Dr. Comperat notes that the pathology of renal cell carcinoma is in evolution with two histological entities present in 1975, up to 50 entities in 2004, up to 55 entities in 2016, and now 40 histological entities in 2021. Since 2009 there has been an evolution in reporting of renal cell carcinoma, which has been promoted by the International Society of Uropathology (ISUP), notably that ISUP has moved away from using Fuhrman grade and since 2012 has used ISUP grade for kidney cancer.
The first paper discussed by Dr. Comperat was by Avulova et al. “Grading Chromophobe Renal Cell Carcinoma: Evidence for a Four-Tiered Classification Incorporating Coagulative Necrosis” published in European Urology.1 To objective of this study was to validate a previously published grading scheme (Paner) and propose a scheme that includes tumor necrosis. Among 266 patients with chromophobe RCC undergoing nephrectomy, 29 patients died from RCC over a median follow-up of 11.0 (IQR 7.9-15.9) years. Chromophobe RCC grade according to the Paner system was significantly associated with cancer-specific survival, including the difference in outcome between grade 1 and 2 tumors. As follows are the Kaplan-Meier curves for distant metastasis-free survival and cancer-specific survival stratified by Paner grade:
Among patients with Paner grade 2 tumors, the presence of tumor necrosis helped delineate patients with worse cancer-specific survival. As such, the Paner system was expanded to four tiers separating grade 2 into those with and without tumor necrosis. As follows are the Kaplan-Meier curves for distant metastasis free survival and cancer-specific survival stratified by the new 4-tiered proposed grading system:
Hazard ratios for associations of the proposed grade 2, 3, and 4 tumors with cancer specific survival were 4.63 (p=0.007), 17.8 (p<0.001), and 20.9 (p<0.001), respectively.
The second paper discussed by Dr. Comperat was by Trpkov et al. “Novel, emerging and provisional renal entities: The Genitourinary Pathology Society (GUPS) update on renal neoplasia” published in Molecular Pathology.2 One of the goals of this update was to bring more clarity regarding the evolving classification of renal neoplasia that will further reduce the category of "unclassifiable renal carcinomas/tumors". GUPS proposed three categories of novel entities:
- "Novel entity": validated by multiple independent studies
- "Emerging entity": good compelling data available from at least two or more independent studies, but additional validation is needed
- "Provisional entity": limited data available from one or two studies, with more work required to validate them
- Eosinophilic solid and cystic renal cell carcinoma (ESC renal cell carcinoma)
- Renal cell carcinoma with fibromyomatous stroma (Renal cell carcinoma FMS) (formerly renal cell carcinoma with leiomyomatous or smooth muscle stroma)
- Anaplastic lymphoma kinase rearrangement-associated renal cell carcinoma (ALK-renal cell carcinoma).
Dr. Comperat also provided the following update of what’s new in classification with the categorization as follows:
ESC-renal cell carcinoma has a greater incidence in females with a mean age of 57 years at diagnosis (range: 31-75). It is typically unifocal if sporadic and is more commonly a benign tumor. The sporadic incidence is estimated at 0.2%, however, incidence is 10% if linked to TSC syndrome as there are mutations in the TSC1 or TSC2 genes. ELOC (formerly TCEB1) mutated renal cell carcinoma is part of the VHL complex, with inactivation of the ELOC1 by mutation resulting in loss of the entirety of chromosome 9 and abrogating the tumor suppressor gene Elongin C. There is no HIF1 alpha degradation and no VHL inactivation and this tumor is mostly associated with a good prognosis. ALK translocation renal cell carcinoma is associated with translocations resulting in gene fusions involving anaplastic lymphoma kinase gene (ALK) at chromosome 2p23. The morphology of this tumor can be variable, and since there are so few cases assessing prognosis is difficult. Finally, the SMARCB1/INI1-deficient renal cell carcinoma derives from the renal tubular epithelium with complete loss of SMARCB1/INI1. These mutations are associated with malignant rhabdoid tumors and are associated with high pT stage and metastasis at presentation and poor outcomes:
Dr. Comperat provided the following conclusions and take-away messages from her presentation on what’s new in the pathology of renal cell carcinoma:
- Stage, grade, tumor type, and necrosis are important for prognosis
- Grading is probably only useful for clear cell and papillary renal cell carcinoma, but integration of necrosis of chromophobe renal cell carcinoma may be on the horizon
- There are several upcoming entities, but more studies are required for clarification and impact on prognosis
Presented by: Eva Comperat, MD, Sorbonne University, Tenon Hospital, Paris, France
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021
References:
- Avulova S, Cheville JC, Lohse CM, et al. Grading Chromophobe Renal Cell Carcinoma: Evidence for a Four-Tiered Classification Incorporating Coagulative Necrosis. Eur Urol 2021 Feb;79(2):225-231.
- Trpkov K, Williamson SR, Gill AJ, et al. Novel, emerging and provisional renal entities: The Genitourinary Pathology Society (GUPS) update on renal neoplasia. Mol Pathol 2021 Feb 1 [Epub ahead of print].