Uterus
Stromal tumors
Malignant Mixed Müllerian Tumor (MMMT)

Author: Mohamed Mokhtar Desouki, M.D., Ph.D. (see Authors page)

Revised: 3 February 2017, last major update September 2011

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed search: malignant mixed müllerian tumor uterus

Cite this page: Malignant Mixed Mullerian Tumor (MMMT). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/uterusMMMT.html. Accessed February 24th, 2017.
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
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

Micro 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)
Micro 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
  • Keratin (both components), p53 (usually positive or negative in both components), EMA (often both components)
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