Cytomorphologic analysis of clear cell papillary renal cell carcinoma: Distinguishing diagnostic features

Background Clear cell papillary renal cell carcinoma (CCPRCC) shares histomorphologic and immunophenotypic features with clear cell RCC (CCRCC) and papillary RCC (PRCC). Methods We compared the cytomorphology, immunoprofile, and clinical management of CCPRCC (n = 18), CCRCC (n = 20), and PRCC (n = 18). Results Useful cytomorphologic features for comparing CCPRCC with CCRCC include 3-dimensional clusters (72% vs 0%), papillae (50% vs 0%) and sheets (22% vs 70%), vasculature (papillary vs traversing), naked nuclei (17% vs 100%), prominent nucleoli (0% vs 65%), and amount of cytoplasm (small vs large). Useful cytomorphologic features for comparing CCPRCC with PRCC include sheets (22% vs 61%), naked nuclei (17% vs 67%), nuclear grooves (5% vs 67%) and inclusions (17% vs 67%), and pigmented cytoplasm (17% vs 83%). At on-site evaluation, 16 of 18 (86%) CCPRCC specimens were deemed adequate, with suspicion for CCPRCC in 5 of 16 (31%) cases. Core histology of CCPRCC showed low-grade malignant cells in nests (67%), tubules (100%), and papillae (72%), frequently in myxohyaline stroma (67%). Immunostains demonstrated expression of cytokeratin 7 (CK7; 100%), carbonic anhydrase IX (CA IX; 100%, cup-like), CD10 (53%, reverse cup-like), and alpha-methylacyl-CoA racemase (AMACR; 35%). Among 18 CCPRCC patients, 9 (50%) underwent nephrectomy, 5 (28%) underwent cryo-ablation, and 4 (22%) were under surveillance with serial imaging. Conclusion Certain morphologic features represent diagnostic criteria of CCPRCC in cytology specimens and help distinguish CCPRCC from CCRCC and PRCC. Immunostaining patterns with CK7, CA IX, CD10, and AMACR can confirm the diagnosis. Delineating CCPRCC from more biologically aggressive RCC types in cytology specimens enhances presurgical and clinical management of patients given CCPRCC's low-grade, indolent behavior.