Birt-Hogg-Dubé Renal Tumors Express Characteristic Ultrastructural Features Which Distinguish Them from Other Hereditary and Sporadic Renal Neoplasms
S Hebert-Magee, MJ Merino, WM Linehan, M Tsokos. National Institutes of Health, Bethesda, MD
Background: Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant genodermatosis characterized by a predisposition to hamartomatous cutaneous lesions, spontaneous pneumothoraces, pulmonary cysts and renal neoplasms. Light microscopic evaluation of the BHD renal tumors has suggested the existence of various morphologies including chromophobe, oncocytic and hybrid variants. To date, there has been no ultrastructural analysis of these tumors.
Design: We utilized the collection of BHD renal neoplasms at our institution and evaluated their ultrastructural features in comparison to those of sporadic or familial chromophobe carcinomas and oncocytomas. Eleven cases were evaluated, 5 of which BHD associated and 6 sporadic or familial.
Results: We found that all 5 BHD renal tumors expressed a hybrid chromophobe/oncocytic phenotype, which was apparent in individual tumor cells. Specifically, tumor cells exhibited numerous mitochondria (oncocytic phenotype) and microvesicles (chromophobe phenotype). The mitochondria were similar to those described in sporadic oncocytomas, i.e. small and round with lamellar cristae. Many tumors contained cells with apical villi and formation of lumina and with elaborate cytoplasmic interdigitations. Sporadic or familial tumors without BHD mutation were of pure morphology, either oncocytic (5 tumors), or chromophobe (1 tumor). The chromophobe tumor also had many mitochondria, but they were of variable size including large ones and had the characteristic tubulovesicular cristae. Luminal differentiation was present in the chromophobe carcinoma, but not in the oncocytomas. All but one oncocytomas had focal intracytoplasmic aggregates of filaments and consisted of groups of cells surrounded by thick basement membrane. The cytoplasmic contours were smooth, except in one tumor, which showed basal interdigitations. Lipid droplets and glycogen were present but not abundant in all tumors.
Conclusions: Our study showed that all BHD renal tumors exhibit a hybrid chromophobe/oncocytic ultrastructural phenotype, which distinguishes them from oncocytic or chromophobe tumors in sporadic or other familial settings. Therefore, electron microscopy can be instrumental in identifying BHD patients without overt clinical manifestations.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 262, Monday Morning