Mixed Epithelial and Stromal Tumor of the Kidney and Cystic Nephroma Share Overlapping Features: Reappraisal of 15 Lesions

Abstract

Abstract Context.—Cystic nephroma is a rare cystic tumor, which only recently has been recognized as an exclusively adult lesion. Mixed epithelial and stromal tumor of the kidney is also a rare, recently recognized, biphasic tumor composed of tubular and cystic elements embedded in grossly recognizable spindle cell stroma. The histogenesis of both lesions is unclear. Objectives.—To compare clinical phenotype, morphology, and immunohistochemistry in mixed epithelial and stromal tumor of the kidney and cystic nephroma in order to explore the relationship between these 2 lesions. Design.—Fifteen biphasic lesions (8 mixed epithelial and stromal tumors of the kidney and 7 cystic nephromas) were studied. All cases were reviewed and subjected to detailed pathologic studies, and the results were correlated with clinical findings. Results.—Mixed epithelial and stromal tumor of the kidney occurred exclusively in women aged 36 to 80 years (mean, 49.7 years), all of whom had a history of estrogen therapy and/or obesity. Cystic nephroma occurred in both sexes; patients were aged 22 to 71 years (mean, 50.4 years), and a history of hormonal therapy was present on occasion. All 15 lesions were benign. Lesions varied by size, the proportion of cystic component, and the amount and cellularity of stroma. However, in all lesions tested, the stroma was diffusely positive for smooth muscle actin, and smooth muscle differentiation was confirmed by electron microscopy. In mixed epithelial and stromal tumors of the kidney, the stroma was positive for estrogen and progesterone receptors in 4 of 5 lesions tested. In cystic nephroma, focal positivity for hormone receptors was seen in 2 of 7 tumors tested; both positive lesions were from women. The epithelial lining in both mixed epithelial and stromal tumor of the kidney and cystic nephroma lesions was variable with regard to shape, cytoplasmic appearance, and immunophenotype (with focal positivity for CD10, cytokeratin 7, high-molecular-weight keratin, and Ulex europaeus detectable in both lesions). This pattern suggests variable differentiation, which was confirmed by electron microscopic studies (performed in 1 case). Conclusions.—While mixed epithelial and stromal tumor of the kidney has a strong association with the female sex and hormonal milieu, cystic nephroma can affect both sexes and, on occasion, may also have hormonal associations. Morphologically, there is considerable overlap between both lesions, which suggests that they may represent opposite ends of the spectrum of the same process. Our studies also suggest that the tubules may be entrapped rather than comprising an intrinsic component of the tumor. However, further studies, including molecular studies, are needed to support this hypothesis.