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Context.—: Localized amyloidosis of the bladder is rare and often mimics bladder malignancy. It is typically associated with the extracellular deposition of monoclonal light chains, either κ or λ. The cause is unknown, but it is thought to be due to chronic inflammation/cystitis., Objective.—: To highlight the importance of localized urinary bladder amyloidosis as a rare mimicker of urothelial malignancy and elucidate its clinical, histopathologic, and cytopathologic manifestations., Design.—: Cases of urinary bladder amyloidosis diagnosed during 2000-2023 were retrieved retrospectively from pathology archives. Electronic medical records, including cystoscopy findings and pathology slides including Congo red stain, were reviewed., Results.—: Here we present 6 patients with localized urinary bladder amyloidosis. Four of the 6 patients were women, with ages ranging from 46 to 69 years, and a mean age of 58 years. Five of 6 patients presented with hematuria, while in 1 patient, bladder amyloidosis was discovered incidentally. Cystoscopy findings invariably were concerning for malignancy, with raised erythema in 5 patients and fungating mass protruding into the bladder lumen in 1 patient. Bladder biopsies and urine cytology were negative for malignancy in all cases. Congo red-positive amyloid deposits involved lamina propria with sparing of the detrusor muscle. In 5 cases, the deposits were typed as derived from the λ light chain, whereas no information was available for 1 patient. Subsequent clinical workup ruled out systemic amyloidosis., Conclusions.—: These cases of urinary bladder amyloidosis highlight the importance of considering rare amyloidosis in the differential diagnosis of hematuria and cystoscopy with a lesion mimicking malignancy., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2025 College of American Pathologists.)

Oncocytic renal neoplasms are a major source of diagnostic challenge in genitourinary pathology; however, they are typically nonaggressive in general, raising the question of whether distinguishing different subtypes, including emerging entities, is necessary. Emerging entities recently described include eosinophilic solid and cystic renal cell carcinoma (ESC RCC), low-grade oncocytic tumor (LOT), eosinophilic vacuolated tumor (EVT), and papillary renal neoplasm with reverse polarity (PRNRP). A survey was shared among 65 urologic pathologists using SurveyMonkey.com (Survey Monkey, Santa Clara, CA, USA). De-identified and anonymized respondent data were analyzed. Sixty-three participants completed the survey and contributed to the study. Participants were from Asia (n = 21; 35%), North America (n = 31; 52%), Europe (n = 6; 10%), and Australia (n = 2; 3%). Half encounter oncocytic renal neoplasms that are difficult to classify monthly or more frequently. Most (70%) indicated that there is enough evidence to consider ESC RCC as a distinct entity now, whereas there was less certainty for LOT (27%), EVT (29%), and PRNRP (37%). However, when combining the responses for sufficient evidence currently and likely in the future, LOT and EVT yielded > 70% and > 60% for PRNRP. Most (60%) would not render an outright diagnosis of oncocytoma on needle core biopsy. There was a dichotomy in the routine use of immunohistochemistry (IHC) in the evaluation of oncocytoma (yes = 52%; no = 48%). The most utilized IHC markers included keratin 7 and 20, KIT, AMACR, PAX8, CA9, melan A, succinate dehydrogenase (SDH)B, and fumarate hydratase (FH). Genetic techniques used included TSC1/TSC2/MTOR (67%) or TFE3 (74%) genes and pathways; however, the majority reported using these very rarely. Only 40% have encountered low-grade oncocytic renal neoplasms that are deficient for FH. Increasing experience with the spectrum of oncocytic renal neoplasms will likely yield further insights into the most appropriate work-up, classification, and clinical management for these entities., Competing Interests: Declarations Conflict of interest The authors declare no competing interests., (© 2024. The Author(s).)

Aims: Urothelial carcinoma (UC) demonstrates significant molecular and histologic heterogeneity. The WHO 2022 classification has hinted at adding molecular signatures to the morphologic diagnosis. As morphology and associated molecular repertoire may potentially translate to choices of and response to therapy and relapse rate, broader acceptability of recognizing these key features among uropathologists is needed. This prompted an international survey to ascertain the practice patterns in classical/subtype UC among uropathologists across the globe., Methods and Results: A survey instrument was shared among 98 uropathologists using SurveyMonkey software. Anonymized respondent data were analysed. The response rate was 85%. A majority were in concordance with the profiles of luminal (93%) and basal (82%) types. Opinion on the FGFR3 testing platform was variable. While 95% concurred that TERT promoter mutation is the key driver in UC, 72% had the opinion that APOBEC mutagenesis is the main signature in muscle invasive bladder cancer (MIBC). Uropathologists have divergent opinions on MIBC and ERCC2 mutations. Among the participants, 94% would quantify aggressive micropapillary and sarcomatoid histology, while 88% would reevaluate another transurethral resection of the bladder tumour specimen in nonmuscle invasive tumour with micropapillary, small cell, or sarcomatoid histology. A leading number agreed to specific molecular signatures of micropapillary (93%), plasmacytoid (97%), and small cell (86%) subtypes. Ninety-six percent of participants agreed that a small-cell component portends a more aggressive course and should be treated with neoadjuvant chemotherapy and 63% would perform HER2/neu testing only on oncologist's request in advanced tumours. Ninety percent agreed that microsatellite instability testing, although not a standard protocol, should be considered in young patients with upper tract UC. Eighty-six percent agreed that UC with high tumour mutational burden would be a better candidate for immunotherapy., Conclusion: In the era of precision medicine, enhanced understanding of molecular heterogeneity of UC will contribute to better therapeutic options, novel biomarker discovery, innovative management protocols, and outcomes. Our survey provides a broad perspective of pathologists' perceptions and experience regarding incorporation of histomolecular approaches to "personalize" therapy. Due to variable clinical adoption, there is a need for additional data using uniform study criteria. This will drive generation of best practice guidelines in this area for widespread and consistent clinical utility., (© 2024 John Wiley & Sons Ltd.)

Purpose: Few studies have quantified differences in histology and implications for survival between male children and adults with germ cell tumors (GCT). We evaluated these differences and associations with cancer-specific survival (CSS) using Surveillance, Epidemiology, and End Results (SEER) cancer registries., Methods: SEER (1988-2016) was used to identify male patients 0 to 40 years of age diagnosed with seminoma and nonseminomatous GCT (NSGCT). Demographic and tumor characteristics were tabulated with histology distributions compared by age group (0-4, 12-18, 19-40 years old). CSS was evaluated in multivariable Cox proportional hazards regression models., Results: Among 27,204 patients identified, 1,538 (5.7%) were pediatric (0-18 years). Seminoma (54.3%) predominated in adult patients (ages 19-40). Among 0 to 4 years-old, yolk sac tumor (71.2%) and teratoma (21.5%) were most common. Mixed GCT (52.7%) was most prevalent among 12 to 18 years-old with seminoma, embryonal, and teratoma occurring in 12 to 15% each. Relative to pediatric patients, adult patients had similar CSS for seminoma but worse CSS for NSGCT on Kaplan-Meier curves with 9 years mean follow-up. Choriocarcinoma and yolk sac tumors carried the worst prognosis relative to seminoma for both children (HR 5.7 and HR 11.1, respectively, both P < 0.01) and adults (HR 4.6 and HR 4.6, respectively, both P < 0.01) adjusted for stage., Conclusion: Histology of GCTs vary by age with yolk sac tumors and teratoma predominating for male patients 0 to 4 years, mixed GCT for 12 to 18 years, and seminoma for 19 to 40 years. Pediatric patients with NSGCT had higher CSS than their adult counterparts. Mixed GCT represented an increasing proportion of GCT over the study period. Age, stage, and histology impact CSS in both pediatric and adult populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Nephrogenic adenoma (NA) is a benign, reactive lesion seen predominantly in the urinary bladder and often associated with antecedent inflammation, instrumentation, or an operative history. Its histopathologic diversity can create diagnostic dilemmas and pathologists use morphologic evaluation along with available immunohistochemical (IHC) markers to navigate these challenges. IHC assays currently do not designate or specify NA's potential putative cell of origin. Leveraging single-cell RNA-sequencing technology, we nominated a principal (P) cell-collecting duct marker, L1 cell adhesion molecule (L1CAM), as a potential biomarker for NA. IHC characterization revealed L1CAM to be positive in all 35 (100%) patient samples of NA; negative expression was seen in the benign urothelium, benign prostatic glands, urothelial carcinoma (UCA) in situ, prostatic adenocarcinoma, majority of high-grade UCA, and metastatic UCA. In the study, we also used single-cell RNA sequencing to nominate a novel compendium of biomarkers specific for the proximal tubule, loop of Henle, and distal tubule (DT) (including P and intercalated cells), which can be used to perform nephronal mapping using RNA in situ hybridization and IHC technology. Employing this technique on NA we found enrichment of both the P-cell marker L1CAM and, the proximal tubule type-A and -B cell markers, PDZKI1P1 and PIGR, respectively. The cell-type markers for the intercalated cell of DTs (LINC01187 and FOXI1), and the loop of Henle (UMOD and IRX5), were found to be uniformly absent in NA. Overall, our findings show that based on cell type-specific implications of L1CAM expression, the shared expression pattern of L1CAM between DT P cells and NA. L1CAM expression will be of potential value in assisting surgical pathologists toward a diagnosis of NA in challenging patient samples., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Hepatic glomerulosclerosis, a renal complication of liver cirrhosis, presents challenges in diagnosis and management. This case report discusses the rarity of kidney biopsy findings resembling lecithin-cholesterol acyltransferase (LCAT) deficiency post liver transplantation. We present the case of a patient with end-stage liver disease (ESLD) from alcohol-related cirrhosis, who underwent orthotopic liver transplantation (OLT) with persistent proteinuria after transplantation. Kidney biopsy revealed features of hepatic glomerulopathy resembling both IgA nephropathy (IgAN) and LCAT deficiency. The histopathological similarities between hepatic glomerulosclerosis and LCAT deficiency suggest a potential link between liver disease and lipid deposition in the kidneys. The clinical course and outcomes of such renal alterations post liver transplantation remain uncertain, highlighting the need for further research in glomerular pathology in the context of liver transplantation. This case underscores the importance of kidney biopsy in ESLD patients and the necessity for more attention to glomerular pathology post liver transplantation, especially in the current era of increasing liver transplantation rates., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Zghayer et al.)

In this study, we investigated the association between intraductal carcinoma of the prostate (IDCP) along with several histopathological features on prostate biopsy and downgrading of grade group 4 (GG4) prostate cancer (PCa) in patients with the highest grade tumor of GG4 PCa in at least one core. A total of 29 cases had the highest grade tumor of GG4 PCa and radical prostatectomy performed between 2016 and 2021. IDCP was detected in 11 out of 29 cases on biopsy. The cases without IDCP were more likely to be downgraded on prostatectomy than with IDCP, with statistical significance (88.9% vs 36.4%, p = 0.003). The proportions of the highest-grade tumors by length and cores involved, average numbers of PCa-positive cores, and mean patient's age did not differ between cases that were downgraded and not downgraded at prostatectomy. Our results suggest that the absence of IDCP on biopsy could be a predictor of downgrading at prostatectomy for patients with the highest grade tumor of GG4 PCa., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Birt-Hogg-Dubé (BHD) syndrome is associated with an increased risk of multifocal renal tumors, including hybrid oncocytic tumor (HOT) and chromophobe renal cell carcinoma (chRCC). HOT exhibits heterogenous histologic features overlapping with chRCC and benign renal oncocytoma, posing challenges in diagnosis of HOT and renal tumor entities resembling HOT. In this study, we performed integrative analysis of bulk and single-cell RNA sequencing data from renal tumors and normal kidney tissues, and nominated candidate biomarkers of HOT, L1CAM, and LINC01187 , which are also lineage-specific markers labeling the principal cell and intercalated cell lineages of the distal nephron, respectively. Our findings indicate the principal cell lineage marker L1CAM and intercalated cell lineage marker LINC01187 to be expressed mutually exclusively in a unique checkered pattern in BHD-associated HOTs, and these 2 lineage markers collectively capture the 2 distinct tumor epithelial populations seen to co-exist morphologically in HOTs. We further confirmed that the unique checkered expression pattern of L1CAM and LINC01187 distinguished HOT from chRCC, renal oncocytoma, and other major and rare renal cell carcinoma subtypes. We also characterized the histopathologic features and immunophenotypic features of oncocytosis in the background kidney of patients with BHD, as well as the intertumor and intratumor heterogeneity seen within HOT. We suggest that L1CAM and LINC01187 can serve as stand-alone diagnostic markers or as a panel for the diagnosis of HOT. These lineage markers will inform future studies on the evolution and interaction between the 2 transcriptionally distinct tumor epithelial populations in such tumors., Competing Interests: Conflicts of Interest and Source of Funding: This study is supported by internal institutional funding. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Prostate-specific membrane antigen positron emission tomography (PSMA PET) has been approved by the Food and Drug Administration (FDA) to identify prostate cancer in the setting of biochemical recurrence but can also identify other malignancies. 18F-PSMA PET has not been studied as a potential tool for hepatocellular carcinoma (HCC). We describe the case of a 76-year-old male with a rising prostate-specific antigen (PSA) after definitive prostate cancer treatment and no prior liver pathology who was incidentally found to have HCC on 18F-PSMA PET., Competing Interests: The authors have no relevant conflicts of interest to disclose., (Copyright © 2023 Lauren Hekman et al.)

Plasma cell leukemia (PCL) is a rare aggressive variant of plasma cell myeloma. The differential diagnosis of PCL includes multiple myeloma (MM), other leukemias, and lymphomas with abnormal cells circulating in the peripheral blood. In addition, infectious or autoimmune diseases can cause reactive polyclonal plasmacytosis, which could confuse us with PCL occasionally. Sometimes, blastoid morphology can cause confusion in diagnosis, and immunohistochemistry is needed to differentiate PCL from other forms of leukemias and lymphomas. Here, we present a rare case of PCL diagnosed as acute myeloid leukemia (AML) with kidney biopsy establishing the correct diagnosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Rasheed et al.)

Amyloidosis is the process of extracellular deposition of protein fibrils and manifests pathologically as a systemic or localized process. Localized amyloidosis of the head and neck is uncommon, and involvement of the sphenoid sinus is exceedingly rare. We describe a case of localized amyloidosis isolated from the sphenoid sinus. A descriptive literature search was conducted to highlight presentation, management, and outcomes related to this pathology. Our patient was a 65-year-old male who presented to our clinic with nasal congestion and an incidental finding of a large expansile mass within the sphenoid sinuses. The mass was seen to displace the pituitary gland, and thus a multidisciplinary care approach ensued. The mass was removed via a transnasal endoscopic approach. Pathology revealed fibrocollagenous tissue with calcifications that were positive on Congo red staining. The patient underwent further workup to rule out systemic involvement, which was unremarkable. Based on the findings of his workup, he was ultimately diagnosed with localized amyloidosis. A comprehensive review of the literature revealed 25 other reported cases of localized amyloidosis within the sinonasal region, with only one other case of isolated sphenoid sinus disease. Common presenting symptoms are nonspecific and may mimic other, more frequently seen regional pathologies, including nasal obstruction, rhinorrhea, and epistaxis. The treatment for localized disease is surgical resection. While localized amyloidosis within the sinonasal region is rare, it is important to recognize, work up, and treat it appropriately. A multidisciplinary team approach is necessary for appropriate diagnosis and management, and these patients should be followed closely after treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Wentland et al.)

Overlap syndrome is a connective tissue disorder that satisfies the diagnostic criteria for at least two well-known autoimmune diseases. In this report, we describe a rare case of lupus overlap in an elderly woman with primary Sjögren's syndrome who presented with features of nephritic-nephrotic syndrome and renal biopsy results typical of lupus nephritis combined with multiple positive autoantibodies. The kidney biopsy results were assigned the highest weightage based on the revised 2019 systemic lupus erythematosus (SLE) classification criteria developed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). The patient's condition significantly improved after appropriate immunosuppressive therapy was initiated. With the revised ACR/EULAR-2019 criteria, we anticipate that more SLE patients with typical lupus nephritis biopsy findings will be diagnosed accurately., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Palleti et al.)

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE), though they share similar clinical characteristics, are distinguishable based on specific characteristics. The concomitant presentation of SLE and AAV as overlap syndrome is rare and makes the diagnosis challenging. Here, we describe a rare case of SLE and AAV overlaps presenting with hemorrhagic stroke as initial presentation, which has been reported only once before. The presence of several positive autoantibodies made the diagnosis challenging, but a kidney biopsy provided the definitive diagnosis and aided in initiating immunosuppressive therapy. The patient did not respond to standard initial surgical measures to lower elevated intracranial pressure and showed significant improvement to immunosuppressive therapy proving the temporal relationship. The authors of this case study aim to highlight the importance of considering SLE-AAV overlap in patients presenting with features similar to those described in the case report and intervening early, as delays in diagnosis can be fatal., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Palleti et al.)

Adenoviral infections in post-transplant patients have been described in multiple organ systems, most classically the lung, liver, and alimentary tract. In the genitourinary tract, hemorrhagic cystitis is most frequently observed. Clinically apparent renal involvement with adenovirus is rare, and adenovirus-associated interstitial nephritis (AAIN) is an uncommon cause of renal allograft failure. Here, we present three cases of AAIN in patients who, after prompt diagnosis and treatment adjustment, experienced a return of allograft function. All patients were on standard triple therapy with tacrolimus levels within the target range at the time of biopsy. None of the patients had respiratory symptoms, and despite diarrhea, colon biopsies were negative. Only case one had positive adenovirus serology (IgG only) and case three had positive urine; two patients had leukopenia without neutropenia. Renal biopsies showed a characteristic granulomatous tubulocentric mixed lymphocytic and neutrophilic infiltrate. Adenovirus immunohistochemistry (IHC) showed strong staining in the tubular epithelium (nuclear and cytoplasmic) while staining for polyomavirus was negative. A follow-up biopsy two months after the diagnosis of AAIN in one patient revealed persistent cytopathic effects with negative adenoviral IHC staining while a biopsy at one year in another patient showed glomerular and tubulointerstitial scarring. AAIN is an uncommon but important etiology to consider in cases of acute renal allograft dysfunction. Although the presenting symptoms for AAIN are nonspecific, hematuria is frequently noted. Adenovirus IHC should be considered in cases with granulomatous inflammation associated with necrosis and mixed inflammatory infiltrate. As demonstrated in this single-institution case series, prompt diagnosis can result in the preservation of the renal allograft. Lasting cytopathic effects after adenoviral infection should also be considered in patients with a history, or potential history, of AAIN., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Lilley et al.)

While reports on the long-term pathology in mismatched allografts have been focused on the donor and recipient body surface area, evidence is emerging to support donor-recipient age difference as an additional prognostic factor. Most reports are based on pediatric recipients receiving older/bigger allografts. Here, we describe three cases with age mismatch including two cases of adult patients receiving pediatric allografts and a third case of a younger patient receiving an allograft from an older donor exhibiting findings not described in extant literature. Each of these cases exhibits unique changes seen in mismatched donor-recipient size/age post-transplant pathology. These non-rejection changes should be suspected in cases of donor-recipient size/age mismatch. In cases of allograft function decline, a full biopsy workup, including electron microscopy, should be considered., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Lilley et al.)

Chronic kidney disease (CKD) has a strong genetic component; however, the underlying pathways are not well understood. Dahl salt-sensitive (SS)/Jr rats spontaneously develop CKD with age and are used to investigate the genetic determinants of CKD. However, there are currently several genetically diverse Dahl SS rats maintained at various institutions and the extent to which some exhibit age-related CKD is unclear. We assessed glomerulosclerosis (GS) and tubulointerstitial fibrosis (TIF) in 3- and 6-mo-old male and female SS/JrHsdMcwi, BN/NHsd/Mcwi [Brown-Norway (BN)], and consomic SS-Chr 1 BN /Mcwi (SS.BN1) rats, in which chromosome 1 from the BN rat was introgressed into the genome of the SS/JrHsdMcwi rat. Rats were fed a 0.4% NaCl diet. GS (31 ± 3% vs. 7 ± 1%) and TIF (2.3 ± 0.2 vs. 0.5 ± 0.1) were significantly greater in 6-mo-old compared with 3-mo-old SS/JrHsdMcwi rats, and CKD was exacerbated in males. GS was minimal in 6- and 3-mo-old BN (3.9 ± 0.6% vs. 1.2 ± 0.4%) and SS.BN1 (2.4 ± 0.5% vs. 1.0 ± 0.3%) rats, and neither exhibited TIF. In SS/JrHsdMcwi and SS.BN1 rats, mean arterial blood pressure was significantly greater in 6-mo-old compared with 3-mo-old SS/JrHsdMcwi (162 ± 4 vs. 131 ± 2 mmHg) but not SS.BN1 (115 ± 2 vs. 116 ± 1 mmHg) rats. In 6-mo-old SS/JrHsdMcwi rats, blood pressure was significantly greater in females. RNA-sequencing analysis revealed that inflammatory pathways were upregulated in isolated medullary thick ascending tubules in 7-wk-old SS/JrHsdMcwi rats, before the development of tubule pathology, compared with SS.BN1 rats. In summary, SS/JrHsdMcwi rats exhibit robust age-related progression of medullary thick ascending limb abnormalities, CKD, and hypertension, and gene(s) on chromosome 1 have a major pathogenic role in such changes. NEW & NOTEWORTHY This study shows that the robust age-related progression of kidney disease in Dahl SS/JrHsdMcw rats maintained on a normal-salt diet is abolished in consomic SS.BN1 rats. Evidence that medullary thick ascending limb segments of SS/JrHsdMcw rats are structurally abnormal and enriched in proinflammatory pathways before the development of protein casts provides new insights into the pathogenesis of kidney disease in this model.

Adverse reaction to metal debris (ARMD) is a known complication of metal-on-metal hip arthroplasty. There has been one previously reported case of ARMD with concomitant gout in the setting of a hip arthroplasty. We report a case of ARMD with accompanying monosodium urate crystals as well as amyloid deposition in the hip of a patient who had undergone a metal-on-metal hip arthroplasty. This is the only published case to date of these 3 conditions co-existing, although it is possible that the incidence is higher since these require special diagnostic tests that are not routinely performed. It is postulated that these entities are biochemically associated with each other rather than being purely coincidental., (© 2022 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Introduction: Ductal adenocarcinoma (DA) and intraductal carcinoma (IDC) of the prostate are associated with higher stage disease at radical prostatectomy (RP). We evaluated diagnostic accuracy of biopsy, MRI-visibility, and outcomes for patients undergoing RP with DA/IDC histology compared to pure acinar adenocarcinoma (AA) of the prostate., Materials and Methods: A retrospective cohort study of men receiving RP between 2014 and 2021 revealing AA, DA, or IDC on final pathology was conducted. Multivariable logistic regression and Cox proportional hazards regression models were employed., Results: A total of 609 patients were included with 103 found to have DA/IDC. Patients with DA/IDC were older and had higher PSA, biopsy grade group (GG), RP GG, and other pathologic findings (extraprostatic extension, lymphovascular invasion, perineural invasion, pN stage) compared to AA patients (all P < 0.05). On multivariable analysis, higher age, RP GG, and pT3a were associated with DA/IDC on RP (all P < 0.05). Sensitivity and specificity of biopsy compared to RP for diagnosis of DA/IDC was 29.1% (16.7% DA, 27.8% IDC) and 96.6% (99.3% DA, 96.6% IDC), respectively. In a subset of 281 men receiving MRI, PI-RADS distribution was similar for patients with DA/IDC vs. AA (90.7% vs. 80.7% with PI-RADS 4-5 lesions, P = 0.23) with slightly higher biopsy sensitivity (41.9%). DA/IDC was associated with worse BCR (HR = 1.77, P = 0.02) but not biopsy DA/IDC (P = 0.90)., Conclusions: Sensitivity of prostate biopsy was low for detection of DA/IDC histology at RP. Patients with DA/IDC histology had unfavorable pathologic features at RP and worse BCR. Of patients with DA/IDC at RP, 90.7% were categorized as PI-RADS 4 to 5 on preoperative MRI., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Amyloidosis is a group of diverse disorders caused by misfolded proteins that aggregate into insoluble fibrils and ultimately cause organ damage. In medical practice, amyloidosis classification is based on the amyloid precursor protein type, of which amyloid immunoglobulin light chain, amyloid transthyretin, amyloid leukocyte chemotactic factor 2, and amyloid derived from serum amyloid A protein are the most common. Distinct mechanisms appear to be predominantly operational in the pathogenesis of particular types of amyloidosis, including increased protein precursor synthesis, somatic or germ line mutations, and inherent instability in the precursor protein in its wild form. An increased supply of misfolded proteins and/or a decreased capacity of the protein quality control systems can result in an imbalance that leads to increased circulation of misfolded proteins. Although the detection of mature fibrils is the basis for diagnosis of amyloidosis, a growing body of evidence has implicated the prefibrillar species as proteotoxic and key contributors to the development of the disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Most surgically resected benign renal tumors are found to be oncocytomas or indolent hybrid oncocytic tumors, which are difficult to differentiate from chromophobe renal cell carcinoma (chRCC) on renal mass biopsy. Both often exhibit CD117 + staining., Objective: To evaluate the ability of the peak early-phase enhancement ratio (PEER) to distinguish oncocytomas from chRCC and compare its discrimination to traditional clinical risk factors and blinded clinical raters., Design Setting and Participants: This was a diagnostic case-control study of patients (2006-2020) with oncocytoma or chRCC according to surgical pathology., Intervention: Partial or radical nephrectomy., Outcome Measurements and Statistical Analysis: Three clinical raters blinded to histology measured the PEER and the presence of stellate scar and predicted the final histology for each tumor. Averaged and individual PEER values were compared to surgical pathology and assessed for interobserver variability. Subanalyses were conducted for patients with confirmed CD117 + status., Results and Limitations: For the 76 patients identified, PEER was higher among the 32 (42.1%) oncocytomas than among the 44 (57.9%) chRCCs (median 0.81 vs 0.43; p  < 0.001), with high correlation across raters (correlation coefficients ≥0.85). A PEER cutoff of <0.60 was strongly associated with identification of chRCC (OR 95.7 (95% CI 19.9-460.8), p  < 0.001). In the overall and CD117 + cohorts, sensitivity was 93.2% and 97.0%, the negative predictive value was 90.3% and 95.5%, and the area under the receiver operating characteristic curve (AUC) on multivariable modeling was 95.0% and 98.1%, respectively. PEER outperformed models with clinical risk factors alone (AUC 70.4%) and histology predictions by three raters (AUC 51.6%, 62.5%, and 63.1%). Limitations include reliance on surgical pathology and inclusion of a mix of early contrast-enhanced phases., Conclusions: PEER reliably differentiated benign renal oncocytomas and indolent hybrid tumors from malignant chRCC with excellent diagnostic performance. A diagnostic pathway with biopsy, CD117 staining, and PEER deserves further study to potentially avoid unnecessary surgery for oncocytic renal tumors., Patient Summary: We assessed a measurement called PEER on computed tomography (CT) scans and found higher values for benign and lower values for malignant kidney masses, so we were able to tell these apart. PEER was reliable for identifying tumors with positive staining for the CD117 protein biomarker as well as in the overall patient group. Our results show that PEER could be considered for use with biopsy and CD117 staining to potentially avoid unnecessary surgery for benign kidney masses., (© 2022 The Authors.)

Purpose: Sarcomatoid dedifferentiation in renal cell carcinoma (RCC) represents an aggressive histology where degree of sarcomatoid histology (SH) may impact prognosis for cM0 and cM1 patients. We aimed to evaluate the association of percentage of SH with survival., Materials and Methods: Patients ≥18 years old diagnosed with RCC with any degree of SH after nephrectomy were included (2005-2020) from a single-center. Associations of degree of SH and cM stage with overall survival (OS) and recurrence-free survival (RFS) were evaluated by Kaplan-Meier curves and Cox proportional hazards regression., Results: One hundred twenty-eight patients were included with 80 (62.5%) cM0 and 48 (37.5%) cM1. cM1 patients were more likely to be male with higher clinical T stage (P = 0.001) than cM0, but a similar proportion had ≥20% SH (47.9% vs. 42.5%, P = 0.55). With median 19.4 months follow-up, SH was associated with worse OS per 10% increase (hazard ratio [HR] 1.12 [95% confidence interval {CI} 1.03-1.23], P = 0.009) and a ≥20% cutoff (HR 2.87 [95% CI 1.27-6.47], P = 0.01). Patients with cM0 disease and <20% SH had better 2-year OS (81.4%) compared to cM0 and ≥20% SH (44.8%) or cM1 patients who received nephrectomy (54.8%). Tumor size was also an independent predictor. Sites of distant metastasis and lines of therapy were similar for metachronous and synchronous patients. SH stratified 2-year RFS (cM0: 70.2% for <20% SH vs. 32.1% for ≥20% SH)., Conclusions: SH in RCC is independently associated with OS and RFS. Patients who are cM0 with any SH may be candidates for adjuvant immunotherapy while those with ≥20% SH likely carry micrometastatic disease and should receive closer surveillance., Competing Interests: Conflicts of interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A reliable diagnosis of amyloidosis is usually based on a tissue biopsy. With increasing options for specific treatments of the different amyloid diseases, an exact and valid diagnosis including determination of the biochemical fibril nature is imperative. Biopsy sites as well as amyloid typing principles vary and this paper describes methods employed at some laboratories specialised in amyloidosis in Europe, Japan and USA.

Mutations underlying disease in tuberous sclerosis complex (TSC) give rise to tumors with biallelic mutations in TSC1 or TSC2 and hyperactive mammalian target of rapamycin complex 1 (mTORC1). Benign tumors might exhibit de novo expression of immunogens, targetable by immunotherapy. As tumors may rely on ganglioside D3 (GD3) expression for mTORC1 activation and growth, we compared GD3 expression in tissues from patients with TSC and controls. GD3 was overexpressed in affected tissues from patients with TSC and also in aging Tsc2+/- mice. As GD3 overexpression was not accompanied by marked natural immune responses to the target molecule, we performed preclinical studies with GD3 chimeric antigen receptor (CAR) T cells. Polyfunctional CAR T cells were cytotoxic toward GD3-overexpressing targets. In mice challenged with Tsc2-/- tumor cells, CAR T cells substantially and durably reduced the tumor burden, correlating with increased T cell infiltration. We also treated aged Tsc2+/- heterozygous (>60 weeks) mice that carry spontaneous Tsc2-/- tumors with GD3 CAR or untransduced T cells and evaluated them at endpoint. Following CAR T cell treatment, the majority of mice were tumor free while all control animals carried tumors. The outcomes demonstrate a strong treatment effect and suggest that targeting GD3 can be successful in TSC.

Background Abnormal renal hemodynamic responses to salt-loading are thought to contribute to salt-sensitive (SS) hypertension. However, this is based largely on studies in anesthetized animals, and little data are available in conscious SS and salt-resistant rats. Methods and Results We assessed arterial blood pressure, renal function, and renal blood flow during administration of a 0.4% NaCl and a high-salt (4.0% NaCl) diet in conscious, chronically instrumented 10- to 14-week-old Dahl SS and consomic SS rats in which chromosome 1 from the salt-resistant Brown-Norway strain was introgressed into the genome of the SS strain (SS.BN1). Three weeks of high salt intake significantly increased blood pressure (20%) and exacerbated renal injury in SS rats. In contrast, the increase in blood pressure (5%) was similarly attenuated in Brown-Norway and SS.BN1 rats, and both strains were completely protected against renal injury. In SS.BN1 rats, 1 week of high salt intake was associated with a significant decrease in renal vascular resistance (-8%) and increase in renal blood flow (15%). In contrast, renal vascular resistance failed to decrease, and renal blood flow remained unchanged in SS rats during high salt intake. Finally, urinary sodium excretion and glomerular filtration rate were similar between SS and SS.BN1 rats during 0.4% NaCl and high salt intake. Conclusions Our data support the concept that renal vasodysfunction contributes to blood pressure salt sensitivity in Dahl SS rats, and that genes on rat chromosome 1 play a major role in modulating renal hemodynamic responses to salt loading and salt-induced hypertension.

Purpose of Review: Amyloidoses are a group of rare and heterogeneous diseases in which abnormally folded proteins deposit in tissues and lead to organ damage. A brief review of advances in the diagnosis of extracerebral systemic amyloidoses in the context of recent advances in their clinical management is provided., Recent Findings: Although steady progress in the treatment of AL and AA has evolved over many years, significant advances in the treatment of ATTR, transthyretin-derived amyloidosis, have been achieved only recently. This coincides with the emergence of nontissue diagnosis of cardiac ATTR in both the hereditary and wild-type settings. The latter is emerging as possibly the most prevalent type of systemic amyloidosis.Available treatments are amyloid protein type dependent and, hence, following amyloid detection, amyloid protein typing is necessary. Although mass spectrometry has emerged as the preferred method of amyloid typing, careful application of immune methods is still clinically useful but caution and experience, as well as awareness of the limitations of each method, are necessary in their interpretation., Summary: Despite significant advances in the treatment of the systemic amyloidoses, outcomes remain poor, primarily due to delays in diagnosis. Precise diagnosis of the amyloid protein type is critical for treatment selection., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Human penile ossification is a rare urologic condition with approximately 40 cases reported in the literature so far. While bone is essential for penetrative intercourse in many non-human mammals, human penile ossification appears to be part of a metaplastic process occurring after injury or trauma. Conditions such as Peyronie's disease, diabetes mellitus, local trauma, and end-stage renal disease have been associated with this entity. We report the case of a 65-year-old male with penile curvature and a history of painful intercourse who underwent partial excision and grafting with bovine pericardial graft and was found on pathologic examination to have penile ossification., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Belshoff et al.)

Case reports of acute kidney injury in patients taking the glucagon-like peptide 1 (GLP-1) receptor agonists exenatide and liraglutide have been reported. We report 2 patients with chronic kidney disease due to diabetic kidney disease who experienced rapid worsening of kidney function and increased proteinuria after being prescribed the GLP-1 receptor agonist semaglutide. In 1 patient, kidney biopsy showed advanced diffuse and nodular glomerulosclerosis accompanied by interstitial lymphoplasmacytic and eosinophilic infiltrate and evidence of acute tubular injury. At this time, the long-term outcomes of patients who experience acute kidney injury associated with GLP-1 receptor agonists is not known. We recommend that caution be used with these agents in patients with moderate to severe chronic kidney disease due to limited kidney reserve in the event of an adverse kidney event. Because most adverse kidney events have occurred in patients who experience adverse gastrointestinal symptoms, such patients should have laboratory tests and discontinuation of the medication if there is acute worsening of kidney function.

Renal cell carcinoma (RCC) with invasion into the renal vein is well described; however, invasion into the gonadal vein is a rare event with less than five cases reported in the literature. RCC occasionally presents with metastasis to the ovaries or the fallopian tubes, although this is also a rare occurrence. We present a case of locally advanced left RCC with direct extension into the ipsilateral gonadal vein with extension into the bilateral ovaries and uterus, which has not been previously described. Computed tomography (CT) in a 72-year-old female with a 35-pound weight loss indicated the presence of a 16-cm left renal mass with caudal tumor extension through the left gonadal vein and regional lymphadenopathy. There was no evidence of distant metastasis, and she underwent an open left radical nephrectomy. Intraoperatively, she was found to have direct extension of the tumor through the left gonadal vein into the uterus, bilateral ovaries, and the left fallopian tube. All visible disease was resected, and retroperitoneal and pelvic lymphadenectomy were performed. The patient had an uneventful hospital course. Pathology revealed clear cell RCC, Fuhrman grade 3. The final pathologic stage was pT4N1M1. The patient was ultimately noted to have pulmonary metastasis and was treated with immunotherapy with no evidence of disease progression., Competing Interests: The authors declare no potential conflicts of interest with respect to research, authorship, and/or publication of this article, (Copyright: Sweigert SE et al.)

Unilateral ischemia-reperfusion (UIR) injury leads to progressive renal atrophy and tubulointerstitial fibrosis (TIF) and is commonly used to investigate the pathogenesis of the acute kidney injury-chronic kidney disease transition. Although it is well known that contralateral nephrectomy (CNX), even 2 wk post-UIR injury, can improve recovery, the physiological mechanisms and tubular signaling pathways mediating such improved recovery remain poorly defined. Here, we examined the renal hemodynamic and tubular signaling pathways associated with UIR injury and its reversal by CNX. Male Sprague-Dawley rats underwent left UIR or sham UIR and 2 wk later CNX or sham CNX. Blood pressure, left renal blood flow (RBF), and total glomerular filtration rate were assessed in conscious rats for 3 days before and over 2 wk after CNX or sham CNX. In the presence of a contralateral uninjured kidney, left RBF was lower ( P < 0.05) from 2 to 4 wk following UIR (3.6 ± 0.3 mL/min) versus sham UIR (9.6 ± 0.3 mL/min). Without CNX, extensive renal atrophy, TIF, and tubule dedifferentiation, but minimal pimonidazole and hypoxia-inducible factor-1α positivity in tubules, were present at 4 wk post-UIR injury. Conversely, CNX led ( P < 0.05) to sustained increases in left RBF (6.2 ± 0.6 mL/min) that preceded the increases in glomerular filtration rate. The CNX-induced improvement in renal function was associated with renal hypertrophy, more redifferentiated tubules, less TIF, and robust pimonidazole and hypoxia-inducible factor-1α staining in UIR injured kidneys. Thus, contrary to expectations, indexes of hypoxia are not observed with the extensive TIF at 4 wk post-UIR injury in the absence of CNX but are rather associated with the improved recovery of renal function and structure following CNX.

Context.—: Amyloidoses are rare but heterogeneous disorders for which diagnosis is contingent upon the detection of deposits by Congo red stain and amyloid protein typing determines the treatment options., Objective.—: To address the reporting of bone marrow (BM) involvement by amyloid in relation to the spatial distribution of deposits and to explore whether the location of deposits may have clinical relevance., Design.—: We examined 66 BM biopsies positive for amyloid with regard to the location and type of amyloid, the percentage and clonality of plasma cells, other organ involvement, and relevant clinical information., Results.—: In 21 cases, amyloid deposits involved BM stroma, whereas 45 cases were nonstromal. All cases of stromal involvement were typed as AL amyloidosis (or presumed AL), whereas nonstromal involvement was associated with at least 3 types of amyloidosis: AL, ATTR, and AA. The initial diagnosis of amyloidosis was made in a BM specimen in 21 of 66 cases (31.8%). Plasma cells ranged from 1% to 80% (mean, 13.4%; median, 8%; <10% in 44 of 66 specimens [66.6%]) and were monoclonal in 58 of 66 cases (87.8%), and in 54 of 66 cases (81.8%) amyloid deposits were documented in at least one other organ., Conclusions.—: This study demonstrates that there is significant heterogeneity in the spatial distribution of amyloid in BM biopsy specimens with medullary, extramedullary, purely vascular, or combined involvement. Whereas stromal deposits were associated exclusively with AL, nonstromal and purely vascular deposits were seen in at least 3 types of systemic amyloidosis (AL, AA, and ATTR). We discuss the reporting of BM biopsy tissue positivity for amyloid deposits.

Background: The amyloidoses are a rare and heterogeneous group of disorders that are characterized by the deposition of abnormally folded proteins in tissues ultimately leading to organ damage. The deposits are mainly extracellular and are recognizable by their affinity for Congo red and their yellow-green birefringence under polarized light. Current classification of amyloid in medical practice is based on the amyloid protein type. To date, 36 proteins have been identified as being amyloidogenic in humans., Summary: in clinical practice, it is critical to distinguish between treatable versus non-treatable amyloidoses. Moreover, amyloidoses with a genetic component must be distinguished from the sporadic types and systemic amyloidoses must be distinguished from the localized forms. Among the systemic amyloidoses, AL continues to be the most common amyloid diagnosis in the developed world; other clinically significant types include AA, ALECT2, and ATTR. The latter is emerging as an underdiagnosed type in both the hereditary and wild-type setting. Other hereditary amyloidoses include AFib, several amyloidoses derived from apolipoproteins, AGel, ALys, etc. In a dialysis setting, systemic amyloid derived from β2 microglobulin (Aβ2M) should be considered, although a very rare hereditary variant has also been reported; several amyloidoses may be typically associated with aging and several iatrogenic types have also emerged. Determination of the amyloid protein type is imperative before specific therapy can be implemented and the current methods are briefly summarized. A brief overview of the target organ involvement by amyloid type is also included. Key Messages: (1) Early diagnosis of amyloidosis continues to pose a significant challenge and requires the participation of many clinical and laboratory specialties. (2) Determination of the protein type is imperative before specific therapy can be implemented. (3) While mass spectrometry has emerged as the preferred method of amyloid typing, careful application of immune methods is still clinically useful but caution and experience, as well as awareness of the limitations of each method, are necessary in their interpretation. (4) While the spectrum of amyloidoses continues to expand, it is critical to distinguish between those that are currently treatable versus those that are untreatable and avoid causing harm by inappropriate treatment., (© 2020 S. Karger AG, Basel.)

Introduction: Oncocytic neoplasms are renal tumors similar to oncocytoma, but their morphologic variations preclude definitive diagnosis. This somewhat confusing diagnosis can create treatment and surveillance challenges for the treating urologist. We hypothesize that these subtle morphologic variations do not drastically affect the malignant potential of these tumors, and we sought to demonstrate this by comparing clinical outcomes of oncocytic neoplasms to those of classic oncocytoma and chromophobe., Methods: We gathered demographic and outcomes data for patients with variant oncocytic tumors. Oncologic surveillance was conducted per institutional protocol in accordance with NCCN guidelines. Descriptive statistics were used to compare incidence of metastasis and death against those for patients with oncocytoma and chromophobe. Three hundred and fifty-one patients were analyzed: 164 patients with oncocytoma, 28 with oncocytic neoplasms, and 159 with chromophobe tumors., Results: Median follow-up time for the entire cohort was 32.4 months, (interquartile range 9.2-70.0). Seventeen total patients (17/351, 4.9%) died during the course of the study. In patients with oncocytoma or oncocytic neoplasm, none were known to metastasize or die of their disease. Only chromophobe tumors >6 cm in size in our series demonstrated metastatic progression and approximately half of these metastasized tumors demonstrated sarcomatoid changes., Conclusion: Variant oncocytic neoplasms appear to have a natural course similar to classic oncocytoma. These tumors appear to have no metastatic potential, and oncologic surveillance may not be indicated after surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The term monoclonal gammopathy of renal significance (MGRS) was introduced by the International Kidney and Monoclonal Gammopathy Research Group (IKMG) in 2012. The IKMG met in April 2017 to refine the definition of MGRS and to update the diagnostic criteria for MGRS-related diseases. Accordingly, in this Expert Consensus Document, the IKMG redefines MGRS as a clonal proliferative disorder that produces a nephrotoxic monoclonal immunoglobulin and does not meet previously defined haematological criteria for treatment of a specific malignancy. The diagnosis of MGRS-related disease is established by kidney biopsy and immunofluorescence studies to identify the monotypic immunoglobulin deposits (although these deposits are minimal in patients with either C3 glomerulopathy or thrombotic microangiopathy). Accordingly, the IKMG recommends a kidney biopsy in patients suspected of having MGRS to maximize the chance of correct diagnosis. Serum and urine protein electrophoresis and immunofixation, as well as analyses of serum free light chains, should also be performed to identify the monoclonal immunoglobulin, which helps to establish the diagnosis of MGRS and might also be useful for assessing responses to treatment. Finally, bone marrow aspiration and biopsy should be conducted to identify the lymphoproliferative clone. Flow cytometry can be helpful in identifying small clones. Additional genetic tests and fluorescent in situ hybridization studies are helpful for clonal identification and for generating treatment recommendations. Treatment of MGRS was not addressed at the 2017 IKMG meeting; consequently, this Expert Consensus Document does not include any recommendations for the treatment of patients with MGRS.

Mixed epithelial and stromal tumor (MEST) is a biphasic adult renal lesion composed of solid and cystic areas containing spindle cell stroma and epithelium that lines the tubules and cystic spaces. While most MEST lesions are benign, rare cases with malignant morphology and biology have been reported. We present a case of mixed epithelial and stromal tumor of the kidney (MEST) with extension into the inferior vena cava in a young adult male. We discuss the differential diagnosis of MEST in the context of other biphasic cystic renal lesions and the significance of vascular involvement in the setting of an otherwise benign tumor morphology.

Staging criteria for renal cell carcinoma differ from many other cancers, in that renal tumors are often spherical with subtle, finger-like extensions into veins, renal sinus, or perinephric tissue. We sought to study interobserver agreement in pathologic stage categories for challenging cases. An online survey was circulated to urologic pathologists interested in kidney tumors, yielding 89% response (31/35). Most questions included 1 to 4 images, focusing on: vascular and renal sinus invasion (n=24), perinephric invasion (n=9), and gross pathology/specimen handling (n=17). Responses were collapsed for analysis into positive and negative/equivocal for upstaging. Consensus was regarded as an agreement of 67% (2/3) of participants, which was reached in 20/33 (61%) evaluable scenarios regarding renal sinus, perinephric, or vein invasion, of which 13/33 (39%) had ≥80% consensus. Lack of agreement was especially encountered regarding small tumor protrusions into a possible vascular lumen, close to the tumor leading edge. For gross photographs, most were interpreted as suspicious but requiring histologic confirmation. Most participants (61%) rarely used special stains to evaluate vascular invasion, usually endothelial markers (81%). Most agreed that a spherical mass bulging well beyond the kidney parenchyma into the renal sinus (71%) or perinephric fat (90%) did not necessarily indicate invasion. Interobserver agreement in pathologic staging of renal cancer is relatively good among urologic pathologists interested in kidney tumors, even when selecting cases that test the earliest and borderline thresholds for extrarenal extension. Disagreements remain, however, particularly for tumors with small, finger-like protrusions, closely juxtaposed to the main mass.

Multilocular cystic renal cell carcinoma has been recently excluded from clear cell renal cell carcinoma (CCRCC) category and re-designated as multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) due to its uniformly good outcomes. While strict distinction between MCRNLMP from predominantly cystic CCRCC (pc-CCRCC) is being emphasized, the significance of extensive true cystic component in CCRCC has not been investigated. Herein, we analyzed 57 MCRNLMP, 69 pc-CCRCC, and 46 non-cystic CCRCC. There were no statistically significant differences between the three subtypes in age, gender, and laterality. ISUP grades were 1 (73%) or 2 (27%) for MCRNLMP; for pc-CCRCC were 1 (31%), 2 (60%), and 3 (9%); and for non-cystic CCRCC were 1 (9%), 2 (52%), 3 (26%), and 4 (13%). MCRNLMP were either pT stage 1 (91%) or 2 (9%), pT stages for pc-CCRCC were 1 (92.5%), 2 (1.5%), and 3 (6%) and for non-cystic CCRCC were 1 (58.7%), 2 (6.5%), and 3 (34.8%). None of MCRNLMP patients developed recurrences or metastases, and only 1 contralateral kidney tumor and 1 metastasis developed in pc-CCRCC. In contrast, 19 patients with non-cystic CCRCC developed metastases (5-year PFS 58%, CI 38.3-73.5%), and 1 patient died of disease. Monosomy 3 was common in both MCRNLMP (3/3) and pc-CCRCC (6/7). This large series of MCRNLMP confirms its indolent behavior, shows that pc-CCRCC has significantly better prognosis than non-cystic CCRCC and may define the lower grade spectrum of CCRCC. We recommend that the presence and extent of CCRCC cystic component should be documented in the pathology report.

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.

A 49-year-old woman with a distant history of uterine leiomyosarcoma underwent robotic-assisted laparoscopic partial nephrectomy for a 3.5 cm right renal mass, which was presumed to be a primary renal cell carcinoma. Surgical margins were negative, and the histologic analysis confirmed leiomyosarcoma. Uterine leiomyosarcoma is traditionally a locally aggressive disease with only rare reports of renal involvement. We report a case of a metastatic leiomyosarcoma to the kidney four years following initial treatment for uterine leiomyosarcoma., Competing Interests: The authors have declared that no competing interests exist.

Objectives: We studied the frequency, inter-pathologist variation, appropriateness and utility of immunohistochemistry (IHC) performed on prostate biopsies (PB) to determine the significance of foci of suspicious glands/atypical small acinar proliferations (ASAP)., Methods: We calculated the rate of IHC use and diagnostic rate of ASAP and adenocarcinoma in PB from 01/01/2008 to 06/30/2015 for individual pathologists working in a tertiary academic institution, and correlated them with the pathologists' experience, subspecialization and PB volume with the aim of determining the interpathologist variation and appropriateness of use of IHC according to recently published recommendations, and the usefulness of IHC to resolve foci of ASAP as either benign or adenocarcinoma., Results: IHC was used in 966/2652 (36.4%, 95% CI 33.4-39.4%) PB cases and 1915 of 16,359 (11.7%, 95% CI 11.2%-12.2%) of PB blocks and allowed definitive diagnosis of either benign or malignant in 75.8% (95% CI 73.9-77.7%) of blocks. By pathologist, IHC use rates varied more than twofold (22.8-50.5%); higher use was found for pathologists with genitourinary pathology specialization, higher PB volume and more experience, and correlated with higher rates of both ASAP and adenocarcinoma diagnoses. The use of IHC stains was considered appropriate in 822/966 (85.1%, 95% CI 82.9-87.4%) cases., Conclusions: Despite the fact that the use of IHC stains was considered useful and deemed appropriate in the majority of cases, it showed wide variation between pathologists, suggesting monitoring of IHC use rates may be useful to standardize its use., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Approaches to nephron-sparing surgeries (NSS) of renal lesions include partial nephrectomy (PN) and tumor enucleation (TE). Our objective was to examine the pathology of the pseudocapsule and status of the surgical margin in small renal masses treated by NSS and to correlate these findings with the surgical and oncological outcomes. All consecutive renal TE and PN specimens obtained during the period between January 2012 and December 2014, of which clinical follow-up was available, were included in this study. Pathologic features and clinical data were reviewed and analyzed. A total of 117 NSS specimens (59 EN, 58 PN) were reviewed. Clear cell renal cell carcinomas and paraganglioma had the thickest pseudocapsules (0.36 mm), while angiomyolipomas did not form a well-defined pseudocapsule. Other tumors were intermediate in their characteristics. The positive margin rate for TE and PN was 17.2 and 0 %, respectively. Compared to PN, TE involved a significantly shorter procedure time, less blood loss, and fewer post-operative complications. None of the patients from either group was found to have a local recurrence after follow-up imaging. Although positive surgical margins were more frequently seen in TE specimens, local tumor recurrence was comparable to PN. Thus, TE is a reasonable choice for pT1 renal tumors, especially for those without a prominent infiltrative growth pattern.