Carcinosarcomas (Malignant Mixed Müllerian Tumor) of the Uterus: Advances in Elucidation of Biologic and Clinical Characteristics

View More View Less
  • 1 Department of Pathology, University of Washington School of Medicine, Seattle, Washington
  • 2 Journal of the National Comprehensive Cancer Network
View More View Less
  • 1 Department of Pathology, University of Washington School of Medicine, Seattle, Washington
  • 2 Journal of the National Comprehensive Cancer Network

Carcinosarcoma of the uterus (malignant mixed Müllerian tumor [MMMT]) is an uncommon, typically extremely aggressive neoplasm histologically composed of malignant epithelial and mesenchymal (stromal) elements. Although the literature contains some debate, most authors now agree that most MMMTs derive from sarcomatous differentiation in a high-grade carcinoma. This article reviews the clinical and histopathologic features of this interesting neoplasm, with particular emphasis on recent data supporting MMMTs as primarily epithelial malignant neoplasms with areas of mesenchymal/spindle cell differentiation.

If the inline PDF is not rendering correctly, you can download the PDF file here.

Correspondence: Rochelle L. Garcia, MD, Department of Pathology, University of Washington Medical School, Box 356100, 1959 N.E. Pacific, Seattle, WA 98195. E-mail: rochelle@u.washington.edu

Disclosure: Lauren E. Kernochan, MD, has disclosed no relevant financial relationships.

Disclosure: Rochelle L. Garcia, MD, has disclosed no relevant financial relationships.

Disclosure: Kerrin G. Robinson, MA, has disclosed no relevant financial relationships.

  • 1

    Vaidya AP, Horowitz NS, Oliva E. Uterine malignant mixed mullerian tumors should not be included in studies of endometrial carcinoma. Gynecol Oncol 2006;103:684687.

    • Search Google Scholar
    • Export Citation
  • 2

    Wada H, Enomoto T, Fujita M. Molecular evidence that most but not all carcinosarcomas of the uterus are combination tumors. Cancer Res 1997;57:53795385.

    • Search Google Scholar
    • Export Citation
  • 3

    Abeln EC, Smit VT, Wessels JW. Molecular genetic evidence for the conversion hypothesis of the origin of malignant mixed mullerian tumours. J Pathol 1997;183:424431.

    • Search Google Scholar
    • Export Citation
  • 4

    Bansal N, Herzog TJ, Seshan VE. Uterine carcinosarcomas and grade 3 endometrioid cancers: evidence for distinct tumor behavior. Obstetrics and Gynecology 2008;112:6470.

    • Search Google Scholar
    • Export Citation
  • 5

    Di Cristofano E, Ellenson LH. Endometrial carcinoma. Annu Rev Pathol Mech Dis 2007;2:5785.

  • 6

    Sreenan JJ, Hart WR. Carcinosarcomas of the female genital tract. A pathologic study of 29 metastatic tumors: further evidence for the dominant role of the epithelial component and the conversion theory of histogenesis. Am J Surg Pathol 1995;19:666674.

    • Search Google Scholar
    • Export Citation
  • 7

    Jin Z, Ogata S, Tamura G. Carcinosarcomas (malignant mullerian mixed tumors) of the uterus and ovary: a genetic study with special reference to histogenesis. Int J Gynecol Pathol 2003;22:368373.

    • Search Google Scholar
    • Export Citation
  • 8

    Barnholtz-Sloan JS, Morris R, Malone JM Jr, Munkarah AR. Survival of women diagnosed with malignant, mixed mullerian tumors of the ovary (OMMMT). Gynecol Oncol 2004;93:506512.

    • Search Google Scholar
    • Export Citation
  • 9

    Lim BJ, Kim JW, Yang WI, Cho NH. Malignant mixed mullerian tumor of fallopian tube with multiple distinct heterologous components. Int J Gynecol Cancer 2004;14:690693.

    • Search Google Scholar
    • Export Citation
  • 10

    Sebenik M, Yan Z, Khalbuss WE, Mittal K. Malignant mixed mullerian tumor of the vagina: case report with review of the literature, immunohistochemical study, and evaluation for human papilloma virus. Hum Pathol 2007;38:12821288.

    • Search Google Scholar
    • Export Citation
  • 11

    Robboy SJ, Mutter GL, Prat J., eds. Robboy’s Pathology of the Female Reproductive Tract. 2nd ed. China: Churchill Livingstone Elsevier; 2009.

    • Search Google Scholar
    • Export Citation
  • 12

    Teo SY, Babagbemi KT, Peters HE, Mortele KJ. Primary malignant mixed mullerian tumor of the uterus: findings on sonography, CT, and gadolinium-enhanced MRI. AJR Am J Roentgenol 2008;191:278283.

    • Search Google Scholar
    • Export Citation
  • 13

    Zelmanowicz A, Hildesheim A, Sherman ME. Evidence for a common etiology for endometrial carcinomas and malignant mixed mullerian tumors. Gynecol Oncol 1998;69:253257.

    • Search Google Scholar
    • Export Citation
  • 14

    McCluggage WG. Uterine carcinosarcomas (malignant mixed Mullerian tumors) are metaplastic carcinomas. Int J Gynecol Cancer 2002;12:687690.

    • Search Google Scholar
    • Export Citation
  • 15

    Curtis RE, Freedman DM, Sherman ME, Fraumeni JF Jr. Risk of malignant mixed mullerian tumors after tamoxifen therapy for breast cancer. J Natl Cancer Inst 2004;96:7074.

    • Search Google Scholar
    • Export Citation
  • 16

    Cotran RS, Kumar V, Collins T, eds. Robbins Pathologic Basis of Disease. 6th ed. Philadelphia: W.B. Saunders Company; 1999.

  • 17

    Crum CP, Lee KR, eds. Diagnostic Gynecologic and Obstetric Pathology. China: Elsevier Saunders; 2006.

  • 18

    Bitterman P, Chun B, Kurman RJ. The significance of epithelial differentiation in mixed mesodermal tumors of the uterus. A clinicopathologic and immunohistochemical study. Am J Surg Pathol 1990;14:317328.

    • Search Google Scholar
    • Export Citation
  • 19

    Chung MT, Mukai K, Teshima S. Expression of various antigens by different components of uterine mixed mullerian tumors. An immunohistochemical study. Acta Pathol Jpn 1988;38:3545.

    • Search Google Scholar
    • Export Citation
  • 20

    Dupont J, Wang X, Marshall DS. Wilms Tumor Gene (WT1) and p53 expression in endometrial carcinomas: a study of 130 cases using a tissue microarray. Gynecol Oncol 2004;94:449455.

    • Search Google Scholar
    • Export Citation
  • 21

    Kounelis S, Jones MW, Papadaki H. Carcinosarcomas (malignant mixed mullerian tumors) of the female genital tract: comparative molecular analysis of epithelial and mesenchymal components. Hum Pathol 1998;29:8287.

    • Search Google Scholar
    • Export Citation
  • 22

    Schipf A, Mayr D, Kirchner T, Diebold J. Molecular genetic aberrations of ovarian and uterine carcinosarcomas—a CGH and FISH study. Virchows Arch 2008;452:259268.

    • Search Google Scholar
    • Export Citation
  • 23

    Silverberg SG, Major FJ, Blessing JA. Carcinosarcoma (malignant mixed mesodermal tumor) of the uterus. A Gynecologic Oncology Group pathologic study of 203 cases. Int J Gynecol Pathol 1990;9:119.

    • Search Google Scholar
    • Export Citation
  • 24

    Amant F, Vloeberghs V, Woestenborghs H. Transition of epithelial toward mesenchymal differentiation during ovarian carcinosarcoma tumorigenesis. Gynecol Oncol 2003;90:372377.

    • Search Google Scholar
    • Export Citation
  • 25

    Inthasorn P, Carter J, Valmadre S. Analysis of clinicopathologic factors in malignant mixed Mullerian tumors of the uterine corpus. Int J Gynecol Cancer 2002;12:348353.

    • Search Google Scholar
    • Export Citation
  • 26

    Wolfson AH, Brady MF, Rocereto T. A gynecologic oncology group randomized phase III trial of whole abdominal irradiation (WAI) vs. cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I-IV carcinosarcoma (CS) of the uterus. Gynecol Oncol 2007;107:177185.

    • Search Google Scholar
    • Export Citation
  • 27

    Cicin I, Saip P, Eralp Y. Ovarian carcinosarcomas: clinicopathological prognostic factors and evaluation of chemotherapy regimens containing platinum. Gynecol Oncol 2008;108:136140.

    • Search Google Scholar
    • Export Citation
  • 28

    Homesley HD, Filiaci V, Markman M. Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study. J Clin Oncol 2007;25:526531.

    • Search Google Scholar
    • Export Citation
  • 29

    Silasi DA, Illuzzi JL, Kelly MG. Carcinosarcoma of the ovary. Int J Gynecol Cancer 2008;18:2229.

  • 30

    Sutton G, Brunetto VL, Kilgore L. A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: a Gynecologic Oncology Group study. Gyn Oncol 2000;79:147153.

    • Search Google Scholar
    • Export Citation
  • 31

    Schulten HJ, Gunawan B, Enders C. Overrepresentation of 8q in carcinosarcomas and endometrial adenocarcinomas. Am J Clin Pathol 2004;122:546551.

    • Search Google Scholar
    • Export Citation
  • 32

    Jeffers MD, Richmond JA, Macaulay EM. Overexpression of the c-myc proto-oncogene occurs frequently in uterine sarcomas. Mod Pathol 1995;8:701704.

    • Search Google Scholar
    • Export Citation
  • 33

    Fujii H, Yoshida M, Gong ZX. Frequent genetic heterogeneity in the clonal evolution of gynecological carcinosarcoma and its influence on phenotypic diversity. Cancer Res 2000;60:114120.

    • Search Google Scholar
    • Export Citation
  • 34

    Seidman JD, Chauhan S. Evaluation of the relationship between adenosarcoma and carcinosarcoma and a hypothesis of the histogenesis of uterine sarcomas. Int J Gynecol Pathol 2003;22:7582.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 542 217 11
PDF Downloads 366 197 16
EPUB Downloads 0 0 0