The International Society of Urological Pathology 2012 Consensus Conference made recommendations regarding classification, prognostic factors, staging, and immunohistochemical and molecular assessment of adult renal tumors. Issues relating to prognostic factors were coordinated by a workgroup who identified tumor morphotype, sarcomatoid/rhabdoid differentiation, tumor necrosis, grading, and microvascular invasion as potential prognostic parameters. There was consensus that the main morphotypes of renal cell carcinoma (RCC) were of prognostic significance, that subtyping of papillary RCC (types 1 and 2) provided additional prognostic information, and that clear cell tubulopapillary RCC was associated with a more favorable outcome. For tumors showing sarcomatoid or rhabdoid differentiation, there was consensus that a minimum proportion of tumor was not required for diagnostic purposes. It was also agreed upon that the underlying subtype of carcinoma should be reported. For sarcomatoid carcinoma, it was further agreed upon that if the underlying carcinoma subtype was absent the tumor should be classified as a grade 4 unclassified carcinoma with a sarcomatoid component. Tumor necrosis was considered to have prognostic significance, with assessment based on macroscopic and microscopic examination of the tumor. It was recommended that for clear cell RCC the amount of necrosis should be quantified. There was consensus that nucleolar prominence defined grades 1 to 3 of clear cell and papillary RCCs, whereas extreme nuclear pleomorphism or sarcomatoid and/or rhabdoid differentiation defined grade 4 tumors. It was agreed upon that chromophobe RCC should not be graded. There was consensus that microvascular invasion should not be included as a staging criterion for RCC.

Context.— Controversies and uncertainty persist in prostate cancer grading. Objective.— To update grading recommendations. Data Sources.— Critical review of the literature along with pathology and clinician surveys. Conclusions.— Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace “tertiary grade pattern” in radical prostatectomy (RP) with “minor tertiary pattern 5 (TP5),” and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)-targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDC-P) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (>50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) “atypical intraductal proliferation (AIP)” is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice.

The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) pandemic has had devastating effects on global health and worldwide economy. Despite an initial reluctance to perform autopsies due to concerns for aerosolization of viral particles, a large number of autopsy studies published since May 2020 have shed light on the pathophysiology of Coronavirus disease 2019 . This review summarizes the histopathologic findings and clinicopathologic correlations from autopsies and biopsies performed in patients with COVID-19. PubMed and Medline (EBSCO and Ovid) were queried from June 4, 2020 to September 30, 2020 and histopathologic data from autopsy and biopsy studies were collected based on 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 58 studies reporting 662 patients were included. Demographic data, comorbidities at presentation, histopathologic findings, and virus detection strategies by organ system were collected. Diffuse alveolar damage, thromboembolism, and nonspecific shock injury in multiple organs were the main findings in this review. The pathologic findings emerging from autopsy and biopsy studies reviewed herein suggest that in addition to a direct viral effect in some organs, a unifying pathogenic mechanism for COVID-19 is ARDS with its known and characteristic inflammatory response, cytokine release, fever, inflammation, and generalized endothelial disturbance. This study supports the notion that autopsy studies are of utmost importance to our understanding of disease features and treatment effect to increase our knowledge of COVID-19 pathophysiology and contribute to more effective treatment strategies.

Autoantibodies are central to the pathogenesis of several autoimmune diseases including systemic lupus erythematosus. Plasma cells secrete these autoantibodies, but the anatomical sites of these cells are not well defined. Here, we found that although dsDNA-specific plasma cells in NZB/W mice were present in spleen and bone marrow, a large number were in the kidneys and their number correlated with the serum dsDNA-IgG titer. We observed renal plasma cells only in mice with nephritis, where they located mainly to the tubulointerstitium of the cortex and outer medulla. These cells had the phenotypic characteristics of fully differentiated plasma cells and, similar to long-lived bone marrow plasma cells, they were not in cell cycle. In patients with lupus nephritis, plasma cells were often present in the medulla in those with the most severe disease, especially combined proliferative and membranous lupus nephritis. The identification of the kidney as a major site of autoreactive plasma cells has implications for our understanding of the pathogenesis of lupus nephritis and for strategies to deplete autoreactive plasma cells, a long-standing therapeutic aim.

The International Society of Urological Pathology convened a consensus conference on renal cancer, preceded by an online survey, to address issues relating to the diagnosis and reporting of renal neoplasia. In this report, the role of biomarkers in the diagnosis and assessment of prognosis of renal tumors is addressed. In particular we focused upon the use of immunohistochemical markers and the approach to specific differential diagnostic scenarios. We enquired whether cytogenetic and molecular tools were applied in practice and asked for views on the perceived prognostic role of biomarkers. Both the survey and conference voting results demonstrated a high degree of consensus in participants’ responses regarding prognostic/predictive markers and molecular techniques, whereas it was apparent that biomarkers for these purposes remained outside the diagnostic realm pending clinical validation. Although no individual antibody or panel of antibodies reached consensus for classifying renal tumors, or for confirming renal metastatic disease, it was noted from the online survey that 87% of respondents used immunohistochemistry to subtype renal tumors sometimes or occasionally, and a majority (87%) used immunohistochemical markers (Pax 2 or Pax 8, renal cell carcinoma [RCC] marker, panel of pan-CK, CK7, vimentin, and CD10) in confirming the diagnosis of metastatic RCC. There was consensus that immunohistochemistry should be used for histologic subtyping and applied before reaching a diagnosis of unclassified RCC. At the conference, there was consensus that TFE3 and TFEB analysis ought to be requested when RCC was diagnosed in a young patient or when histologic appearances were suggestive of the translocation subtype; whereas Pax 2 and/or Pax 8 were considered to be the most useful markers in the diagnosis of a renal primary.