The category of "oncocytic renal tumors'' includes well-recognized entities, such as renal oncocytoma (RO) and eosinophilic variant of chromophobe renal cell carcinoma (eo-ChRCC), as well as a group of "gray zone" oncocytic tumors, with overlapping features between RO and eo-ChRCC that create ongoing diagnostic and classification problems. These types of renal tumors were designated in the past as "hybrid oncocytoma-chromophobe tumors". In a recent update, the Genitourinary Pathology Society (GUPS) proposed the term "oncocytic renal neoplasm of low malignant potential, not further classified", for such solitary and sporadic, somewhat heterogeneous, but relatively indolent tumors, with equivocal RO/eo-ChRCC features. GUPS also proposed that the term "hybrid oncocytic tumor" be reserved for tumors found in a hereditary setting, typically arising as bilateral and multifocal ones (as in Birt-Hogg-Dubé syndrome). More recent developments in the "gray zone" of oncocytic renal tumors revealed that potentially distinct entities may have been "hidden" in this group. Recent studies distinguished two new entities: "Eosinophilic Vacuolated Tumor" (EVT) and "Low-grade Oncocytic Tumor" (LOT). The rapidly accumulated evidence on EVT and LOT has validated the initial findings and has expanded the knowledge on these entities. Both are uniformly benign and are typically found in a sporadic setting, but rarely can be found in patients with tuberous sclerosis complex. Both have readily distinguishable morphologic and immunohistochemical features that separate them from similar renal tumors, without a need for detailed molecular studies. These tumors very frequently harbor TSC/MTOR mutations that are however neither specific nor restricted to these two entities. In this review, we outline a proposal for a working framework on how to classify such low-grade oncocytic renal tumors. We believe that such framework will facilitate their handling in practice and will stimulate further discussions and studies to fully elucidate their spectrum.

• MeSH
• Carcinoma, Renal Cell * genetics   MeSH
• Kidney pathology   MeSH
• Humans MeSH
• Biomarkers, Tumor genetics   MeSH
• Kidney Neoplasms * genetics   MeSH
• Adenoma, Oxyphilic * pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Biomarkers, Tumor MeSH

Most succinate dehydrogenase (SDH)-deficient renal cell carcinomas (RCCs) demonstrate stereotypical morphology characterized by bland eosinophilic cells with frequent intracytoplasmic inclusions. However, variant morphologic features have been increasingly recognized. We therefore sought to investigate the incidence and characteristics of SDH-deficient RCC with variant morphologies. We studied a multi-institutional cohort of 62 new SDH-deficient RCCs from 59 patients. The median age at presentation was 39 years (range 19-80), with a slight male predominance (M:F = 1.6:1). A relevant family history was reported in 9 patients (15%). Multifocal or bilateral tumors were identified radiologically in 5 patients (8%). Typical morphology was present at least focally in 59 tumors (95%). Variant morphologies were seen in 13 (21%) and included high-grade nuclear features and various combinations of papillary, solid, and tubular architecture. Necrosis was present in 13 tumors, 7 of which showed variant morphology. All 62 tumors demonstrated loss of SDHB expression by immunohistochemistry. None showed loss of SDHA expression. Germline SDH mutations were reported in all 18 patients for whom the results of testing were known. Among patients for whom follow-up data was available, metastatic disease was reported in 9 cases, 8 of whom had necrosis and/or variant morphology in their primary tumor. Three patients died of disease. In conclusion, variant morphologies and high-grade nuclear features occur in a subset of SDH-deficient RCCs and are associated with more aggressive behavior. We therefore recommend grading all SDH-deficient RCCs and emphasize the need for a low threshold for performing SDHB immunohistochemistry in any difficult to classify renal tumor, particularly if occurring at a younger age.

• MeSH
• Adult MeSH
• Hyperplasia MeSH
• Immunohistochemistry MeSH
• Carcinoma, Renal Cell * genetics   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Kidney Neoplasms * genetics   pathology   MeSH
• Necrosis MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Succinate Dehydrogenase genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Succinate Dehydrogenase MeSH

The Genitourinary Pathology Society (GUPS) reviewed recent advances in renal neoplasia, particularly post-2016 World Health Organization (WHO) classification, to provide an update on existing entities, including diagnostic criteria, molecular correlates, and updated nomenclature. Key prognostic features for clear cell renal cell carcinoma (RCC) remain WHO/ISUP grade, AJCC/pTNM stage, coagulative necrosis, and rhabdoid and sarcomatoid differentiation. Accrual of subclonal genetic alterations in clear cell RCC including SETD2, PBRM1, BAP1, loss of chromosome 14q and 9p are associated with variable prognosis, patterns of metastasis, and vulnerability to therapies. Recent National Comprehensive Cancer Network (NCCN) guidelines increasingly adopt immunotherapeutic agents in advanced RCC, including RCC with rhabdoid and sarcomatoid changes. Papillary RCC subtyping is no longer recommended, as WHO/ISUP grade and tumor architecture better predict outcome. New papillary RCC variants/patterns include biphasic, solid, Warthin-like, and papillary renal neoplasm with reverse polarity. For tumors with 'borderline' features between oncocytoma and chromophobe RCC, a term "oncocytic renal neoplasm of low malignant potential, not further classified" is proposed. Clear cell papillary RCC may warrant reclassification as a tumor of low malignant potential. Tubulocystic RCC should only be diagnosed when morphologically pure. MiTF family translocation RCCs exhibit varied morphologic patterns and fusion partners. TFEB-amplified RCC occurs in older patients and is associated with more aggressive behavior. Acquired cystic disease (ACD) RCC-like cysts are likely precursors of ACD-RCC. The diagnosis of renal medullary carcinoma requires a negative SMARCB1 (INI-1) expression and sickle cell trait/disease. Mucinous tubular and spindle cell carcinoma (MTSCC) can be distinguished from papillary RCC with overlapping morphology by losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22. MTSCC with adverse histologic features shows frequent CDKN2A/2B (9p) deletions. BRAF mutations unify the metanephric family of tumors. The term "fumarate hydratase deficient RCC" ("FH-deficient RCC") is preferred over "hereditary leiomyomatosis and RCC syndrome-associated RCC". A low threshold for FH, 2SC, and SDHB immunohistochemistry is recommended in difficult to classify RCCs, particularly those with eosinophilic morphology, occurring in younger patients. Current evidence does not support existence of a unique tumor subtype occurring after chemotherapy/radiation in early childhood.

• MeSH
• Humans MeSH
• Kidney Neoplasms * MeSH
• World Health Organization MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Practice Guideline MeSH

Comprehensive understanding of molecular principles in cancer and the diversification of oncological therapy promise individual therapeutic concepts, which have not yet found their way into urogenital cancer therapy. In March 2019 the International Society of Urogenital Pathology (ISUP) therefore held a consensus conference on recommendations for molecular diagnostics of genitourinary tumors, which were published in five separate manuscripts and are summarized in this article.In preparation for the conference, a comprehensive survey of current practices for molecular testing of urogenital tumors was carried out by members of the ISUP. At the conference, the results and the corresponding background information were presented by five working groups and recommendations for action for diagnostics were developed. An agreement between 66% of the conference participants was defined as consensus.

Das zunehmende Verständnis molekularer Grundlagen von Tumoren sowie der Fortschritt in der Diversifizierung der onkologischen Therapien versprechen individualisierte Therapieoptionen, welche bislang jedoch nur ansatzweise in die Therapieplanung von urologischen Tumoren eingegangen sind. Daher hat die Internationale Gesellschaft für Urologische Pathologie (ISUP) im März 2019 eine Konsenskonferenz zur Erarbeitung evidenzbasierter Handlungsempfehlungen zur molekularpathologischen Diagnostik beim Urothelkarzinom, Nierenzellkarzinom, Prostatakarzinom, Peniskarzinom und testikulären Keimzelltumoren durchgeführt. Die auf dieser Konsenskonferenz erarbeiteten Empfehlungen sind kürzlich in 5 separaten Manuskripten veröffentlich worden und werden in der vorliegenden Arbeit zusammengefasst.Im Rahmen der Konferenzvorbereitung wurde eine umfassende Umfrage zur derzeitigen Praxis molekularer Testungen bei urogenitalen Tumoren unter den Mitgliedern der ISUP durchgeführt. Auf der Konferenz wurden die Ergebnisse und die entsprechenden Hintergrundinformationen durch 5 Arbeitsgruppen präsentiert und Handlungsempfehlungen für die Diagnostik erarbeitet. Eine Übereinstimmung von 66 % der Konferenzteilnehmer wurde als Konsens definiert.

• Keywords
• Bladder cancer, Kidney cancer, Molecular biomarker, Prostate cancer, Targeted therapy,
• MeSH
• Humans MeSH
• Pathology, Molecular MeSH
• Prostatic Neoplasms * MeSH
• Urogenital Neoplasms * genetics   therapy   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Review MeSH