Stromal tumors
Malignant Mixed Müllerian Tumor (MMMT)

Topic Completed: 1 September 2011

Minor changes: 10 May 2020

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PubMed search: malignant mixed Müllerian tumor uterus

Mohamed Mokhtar Desouki, M.D., Ph.D.
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Cite 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)
  • Also called carcinosarcoma, malignant mesodermal mixed tumor, metaplastic carcinoma
  • "Sarcomatoid carcinoma" is considered a different entity
  • Rare, almost always in postmenopausal women (median age 65 years), small number of women < age 40 years
  • Constitutes half of all uterine sarcomas
  • Uterine corpus, cervix, ovaries, fallopian tubes, vagina, peritoneum; also extragenital sites
  • 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
  • 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
  • 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
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