Hybrid Tumors: All You Need To Know and More.
Pablo Cannata-Ortiz, Beatriz Walter Rodriguez, Gennady Bratslavsky, W Marston Linehan, Maria J Merino. National Cancer Institute, Bethesda, MD
Background: Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant genodermatosis caused by mutations in the FLCN or BHD gene (17p11.2) that predisposes to the development of skin fibrofolliculomas, lung cysts and renal neoplasms. Most of the renal tumors in BHD share morphological features of both oncocytoma and chromophobe RCC and are called hybrid tumors. Knowledge about renal tumors in BHD syndrome is limited and questions remain about the morphology and clinical impact of these neoplasms.
Design: To better characterize these BHD renal neoplasms and to investigate if predominance of different cell elements has clinical significance, we studied 458 renal tumors from 68 BHD patients (39 males; 29 females). Clinico-pathological correlation, proliferative and prognostic markers were evaluated by IHC.
Results: Histology confirmed that hybrid tumors were the most frequent renal tumor (53.9%) followed by chromophobe RCC (39.5%) and clear cell RCC (3%). Multiple bilateral tumors were noted in 47% of the patients (average: 6.7 tumors per patient) at a mean age of 49.7 years. The mean size was 2.2 cm (range 0.5-9). Hybrid tumors are characterized by the presence of oncocytoma-like cells and chromophobe cells with granular eosinophilic cytoplasm and perinuclear halos. Cells with clear/pale cytoplasm and crisp borders are present. Typically, hybrid tumors show an admixture of all these types of cells. These tumors are not encapsulated and may have a central myxohyaline scar. Non-tumoral renal parenchyma showed oncocytosis in 56% of the cases. Nodules of classical chromophobe RCC can be found growing within some hybrid tumors and compress the hybrid component to the periphery. These nodules exhibit only one type of chromophobe cells and their homogeneity differentiates them from the hybrid tumor, where the admixture of different types of cells confers a more heterogeneous appearance. IHC showed that Mib1 proliferation index was under 10%, p53 stained rare cells and CD10 and CD117 showed patchy staining in the hybrid component in contrast to the diffuse staining of chromophobe RCC. The percentage of different cells in the hybrid tumors had no clinical impact as no patient with hybrid tumors only has developed metastatic disease.
Conclusions: Our study demonstrates that hybrid tumors are the predominant renal neoplasias in BHD syndrome and that the percentage of different cell types in the hybrid tumor does not seem to have prognostic significance. Prognostic/proliferative markers suggest slow growth, with the prognosis of the patients likely dictated by the coexistence of other aggressive variants of renal cancer.
Category: Genitourinary (including renal tumors)
Tuesday, March 1, 2011 8:00 AM
Platform Session: Section A, Tuesday Morning