Diffuse and Strong Expression of PAX2 and PAX8 in the Cystic Epithelium of Angiomyolipoma with Epithelial Cysts (AMLEC) and Mixed Epithelial Stromal Tumor (MEST) Supports Distal Tubular Differentiation
M Karafin, A Parwani, G Netto, P Illei, J Epstein, P Argani. Johns Hopkins Medical Institutions, Baltimore, MD; University of PittsBurgh Medical Center, Pittsburgh, PA
Background: PAX2 and PAX8 are tissue specific transcription factors expressed in the renal and Müllerian systems. Their expression has not been examined in the recently described cystic renal lesions AMLEC and MEST. The nature of the epithelium in these lesions is not clear, postulated by some to represent entrapped renal tubular epithelium. Others disagree, based largely upon extrarenal localization in some reported cases.
Design: PAX2 and PAX8 immunohistochemistry was performed on representative sections of cases of AMLEC (7) and MEST (8). The relative percentage and intensity (none, weak, moderate, strong) of nuclear labeling were evaluated in both the benign adjacent renal tubules and the lesion's epithelial cysts.
Results: In the adjacent kidney, distal convoluted tubules (DCT) labeled strongly for PAX2 and PAX8, while proximal convoluted tubules labeled minimally. The cystic epithelium of 7 of 7 AMLEC, including 4 which extended beyond the renal capsule into the perirenal fat, demonstrated strong diffuse labeling for both PAX2 and PAX8. In the course of this review, we uncovered a mimic of entirely extrarenal AMLEC: extrarenal angiomyolipoma (AML) involved by endosalpingiosis. The epithelium of the latter labeled for estrogen receptor (ER) (unlike that of AMLEC) in addition to PAX2 and PAX8. PAX2 and PAX8 diffusely and strongly labeled the epithelial component of 8 of 8 MESTs, including all architectural (phyllodes-like, large cysts, small cysts, clustered microcysts) and cytologic (hobnail, flat, cuboidal, columnar, apocrine, ciliated, and clear cell) epithelial variants present. Cyst epithelial labeling intensity was similar to that of renal DCT in all cases.
Conclusions: The diffuse labeling for PAX2/PAX8 in the epithelial cysts of AMLEC, taken together with their consistent negativity for ER and HMB45, supports the hypothesis that this epithelium represents entrapped, cystically dilated DCT. Renal AMLEC commonly herniate beyond the renal capsule: previously reported cases of entirely extrarenal AMLEC may represent extrarenal AML involved by endosalpingiosis. The diffuse labeling for PAX2/PAX8 in MEST epithelium, coupled with its usual ER negativity, suggests that the epithelium of MEST is derived from the entrapped DCT which may undergo cytologic changes as it grows along with the stromal component.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 127, Monday Morning