymal elements.
Uterine carcinosarcoma is a rare, highly aggressive uterine malignancy characterized by both malignant epithelial and malignant mesenchymal (sarcomatous) components within the same tumor.
A malignant mixed Müllerian tumor, is a cancer found in the uterus, the ovaries, the fallopian tubes and other parts of the body that contains both carcinomatous (epithelial tissue) and sarcomatous (connective tissue) components.
It is divided into two types, homologous and heterologous.
Homologous is the sarcomatous component is made of tissues found in the uterus such as endometrial, fibrous and/or smooth muscle tissues.
The heterologous type is made up of tissues not found in the uterus, such as cartilage, skeletal muscle and/or bone.
This biphasic tumor arises from the endometrial lining and is now understood to be a metaplastic carcinoma, where the sarcomatous component develops from the carcinomatous element through epithelial-mesenchymal transition (EMT).
Molecular studies confirm a monoclonal origin, with shared genomic alterations—most commonly TP53 mutations—between both components.
20% of patients with tumor clinically confined to the uterus have surgically documented metastases.
A MMT accounts for between two and five percent of all tumors derived from the body of the uterus.
MMTs are found predominantly in postmenopausal women with an average age of 66 years.
Risk factors include obesity, exogenous estrogen therapies, and nulliparity.
Other potential risk factors include tamoxifen therapy and pelvic irradiation.
The epithelial component, often serous or endometrioid, drives the tumor’s aggressive behavior and is responsible for most metastases and vascular invasion.
Uterine carcinosarcoma presents most often in postmenopausal women and is associated with a poor prognosis, high recurrence rates, and frequent extrauterine spread at diagnosis.
It is staged and treated as a high-grade endometrial carcinoma, not as a true sarcoma.
Standard management includes surgical resection (hysterectomy with bilateral salpingo-oophorectomy and staging), followed by adjuvant chemotherapy (typically carboplatin and paclitaxel) and, in selected cases, radiotherapy.
Despite multimodal therapy, survival outcomes remain poor, with 5-year overall survival rates below 50%.
Stage I and II patients have a recurrence rate of greater than 50%.
The behavior of MMT 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.
When purely endometrial tumors are compared to MMTs, the MMT tumor tends to have a worse prognosis.
Sarcoma dominant tumors in which more than half of the tumor has sarcoma histology have a worse prognosis than carcinoma dominant tumors.
Almost 40% of cases are noted to be sarcoma dominant.
Carcinosarcoma of the uterus are fleshier than adenocarcinomas, may be bulky and polypoid, and sometimes protrude through the cervical os.
The carcinoma elements are more likely to metastasize and spread distally, whereas the sarcoma elements are more likely to spread locally.
The tumors consist of adenocarcinoma (endometrioid, serous or clear cell) mixed with the malignant mesenchymal sarcoma elements;
Sarcomatous components may also mimic extrauterine tissues Ike striated muscle, cartilage, adipose tissue, and bone.
Metastases usually contain only epithelial components.
Outcome of MMTs is determined primarily by depth of invasion and stage.
The prognosis is influenced by the grade and type of the adenocarcinoma, being poorest with serous differentiation.
The carcinoma component is usually serious or undifferentiated.
MMTs 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 MMTs:
Stage I. Carcinoma is confined to the corpus uteri itself.
Stage II. Carcinoma involves the corpus and the cervix.
Stage III. Carcinoma extends outside the uterus but not outside the lesser pelvis.
Stage IV. Carcinoma extends outside the true pelvis or involves the mucosa of the bladder or the rectum.
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.
Radiotherapy to the abdomen is not associated with improved survival, however, retrospective data suggest outcomes in women with carcinosarcoma or better with edge of chemo radiotherapy, then with chemotherapy alone, or adjuvant radiotherapy alone.