Uterus
Stromal tumors
Malignant Mixed Müllerian Tumor (MMMT)
Copyright: 2002-2018, PathologyOutlines.com, Inc.
PubMed search: malignant mixed Müllerian tumor uterus
Stromal tumors
Malignant Mixed Müllerian Tumor (MMMT)
Topic Completed: 1 September 2011
Minor changes: 10 May 2020
Copyright: 2002-2018, PathologyOutlines.com, Inc.
PubMed search: malignant mixed Müllerian tumor uterus
Table of Contents
Definition / general | Terminology | Epidemiology | Sites | Etiology | Clinical features | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Electron microscopy description | Molecular / cytogenetics description | Differential diagnosisCite this page: Desouki M. Malignant Mixed Müllerian Tumor (MMMT). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/uterusmmmt.html. Accessed May 30th, 2020.
Definition / general
- Biphasic, high grade tumor with malignant epithelial and stromal components
- Benign (both components): adenofibroma, adenomyoma and atypical polypoid adenomyoma
- Malignant (mesenchymal component): adenosarcoma
- Malignant (epithelial component): carcinofibroma
- Malignant (both components): MMMT (carcinosarcoma)
Terminology
- Also called carcinosarcoma, malignant mesodermal mixed tumor, metaplastic carcinoma
- "Sarcomatoid carcinoma" is considered a different entity
Epidemiology
- Rare, almost always in postmenopausal women (median age 65 years), small number of women < age 40 years
- Constitutes half of all uterine sarcomas
Sites
- Uterine corpus, cervix, ovaries, fallopian tubes, vagina, peritoneum; also extragenital sites
Etiology
- Associated with chronic estrogen stimulation
- 30% with heterologous MMMT and 13% with homologous MMMT have history of radiation therapy (median 16 years previous, often pelvic)
- Other predisposing factors include nulliparity, diabetes, obesity
- Cases of tamoxifen associated uterine MMMTs have been reported
Clinical features
- Vaginal bleeding, abdominal mass and pelvic pain are the usual presenting symptoms
- Usually elevated serum CA125
- Extrauterine spread in up to 1/3
Prognostic factors
Highly aggressive:
- 5 year disease free survival by stage is poor (stage I, 56%; stage II, 31%; stage III, 13%; stage IV, 0%) with most patients developing extrapelvic disease (J Clin Oncol 2010;28:2727)
- Cure possible only if tumor is restricted to inner half of myometrium
- Heterologous differentiation has no prognostic importance
Case reports
- 54 year old woman with tamoxifen associated tumor (Indian J Pathol Microbiol 2010;53:886)
Treatment
- TAHBSO with pelvic lymphadenectomy
- Radiotherapy and chemotherapy (initially chemosensitive, but relapse quickly)
- Recurs in lung and abdomen
Gross description
- Fleshy, bulky, polypoid, may be friable
- May fill uterine cavity and protrude through cervical os
- Hemorrhage and necrosis common
- Usually extensive myoinvasion
Gross images
Images hosted on other servers:
Polypoid fleshy mass at fundus of uterus
Various images
Various images
Microscopic (histologic) description
- Biphasic tumor with carcinomatous and sarcoma-like elements
- Most common epithelial component is glandular (endometrioid, clear cell, serous) and usually poorly differentiated
- Most common sarcomatous components are homologous (endometrial stromal sarcoma, leiomyosarcoma) or heterologous (muscle, cartilage, osteoid, fat)
- Angiolymphatic invasion common
- Peritoneal metastases may have scanty stromal component, psammoma bodies, and form papillary structures resembling ovarian serous carcinoma metastases
- Rarely neuroectodermal differentiation (Am J Surg Pathol 2008;32:219)
Microscopic (histologic) images
Images hosted on other servers:
Various images
With rhabdomyosarcoma
With chrondrosarcoma
With osteosarcoma
H&E and immunostains
Left: biphasic pattern; right: sarcomatous elements
Various images
Positive stains
Electron microscopy description
- Hybrid epithelial / stromal cells
Molecular / cytogenetics description
- p53 alteration occurs early before clonal expansion
- Loss of heterozygosity involving 17p, 17q, 11q, 15q and 21q
- Overexpression of c-myc
- Altered methylation of H19 gene
- Stromal and glandular cells may have same cell of origin; identical alleles are lost in epithelial and mesenchymal cells (J Pathol 1997;183:424)
- Mutations (loss of immunostaining): PTEN (39%), MLH1 (33%), MSH2 (22%), MSH6 (21%); p53 overexpression (38%, Mod Pathol 2011;24:1368)
Differential diagnosis
- Teratoma: younger age, components include skin appendages, glia, thyroid; MMMT only rarely contains neuroectodermal elements
- Botryoid rhabdomyosarcoma: children / teens, cervical or vaginal primaries, no carcinomatous component
- Metastatic ovarian serous cystadenocarcinoma: papillae and psammoma bodies present; also anaplastic carcinoma; keratin may not be helpful
