Subclassification of renal cell neoplasms: an update for the practising pathologist

The classification of renal cell neoplasms has been extensively studied in the last decade, and a standardized nomenclature adopted. Although this system is based on a combination of genetic, histological and immunohistological features, in most cases accurate classification can be based on histological features alone. This review summarizes the key features of the tumours included in this system, and then focuses on diagnostic difficulties that can arise when using this system, as well as reviewing several recently characterized tumours that are not yet included.     

New and emerging renal entities: a perspective post‐WHO 2016 classification

Renal tumours include a heterogeneous and diverse spectrum of neoplasms. Recent advances in this field have significantly improved our understanding of the morphological, immunohistochemical, molecular, epidemiological and clinical characteristics of renal tumours, which led to the new Vancouver classification of renal neoplasia and the new World Health Organization (WHO) classification of renal cell tumours. This review aims to summarise the new information and evidence on several new and emerging/provisional renal entities, which were mostly generated after the recent classification of renal neoplasia. We include in this review the following new and emerging/provisional renal entities: succinate dehydrogenase‐deficient renal cell carcinoma, thyroid‐like follicular carcinoma of the kidney, anaplastic lymphoma kinase rearrangement‐associated renal cell carcinoma, renal cell carcinomas with prominent smooth muscle stroma, fumarate hydratase‐deficient renal cell carcinoma, biphasic squamoid papillary renal cell carcinoma, eosinophilic solid and cystic renal cell carcinoma, atrophic kidney‐like renal cell carcinoma, clear cell renal cell carcinoma with giant cells and emperipolesis, Warthin‐like papillary renal cell carcinoma, and low‐grade oncocytic renal tumour (CD117‐negative; cytokeratin 7‐positive). Some of these entities, such as succinate dehydrogenase‐deficient renal cell carcinoma, have already been recognised as new entities in the WHO classification, and some have been recognised as provisional/emerging entities. However, we include in this review several additional entities that, on the basis of the published evidence, also warrant this designation. We hope that this review will ease the navigation through this complex and evolving field, and will inform and stimulate new studies and discussions.     

Acquired cystic disease‐associated renal cell carcinoma is the most common subtype in long‐term dialyzed patients: Central pathology results according to the 2016 WHO classification in a multi‐institutional study

New pathological subtypes of renal cell carcinoma (RCC) were designated in the 2016 World Health Organization (WHO) classification corresponding to the features commonly seen in patients with end‐stage renal disease (ESRD). To determine the clinicopathological findings of new subtypes, we reanalyzed all sections from 315 kidneys in 291 ESRD patients bearing RCC tumors surgically resected in three Japanese institutes by the central pathologist. Clear cell RCC was diagnosed in 144 kidneys (45.7%), acquired cystic disease (ACD)‐associated RCC in 100 (31.7%), papillary RCC in 41 (13.0%), and other minor subtypes in 30 (9.52%). Multivariate analysis showed that longer duration of dialysis, young age, and male sex were independent prognostic clinical factors for the occurrence of ACD‐associated RCC. ACD‐associated RCC included more WHO/International Society of Urologic Pathology (ISUP) grade 3/4 cases compared to other RCCs. In contrast, other unfavorable findings were less frequent in ACD‐associated RCC, including the presence of a sarcomatoid component, lymphovascular invasion, and necrosis. In conclusion, ACD‐associated RCC is a common histology in Japanese patients with ESRD. In addition, ACD‐associated RCC showed more cases with a higher WHO/ISUP grade, but fewer cases with other unfavorable pathological features, suggesting a favorable prognosis of ACD‐associated RCC.     

The 2022 World Health Organization classification of germ cell tumors and updates of American Joint Committee for Cancer tumor staging classification

Testicular tumors are most common in young men between 15 and 45 years of age. Germ cell tumors make up the biggest proportion of malignant tumors of the testis. Due to the diverse morphologic spectrum and overlapping morphologies, it is a very challenging area in the anatomic pathology field, which needs significant expertise and experience to render a precise diagnosis. The World Health Organization (WHO) has recently presented a new tumor classification with significant modifications in nomenclature as well as some refinement of criteria. The changes encompass germ cell tumors, sex cord stromal tumors, and tumors arising from testicular appendages. The "primitive neuroectodermal tumor (PNET)" terminology is replaced with "embryonic-type neuroectodermal tumor (ENET). The carcinoid terminology is replaced with neuroendocrine tumors (NET). In sex cord stromal tumors, two new entities were included, "Signet ring stromal tumor" and "Myoid gonadal stromal tumor" in the new classification. Sertoliform cystadenoma is now considered a sertoli cell tumor (NOS). "Well-differentiated papillary mesothelioma" is now termed as "well-differentiated papillary mesothelial tumor." Tumor Node Metastasis (TNM) Classification published by the American Joint Committee for Cancer (AJCC) is recommended for testicular tumors listed as germ cell tumors. In its 8th edition, the AJCC has provided regular updates in printed form as AJCC tumor classification. Currently, the AJCC has changed its process of publishing the TNM classification and is moving away from editions, and the new updates will be released as versions. Several organ systems have already updated the content, while the remaining will be updated per their scheduled timeline.     

The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 cases

AIMS: To demonstrate the diagnostic utility of MOC31, BerEP4, renal cell carcinoma marker (RCC Ma) and CD10 in the classification of RCC and renal oncocytoma, based upon a comprehensive immunohistochemical analysis. METHODS AND RESULTS: Immunohistochemistry was performed on 328 samples consisting of 256 clear cell/conventional, 27 papillary, 28 chromophobe, five collecting duct, five unclassified RCCs and seven renal oncocytomas using antibodies MOC31, BerEP4 and antibodies against cytokeratins (KL-1, CAM5.2, 34betaE12, cytokeratin 7), RCC Ma, epithelial membrane antigen, E-cadherin, CD10, CD15 and vimentin. Multivariate analysis showed that MOC31, BerEP4, RCC Ma and CD10 have discriminatory value. MOC31 and BerEP4 chiefly labelled distal tubules of normal kidney while RCC Ma and CD10 labelled the proximal tubules. Twenty-three chromophobe RCCs (82%) were reactive for MOC31, while only four clear cell RCCs and three papillary RCCs were positive for this marker. Clear cell RCCs were characterized by a high positive rate for CD10 (82%) and a low positive rate for BerEP4 (27%). Papillary RCCs frequently coexpressed RCC Ma and BerEP4 (51%). All renal oncocytomas were negative for MOC31 and CD10. CONCLUSIONS: MOC31 has diagnostic merit in discerning chromophobe RCC. The CD10+/BerEP4- profile and RCC Ma+/BerEP4+ profile achieve moderate sensitivity and good specificity for clear cell RCC and papillary RCC, respectively. The non-reactivity for both MOC31 and CD10 is helpful in distinguishing renal oncocytoma from RCC. When properly selected, antibodies have immunohistochemical diagnostic utility for the classification of renal cortical epithelial tumours.     

An overview of recent WHO classification and AJCC pTNM staging changes for testicular neoplasms and their impact on the handling and reporting of orchidectomy specimens

The World Health Organization 2016 Classification of Testicular Tumours and the 8^th Edition of the American Joint Cancer Commission Staging Manual released in 2017 introduced a number of significant changes which impact the way pathologists will be expected to examine and report tumour-containing orchidectomy specimens. The purpose of this review is to highlight the changes to classification nomenclature and pathologic staging criteria for commonly encountered testicular neoplasms of either germ cell or sex-cord stromal origin and to provide an overview of resources available to assist pathologists in the task of providing complete and clinically relevant histopathology reports for orchidectomy specimens.