Residency Program - Case of the Month

Answer:

Transitional cell carcinoma

Discussion:

Transitional cell carcinoma (TCC) of the ovary is a rare, recently recognized, subtype of ovarian surface epithelial cancer. It has been described as a primary ovarian carcinoma in which definite urothelial features are present but no benign, metaplastic and/or proliferating Brenner tumor can be identified (1). In addition to not having a benign Brenner tumor component, TCC lacks the prominent stromal calcification. The true incidence of TCC of the ovary remains unknown. Because TCC of the ovary has close morphologic similarities to TCC of the bladder and it behaves more aggressively than malignant Brenner tumor, it was concluded that ovarian TCC arises directly from the pluripotential surface epithelium of the ovary and from cells with urothelial potential, rather than from a benign or proliferative Brenner tumor precursor. The metastatic pathways of the tumor are mimicking the transitional cell carcinoma of the bladder which implicate a loss of the integrity of E-cadherin (2).

Pure forms of transitional cell carcinoma account for only 1% of surface epithelial carcinomas, mixed carcinomas with a predominant transitional cell component for 5%, and those with a minor transitional cell component for 3% (3). TCCs may be solid or solid and cystic on gross examination. In a study of 100 cases, Eichhorn and Young (4) found a variety of histologic features that, in aggregate, produced a distinctive appearance. The patterns included, in order of frequency, undulating, diffuse, insular, and trabecular. “Punchedout” microspaces, large cystic spaces, and large, blunt papillae were also common. The tumor cells tend to be relatively monomorphic with typically pale and granular cytoplasm, although occasionally it is clear or oxyphilic. The round to oblong nuclei have a large, single nucleolus or a longitudinal groove. More than 90% of the tumors in the cited series (4) were grade 2 or 3. The immunoprofile of TCCs is similar to that of other surface epithelial carcinomas. Most tumors are immunoreactive for WT1 and, in contrast to Brenner tumors and extraovarian urothelial tumors, ovarian TCCs typically lack reactivity for uroplakin, thrombomodulin, and CK20.  

Differential diagnosis:

Benign Brenner tumors with large, mucinous cysts that have not formed a grossly recognizable mass may be misdiagnosed as mucinous cystadenomas if the focal presence of transitional cells at the periphery of the mucinous cells is not recognized. Borderline and malignant Brenner tumors are distinguished from metastatic TCCs from the urinary tract by the finding of benign Brenner nests or glands lined by mucinous epithelium in the former tumors. Primary TCC, however, can be closely mimicked by metastatic disease (5). The usual clinical, gross, and microscopic criteria for differentiating primary from secondary ovarian tumors are helpful in this differential diagnosis; IHC staining may also be of assistance. Urinary tract tumors of this type have been shown to be reactive for CK20 and thrombomodulin, in contrast to primary ovarian TCC (6, 7, and 8). A more common problem is distinguishing moderate to high-grade TCCs from other poorly differentiated surface epithelial carcinomas, particularly poorly differentiated serous carcinomas and undifferentiated carcinomas. Such tumors have a greater tendency to grow in diffuse masses; when they have a pattern simulating that of papillary TCCs, it is much more often caused by the presence of pseudopapillae resulting from necrosis with dropout of necrotic cellular debris. TCCs have broad papillae lined by cells, some of which are recognizable as transitional cells; similar cells form undulating, thick bands. Scattered microspaces, which are often numerous, also favor a diagnosis of TCC.

References:

1. EM Tazi, I Lalya, MF Tazi, Y Ahellal, H M’rabti, H Errihani, Transitional cell carcinoma of the ovary: A rare case and review of literature, world journal of surgical oncology, 2010, 8:98

2. Austin RM, Norris HJ: Malignant Brenner tumor and transitional cell carcinoma of the ovary: a comparison. Int J Gynecol Pathol 1987, 6:29-39.

3. Silva EG, Robey-Cafferty SS, Smith TL, et al. Ovarian carcinomas with transitional cell carcinoma pattern. Am J Clin Pathol 1990;93:457-465.

4. Eichhorn JH, Young RH. Eichhorn JH, Young RH. Transitional cell carcinoma of the ovary. A morphologic study with emphasis on differential diagnosis. Am J Surg Pathol 2004; 28:453-463.

5. Young RH, Scully RE. Urothelial and ovarian carcinomas of identical cell types: problems in interpretation. A report of three cases and review of the literature. Int J Gynecol Pathol 1988;7:197-211.

6. Ordonez NG. Transitional cell carcinomas of the ovary and bladder are immunophenotypically different. Histopathology 2000;36:433-438.

7. Soslow RA, Rouse RV, Hendrickson MR, et al. Transitional cell neoplasms of the ovary and urinary bladder: a comparative immunohistochemical analysis. Int J Gynecol Pathol 1996;15:257-265.

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