Papillary renal cell carcinoma revisited: impact of the World Health Organization 2022 classification on prognostication.

Objectives: To investigate the impact of the revised papillary renal cell carcinoma (PRCC) classification and evaluate its validity with regard to oncological outcome stratification.

Patients And Methods: Identifying 527 patients with PRCC who underwent surgical resection from 1995 to 2022, a tissue microarray was constructed for immunohistochemical and molecular characterisation. Re-classification according to the World Health Organization (WHO) 2022 criteria and nuclear grading according to the WHO/International Society of Urological Pathologists criteria were done. In addition to the revised subtype, alleged clinicopathological prognosticators were analysed with respect to progression-free (PFS) and cancer-specific survival (CSS).

Results: Initially, 247 (46.9%) cases were Type 1, 234 (44.4%) were Type 2, and 46 (8.7%) were papillary not-otherwise-specified. According to the revised criteria, 29.9% of Type 1 and 57.7% of Type 2 PRCC cases were re-classified. Re-classified from Type 1 included more indolent tumours while from Type 2 PRCC many molecularly defined tumours were newly identified. After re-classification, still 373 tumours remained with distinct histomorphological features of Type 1 (254 [70%]) and Type 2 (119 [42.2%]) PRCC. Furthermore, significant differences in survival outcomes were obtained when the revised criteria was used particularly for tumours of ≤4 cm. For a median (interquartile range) follow-up of 79 (38.2-132.8) months, the 5-year PFS was 97% for Type 1, 80% for Type 2, 75% for transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3)-rearranged, and 43.5% for fumarate hydratase-deficient RCC. No disease progression was observed in patients with papillary renal neoplasm with reverse polarity.

Conclusion: The revised WHO 2022 classification enhanced prognostic accuracy for PRCC particularly for small tumours. Retaining previous subtypes may confer further clinical as well as prognostic value.