Renal Tumors in Patients with Von Hippel-Lindau Disease – A Single Institutional Study over 15 Years
Priya Rao, Federico A Monzon, Eric Jonasch, Pheroze Tamboli. MD Anderson Cancer Center, Houston, TX; Baylor College of Medicine, Houston, TX
Background: Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder. Patients with this disease are typically prone to develop renal tumors, CNS hemangioblastomas, retinal angiomas and pheochromocytomas. We present the largest series of cases from a single institute documenting the pathology of renal tumors arising in patients with VHL disease, encompassing a 15 year period (1996-2011).
Design: We identified 30 patients from our VHL clinic database that had a documented history of a surgical resection. All patients had a clinical diagnosis of VHL. Histologic slides from 16 nephrectomy specimens were available for review.
Results: Mean age at diagnosis was 37 years (range 10-56). Patients included 6 women and 10 men. Other clinical stigmata of VHL disease included CNS hemangioblastomas (n=10), retinal angiomas (n=7), pancreatic cysts (n=7) and adrenal pheochromocytomas (n=2). Eight patients had 2 or more clinical stigmata of VHL, in addition to a renal tumor. Nine patients presented with bilateral renal tumors. Pathologic stages included pT1 (n=10), pT2 (n=1), pT3 a or b (n=5). Five patients presented with multiple renal tumors (5 or more). The most common histologic subtype was clear cell RCC (n=12) followed by clear-cell papillary RCC (n=3) and chromophobe RCC (n=1). Most tumors were of low Fuhrman nuclear grade (1 or 2) with only one tumor displaying Fuhrman nuclear grade 4 features. The latter was the sole case of chromophobe RCC in our series which displayed extensive sarcomatoid differentiation. It was not uncommon for multiple tumors within a single resection specimen to display varying Fuhrman nuclear grades, often ranging from 1-3. Only 2 patients developed metastatic disease; 1 to the lung and bone (pT3b chromophobe RCC; time to metastasis 6 mos) and the other to the retroperitoneum (pT3a clear cell RCC; time to metastasis 36 mos). Genomic analysis (using SNP arrays) of a subset of these tumors is currently underway.
Conclusions: Von Hippel-Lindau has traditionally been known to be associated with multiple bilateral clear cell renal cell carcinomas, which are often extensively cystic. Our study demonstrates that although clear cell RCC remains the most common histologic subtype, other histologic subtypes including clear-cell papillary RCC and chromophobe RCC may also be associated with this syndrome. Most tumors behave in an indolent fashion and prognosis is related to tumor stage at diagnosis.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 9:00 AM
Platform Session: Section A, Monday Morning