The Distinction of Clear Cell Carcinoma of the Female Genital Tract, Clear Cell Renal Cell Carcinoma, and Translocation-Associated Renal Cell Carcinoma: An Immunohistochemical Study Using Tissue Microarray

Clear cell carcinoma of the female genital tract (CCCa) shares many histologic features with clear cell renal cell carcinoma (CCRCC) and translocation-associated renal cell carcinoma (TA-RCC), the latter in particular. When CCRCC or TA-RCC metastasizes to the female genital tract, or when patients have a history of both CCCa- and RCC-developed metastatic lesions, it is critical to distinguish the 3 lesions. Such a distinction is not always possible based on the morphology alone and often requires immunostains. We therefore investigated the utility of a panel of routinely used immunohistochemical markers including cytokeratin (CK) 7 and 20, CD10, alpha-methylacyl-CoA racemase, carbonic anhydrase IX (CA IX), TFE3, and WT-1 in the distinction of the 3 lesions on a tissue microarray of 12 CCCa, 5 TA-RCC, and 23 CCRCC cases. CK7 was positive in all CCCa cases, but only in 20% of TA-RCCs and 4.3% of CCRCCs. In contrast, CD10 was positive in all TA-RCCs and 91.3% of CCRCCs, but in only 7.5% of CCCa cases. TFE3 was positive in all TA-RCCs, but negative in all CCCa and CCRCC cases. CA IX was positive in 87% of CCRCCs, but in only 20% of TA-RCCs, and was negative in all CCCa cases. CK20, alpha-methylacyl-CoA racemase, and WT-1 were not contributory to the distinction. Although morphologically similar, CCCa can be reliably distinguished from TA-RCC and CCRCC. CCCa is mostly CK7(+)/CD10(-)/CA IX-/TFE3(-), TA-RCC is usually CK7(-)/CD10(+)/CA IX-/TFE3(+), whereas CCRCC is mostly CK7(-)/CD10(+)/CA IX+/TFE3(-). To the best of our knowledge, this was the first study to directly compare the immunophenotypes of these 3 lesions.