Residency Program - Case of the Month

Answer:

High-grade Mullerian carcinoma

Discussion:

This is a challenging tumor to classify precisely. There are areas of broad and undulating papillae, morphologically consistent with transitional cell carcinoma.  However, there are other areas that have glandular architecture with slit-like spaces or cribriform pattern, suggestive of serous or endometrioid adenocarcinoma, respectively.  Immunohistochemical stains were attempted to further classify this tumor.  However, the different morphologic areas show similar staining pattern, suggesting the entire mass is likely represented by one tumor type.  Recent study has suggested that transitional cell carcinoma is not a distinct entity, but represents a poorly differentiated form of serous or endometrioid adenocarcinoma. On the basis of the World Health Organization (WHO) classification, transitional cell tumors of the ovary include Brenner tumors (BTs; benign, borderline, and malignant) and transitional cell carcinomas (TCCs; non-BTs). In the field of ovarian transitional cell tumors, some studies suggested that BTs represent low-grade transitional cell tumors, whereas transitional cell carcinomas (TCCs) represent high-grade transitional tumors, on the basis of their different molecular genetic  alterations (PIK3CA exon 9 mutations in BTs, and TP53 gene mutations in TCCs). In contrast, some investigators appear to believe that TCC represents a morphologic variation of high-grade serous adenocarcinoma (HG-SC). In a study by Takeuchi et al.  a high frequency of aberrant p53 expression and positive expression of WT1 were observed in HG-SC, pure TCC, and TCC-s but not in BT, and these results were consistent with those of the previous studies in that many cases diagnosed as TCC were immunophenotypically similar to HG-SC but not to BT. In this study they concluded that TCC is not a distinct entity but a poorly differentiated form of HG-SC or EC, as most TCCs coexist with HG-SC (mostly) or EC (occasionally), and the immunophenotype and molecular features are similar to those of HG-SC (mostly) or EC (occasionally) but different from those of BTs.

References:

1. Takeuchi, T. et. al., Ovarian transitional cell carcinoma represents a poorly differentiated form of high-grade serous or endometrioid adenocarcinoma. Am J Surg Pathol, 2013 37:1091-1099.

2. Cuatrecasas M, Catasus L, Palacios J, et al. Transitional cell tumors of the ovary: a comparative clinicopathologic, mmunohistochemical, and molecular genetic analysis of Brenner tumors and transitional cell carcinomas. Am J Surg Pathol. 2009;33:556–567.

3. Ali RH, Seidman JD, Luk M, et al. Transitional cell carcinoma of the ovary is related to high-grade serous carcinoma and is distinct from malignant Brenner tumor. Int J Gynecol Pathol. 2012;31:499–506.

4. McCluggage WG. My approach to and thoughts on the typing of ovarian carcinomas. J Clin Pathol. 2008;61:152–163.

5. Logani S, Oliva E, Amin MB, et al. Immunoprofile of ovarian tumors with putative transitional cell (urothelial) differentiation
using novel urothelial markers: histogenetic and diagnostic implications. Am J Surg Pathol. 2003;27:1434–1441.

6. Tavassoli FA, Devilee P. World Health Organization Classification of Tumours. Pathology and Genetics. Tumours of the Breast and Female Genital Organs. Lyon: IARC Press; 2003.