Renal medullary carcinomas (RMCs) and collecting duct carcinomas (CDCs) are rare subsets of lethal high-stage, high-grade distal nephron-related adenocarcinomas with a predilection for the renal medullary region. Recent findings have established an emerging group of fumarate hydratase (FH)-deficient tumors related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC-RCCs) syndrome within this morphologic spectrum. Recently developed, reliable ancillary testing has enabled consistent separation between these tumor types. Here, we present the clinicopathologic features and differences in the morphologic patterns between RMC, CDC, and FH-deficient RCC in consequence of these recent developments. This study included a total of 100 cases classified using contemporary criteria and ancillary tests. Thirty-three RMCs (SMARCB1/INI1-deficient, hemoglobinopathy), 38 CDCs (SMARCB1/INI1-retained), and 29 RCCs defined by the FH-deficient phenotype (FH/2SC or FH/2SC with FH mutation, regardless of HLRCC syndromic stigmata/history) were selected. The spectrum of morphologic patterns was critically evaluated, and the differences between the morphologic patterns present in the 3 groups were analyzed statistically. Twenty-five percent of cases initially diagnosed as CDC were reclassified as FH-deficient RCC on the basis of our contemporary diagnostic approach. Among the different overlapping morphologic patterns, sieve-like/cribriform and reticular/yolk sac tumor-like patterns favored RMCs, whereas intracystic papillary and tubulocystic patterns favored FH-deficient RCC. The tubulopapillary pattern favored both CDCs and FH-deficient RCCs, and the multinodular infiltrating papillary pattern favored CDCs. Infiltrating glandular and solid sheets/cords/nested patterns were not statistically different among the 3 groups. Viral inclusion-like macronucleoli, considered as a hallmark of HLRCC-RCCs, were observed significantly more frequently in FH-deficient RCCs. Despite the overlapping morphology found among these clinically aggressive infiltrating high-grade adenocarcinomas of the kidney, reproducible differences in morphology emerged between these categories after rigorous characterization. Finally, we recommend that definitive diagnosis of CDC should only be made if RMC and FH-deficient RCC are excluded.

• MeSH
• biopsie MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• dospělí MeSH
• dřeň ledvin enzymologie   patologie   MeSH
• fenotyp MeSH
• fumarasa nedostatek   genetika   MeSH
• genetická predispozice k nemoci MeSH
• imunohistochemie MeSH
• karcinom z renálních buněk klasifikace   enzymologie   genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• nádorové biomarkery nedostatek   genetika   MeSH
• nádory ledvin klasifikace   enzymologie   genetika   patologie   MeSH
• prediktivní hodnota testů MeSH
• retrospektivní studie MeSH
• sběrací ledvinové kanálky enzymologie   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň nádoru MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Austrálie MeSH
• Brazílie MeSH
• Evropa MeSH
• Kanada MeSH
• Spojené státy americké MeSH
• Názvy látek
• fumarasa MeSH
• nádorové biomarkery MeSH

Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare and aggressive tumor affecting mostly younger patients. This is the first study to assess the expression of programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) in FH-RCC. Formalin-fixed paraffin-embedded samples from 13 FH-RCCs collected in an international multi-institutional study, were evaluated by immunohistochemistry (IHC) for PD-1/PD-L1 reactivity in tumor cells and tumor infiltrating lymphocytes (TILs). PD-1/PD-L1 expression was further evaluated by qPCR. By IHC, PD-1 was negative in tumor cells in all 13 cases. PD-L1 was positive in tumor cells in 2/13 cases, weak positive in 7/13, and negative in 4/13 cases, respectively. In TILs, PD-1 was positive in 1/13, weak positive in 3/13, and negative in 9/13 cases. In TILs, PD-L1 was weak positive by IHC in 5/13, and negative in 8/13 cases, respectively. qPCR confirmed the result for 2 of 3 IHC weak positive PD-1 samples. Of 7 IHC weak positive samples (in tumor cells), PD-L1 mRNA was detected in all 7 tumors. The majority of FH-RCCs did not express PD-1/PD-L1 by IHC, which was confirmed by molecular analysis. PD-1/PD-L1 expression in FH-RCC is restricted to a proportion of cases which may benefit from targeted therapies.

• Klíčová slova
• Fumarate hydratase-deficient renal cell carcinoma, Kidney, PD-1 ligand (PD-L1) receptor, Programmed death-1 (PD-1) receptor,
• MeSH
• antigeny CD274 metabolismus   MeSH
• antigeny CD279 metabolismus   MeSH
• dospělí MeSH
• fumarasa nedostatek   metabolismus   MeSH
• imunohistochemie metody   MeSH
• karcinom z renálních buněk metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory ledvin metabolismus   patologie   MeSH
• přežití bez známek nemoci MeSH
• tumor infiltrující lymfocyty metabolismus   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD274 MeSH
• antigeny CD279 MeSH
• CD274 protein, human MeSH Prohlížeč
• fumarasa MeSH
• PDCD1 protein, human MeSH Prohlížeč