Diffuse expression of PAX2 and PAX8 in the cystic epithelium of mixed epithelial stromal tumor, angiomyolipoma with epithelial cysts, and primary renal synovial sarcoma: evidence supporting renal tubular differentiation.

Over the past decade, 3 novel, typically cystic renal neoplasms have been described: angiomyolipoma with epithelial cysts (AMLEC), mixed epithelial stromal tumor (MEST), and primary renal synovial sarcoma (SS). In all 3 neoplasms, the nature of the cystic epithelium is not clear; some have postulated that the cysts represent cystically dilated, entrapped renal tubular epithelium, whereas an alternative interpretation is that the epithelium represents epithelial differentiation by the stromal component of the neoplasm. The latter is supported by the extrarenal location of the epithelium in some cases. PAX2 and PAX8 are tissue-specific transcription factors expressed primarily in the renal and Müllerian systems and also in Wolffian duct structures (such as seminal vesicle). Their expression has not been examined in these lesions. We performed PAX2 and PAX8 immunohistochemistry on representative sections of cases of AMLEC (8 cases), MEST (8 cases), and renal SS (3 cases). The relative percentage and intensity (none, weak, moderate, and strong) of nuclear labeling were evaluated in both the benign adjacent renal tubules and the lesion's epithelial cysts. In the benign kidney, distal convoluted tubules (DCTs) labeled strongly for PAX2 and PAX8, whereas proximal convoluted tubules labeled minimally. The cystic epithelium of all 8 cases of AMLEC, including 5 that protruded beyond the renal capsule into the perirenal fat, demonstrated strong diffuse labeling for both PAX2 and PAX8. We also identified a mimic of entirely extrarenal AMLEC, angiomyolipoma with endosalpingiosis. PAX2 and PAX8 diffusely and strongly labeled the epithelial component of all 8 cases of MEST, including all architectural (phyllodes-like, large cysts, small cysts, clustered microcysts) and virtually all cytologic (hobnail, flat, cuboidal, columnar, apocrine, and clear cell) epithelial variants present. The epithelial cysts of all 3 cases of primary renal SS labeled diffusely and strongly for PAX2 and PAX8. Cyst epithelial labeling intensity was similar to that of renal DCT in all cases. The diffuse labeling for PAX2/PAX8 in the epithelial cysts of AMLEC, taken together with their consistent negativity for estrogen receptor and HMB45, supports the hypothesis that this epithelium represents entrapped, cystically dilated renal tubules that commonly herniate beyond the renal capsule. The diffuse labeling of the cyst epithelium of renal SS supports the previously proposed hypothesis that this cyst epithelium represents entrapped dilated renal tubules in a monophasic spindle cell lesion and not neoplastic epithelial differentiation. The diffuse labeling for PAX2/PAX8 in MEST epithelium, coupled with its usual estrogen receptor negativity, is consistent with the hypothesis that the epithelium of MEST demonstrates renal tubular differentiation and undergoes architectural and cytologic changes as it grows along with the stromal component. Whether this complex epithelium represents entrapped or neoplastic renal tubular epithelium remains an open question.