Multilocular Cystic Renal Cell Carcinoma Similarities and Differences in Immunoprofile Compared With Clear Cell Renal Cell Carcinoma

Multilocular cystic renal cell carcinoma (RCC) is an uncommon renal neoplasm composed of thin fibrous septa lining multiple cystic spaces and associated with an excellent prognosis. Clear cells with generally low-grade nuclear features line the cystic spaces and may be present within the fibrous septa, although solid mass-forming areas are by definition absent. Despite the excellent prognosis, molecular-genetic alterations are similar to those of clear cell RCC. Immunohistochemical staining characteristics, however, have not been well elucidated. We studied 24 cases of multilocular cystic RCC, classified according to the 2004 World Health Organization System. Immunohistochemical analysis was performed using an automated immunostainer for CD10, cytokeratin 7 (CK7), alpha-methylacyl-CoA-racemase, epithelial membrane antigen (EMA), cytokeratin CAM 5.2, carbonic anhydrase IX (CA-IX), estrogen/progesterone receptors, smooth muscle actin, PAX-2, and vimentin. Twenty-four cases of grade 1 to 2 clear cell RCC were stained for comparison. Multilocular cystic RCC and control cases of clear cell RCC showed the following results, respectively: CD10 (63%, 96%), CK7 (92%, 38%), a-methylacyl-CoA-racemase (21%, 67%), vimentin (58%, 33%), estrogen receptor (8%, 8%), CAM 5.2 (100%, 96%), EMA, CA-IX, PAX-2 (all 100%), and progesterone receptor (0%). Smooth muscle actin highlighted myofibroblastic cells within the septa of multilocular cystic RCC and the fine capillary vascular network of clear cell RCC. In summary, multilocular cystic RCC showed expression of common clear cell RCC markers CA-IX, EMA, and PAX-2, supporting the hypothesis that multilocular cystic RCC is a subtype of clear cell RCC. In contrast to clear cell RCC, tumors less frequently expressed CD10 (63% and often focal vs. 96% and diffuse) and more frequently expressed CK7 (92%), often diffusely (63%). Coexpression of CA-IX and CK7 represents a point of overlap with the recently described clear cell papillary RCC, which also may show a prominent cystic architecture. However, the latter lacks mutation of the VHL gene and deletion of chromosome 3p by molecular methodologies.