Aggressive Variants of Chromophobe Renal Cell Carcinoma: Importance of Recognition and Grading
Meghna Alimchandani, Carlos Neira de Paz, Silke Williams, Karlena Lara-Otero, WM Linehan, Maria J Merino. National Institutes of Health, Bethesda, MD
Background: Chromophobe renal cell carcinoma (ChRCC) comprises 5% of all renal cell carcinomas (RCCs) and has been known to have a better prognosis. It has been reported that tumor grading rather than Fuhrman nuclear grading is more appropriate to predict biologic behavior and prognosis. In this study we evaluate 97 cases of ChRCC and provide clinico-pathological and molecular support for tumor grading and for a better understanding and treatment of this rare neoplasm.
Design: Ninety five nephrectomy specimens and 2 core biopsies obtained from 97 patients diagnosed as RCC, Chromophobe type, were reviewed at the NIH from 1999 – 2012. Normal and tumor tissue were microdissected for loss of heterozygosity (LOH) analysis using polymorphic markers for chromosomes 3p25, 1p35-36 and 1q42-43. IHC was performed for (MIB1), p53, CK7, CKAE1/AE3, CD10, CD117, SMA on selected specimens. In tumors with spindle (sarcomatoid) differentiation, both elements were studied.
Results: Males and females were affected equally and range in age from 15-82 years. Three distinct morphologies were encountered, and graded according to Paner (2010). Seventy-five cases (77%) were designated Grade 1 (G1) histology and consisted of large polygonal cells with granular eosinophilic cytoplasm, prominent cell borders and irregular nuclei with the characteristic perinuclear halo. The Grade 2 (G2) intermediate morphology consisted of 15 cases (16%) with marked atypia of nuclei and lipidized clear cytoplasm. Seven cases (7%) displayed sarcomatoid transformation with a spindle cell component that varied in cellularity and pleomorphism, Grade 3 (G3). Metastasis occurred in 2/ 75 G1 tumors, 7/ 15 G2 tumors and 4/7 G3 tumors. Metastasis involved lymph nodes (either epithelial or sarcomatoid), liver and bones. One patient had massive retroperitoneal lymphangitic carcinomatosis. Genetic studies of selected G3 cases showed LOH in chromosomes 1p and 1q in tumor cells of epithelial morphology while tumor cells of spindle cell morphology displayed LOH in chromosomes 3p in addition of 1p and 1q. Survival correlates with tumor grading.
Conclusions: Despite the favorable prognosis of ChRCC, it is important to realize that aggressive variants of chromophobe can occur with potential to metastasize and poor prognosis. Grading of tumors assist in the recognition of these aggressive forms. The finding of additional genetic changes in the sarcomatoid elements suggest tumor progression.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 8:30 AM
Proffered Papers: Section A, Tuesday Morning