Mixed mullerian tumor
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]
Synonyms and keywords: Mixed Müllerian tumor; MMMT; Malignant mixed Müllerian tumor; Carcinosarcoma of the uterus; Sarcomatoid carcinoma of the uterus; Malignant mesodermal mixed tumor; Metaplastic carcinoma
Overview
Mixed Mullerian tumor (MMMT) is a rare uterine sarcoma or carcinosarcoma.
Historical Perspective
- Mixed Mullerian tumor was first described by Ferriera and colleagues in 1951.[1]
Classification
- Mixed Mullerian tumors are normally composed of both carcinomatous (epithelial) and sarcomatous (mesodermal) components.
- Mixed Mullerian tumor may be classified according to pathology findings into 2 types:
Epitheloid subtype
- Endometroid adenocarcinoma (most common)
- Clear cell carcinoma
- Mucinous carcinoma
- Papillary-serous carcinoma
Sarcomatoid subtype
- Undifferentiated sarcoma
- Rhabdomyosarcoma
- Mixed Mullerian tumor may also be classified according to antomical location into 7 types:
- Uterine corpus
- Cervix
- Ovaries
- Fallopian tubes
- Vagina
- Peritoneum
- Extragenital sites
Pathophysiology
- The pathogenesis of mixed Mullerian tumor is characterized by
- Mixed Mullerian tumor
- On gross pathology, a large cervical mass is a characteristic finding of mixed Mullerian tumor.
- On microscopic histopathological analysis, high-grade stromal sarcoma, poorly differentiated epithelial cells, and angiolymphatic invasion are characteristic findings of mixed Mullerian tumor.
Causes
- Mixed Mullerian tumor may be caused by precursor lesions, such as
- Mixed Mullerian tumor is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
- There are no established causes for mixed Mullerian tumor.
Differentiating mixed Mullerian tumor from other Diseases
- Mixed Mullerian tumor must be differentiated from other diseases that cause abnormal vaginal bleeding, abdominal pain, and metrorrhagia, such as:
- Uterine leiomyosarcoma
- Adenocarcinoma of the uterus
- Endometrial cancer
Epidemiology and Demographics
- The prevalence of mixed Mullerian tumor is approximately [number or range] per 100,000 individuals worldwide.
- In [year], the incidence of mixed Mullerian tumor was estimated to be [number or range] cases per 100,000 individuals in [location].
Age
- The median age at diagnosis of Mixed Mullerian tumor is 66 years
- Mixed Mullerian tumor is more commonly observed among patients aged between 50 and 60 years old.
- Mixed Mullerian tumor is more commonly observed among postmenopausal women
Race
- There is no racial predilection for mixed Mullerian tumor.
Risk Factors
- Common risk factors in the development of mixed Mullerian tumor are exposure to radiation, excessive estrogen exposure, obesity, and nulliparity.[2]
Natural History, Complications and Prognosis
- Early clinical features include postmenopausal vaginal bleeding, abdominal pain, and metrorrhagia.
- If left untreated, the majority of patients with mixed Mullerian tumor may progress quickly to develop lymph node invasion, metastasis, and death.
- Common complications of mixed Mullerian tumor include
- Prognosis is generally poor, and the 5-year survival rate of patients with Mixed Mullerian tumor is approximately 33% to 39%.
- Findings associated with good prognosis includes p16 and Mcl-1 genetic expression.
Diagnosis
Diagnostic Criteria
- The diagnosis of mixed Mullerian tumor is made with biopsy.
- Biopsy findings of mixed Mullerian tumor, include:
- Tumor with carcinomatous and sarcoma-like elements
- Angiolymphatic invasion
Symptoms
- Mixed Mullerian tumor is usually asymptomatic.
- Symptoms of mixed Mullerian tumor may include the following:[2]
- Early symptoms may include:
- Abnormal vaginal bleeding, abnormal menstrual periods
- Metrorrhagia in premenopausal women
- Postmenopausal vaginal bleeding [3]
- Postcoital bleeding
- Advanced symptoms may include:
- Polyuria and dysuria, If a tumor places pressure on the bladder or urethra
- Pelvic pain and dyspareunia
- Fatigue and unexplained weight loss
Physical Examination
- Patients with mixed Mullerian tumor may have a normal appearance.
- Pelvic examination may be remarkable for:
- Vaginal bleeding
- Enlarged uterus (advanced stage)
Laboratory Findings
- Laboratory findings associated with mixed Mullerian tumor, may include:
- Elevated CA-125
Imaging Findings
- Enhanced CT scan and MRI is the imaging modalities of choice for mixed Mullerian tumor.
- On MRI, findings of mixed Mullerian tumor, may include:
- T1: predominantly isointense to both myometrium (75%) and endometrium (70%)
- T2:hyper-intense to myometrium (90%) either hypo-intense (55%) or isointense (41%) to endometrium.
- On enhanced CT, findings of mixed Mullerian tumor, may include:
- Heterogeneously hypodense and ill defined mass
- Dilatation of uterine cavity
Other Diagnostic Studies
- Mixed Mullerian tumor may also be diagnosed using laparoscopy.
Treatment
Medical Therapy
- There is no treatment for mixed Mullerian tumor; the mainstay of therapy is supportive care.
- The medical management for mixed Mullerian tumor, include:
Surgery
- Surgery is the mainstay of therapy for mixed Mullerian tumor.
- Total hysterectomy in conjunction with surgical staging is the most common approach to the treatment of mixed Mullerian tumor.
- Different surgical procedures for the treatment of mixed Mullerian tumor, include:
- Total hysterectomy
- Bilateral salpingo-oophorectomy
- Pelvic and para-aortic lymph node dissection
- Cytology of peritoneal washings
- Omentectomy
- Biopsies of peritoneal surfaces
Prevention
- There are no primary preventive measures available for mixed Mullerian tumor.
- Once diagnosed and successfully treated, patients with mixed Mullerian tumor are followed-up every 6 or 12 months.
- Follow-up testing include pelvic examination, ultrasound, and biomarker monitorization.
References
- ↑ Wright JD, Rosenblum K, Huettner PC, Mutch DG, Rader JS, Powell MA, Gibb RK (2005). "Cervical sarcomas: an analysis of incidence and outcome". Gynecol. Oncol. 99 (2): 348–51. doi:10.1016/j.ygyno.2005.06.021. PMID 16051326.
- ↑ 2.0 2.1 Kanthan R, Senger JL, Diudea D (2010). "Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins". World J Surg Oncol. 8: 60. doi:10.1186/1477-7819-8-60. PMC 2913917. PMID 20642852.
- ↑ Kong A, Johnson N, Kitchener HC, Lawrie TA (2012). "Adjuvant radiotherapy for stage I endometrial cancer". Cochrane Database Syst Rev. 4: CD003916. doi:10.1002/14651858.CD003916.pub4. PMC 4164955. PMID 22513918.