Hybrid Oncoctyic Tumors of the Kidney in Patients with Birt-Hogg-Dubé (BHD) Syndrome
LJ Eisengart, M Tretiakova, SM Rohan, J Zhang, M Zhou, C Luan, BT Teh, XJ Yang. Northwestern University, Chicago, IL; University of Chicago, Chicago, IL; Mayo Clinic, Rochester, MN; Cleveland Clinic, Cleveland, OH; Van Andel Research Institute, Grand Rapids, MI
Background: BHD is a rare autosomal dominant disorder characterized by cutaneous fibrofolliculomas, renal tumors and pulmonary cysts. Oncocytic hybrid tumors represent 50% of BHD associated renal tumors. Studies characterizing these hybrid tumors are limited; expression microarray, immunohistochemistry (IHC) and electron microscopy (EM) have never been reported to our knowledge.
Design: We studied 12 hybrid tumors from 8 patients with BHD syndrome. Gene expression microarrays were performed on 4 cases and compared to our established database of kidney neoplasms. Histopathologic and IHC features (CA9, vimentin, c-Kit and CK7) were evaluated. EM was performed on one case.
Results: Histologically, hybrid tumors showed prominent cell membranes and dense eosinophilic cytoplasm, similar to both chromophobe RCC and oncocytoma. Hybrid tumors contained scattered clear epithelial cells of low Fuhrman grade intermingled with oncocytic cells, composing from 5 to 25% of cells. By molecular clustering analysis, hybrid tumors were located between the cluster of 7 chromophobe renal cell carcinomas (RCCs) and the cluster of 7 oncocytomas. Comparative genomic microarray analysis showed minimal chromosomal losses in hybrid tumors similar to oncocytomas; chromophobe RCCs show numerous chromosomal losses. Hybrid tumors were positive for C-kit and showed patchy Ck7 positivity, different from the diffuse CK7 positivity in chromophobe RCCs or CK7 negativity in oncocyotmas. The intermingled clear cells were negative for clear cell RCC markers such as vimentin or CA9. By EM, hybrid tumor cells contained small membrane-bound microvesicles (similar to chromophobe RCC) and abundant pleomorphic mitochondria (typical of oncocytoma). Some tumor cells contained cytoplasmic lipid vacuoles as typically seen in clear cell RCC.
Conclusions: In this study, the molecular signature of BHD associated hybrid oncocytic tumors has been defined. We also report here the morphological and immunohistochemical characteristics of these tumors. Recognition of hybrid tumors is important, as they suggest the presence of BHD syndrome. These hybrid tumors should be considered a distinct subtype based on their morphologic, molecular genetic and immunohistochemical characteristics.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 2:30 PM
Platform Session: Section A, Monday Afternoon