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.