International Journal of Gynecological Pathology 31:499–506, Lippincott Williams & Wilkins, Baltimore r 2012 International Society of Gynecological Pathologists Original Article Transitional Cell Carcinoma of the Ovary is Related to High-grade Serous Carcinoma and is Distinct From Malignant Brenner Tumor Rola H. Ali, M.D., Jeffrey D. Seidman, M.D., Margaret Luk, B.Sc., Steve Kalloger, M.Sc., and C. Blake Gilks, M.D., F.R.C.P.C. Summary: Transitional cell tumors of the ovary include benign, borderline (atypically proliferating), and malignant Brenner tumors (BT), as well as transitional cell carcinoma (TCC). Some TCCs could conceivably be examples of malignant BT where the benign component has been overgrown. Our objectives were: (A) compare the immunopheno- types of BT and TCC and (B) examine a large cohort of ovarian carcinomas for cases with the immunophenotype of BT and transitional features but lacking a benign BT component. Seven BTs (3 benign, 3 borderline/atypically proliferating, 1 malignant) and 7 TCCs were stained for WT1, ER, p53, and p16 INK4a . The BTs were negative for WT1, p53 overexpression, ER (except for weak positivity in 1), and negative or weakly positive for p16 INK4a . In contrast, the TCCs stained as follows: 4/6 positive for WT1, 5/7 positive for ER, 2/7 strongly positive for p16 INK4a , and 6/7 showed abnormal p53, an immunophenotype resembling that of high-grade serous carcinoma. A database of 500 cases of ovarian carcinoma was searched and 116 showed an immunoprofile characteristic of BT: WT1 negative, ER negative, p16 INK4a negative or weak positive, p53 negative (77 clear cell carcinoma, 14 endometrioid carcinoma, 12 mucinous carcinoma, 8 high-grade serous carcinoma). None of these tumors showed transitional features on review, indicating that if examples of malignant BT where there has been overgrowth of benign BT components exist, they are rare. Our results suggest that BT and TCC are unrelated, and should not be combined for classification purposes. Key Words: Ovary— Brenner—Transitional cell carcinoma. Transitional cell tumors of the ovary are defined as tumors composed of epithelial elements histologically resembling urothelium and its neoplasms (1). They ac- count for 1% to 2% of all ovarian tumors. The 2003 World Health Organization (WHO) classification system divides them into benign Brenner tumors (BTs), border- line BTs, and malignant transitional cell tumors, which are further divided into transitional cell carcinoma (TCC) non-Brenner type, and malignant BTs (1). By definition, a malignant BT shows an invasive transitional cell as well as a benign BT component, whereas an ovarian TCC resembles malignant ur- othelium tumors of the urinary system and lacks a component of benign or borderline/atypically pro- liferating BT (1–3). Apart from the presence or absence of a benign Brenner component, malignant BT and TCC show overlapping histologic features. Recent studies, however, have demonstrated that BTs and TCCs follow different tumorigenic molecular From the Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver BC, Canada (R.H.A., M.L., S.K., B.G.); and Department of Pathology and Laboratory Medicine, Washington Hospital Center, Washington, DC (J.D.S.). The authors declare no conflict of interest. Address correspondence and reprint requests to C. Blake Gilks, MD, FRCPC, Anatomical Pathology, JP1400, Vancouver General Hospital, 910 West 10th Ave, Vancouver, BC, Canada V5Z 4E3. E-mail: blake.gilks@vch.ca. 499 DOI: 10.1097/PGP.0b013e31824d7445