(UroToday.com) The 2022 International Kidney Cancer Symposium (IKCS) European Annual meeting included a session on surgical approaches to kidney cancer and a presentation by pathologist Dr. Holger Moch discussing the new World Health Organization (WHO) Classification changes. Dr. Moch notes that the previous basis of nomenclature for renal cancer classification is as follows:
- Predominant cytoplasmic features (clear cell)
- Architectural features (papillary)
- Cell type (oncocytoma)
- Combination (clear cell-papillary)
- Resemblance to embryological structures (metanephric adenoma)
- Anatomical background (collecting duct)
- Molecular alterations (translocation)
- Familial predisposition (HLRCC)
However, Dr. Moch notes that there are two new concepts: “morphologically-defined” RCC and “molecularly-defined” RCC. Dr. Moch then discussed several of these new entities. Eosinophilic solid and cystic RCC are macroscopically tan and can have a solid and macrocystic appearance.1 Microscopically, the tumors show solid areas admixed with variably sized macrocysts and microcysts that are lined by cells with a hobnail arrangement. The cells also have a voluminous eosinophilic cytoplasm with prominent granular cytoplasmic stippling and round to oval nuclei with prominent nucleoli. These tumors show cytokeratin 20 immunoreactivity and mutations in TSC1 or TSC2 genes, with occasional immunoreactivity for melan-A. The histopathologic images for eosinophilic solid and cystic RCC is as follows:
ELOC (formerly TCEB1) mutated RCC is a novel subtype of RCC with unique morphologic, immunohistochemical, and molecular characteristics that is distinct from clear cell RCC and clear cell-papillary RCC.2 Pathologically, these tumors share characteristic features with clear cell RCC including thick fibromuscular bands transecting the tumor, pure clear cell cytology frequently with cells showing voluminous cytoplasm, and clear cell renal cell carcinoma-like acinar areas associated with infolding tubular and focally papillary architecture. The presence of voluminous cytoplasm, absence of luminal polarization of tumor nuclei, and lack of extensive cup-like distribution of carbonic anhydrase-IX expression distinguish it from clear cell papillary carcinoma. The histopathologic images for ELOC (formerly TCEB1) mutated RCC is as follows:
ALK rearranged RCC was recently included in 2016 WHO classification as a provisional entity, representing a genetically distinct entity, with unreported metanephric adenoma-like and MTSC-RCC like variants.3 Specifically, for unclassified RCCs, it is important to do ALK immunohistochemical screening. These tumors typically show diverse architectural and cellular morphologies, including papillary, tubular, tubulocystic, solid, sarcomatoid (spindle cell), rhabdoid, signet-ring cell, and intracytoplasmic vacuoles, often set in a mucinous background. By immunohistochemistry, these tumors diffusely stain positive for ALK and PAX8:
Dr. Moch emphasized that based on a morphologically defined RCC we are able to classify eosinophilic solid and cystic RCC, and based on molecularly defined RCC we are able to classify:
- TFEB RCC-amplified or translocated
- SMARCB1 deficient medullary RCC
- ALK-translocation RCC
- ELOC (formerly TCEB1)-mutated RCC
Dr. Moch also highlighted that recently there has been the utilization of integrated proteogenomic characterization of clear cell RCC. In a study of 103 treatment naïve RCC specimens,4 genomic analyses identified a distinct molecular subgroup associated with genomic instability. Subsequently, integration of proteogenomic measurements uniquely identifies protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, microenvironment cell signatures delineate four immune-based clear cell RCC subtypes characterized by distinct cellular pathways: CD8+ inflamed, CD8- inflamed, VEGF immune desert, and metabolic immune desert.
Dr. Moch concluded his presentation of the new WHO classification for RCC with the following summary points:
- We are undergoing an evolution of RCC classification
- The molecular classification schema is not available as of yet, but there are molecularly-defined RCC types
Presented By: Holger Moch, Professor of Pathology, Chairman of the Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland
Written By: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 International Kidney Cancer Symposium (IKCS) Europe Annual Hybrid Meeting, Antwerp, Belgium, Fri, Apr 22 – Sun, Apr 24, 2022.
References:
- Trpkov K, Hes O, Bonert M, et al. Eosinophilic, solid, and cystic renal cell carcinoma: Clinicopathologic study of 16 unique, sporadic neoplasms occurring in women. Am J Surg Path. 2016 Jan;40(1):60-71.
- Hakimi AA, Tickoo SK, Jacobsen A, et al. TCEB1-mutated renal cell carcinoma: A distinct genomic and morphological subtype. Modern Path. 2015;28:845-853.
- Kuroda S, Trpkov K, Gao Y, et al. ALK-rearranged renal cell carcinoma (ALK-RCC): A multi-institutional study of twelve cases with identification of novel partner genes CLIP1, KIF5B, and KIAA1217. Mod Pathol. 2020 Dec;33(12):2564-2579.
- Clark DJ, Dhanasekaran SM, Petralia F, et al. Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma. Cell. 2019 Oct 31;179(4):964-983.