Malignant Mixed Müllerian Tumor (MMMT)

Uterus
Stromal tumors
Malignant Mixed Müllerian Tumor (MMMT)

Author: Mohamed Mokhtar Desouki, M.D., Ph.D.

Topic Completed: 1 September 2011

Revised: 25 February 2019

Copyright: 2002-2018, PathologyOutlines.com, Inc.

PubMed search: malignant mixed Müllerian tumor uterus

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Table of Contents

Cite this page: Desouki M. Malignant Mixed Müllerian Tumor (MMMT). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/uterusmmmt.html. Accessed June 18th, 2019.

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

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