Original Contributions Oncocytic papillary renal cell carcinoma: a clinicopathologic, immunohistochemical, ultrastructural, and interphase cytogenetic study of 12 cases B Ondrej Hes, MD, PhD a , Matteo Brunelli, MD b , Michal Michal, MD a, 4 , Paolo Cossu Rocca, MD c , Milan Hora, MD, PhD d , Marco Chilosi, MD b , Michaela Mina, MD b , Ludmila Boudova, MD, PhD a , Fabio Menestrina, MD b , Guido Martignoni, MD b,c a Department of Special Diagnostics SPAU, University Hospital Plzen, 30460 Czech Republic b Anatomia patologica, Universita di Verona, 37134 Italy c Anatomia patologica, Universita di Sassari, 07100 Italy d Department of Urology, University Hospital Plzen, 30460 Czech Republic Abstract Papillary renal cell carcinoma (RCC) is subclassified in type 1 displaying cells with scanty pale cytoplasm arranged in a single layer and in type 2 showing pseudostratified cells with eosinophilic cytoplasm. However, the existence of more variants of papillary RCC may be inferred by the recognition of few cases with different morphological features. We report the clinicopathologic, immunohistochemical, ultrastructural, and interphase cytogenetic features of 12 papillary RCC composed by oncocytes. Ten patients were males and their median age was 67 years. The tumors were well demarcated and their median diameter was 7.1 cm. Solid oncocytoma-like areas occurred in 11 cases. The cytoplasm of the neoplastic cells was filled by mitochondria with lamellar cristae. All cases were positive for the antimitochondrial antigen and racemase and showed variable immunoreactivity for cytokeratins (AE1/AE3, CK8-18, CK7, CK19), EMA, CD10, vimentin, and parvalbumin. MIB1 was detected in 0 to 6 cells per 1 high-power field. Fluorescent in situ hybridization analysis on formalin-fixed paraffin-embedded tissue showed three or more signals for chromosome 7 and 17 (for both z 30% of nuclei in 7 of 12 neoplasms). In males, signals of chromosome Y were absent in more than 80% of the neoplastic nuclei. One patient died of metastases. Interphase cytogenetic analysis by fluorescent in situ hybridization can be a diagnostic tool in cases mimicking an oncocytoma. D 2006 Elsevier Inc. All rights reserved. Keywords: Kidney; Oncocytoma; Papillary renal cell carcinoma; Oncocytic 1. Introduction Papillary renal cell carcinoma (RCC) is a well-established subtype of RCC with characteristic gross and histological fea- tures. It comprises approximately 10% to 15% of RCCs [1,2]. Papillary RCCs have been separated into two types (type 1 and type 2) based on architectural and cytologic features showing different biologic behavior [3]. Type 1 consists of papillae and tubular structures covered by small cells with pale cytoplasm and characterized by small oval nuclei. The neoplastic cells are arranged in a single layer and foamy macrophages and psammoma bodies are easily found. Type 2 consists of papillae covered by pseudostratified or multilayered large cells with abundant eosinophilic cyto- plasm and large irregular nuclei [3]. Racemase immunore- activity and trisomy or tetrasomy of chromosome 7, trisomy of chromosome 17, and loss of chromosome Y are common findings in both types of papillary RCC [4]. We have identified a group of papillary or solid/papillary neoplasms composed of large cells with deeply granular eosinophilic cytoplasm and spherical nuclei, occasionally 1092-9134/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.anndiagpath.2005.12.002 B This study was supported in part by Fondazione Cassa di Risparmio di Verona (bando 2001), Banco di Sardegna (2003), AIRC, Milan, MIUR, and Diagnostica Molecolare in Oncologia (2003). 4 Corresponding author. Laborator Spec. Diagnostiky SPAU, Univer- sity Hospital, 304 60 Plzen, Czech Republic. Tel.: +42 0 603886633, +42 0 377104630; fax: +42 0 377104650. E-mail address: michal@medima.cz (M. Michal). Annals of Diagnostic Pathology 10 (2006) 133 – 139