Consult the medical resource doctors trust

UpToDate is one of the most respected medical information resources in the world, used by over 360,000 doctors and thousands of patients to find answers to medical questions.

  • Content written by a faculty of over 4,000 physicians from leading medical institutions
  • Unbiased: free of advertising or pharmaceutical funding
  • Evidence-based treatment recommendations
  • Continuously updated to incorporate new medical findings

Uterine carcinosarcoma

INTRODUCTION

Uterine carcinosarcomas are rare and highly aggressive tumors with a poor prognosis. Historically, uterine carcinosarcoma was classified as a uterine sarcoma, and was termed malignant mixed mullerian tumor or mixed mesodermal sarcoma. However, these tumors are now classified as carcinomas since they originate from a monoclonal carcinoma cell which exhibits sarcomatous metaplasia, rather than a mixture of carcinoma and sarcoma. In addition, the epidemiology, risk factors, and clinical behavior associated with carcinosarcoma also suggest a closer relationship to endometrial carcinoma than to sarcoma. (See "Uterine sarcoma: Classification, clinical manifestations, and diagnosis" and "Uterine sarcoma: Staging and treatment".)

Accordingly, the approach to management of carcinosarcomas, in particular the choice of chemotherapy regimens for adjuvant or palliative therapy, has shifted from those used for high grade sarcoma to strategies used in the management of high grade endometrial carcinomas (ie, the uterine papillary and clear cell subtypes) [1,2]. (See "Uterine papillary serous and clear cell cancer".)

It should also be noted that older literature refers to carcinosarcoma by differing names and studies have often combined patients with carcinosarcoma and uterine sarcoma. In this topic review, when possible, we will use current terminology. However, older studies cited in the discussion will use the terminology used in the publication (often, malignant mixed mullerian tumor or mixed mesodermal sarcoma).

The pathology, clinical manifestations, diagnosis, staging, and treatment of uterine carcinosarcoma will be discussed in this topic review. Other types of endometrial cancer and uterine sarcomas are reviewed separately. (See "Uterine sarcoma: Classification, clinical manifestations, and diagnosis" and "Endometrial cancer: Epidemiology, risk factors, clinical features, diagnosis, and screening".)

EPIDEMIOLOGY AND RISK FACTORS

Uterine carcinosarcoma is rare. In the United States the incidence is approximately 7 per 100,000 women over age 35 and comprises only 1.2 percent of uterine neoplasms [3,4]. The median age at diagnosis is 62 to 67 years old [5].
To continue reading this article you need to subscribe.

Read the rest of this article and others like it

The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use (click here) ©2010 UpToDate, Inc.
References Top
  1. McCluggage, WG. Malignant biphasic uterine tumours: carcinosarcomas or metaplastic carcinomas?. J Clin Pathol 2002; 55:321.
  2. National Comprehensive Cancer Network guidelines available online at http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed May 12, 2009).
  3. Kosary, CL. Chapter 15: Cancer of the corpus uteri. In: SEER survival monograph. National Cancer Institute. Available at http://seer.cancer.gov/csr/1975_2004/ (Accessed August 19, 2008).
  4. Brooks, SE, Zhan, M, Cote, T, Baquet, CR. Surveillance, Epidemiology, and End Results analysis of 2677 cases of uterine sarcoma 1989–1999. Gynecol Oncol 2002; 93:204.
  5. Gadducci, A. The management of patients with uterine sarcoma: A debated clinical challenge. Crit Rev Oncol Hematol 2008; 65:129.
  6. Sherman, ME, Devesa, SS. Analysis of racial differences in incidence, survival, and mortality for malignant tumors of the uterine corpus. Cancer 2003; 98:176.
  7. Bansal, N, Herzog, TJ, Seshan, VE, et al. Uterine carcinosarcomas and grade 3 endometrioid cancers: evidence for distinct tumor behavior. Obstet Gynecol 2008; 112:64.
  8. Zelmanowicz, A, Hildesheim, A, Sherman, ME, et al. Evidence for a common etiology for endometrial carcinomas and malignant mixed mullerian tumors. Gynecol Oncol 1998; 69:253.
  9. Schwartz, SM, Weiss, NS, Daling, JR, et al. Exogenous sex hormone use, correlates of endogenous hormone levels, and the incidence of histologic types of sarcoma of the uterus. Cancer 1996; 77:717.
  10. McCluggage, WG, Perenyei, M. Microglandular adenocarcinoma of the endometrium. Histopathology 2000; 37:285.
  11. McCluggage, WG, McManus, DT, Lioe, TF, Hill, CM. Uterine carcinosarcoma in association with tamoxifen therapy. Br J Obstet Gynaecol 1997; 104:748.
  12. Fotiou, S, Hatjieleftheriou, G, Kyrousis, G, et al. Long-term tamoxifen treatment: a possible aetiological factor in the development of uterine carcinosarcoma: two case-reports and review of the literature. Anticancer Res 2000; 20:2015.
  13. Treilleux, T, Mignotte, H, Clement-Chassagne, C, et al. Tamoxifen and malignant epithelial-nonepithelial tumours of the endometrium: report of six cases and review of the literature. Eur J Surg Oncol 1999; 25:477.
  14. Friedrich, M, Villena-Heinsen, C, Mink, D, et al. Carcinosarcoma, endometrial intraepithelial carcinoma and endometriosis after tamoxifen therapy in breast cancer. Eur J Obstet Gynecol Reprod Biol 1999; 82:85.
  15. Evans, MJ, Langlois, NE, Kitchener, HC, Miller, ID. Is there an association between long-term tamoxifen treatment and the development of carcinosarcoma (malignant mixed Mullerian tumor) of the uterus?. Int J Gynecol Cancer 1995; 5:310.
  16. Wickerham, DL, Fisher, B, Wolmark, N ,et al. Association of tamoxifen and uterine sarcoma. J Clin Oncol 2002; 20:2758.
  17. South, SA, Hutton, M, Farrell, C, et al. Uterine carcinosarcoma associated with hereditary nonpolyposis colorectal cancer. Obstet Gynecol 2007; 110:543.
  18. Pothuri, B, Ramondetta, L, Martino, M, et al. Development of endometrial cancer after radiation treatment for cervical carcinoma. Obstet Gynecol 2003; 101:941.
  19. Pothuri, B, Ramondetta, L, Eifel, P, et al. Radiation-associated endometrial cancers are prognostically unfavorable tumors: a clinicopathologic comparison with 527 sporadic endometrial cancers. Gynecol Oncol 2006; 103:948.
  20. Hagiwara, T, Mori, T, Kaku, T. Development of endometrial cancer following radiation therapy for cervical carcinoma. Eur J Gynaecol Oncol 2005; 26:191.
  21. Shimizu, S, Yajima, M, Yoshii, A, et al. Malignant pericardial effusion and cardiac tamponade originating from uterine carcinosarcoma. Arch Gynecol Obstet 2009; 279:373.
  22. Bansal, N, Herzog, TJ, Burke, W, et al. The utility of preoperative endometrial sampling for the detection of uterine sarcomas. Gynecol Oncol 2008; 110:43.
  23. Sagae, S, Yamashita, K, Ishioka, S, et al. Preoperative diagnosis and treatment results in 106 patients with uterine sarcoma in Hokkaido, Japan. Oncology 2004; 67:33.
  24. Gorai, I, Yanagibashi, T, Taki, A, et al. Uterine carcinosarcoma is derived from a single stem cell: an in vitro study. Int J Cancer 1997; 72:821.
  25. Crum, C, Lee, KR. Diagnostic Gynecologic and Obstetric Pathology. Elsevier Saunders, Amsterdam 2006.
  26. Silverberg, SG, Major, FJ, Blessing, JA, et al. Carcinosarcoma (malignant mixed mesodermal tumor) of the uterus. A Gynecologic Oncology Group pathologic study of 203 cases. Int J Gynecol Pathol 1990; 9:1.
  27. 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; 19:666.
  28. Arrastia, CD, Fruchter, RG, Clark, M, et al. Uterine carcinosarcomas: incidence and trends in management and survival. Gynecol Oncol 1997; 65:158.
  29. Yamada, SD, Burger, RA, Brewster, WR, et al. Pathologic variables and adjuvant therapy as predictors of recurrence and survival for patients with surgically evaluated carcinosarcoma of the uterus. Cancer 2000; 88:2782.
  30. Sartori, E, Bazzurini, L, Gadducci, A, et al. Carcinosarcoma of the uterus: a clinicopathological multicenter CTF study. Gynecol Oncol 1997; 67:70.
  31. Major, FJ, Blessing, JA, Silverberg, SG, et al. Prognostic factors in early-stage uterine sarcoma. A Gynecologic Oncology Group study. Cancer 1993; 71:1702.
  32. Dinh, TV, Slavin, RE, Bhagavan, BS, et al. Mixed mullerian tumors of the uterus: a clinicopathologic study. Obstet Gynecol 1989; 74:388.
  33. Podczaski, ES, Woomert, CA, Stevens, CW Jr, et al. Management of malignant, mixed mesodermal tumors of the uterus. Gynecol Oncol 1989; 32:240.
  34. Amant, F, Cadron, I, Fuso, L, et al. Endometrial carcinosarcomas have a different prognosis and pattern of spread compared to high-risk epithelial endometrial cancer. Gynecol Oncol 2005; 98:274.
  35. Temkin, SM, Hellmann, M, Lee, YC, Abulafia, O. Early-stage carcinosarcoma of the uterus: the significance of lymph node count. Int J Gynecol Cancer 2007; 17:215.
  36. Nemani, D, Mitra, N, Guo, M, Lin, L. Assessing the effects of lymphadenectomy and radiation therapy in patients with uterine carcinosarcoma: a SEER analysis. Gynecol Oncol 2008; 111:82.
  37. Callister, M, Ramondetta, LM, Jhingran, A, et al. Malignant mixed Mullerian tumors of the uterus: analysis of patterns of failure, prognostic factors, and treatment outcome. Int J Radiat Oncol Biol Phys 2004; 58:786.
  38. Chi, DS, Mychalczak, B, Saigo, PE, et al. The role of whole-pelvic irradiation in the treatment of early-stage uterine carcinosarcoma. Gynecol Oncol 1997; 65:493.
  39. Kohorn, EI, Schwartz, PE, Chambers, JT, et al. Adjuvant therapy in mixed mullerian tumors of the uterus. Gynecol Oncol 1986; 23:212.
  40. Gerszten, K, Faul, C, Kounelis, S, et al. The impact of adjuvant radiotherapy on carcinosarcoma of the uterus. Gynecol Oncol 1998; 68:8.
  41. Larson, B, Silfversward, C, Nilsson, B, Pettersson, F. Mixed mullerian tumours of the uterus--prognostic factors: a clinical and histopathologic study of 147 cases. Radiother Oncol 1990; 17:123.
  42. Molpus, KL, Redlin-Frazier, S, Reed, G, et al. Postoperative pelvic irradiation in early stage uterine mixed mullerian tumors. Eur J Gynaecol Oncol 1998; 19:541.
  43. Clayton Smith, D, Kenneth Macdonald, O, Gaffney, DK. The impact of adjuvant radiation therapy on survival in women with uterine carcinosarcoma. Radiother Oncol 2008; 88:227.
  44. Wright, JD, Seshan, VE, Shah, M, et al. The role of radiation in improving survival for early-stage carcinosarcoma and leiomyosarcoma. Am J Obstet Gynecol 2008; 199:536.
  45. Le, T. Adjuvant pelvic radiotherapy for uterine carcinosarcoma in a high risk population. Eur J Surg Oncol 2001; 27:282.
  46. Bodner-Adler, B, Bodner, K, Obermair, A, et al. Prognostic parameters in carcinosarcomas of the uterus: a clinico-pathologic study. Anticancer Res 2001; 21:3069.
  47. Reed, NS, Mangioni, C, Malmstrom, H, et al. Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: an European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874). Eur J Cancer 2008; 44:808.
  48. Gadducci, A, Romanini, A. Adjuvant chemotherapy in early stage uterine sarcomas: an open question. Eur J Gynaecol Oncol 2001; 22:352.
  49. Sutton, G, Kauderer, J, Carson, LF, et al. Adjuvant ifosfamide and cisplatin in patients with completely resected stage I or II carcinosarcomas (mixed mesodermal tumors) of the uterus: a Gynecologic Oncology Group study. Gynecol Oncol 2005; 96:630.
  50. Kushner, DM, Webster, KD, Belinson, JL, et al. Safety and efficacy of adjuvant single-agent ifosfamide in uterine sarcoma. Gynecol Oncol 2000; 78:221.
  51. Omura, GA, Blessing, JA, Major, F, et al. A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study. J Clin Oncol 1985; 3:1240.
  52. Wong, L, See, HT, Khoo-Tan, HS, et al. Combined adjuvant cisplatin and ifosfamide chemotherapy and radiotherapy for malignant mixed mullerian tumors of the uterus. Int J Gynecol Cancer 2006; 16:1364.
  53. Manolitsas, TP, Wain, GV, Williams, KE, et al. Multimodality therapy for patients with clinical Stage I and II malignant mixed Mullerian tumors of the uterus. Cancer 2001; 91:1437.
  54. Menczer, J, Levy, T, Piura, B, et al. A comparison between different postoperative treatment modalities of uterine carcinosarcoma. Gynecol Oncol 2005; 97:166.
  55. Makker, V, Abu-Rustum, NR, Alektiar, KM, et al. A retrospective assessment of outcomes of chemotherapy-based versus radiation-only adjuvant treatment for completely resected stage I-IV uterine carcinosarcoma. Gynecol Oncol 2008; 111:249.
  56. Wolfson, AH, Brady, MF, Rocereto, T, et al. 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; 107:177.
  57. Nout, RA, Putter, IM, Jürgenliemk-Schultz, JJ, et al. Vaginal brachytherapy versus external beam pelvic radiotherapy for high-intermediate risk endometrial cancer: Results of the randomized PORTEC-2 trial. J Clin Oncol 2008; 26:1010s. (Available online at www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting/Abstracts?&vmview=abst_detail_vi
    ew&confID=55&abstractID=31299, accessed August 6, 2008.).
  58. Muss, HB, Bundy, B, DiSaia, PJ, et al. Treatment of recurrent or advanced uterine sarcoma. A randomized trial of doxorubicin versus doxorubicin and cyclophosphamide (a phase III trial of the Gynecologic Oncology Group). Cancer 1985; 55:1648.
  59. Sutton, GP, Blessing, JA, Rosenshein, N, et al. Phase II trial of ifosfamide and mesna in mixed mesodermal tumors of the uterus (a Gynecologic Oncology Group study). Am J Obstet Gynecol 1989; 161:309.
  60. Sutton, G, Brunetto, VL, Kilgore, L, et al. A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study. Gynecol Oncol 2000; 79:147.
  61. Curtin, JP, Blessing, JA, Soper, JT, DeGeest, K. Paclitaxel in the treatment of carcinosarcoma of the uterus: a gynecologic oncology group study. Gynecol Oncol 2001; 83:268.
  62. Thigpen, JT, Blessing, JA, Orr, JW Jr, DiSaia, PJ. Phase II trial of cisplatin in the treatment of patients with advanced or recurrent mixed mesodermal sarcomas of the uterus: a Gynecologic Oncology Group Study. Cancer Treat Rep 1986; 70:271.
  63. Thigpen, JT, Blessing, JA, Beecham, J, et al. Phase II trial of cisplatin as first-line chemotherapy in patients with advanced or recurrent uterine sarcomas: a Gynecologic Oncology Group study. J Clin Oncol 1991; 9:1962.
  64. del Carmen, MG, Lovett, D, Goodman, A. A case of Mullerian adenosarcoma of the uterus treated with liposomal doxorubicin. Gynecol Oncol 2003; 88:456.
  65. Miller, DS, Blessing, JA, Schilder, J, et al. Phase II evaluation of topotecan in carcinosarcoma of the uterus: a Gynecologic Oncology Group study. Gynecol Oncol 2005; 98:217.
  66. Homesley, HD, Filiaci, V, Markman, M, et al. Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study. J Clin Oncol 2007; 25:526.
  67. Ramondetta, LM, Burke, TW, Jhingran, A, et al. A phase II trial of cisplatin, ifosfamide, and mesna in patients with advanced or recurrent uterine malignant mixed mullerian tumors with evaluation of potential molecular targets. Gynecol Oncol 2003; 90:529.
  68. van Rijswijk, RE, Vermorken, JB, Reed, N, et al. Cisplatin, doxorubicin and ifosfamide in carcinosarcoma of the female genital tract. A phase II study of the European Organization for Research and Treatment of Cancer Gynaecological Cancer Group (EORTC 55923). Eur J Cancer 2003; 39:481.
  69. Baker, TR, Piver, MS, Caglar, H, Piedmonte, M. Prospective trial of cisplatin, adriamycin, and dacarbazine in metastatic mixed mesodermal sarcomas of the uterus and ovary [published erratum appears in Am J Clin Oncol 1991 Oct;14(5):455]. Am J Clin Oncol 1991; 14:246.
  70. Ramondetta, LM, et al. A phase II multicenter trial of paclitaxel and carboplatin in women with advanced or recurent malignant mixed mullerian tumors (MMMT) of the uterus (abstract). J Clin Oncol 2007; 25:296s. (Abstract available online at www.asco.org/portal/site/ASCO/menuitem.34d60f5624ba07fd506fe310ee37a01d/?vgnext
    oid=76f8201eb61a7010VgnVCM100000ed730ad1RCRD&vmview=abst_detail_view&confID=47&abst
    ractID=35672, accessed June 22, 2007).
  71. Hoskins, PJ, Le, N, Ellard, S, et al. Carboplatin plus paclitaxel for advanced or recurrent uterine malignant mixed mullerian tumors. The British Columbia Cancer Agency experience. Gynecol Oncol 2008; 108:58.
  72. Toyoshima, M, Akahira, J, Matsunaga, G, et al. Clinical experience with combination paclitaxel and carboplatin therapy for advanced or recurrent carcinosarcoma of the uterus. Gynecol Oncol 2004; 94:774.
  73. Powell, MA, Filiaci, VL, Rose, PG, et al. A phase II evaluation of paclitaxel and carboplatin in the treatment of carcinosarcoma of the uterus: a Gynecologic Oncology Group (GOG) study (abstract #5515). J Clin Oncol 2009; 27:280s. (Abstract available online at www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstract
    ID=35468, accessed August 24, 2009).
  74. Fleming, GF, Brunetto, VL, Cella, D, et al. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 2004; 22:2159.
  75. Pectasides, D, Pectasides, E, Papaxoinis, G, et al. Combination chemotherapy with carboplatin, paclitaxel and pegylated liposomal doxorubicin for advanced or recurrent carcinosarcoma of the uterus: clinical experience of a single institution. Gynecol Oncol 2008; 110:299.
  76. Hoskins, PJ, Le, N. Preoperative tumor markers at diagnosis in women with malignant mixed müllerian tumors/carcinosarcoma of the uterus. Int J Gynecol Cancer 2008; 18:1200.
  77. Huang, GS, Chiu, LG, Gebb, JS, et al. Serum CA125 predicts extrauterine disease and survival in uterine carcinosarcoma. Gynecol Oncol 2007; 107:513.
  78. Sood, AK, Buller, RE, Burger, RA, et al. Value of preoperative CA 125 level in the management of uterine cancer and prediction of clinical outcome. Obstet Gynecol 1997; 90:441.
  79. Chung, HH, Kim, JW, Park, NH, et al. Use of preoperative serum CA-125 levels for prediction of lymph node metastasis and prognosis in endometrial cancer. Acta Obstet Gynecol Scand 2006; 85:1501.
  80. Macasaet, MA, Waxman, M, Fruchter, RG, et al. Prognostic factors in malignant mesodermal (mullerian) mixed tumors of the uterus. Gynecol Oncol 1985; 20:32.
  81. Inthasorn, P, Carter, J, Valmadre, S, et al. Analysis of clinicopathologic factors in malignant mixed Mullerian tumors of the uterine corpus. Int J Gynecol Cancer 2002; 12:348.
white circle LOG IN
white circle DEMO