Müllerian Carcinosarcoma: Unique Neoplasm?

Abstract & Commentary

By Robert L. Coleman, MD, Associate Professor, University of Texas; M.D. Anderson Cancer Center, Houston, is Associate Editor for OB/GYN Clinical Alert.

Dr. Coleman reports no financial relationship to this field of study.

Synopsis: The clinical behavior of uterine carcinosarcoma is more aggressive, stage for stage, than grade 3 uterine carcinoma.

Source: Bansal N, et al. Uterine carcinosarcomas and grade 3 endometrioid cancers: Evidence for distinct tumor behavior. Obstet Gynecol 2008;112:64-70.

The objective of this study was to examine and compare the clinical behavior and outcome of uterine carcinosarcoma relative to grade 3 endometrioid carcinoma. Demographic and pathology information and clinical outcomes were obtained over a 6-year period from the Surveillance, Epidemiology, and End Results (SEER) registry. Nearly 9000 patients were identified: 5024 (56%) grade 3 endometrioid cancers; 3962 (44%) carcinosarcomas. Patients with carcinosarcoma were older at diagnosis, more often non-Caucasian, and presented in more advanced disease stage relative to grade 3 endometrioid tumors. They were also less likely to undergo lymphadenectomy and receive adjuvant radiation. In a multivariate analysis of factors predicting disease-specific mortality, carcinosarcoma histology, advanced age, non-Caucasian race, and advanced stage were all adversely independent. The 5-year disease specific mortality rates for each stage were lower for patients with carcinosarcoma — about 50% lower, even in stage I. The overall hazard ratio for survival was 0.55 (95% confidence interval, 0.5-0.6). Given these features and acknowledging the limitations of the SEER dataset, it appears that uterine carcinosarcoma is a distinct clinical entity from high-grade endometrioid cancer and associated with poor clinical outcome.

Commentary

Uterine carcinosarcoma, also known as müllerian mixed mesodermal tumor (MMMT) is a rare uterine neoplasm, which consists, histologically, of epithelial and mesenchymal malignant elements. While the primary lesion may contain a large sarcomatous component, most metastatic and recurrent lesions are often characterized by pure epithelial carcinomas. In light of these observations, many clinicians have begun to consider the disease in the spectrum of endometrial cancer as opposed to sarcoma, such as leiomyosarcoma, where they have been traditionally studied.

The first step of investigation in sorting out this clinical question comes from data mining studies like the current. Carcinosarcomas are rare neoplasms, so while information may be gained from individual institutions, the data are limited in scope, highlighting the value of a registry like SEER. In this current report, nearly 4000 women with carcinosarcoma were investigated against a heterogenous cohort of grade 3 endometrioid tumors. Despite the limited number of variables upon which to interrogate, the authors were able to shed light on the clinical presentation of this tumor and its peripheral clinical behavior — all of which appear to be "worst case scenarios" for the histology. Age, non-Caucasian race, and stage are all relevant to poor endometrioid cancer survival — but all are worse in those with carcinosarcoma. Even in women with non-invasive, uterine-limited disease (Stage IA), those with carcinosarcoma had a 5-year survival of just 59% (compared to 78% in grade 3 endometrioid tumors). All of this points to a unique clinical scenario for this histology despite its appearance as an epithelial malignancy. Our contemporary, albeit crude, treatment studies are distinguishing these tumors in their eligibility.

As with all SEER-based studies, there are severe limitations that must be considered in interpreting the study's conclusion, not the least of which is lack of centralized pathological review. It is not uncommon that pathological dissent occurs in reviewing the rare histologies such as carcinosarcoma, and where the line is drawn distinguishing sarcomatoid carcinoma, adenosarcoma, and carcinosarcoma can be spurious and poorly reproducible. In addition, other uterine pathologies, such as clear cell and serous, have poor clinical scenarios relative to endometrioid carcinoma but are not distinguished in many research protocols. Ultimately, the lens through which we look at these unique tumors needs to be made molecular, particularly in light of the novel agents being developed targeting specific signaling pathways. It is this level of tumor biology enlightenment that needs to be developed to make meaningful strides in therapeutic strategies.

Suggested Reading

  1. McCluggage WG. Uterine carcinosarcomas (malignant mixed Mullerian tumors) are metaplastic carcinomas. Int J Gynecol Cancer 2002;12:687-690.
  2. Sutton G, 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 Oncol2005;96:630-634.
  3. van Rijswijk RE, et al. The effect of chemotherapy on the different components of advanced carcinosarcomas (malignant mixed mesodermal tumors) of the female genital tract. Int J Gynecol Cancer 1994;4:52-60.