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American Journal of Surgical Pathology:
doi: 10.1097/PAS.0b013e3181ff400e
Original Articles

Morphologic Spectrum of Immunohistochemically Characterized Clear Cell Carcinoma of the Ovary: A Study of 155 Cases

DeLair, Deborah MD*; Oliva, Esther MD; Köbel, Martin MD; Macias, Antonio MD*; Gilks, C. Blake MD§; Soslow, Robert A. MD*

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Abstract

Establishing a diagnosis of ovarian clear cell carcinoma (O-CCC) can be subject to significant interobserver variation. Accurately diagnosing this tumor is important because of its chemoresistance and reported association with Lynch syndrome. The spectrum of the morphologic features of O-CCC has not been well described in a series composed of immunohistochemically characterized cases. A total of 155 cases diagnosed as O-CCC were retrieved from the files of 3 institutions to analyze architectural and cytologic features. The immunohistochemical features of these cases have been reported earlier. A comprehensive list of features was recorded, including, but not limited to, architectural patterns, nuclear appearance, cytoplasmic characteristics, and mitotic index. Between 1 and 13 slides were available for review for each case. The cases were divided into 2 groups based on morphologic characteristics, those with features shared by the large majority (the first group, n=138) and those that showed unusual characteristics (second group, n=17). Tumors in the first group typically showed a mixture of architectural patterns, the most frequent being papillary and tubulocystic. Papillae, usually small and round and lacking hierarchical branching and tufting or stratification of more than 3 cells, were present at least focally in almost 3 of 4 cases. The cell shape was predominantly cuboidal, not columnar. Nuclear pleomorphism and prominent nucleoli were frequently present, but never diffusely. Clear cytoplasm was found in nearly every case and hobnail cells were common. Mitoses exhibited a range from 0 to 13 with an average of 3 to 4 per 10 high power fields. The second group of tumors showed numerous unusual morphologic characteristics, despite the presence of clear cytoplasm, including those typically seen in other ovarian epithelial tumors, such as serous and endometrioid carcinoma. Eighty-nine percent of tumors from the first group showed the expected “O-CCC immunophenotype” [hepatocyte nuclear factor (HNF) positive, and estrogen receptor (ER), progesterone receptor (PR), Wilms tumor 1 (WT1) and p53 negative], whereas 4% of tumors showed HNF positivity along with focal ER or PR expression. Seven percent of tumors were not immunoreactive with these markers. Twenty-nine percent of tumors in the second group showed the O-CCC immunophenotype, whereas 24% of tumors were p53 positive, 5% of tumors were WT1 positive, and the remaining cases were negative for all markers. Ninety-seven percent (112 of 117) of HNF-positive tumors in this series were classical O-CCC. Therefore, O-CCC has characteristic morphologic features and a specific, if not unique, immunophenotype in the vast majority of the cases. Clear cell-rich tumors with features that depart from the classical morphologic appearances described herein should suggest the possibility of an alternative diagnosis.

© 2011 Lippincott Williams & Wilkins, Inc.

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