Chromophobe renal cell carcinoma: current and controversial issues

It has been 35 years since Professor Thoenes and his colleagues discovered chromophobe renal cell carcinoma (RCC). Since then, our knowledge about this tumour entity changed novel entities have discovered. The aim of review is to discuss recent molecular findings open questions in diagnosing chromophobe-like/oncocytic neoplasms. broader differential diagnosis chromophobe-like oncocytoma-like neoplasms includes SDH-deficient carcinoma, fumarate hydratase (FH) deficient RCC, epitheloid angiomyolipoma (‘oncocytoma like’), MiT family translocation RCC the emerging eosinophilic solid cystic carcinoma. After separation these tumours from it becomes evident that are low malignant with a 5–6% risk metastasis. Recent next generation sequencing (NGS) DNA methylation profiling studies confirmed Thoenes' theory distal tubule derived origin oncocytomas. Comprehensive genomic analyses demonstrated somatic mutation rate identified TP53 PTEN as most frequently mutated genes, whereas ‘unclassified’ oncocytic or features can show inactivating mutations TSC2 activating MTOR primary alterations. For future, would be desirable create category ‘oncocytic/chromophobe NOS’ potential further for identification TSC1/2 rare tumours. In 1975 United States Armed Forces Institute Pathology (AFIP) Atlas Tumour Pathology1Bennington J. Beckwith Tumors Kidney, Renal Pelvis Ureter. Vol. 12. Pathology, Washington, DC1975Google Scholar 1981 World Health Organization (WHO) classification,2Mostofi F. Histological Typing Kidney Tumors. 25. Organization, Geneva1981Google (RCC) was mainly diagnosed ‘renal adenocarcinoma’, but histological subtyping prognostic significance.3Delahunt B. Eble J.N. 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Seier results large single-institution series.Clin Genitourin 2019; 17: 373-379Abstract (17) accounts approximately 5–7% RCC. sporadic. Birt–Hogg–Dubé (BHD) syndrome, autosomal disorder associated Folliculin gene,24Vocke C.D. Yang Y. Pavlovich C.P. al.High frequency frameshift BHD gene Birt-Hogg-Dube-associated Natl Inst. 97: 931-935Crossref (180) Cowden syndrome germline higher incidence characteristically well circumscribed not encapsulated. Whereas brown mahagony colour, cut surface classic grey tan. Histologically, they grow predominantly sheets, vascular septs 2A,B). Some variable nested, trabecular, alveolar, microcystic even patterns.25Michalova Tretiakova Pivovarcikova al.Expanding morphologic spectrum 8 cases architecture.Ann Diagn 2020; 44: 151448Crossref (19) small percentage exhibits sarcomatoid growth26Ohashi Martignoni Hartmann al.Multi-institutional re-evaluation factors proposal two-tiered grading scheme.Virchows Arch. 476: 409-418Crossref (29) 2F). Classic predominance pale translucent reticulated, sometimes microvesiculated. larger more voluminous foamy (‘hydropic’) often present among cells. Another densely 2B). Pale types mixed 2A). Hyperchromatic nuclei irregular, wrinkled outlines (‘raisinoid’) characteristic. feature presence perinuclear clarity (so called halos). Binucleated virtually all cases. membranes usually appear prominent (‘plant cell-like’), important criterion compared bizarre nuclear atypia similar those common. prevalence differentiation ranges 1.8% 8.8%.27Akhtar Tulbah Kardar Ali M.A. Sarcomatoid connection.Am 21: 1188-1195Crossref (123) Scholar,28Ged Chen Y.B. Knezevic al.Metastatic absence determines clinical course treatment outcomes.Clin e678-e688Abstract (23) Mitotic activity very uncommon between remains difficult some survey urological pathologists regarding immunohistochemistry separation.29Williamson S.R. Gadde Trpkov al.Diagnostic criteria neoplasms: urologic pathologists.Hum 2017; 63: 149-156Crossref (66) More than one mitotic figure regarded incompatible many uropathologists. Minor areas wrinkling, focal clearing, multinucleation did necessarily exclude electron microscopy diagnose vesicular structures possibly endoplasmic reticulum mitochondria oncocytomas.7Thoenes Scholar,9Thoenes Several ultrastructural shown (‘pale cells’) numerous microvesicles, related defective mitochondrial development. abundant.2Mostofi Scholar,6Thoenes 7Thoenes 8Bannasch 9Thoenes 10Kovacs 13Speicher 14Kovacs 15Störkel 16Eble 17Moch 18Crotty 24Vocke 25Michalova 26Ohashi 27Akhtar 28Ged 29Williamson 30Tickoo S.K. 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