Anna Caliò, John N. Eble, David J. Grignon, Brett Delahunt

Cystic nephroma in adults is an uncommon multicystic benign tumor of kidney and, over the last century, only a few small series or case reports have studied it. We analyzed 46 tumors from adults (41 female, median age: 55 y), collecting data on gross, microscopic, and immunohistochemical findings. All of the tumors were composed entirely of cysts separated by septa; the majority were surrounded by a pseudocapsule. Hypocellular fibrous and hypercellular spindle cell stroma were the most common components of the septa. Hypocellular collagenized fibrous stroma predominated in older patients (P=0.027), whereas hypercellular stroma (including wavy spindle cell stroma) prevailed in younger patients (P=0.042). Small foci of stroma of moderate cellularity in which epithelial elements ranging from a handful of cells with no lumen, to tiny cysts with pinpoint lumens to slightly larger cysts were found in 18 tumors. The cysts were lined by flat, cuboidal, or hobnail cells. Rarely, foci of clear cells, delicate papillae, or focal nuclear atypia were observed in the cyst linings. The stroma of all the tumors was positive for smooth muscle actin. Desmin and caldesmon expression were variable. The stroma stained positive for progesterone and estrogen receptors in 85% and 50% of the tumors. Staining for inhibin was present in small clusters of polygonal or rarely spindle cells in the stroma in 41% of the tumors. A positive nuclear reaction for SF1 was detected in the same clusters of cells. On the basis of our findings, we hypothesize that cystic nephroma originates as a stromal proliferation with the epithelial component arising from a stromal-epithelial transition and that the stroma matures with decreasing cellularity over time, ultimately becoming hypocellular and collagenized.