Papillary renal cell carcinoma: a single institutional study of 199 cases addressing classification, clinicopathologic and molecular features, and treatment outcome

Abstract

The morphologic spectrum of type 1 papillary renal cell carcinoma (PRCC) is not well-defined, since a significant proportion of cases have mixed type 1 and 2 histology. We analyzed 199 cases of PRCC with any (even if focal) type 1 features, with a median follow-up of 12 years, to identify clinicopathological features associated with outcome. Ninety-five tumors (48%) of the cohort contained some type 2 component (median amount: 25%; IQR: 10%, 70%). As a group they showed high rates of progression-free (PFS) and cancer-specific survival (CSS). Tumor size, mitotic rate, lymphovascular invasion, sarcomatoid differentiation, sheet-like architecture, and lack of tumor circumscription were significantly associated with CSS (p≤0.015) on univariate analysis. While predominant WHO/ISUP nucleolar grade was associated with PFS (p=0.013) and CSS (p=0.030), the presence of non-predominant (<50%) nucleolar grade did not show association with outcome (p=0.7). PFS and CSS showed no significant association with the presence or the amount of type 2 morphology. We compared the molecular alterations in paired type 1 and type 2 areas in a subset of 22 cases with mixed type 1 and 2 features and identified 12 recurrently mutated genes including TERT , ARID1A, KDM6A, KMT2D, NFE2L2 , MET , APC , and TP53 . Among 78 detected somatic mutations, 61 (78%) were shared between the paired type 1 and type 2 areas. Copy number alterations, including chromosome 7 and 17 gains, were similar between type 1 and 2 areas. These findings support that type 2 features in a PRCC with mixed histology represent either morphologic variance or clonal evolution. Our study underscores the notion that PRCC with any classic type 1 regions is best considered as type 1 PRCC and assigned the appropriate WHO/ISUP nucleolar grade. It provides additional evidence that type 2 PRCC as a separate category should be re-assessed and likely needs to be abandoned.

A novel molecular signature identifies mixed subtypes in renal cell carcinoma with poor prognosis and independent response to immunotherapy

“…The new information provided by PSA becomes specifically apparent when PSA and pathological classification are combined. In line with the novel 2022 WHO classification, subcategorization into pRCC type 1 and type 2 was no longer considered, which was additionally corroborated by a recent publication particularly addressing the co-occurrence of T1 and T2 features in pRCC [ 76 ]. Moreover, PSA applied to an independent histologically informed cohort (C4, n = 92) including 48 pRCC cases, enabled valid classification of main and heterogeneous RCC subtypes.…”

Comprehensive Analysis of Pyroptosis-Related Genes and Tumor Microenvironment Infiltration Characterization in Papillary Renal Cell Carcinoma

“…KIRP is a heterogeneous subtype of RCC that differs from clear cell RCC in terms of clinicopathologic and molecular characteristics ( Chen et al, 2019 ). When compared to clear cell RCC, KIRP is less likely to develop distant metastases upon diagnosis ( Murugan et al, 2021 ). Because the majority of current knowledge about how to diagnose and treat renal tumors is derived from studies on clear cell RCC, the unique characteristics of KIRP may be critical to the illness ( Mendhiratta et al, 2021 ; Yamamoto et al, 2021 ).…”

WHO 2022 landscape of papillary and chromophobe renal cell carcinoma

“…In practice, however, it may be challenging to dichotomize pRCC as such, since well‐sampled tumours frequently harbour mixtures of type 1 and 2 areas 14–16 . Previous analyses suggest that type 2 pRCC may represent several heterogeneous tumour entities, while type 1 pRCC is genetically more homogeneous 17,18 . The nuclear features of type 2 RCC confer these tumours with an overall higher International Society of Urological Pathology (ISUP) grade, and it may be argued that instead of truly representing two independent cancer types, these represent low‐ to high‐grade progression of any pRCC 16,19 .…”