Molecular, Immunohistochemical, and Ultrastructural Characterization of Clear Cell Papillary Renal Cell Carcinoma
CJ Sailey, M Dvorakova, JC Papadimitriou, JF Borin, T Ali, AV Parwani. University of Maryland Med Ctr, Baltimore, MD; University of Pittsburgh Med Ctr, Pittsburgh, PA
Background: Clear cell papillary renal cell carcinoma (CCPRCC), with features of both clear cell (CCC) and papillary (PRC) renal cell carcinomas, is a relatively new entity. CCPRCC has been documented in end stage renal disease (ESRD) kidneys as well as occurring sporadically. Our study characterized the largest known series of CCPRCCs from ESRD and normally functioning kidneys using molecular methods, immunohistochemistry (IHC), and electron microscopy (EM).
Design: Formalin fixed, paraffin embedded tissue of 19 CCPRCCs from 11 ESRD (age 46-74 yr) and 6 sporadic (age 33-79 yr) cases were selected. 11 tumors were subjected to IHC and EM; 10 were analyzed for loss of heterozygosity (LOH) of the VHL gene at 3p and by FISH for abnormalities of chromosomes 7 and 17.
Results: The ESRD tumors ranged in size from 1.1 to 6.3 cm (mean 3.3 cm) with a pathologic stage up to pT1b and displayed relatively low nuclear grade (Fuhrman 1-2). The sporadic tumors ranged from 1.5 to 10.2 cm (mean 5.8 cm) with a higher stage (up to pT2) and higher nuclear grade (Fuhrman 2-3). Morphologically, all of the tumors displayed cystic and or solid architecture with simple branching papillae. Polygonal to columnar cells with abundant clear cytoplasm, delicate membranes and small ovoid basal nuclei lined the papillae. IHC revealed that the tumors were positive for E-cadherin, CAM5.2, CK7, Vimentin (100%), EMA, CK903 (91%), and CD10 (54%); negative for RCC, AMACR, and p63. On EM, the tumor cells showed short microvilli with occasional reverse directionality. Vacuoles of lipids/polysaccharides were apparent. There was prominent rER, and scant mitochondria. The nuclei had regular membranes & clumped chromatin. The basal lamina was regular with distinct collagen. One sporadic case showed VHL LOH; another showed trisomies of both chromosomes 7 and 17. Monosomy 7 was detected in 50% (4 ESRD / 1 sporadic) and monosomy 17 in 20% (1 ESRD / 1 sporadic) of cases.
Conclusions: CCPRCC is a distinct entity with morphologic and IHC overlap between CCC and PRC. Molecular heterogeneity of these tumors and the absence of abnormalities specific for CCC or PRC suggest a separate molecular pathway. Compared to sporadic tumors, the ESRD cases had a lower stage and nuclear grade. Immunophenotypic, genetic, and ultrastructural profiling of this entity can aid in diagnosis.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 136, Monday Morning