Papillary renal cell carcinoma: A single institutional study of 199 cases addressing classification, clinicopathologic and molecular features, and treatment outcome Journal Article
| Authors: | Murugan, P.; Jia, L.; Dinatale, R. G.; Assel, M.; Benfante, N.; Al-Ahmadie, H. A.; Fine, S. W.; Gopalan, A.; Sarungbam, J.; Sirintrapun, S. J.; Hakimi, A. A.; Russo, P.; Chen, Y. B.; Tickoo, S. K.; Reuter, V. E. |
| Article Title: | 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. © 2021, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology. |
| Keywords: | adult; controlled study; human tissue; treatment outcome; aged; gene mutation; major clinical study; somatic mutation; genetics; clinical feature; comparative study; metabolism; progression free survival; tumor volume; molecular dynamics; cohort analysis; pathology; histology; morphology; renal cell carcinoma; kidney neoplasms; kidney tumor; carcinoma, renal cell; cancer specific survival; mitosis rate; cancer classification; univariate analysis; chromosome 17; chromosome 7; dna copy number variations; copy number variation; papillary renal cell carcinoma; clonal evolution; lymph vessel metastasis; humans; human; male; female; article |
| Journal Title: | Modern Pathology |
| Volume: | 35 |
| Issue: | 6 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2022-06-01 |
| Start Page: | 825 |
| End Page: | 835 |
| Language: | English |
| DOI: | 10.1038/s41379-021-00990-9 |
| PUBMED: | 34949764 |
| PROVIDER: | scopus |
| PMCID: | PMC9177523 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 July 2022 -- Source: Scopus |
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