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Introduction: Immunofluorescence (IF) staining for IgG subclasses plays an important role in the classification of kidney disease. However, widely used IgG subclass-specific antibodies are now commercially unavailable. Thus, we compared alternative antibodies for performing IgG subclass staining., Methods: A total of 21 cases were stained by 3 different methods: direct IF using fluorescein isothiocyanate (FITC)-conjugated polyclonal antibodies against IgG1-4 (commercially unavailable method), direct IF using FITC-conjugated monoclonal antibodies (clones HP-6091, 6014, 6050, and 6025), indirect IF using monoclonal antibodies (clones HP-6069, 6002, 6050, and 6025), and FITC-conjugated polyclonal secondary antibody. For cases with discrepancy in IgG1 staining, additional direct IF using FITC-conjugated monoclonal antibody (clone 4E3) was performed., Results: Of 21 cases, 11 (52%) had no staining for IgG1 by direct IF using the clone HP-6091 despite ≥1+ staining by the direct IF using polyclonal antibodies. Similarly, direct IF for IgG1 using the clone 4E3 had negative result in all 10 cases with available tissue. However, indirect IF for IgG1 using the clone HP-6069 had similar staining intensity (within 1 order of magnitude) as direct IF using the polyclonal antibodies (10 of 10). Results of IF for IgG2, IgG3, and IgG4 were similar in most cases., Conclusion: The choice of antibodies influences the result of IgG subclass staining, especially for anti-IgG1 antibodies, in which 2 monoclonal antibodies (HP6091 and 4E3) appear less sensitive. Although this may be due to unaccounted variables and requires confirmation, our results may partially explain the difference in IgG1 staining in the literature and underscore the need for careful validation., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Because of the high rates of false-negative or nondiagnostic ureteral Piranha microbiopsies associated with low cellularity, we assessed the effect of processing these using cytology., Materials and Methods: We included 2 groups of 44 consecutive microbiopsies processed from formalin as a standard surgical biopsy and 22 processed by cytology. All samples were from the ureter or renal pelvis or calyx. The cytology samples were collected in alcohol-based media and were prepared with a Cellient cell block only (n = 9) or with a Cellient cell block for the visible particles, together with ThinPrep, to capture the remaining desquamated cells (n = 13)., Results: Malignancy was diagnosed in 5 of 44 conventionally processed microbiopsies (11%) compared with 14 of 22 cytologically processed microbiopsies (64%; P < 0.001), including 1 case with invasion. Nineteen site-matched biopsies from 2 patients had undergone both cytologic and surgical processing, with 8 of 8 cytologically processed biopsies diagnosed as malignant. None of the 11 surgically processed biopsies from the same patients matched for site were diagnosed as malignant. Of the 11, 2 (18%) were suspicious for high-grade urothelial carcinoma and 6 (55%) were considered atypical. Increased sensitivity from cytologic processing appears related to increased cell recovery; large numbers of well-preserved urothelial cells were identified in the ThinPrep (range, 1000-25,000 cells/slide), and a nonsignificant trend was found toward increased urothelium (defined as >200 cells/profile) in the Cellient cell blocks (14 of 22 [64%]) compared with the histologic biopsies (17 of 44 [39%]; P = 0.070)., Conclusions: Cytologic processing of ureteral microbiopsies showed superior sensitivity for detecting high-grade urothelial carcinoma, apparently owing to the increased cellular recovery., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: Cytopathologist's review of Papanicolaou tests (PTs) screened by cytotechnologists as negative for intraepithelial lesion or malignancy (NILM) that are positive for high-risk human papillomavirus (hrHPV+) may be a useful quality control measure., Materials and Methods: From January 1, 2012 to December 31, 2012 all NILM/hrHPV+ PTs underwent cytopathologist's review before report issuance as per routine quality control procedures. HrHPV status was known at the time of screening and at final review. The rate of upgraded diagnoses resulting from the cytopathologist's review were examined. Two-year follow-up was obtained., Results: Cytopathologist's review upgraded 250 of 1282 PTs (19.5%) by 1 step to atypical squamous cells of undetermined significance and 13 (1%) were upgraded by 2 steps or more to low-grade squamous intraepithelial lesion or higher. During the same period, significantly fewer NILM PTs (of unknown hrHPV status) were upgraded by 2 steps or more as a result of random 10% rescreening by cytotechnologists (0.2%, P < 0.001). Follow-up was available in 740 of 1282 patients (57.7%). The upgraded group was significantly more likely to be referred for colposcopy (68.3% versus 30.5%, P < 0.001) and cervical intraepithelial neoplasia (CIN) 2 or higher (CIN2+) was diagnosed in more upgraded patients (8.9% versus 3.0%, P < 0.01) than in those not upgraded. There was no significant difference in the percentage of colposcopy patients diagnosed with CIN2+ in the 2 groups, respectively (13.1% versus 9.8%, P = 0.47)., Conclusions: cytopathologist's review of NILM/hrHPV+ PTs identified more 2-step discrepancies than routine 10% rescreening. Significantly more patients in the upgraded group were found to harbor CIN2+; however, this could be related to the higher rate of referral to colposcopy in this group., (Copyright © 2015 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction: The goal of Barrett esophagus surveillance is to identify high-grade dysplasia (HGD) for eradication. Surveillance programs currently rely on limited histologic sampling; however, the role of cytology in this setting is not well studied., Materials and Methods: From December 1, 2011 to March 30, 2014, 45 patients underwent 4 circumferential brushings of the distal tubular esophagus followed by standard 4-quadrant biopsies. One ThinPrep slide and 1 Cellient cellblock (Hologic, Boxborough, Mass) were prepared. Six cytopathologists evaluated each for adequacy, intestinal metaplasia (IM) and dysplasia. Findings were classified using the traditional 5-tier system used for biopsies. A prospectively modified 3-tier cytologic classification was also tested: negative for HGD, indeterminate for HGD, and HGD. Sensitivity, specificity, and kappa values (interobserver agreement) for cytology were calculated., Results: Ten of 45 patients had nondiagnostic cytologies; none of whom had dysplasia on biopsy. Cytology had good sensitivity (82%) and specificity (88%) for identifying IM compared with biopsy with moderate interobserver agreement (pairwise average of Fleiss and Krippendorf kappa value = 0.589, 79% agreement). One case had IM on cytology not detected on histology. Six of 45 patients had dysplasia on biopsy including 1 intramucosal adenocarcinoma, 1 indeterminate for dysplasia, 2 high-grade dysplasias, and 2 low-grade dysplasias. A non-negative adequate cytology sample had a sensitivity of 100% and a specificity of 88% and 94% for the 5-tier and the 3-tier classification, respectively., Conclusions: Cytology appears to have good sensitivity and specificity for diagnosis of HGD, and cytology may be poised to synergize with advances in other techniques for management of patients with Barrett esophagus. Improvements in brushing devices may help to decrease the nondiagnostic rate., (Copyright © 2015 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)