Sporadic Hybrid Oncocytic/Chromophobe Tumor of the Kidney: A Clinicopathologic, Histomorphologic, Immunohistochemical, Ultrastructural and Molecular Cytogenetic Study of 14 Cases
O Hes, FB Petersson, Z Gatalica, R Sima, S Bulimbasic, DM Perez Montiel, N Kuroda, I Alvarado Cabrero, M Michal. Charles University Hospital Plzen, Plzen, Czech Republic; National University Health System Hospital, Singapore, Singapore; Creighton University, Omaha; University Hospital Dubrava, Zagreb, Croatia; INCAN, Mexico City, Mexico; Red Cross Hospital, Kochi, Japan; Centro Medico, Mexico City, Mexico
Background: Hybrid oncocytic/chromophobe tumors (HOCT) of the kidney have been described in patients with Birt-Hogg-Dubé syndrome (BHD) and/or in association with renal oncocytosis. We have studied HOCT occurring in patients without any clinical evidence of BHD or renal oncocytosis.
Design: 14 cases of HOCT were identified out of 398 previously diagnosed renal oncocytomas and 351 chromophobe carcinomas. Immunohistochemical, ultrastructural and molecular genetic studies analyzing numerical chromosomal changes, losses of heterozygosity (LOH) and mutational status of folliculin (FLCN) gene were performed.
Results: HOCT were identified in 9 men and 5 women (age range 40 to 79 years). The size of tumors ranged from 2 to 11cm. All tumors displayed a solid-alveolar architecture and were composed of cells with abundant eosinophilic granular oncocytic cytoplasm with perinuclear halos. Occasional binucleated neoplastic cells were seen but irregular, wrinkled (raisinoid) nuclei were absent. Tumors were positive for CK7 (12/14), AE1-AE3 (14/14), antimitochondrial antigen (14/14), E Cadherin (11/13), parvalbumin (12/14), EMA (14/14). Tumors were generally negative for racemase, CK20, CD10 and carboanhydrase IX. Multiple mitochondrias and occasional microvesicle were found in the cytolasm. Tumors showed both multiple monosomies and polysomies in analyzed chromosomes. Monosomy of chromosome 20 was seen in 7/14 cases. Monosomy of chromosome 6 and 9 were present in 4/14 cases, respectively. Polysomy of chromosome 10, 21 and 22 was found in 4/14 cases, respectively. No pathogenic mutations were found in the VHL, c-kit, PDGFR and FLCN genes.
Conclusions: HOCT of the kidney exist outside the setting of BHD and renal oncocytosis. HOCT constitute a morphologically distinctive group of tumors characterized by multiple numerical aberrations of chromosomes 1,2,6,9,10,13,17,21,22. The tumors seem to behave indolently, as no signs of malignancy were documented in our series. Study supported by IGA 9722-4
Category: Genitourinary (including renal tumors)
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 138, Tuesday Morning