Clinicopathologic and Molecular Characterization of Xanthomatous Giant Cell Renal Cell Carcinomas: Further Support for a Close Morphologic Spectrum to Eosinophilic Solid and Cystic Renal Cell Carcinomas.

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  • Additional Information
    • Source:
      Publisher: Wolters Kluwer Health, Inc Country of Publication: United States NLM ID: 7707904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-0979 (Electronic) Linking ISSN: 01475185 NLM ISO Abbreviation: Am J Surg Pathol Subsets: MEDLINE
    • Publication Information:
      Publication: <2015- > : Philadelphia, PA : Wolters Kluwer Health, Inc.
      Original Publication: New York, Masson.
    • Subject Terms:
      Kidney Neoplasms*/genetics ; Kidney Neoplasms*/pathology ; Kidney Neoplasms*/surgery ; Kidney Neoplasms*/chemistry ; Carcinoma, Renal Cell*/genetics ; Carcinoma, Renal Cell*/pathology ; Carcinoma, Renal Cell*/chemistry ; Carcinoma, Renal Cell*/surgery ; Tuberous Sclerosis Complex 2 Protein*/genetics ; Biomarkers, Tumor*/genetics ; Biomarkers, Tumor*/analysis ; Mutation*; Humans ; Male ; Female ; Middle Aged ; Adult ; Young Adult ; Immunohistochemistry ; Xanthomatosis/pathology ; Xanthomatosis/genetics ; DNA Mutational Analysis ; Nephrectomy ; Phenotype ; Genetic Predisposition to Disease ; Diagnosis, Differential
    • Abstract:
      A recent study described a rare subtype of tuberous sclerosis complex ( TSC )-mutated renal cell carcinoma primarily characterized by Xanthomatous giant cell morphology. Only 2 cases in young individuals have been reported so far, making the correct diagnosis challenging from a pathological perspective. It remains unknown whether this tumor represents an independent subtype or belongs to other TSC -mutated tumors. We conducted a clinicopathologic evaluation and immunohistochemical profiling of 5 cases of Xanthomatous Giant Cell Renal Cell Carcinoma (XGC RCC) with confirmed TSC2 mutations through targeted DNA sequencing. In addition, we analyzed transcriptomic profiles using RNA-seq for the following samples: XGC RCC, Low-grade Oncocytic tumors (LOT), High-grade Oncocytic tumors/Eosinophilic Vacuolar Tumors (HOT/EVT), Eosinophilic Solid and Cystic Renal Cell Carcinomas (ESC RCC), Chromophobe cell Renal Cell Carcinomas (ChRCC), Renal Oncocytomas (RO), clear cell Renal Cell Carcinomas (ccRCC), and normal renal tissues. There were 2 female and 3 male patients, aged 22 to 58 years, who underwent radical nephrectomy for tumor removal. The tumor sizes ranged from 4.7 to 9.5 cm in diameter. These tumors exhibited ill-defined boundaries, showed an expansive growth pattern, and featured distinctive tumor giant cells with abundant eosinophilic to Xanthomatous cytoplasm and prominent nucleoli. All tumors had low Ki-67 proliferation indices (<1%) and demonstrated immune reactivity for CD10, PAX8, CK20, CathepsinK, and GPNMB. Next-generation sequencing confirmed TSC2 mutations in all cases. RNA sequencing-based clustering indicated a close similarity between the tumor and ESC RCC. One patient (1/5) died of an accident 63 months later, while the remaining patients (4/5) were alive without tumor recurrences or metastases at the time of analysis, with a mean follow-up duration of 43.4 months. Our research supports the concept that Xanthomatous giant cell renal cell carcinoma (XGC RCC) shares clinicopathological and molecular characteristics with ESC RCC and shows a relatively positive prognosis, providing further support for a close morphologic spectrum between the two. We propose considering XGC RCC as a distinct subtype of ESC RCC.
      Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
      (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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    • Publication Date:
      Date Created: 20240410 Date Completed: 20240515 Latest Revision: 20240515
    • Publication Date:
      20240515
    • Accession Number:
      10.1097/PAS.0000000000002215
    • Accession Number:
      38595297