The Unrecognized Morphology of Renal Tumors in SDH Syndromes. Immunohistochemical and Genetic Changes
MJ Merino, ER Parrilla-Castellar, M Linehan. NCI, Bethesda, MD
Background: More than 35,710 new cases of renal cell carcinoma (RCC) are diagnosed in the US, with about 12,480 deaths per year.Recently our understanding of renal cancer predisposing syndromes has improved, and genes associated with specific tumors have been discovered. Mutations in the genes that encode mitochondrial succinate dehydrogenase can cause the paraganglioma syndromes with development of paraganglioma and pheochromocytoma. The purpose of this study is to provide the first morphological, immunohistochemical and genetic description of the renal tumors found in these syndromes.
Design: Five patients presented with renal tumors.Two had prior history of familial SDH deficiency and one patient presented with metastatic RCC to bone. Microdissected DNA was evaluated for LOH in chromosomes 1p35 and 11q23.
Results: Patients ranged in age from 19-68 years. Four patients were females and 1 was male. Four tumors involved the left kidney and 1 the right. Tumor size varied from 6-2.4 cm. Grossly the lesions had a brown color and were well circumscribed. Histologically the solid masses were composed of uniform cells with clear and light granular eosinophilic cytoplasm. Many of the cells had a signet ring cell appearance and the vacuole seemed to be filled by amorphous pink material. This material could be seen filling small cystic dilated spaces lined by eosinophilic cells resembling oncocytes. The nucleus of the cells was large and with irregular chromatin distribution. A smaller cell with granular cytoplasm and dark nucleous was present and in some cases large darkly pigmented cells were identified. One tumor showed spindle cell differentiation and areas of nuclear pleomorphism and necrosis; but nodules of cells similar to the ones described above were present. The bone metastasis was composed predominantly of eosinophilic spindle cells. IHC was performed for CK7, CK20, CAM5.2, CD10, CD56, CKIT, Synaptophysin, Chromogranin, grimelius, melanin, PAS and colloidal iron stains.
Conclusions: Renal tumors associated with SDH have a unique morphologic appearance. Recognition of this group of tumors is important both, clinically and pathologically, because they are frequently misdiagnosed as oncocytomas and clear cell RCC. Proper diagnosis of these tumors, will allow for identification of specific genes that will allow elucidation of mechanisms responsible for the development of tumors, as well as to establish appropriate therapies and the genetic counseling of the families,
Category: Genitourinary (including renal tumors)
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 161, Tuesday Morning