Clear cell carcinoma of the ovary accounts for 5-10% of malignant ovarian epithelial-stromal tumors and typically occurs in nulliparous woman with a mean age of 52 years (1,2,3,4). The presentation is usually that of a woman with an enlarging abdominal or pelvic mass but can also present with abdominal distention or pain. Clear cell carcinoma of the ovary was originally thought to be mesonephric in origin secondary to it's similar appearance to renal cell carcinoma. It is now, however, thought to be mullerian in origin (5). The evidence for this includes its frequent association with endometriosis (50-70%), the observation that it can arise from the epithelial lining of endometriotic cysts, its coexistence with endometrioid and serous carcinomas, and it's ultrastructural similarity to endometrial, cervical, and vaginal clear cell carcinomas (1,4,6).
Overall, clear cell carcinomas of the ovary are bilateral 15-20% of the time and 60% are limited to the ovary (FIGO I) at presentation. Only 4% of FIGO I tumors are bilateral (1,7). They can be associated with hypercalcemia (7).
Grossly, the appearance of clear cell carcinoma of the ovary is non specific. The size of the tumors are typically 15 cm in greatest dimension but can reach 30 cm. Surface adhesions are common. On cut section they are typically unilocular with tan papillary or solid and nodular areas. They can have areas of necrosis and hemorrhage. Some cases, such as ours, have multilocular cysts containing mucinous or watery fluid.
Microscopically the appearance varies and there are several histological patterns recognized. Common patterns include papillary, tubulocystic, tubulo papillary, cystic, and solid. All patterns may be seen within the same tumor. The cell types seen are typically polygonal clear cells and hobnailed columnar cells. The clear cells have abundant clear cytoplasm which stains with PAS positive/diastase sensitive secondary to their high glycogen content. These cells also contain small amounts of lipid and show luminal staining for mucin although cytoplasmic mucin is rarely observed. The hobnailed cells can have clear or eosinophilic cytoplasm and have an apically placed nucleus. Mitoses are infrequent in this neoplasm. The diagnostic dilemma in clear cells can be related to mixed histologic patterns and variants. There is an oxyphilic variant of clear cell carcinoma of in which eosinophilic granular cells are scattered singly among typically clear cells (8). The other variants include clear cells with coalescent vacuoles containing "targetoid" appearing cytoplasmic eosinophilic globules (9) and also patterns resembling Krukenberg tumors, in which small clusters of clear cell and eosinophilic cells set in loose edematous or hyalinized stroma (10). Please refer to the excellent review of histological and cellular patterns in clear cell carcinoma of the ovary in Blaustein's Pathology of the Female Genital Tract, 4th edition, pages 757-761 and Sternberg's Diagnostic Surgical Pathology, 2nd Edition, pages 2221-2225.
Ultrastructurally, the clear cells are polygonal with prominent nuclei and nucleoli. The most prominent characteristic seen ultrastructurally is abundant cytoplasmic glycogen. Electronmicroscopy also confirms the presence of cytoplasmic lipid and only the rare occurrence of cytoplasmic mucin. Lateral desmosomes are present in the hobnailed cells which also contain a thick basal lamina. The apical surface of the hobnailed cells contain short microvilli (1).
The differential diagnosis for clear cell carcinoma of the ovary includes most notably a yolk sac tumor. This is a vital distinction since the neoplasms are treated differentially. The yolk sac tumor typically occurs in a younger age group (<30 years old) and histologically characterized by "festoon" pattern lined by epithelial cells with hyalin globule and stain positive for alpha-fetoprotein and alpha-1-antitrypsin. There is usually greater nuclear atypia and mitotic activity in a yolk sac tumor as well as Schiller-Duval Bodies (8). Also included in the differential are serous cystadenocarcinoma, metastatic renal cell carcinoma (exceedingly rare), dysgerminomas composed of "clear" appearing cells, and steroid producing neoplasms which can be confused with the oxyphilic variant of clear cell carcinoma (11).
The best indicator for survival is the FIGO stage with an 80-90% five year survival rate in stage I disease (12) and a 17% survival in stage II disease (13). Extrapelvicspread is associated with a dismal prognosis even with therapy (14).