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Lymph node involvement derived from a discrete neo-plastic process fundamentally implies tumor malignancy. However, rarely, inconsequential passive transport of benign neoplastic cells to the lymph node can occur and may cause confusion as to the nature of the neoplasm (ie, malignant vs benign). We describe a 10-cm right renal metanephric adenoma incidentally discovered in a 30-year-old woman during cesarean section for a triplet pregnancy. Subsequent nephrectomy following an equivocal needle biopsy diagnosis showed histologic features classic for meta-nephric adenoma, including the lack of cytologic atypia and mitoses. Necrosis present in this lesion appeared to be secondary to tumor physical disruption. The tumor cells were positive for Wilms tumor 1 (WT1) antigen, pankeratin, and CD57, focally positive for epithelial membrane antigen, and negative for cytokeratin 7, cytokeratin 34DE12, and CD56. Electron microscopy confirmed the tumor's epithelial nature, and cytogenetics revealed a diploid 46XX karyotype. The tumor proliferation index with Ki-67 was only 3% to 5% and the proliferating cell nuclear antigen index was 0%. A single, concurrently resected hilar lymph node contained scattered subcapsular, sinusoidal, and focally intralymphovascular psammoma bodies along with occasional adherent epithelial cells. These cells were highlighted by pankeratin but were nonreactive to WT1 antigen, similar to the nonviable cells in the primary tumor. Clinical surveillance and follow-up showed no disease recurrence 4 years after nephrectomy. We postulate that the lymph node inclusions found in this case represent passive transport of neoplastic cells to the lymph node following manipulation of the renal mass. We conclude that this phenomenon is understudied and underrecognized and can easily be mistaken for metastasis. [ABSTRACT FROM AUTHOR]

Although most renal epithelial tumors are derived from the proximal nephron, approximately 10% are believed to originate in the distal nephron. This latter group encompasses oncocytoma, chromophobe renal cell carcinoma, and several rare types, including collecting duct carcinoma and renal medullary carcinoma. Despite progress in the classification of renal tumors, a small subset of renal carcinomas remains unclassified (ie, renal cell carcinoma, not otherwise specified). We describe a metastatic tumor consisting of cells with overlapping distal nephron morphologies, including foci of oncocytoma, chromophobe renal cell carcinoma, and collecting duct carcinoma, as well as sarcomatoid dediflerentiation. Special stains were inconclusive, and ultrastructural study demonstrated abundant mitochondria and no microvesicles. The karyotype was hypodiploid with 41 chromosomes and abnormalities reported in all 3 phenotypes present. Rearrangements of 1 p and of 11q13 previously seen in divergent subsets of oncocytomas were concomitantly present in the current tumor. Thus, this malignancy has features consistent with distal nephron derivation and demonstrates the convergence of the varied tumor morphologies arising within this site. Furthermore, this case exemplifies the value of cytogenetic analysis in the characterization of renal cell carcinoma, not otherwise specified. In view of recent advances in treatment approach, especially for collecting duct carcinoma, further categorization of this nondescript and heterogeneous group of renal cell carcinomas, not otherwise specified, at least by its derivation in relationship to the renal nephron (distal vs proximal), may be of value in the choice of treatment modality. [ABSTRACT FROM AUTHOR]

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.)

The 5th edition of the World Health Organization (WHO) classification of tumors of the urinary tract and male genital organs introduced both general and specific changes in structure, classification, and nomenclature. This also applies to rarer tumors and tumor subtypes of the urinary system. Knowledge of these changes is relevant for routine histopathological work. This article provides an overview of the main new features of the rarer tumors and tumor subtypes of the urinary system in the new edition of the WHO classification., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

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., (© 2024. The Author(s).)

We present the clinicopathological features of 23 cases of the giant cell subtype of urothelial carcinoma, a rare subtype of bladder cancer recognized in the current World Health Organization classification of urological tumors. Histologically, the architectural pattern of the tumor varied from infiltrating to the solid expansile pleomorphic tumor with giant, bizarre, anaplastic cells. Typical or atypical mitotic figures were frequently present in all cases. Between 10 and 30% of the tumor had a giant cell component. All cases were associated with conventional high-grade urothelial carcinoma, with areas of squamous cell divergent differentiation and micropapillary carcinoma present in six and two cases, respectively. In one case each had sarcomatoid, nested, small cell, or glandular divergent differentiation. At diagnosis, 35% of patients had advanced disease and 12% had distant metastases. When comparing giant cell urothelial carcinoma with conventional urothelial carcinoma in a matched analysis, differences in overall and cancer-specific survival were observed, particularly in the T1 stage category. Immunohistochemical staining showed a similar profile of urothelial lineage with frequent positive expression of uroplakin II, GATA3, CK20, CK7, and S100P in both giant cell and conventional urothelial carcinomas. High Ki67 proliferation (range, 60-90%; mean, 71%) and nuclear p53 accumulation (mutant profile; range, 50-90%; mean, 64%) were observed. Using the 22C3 assay, the expression of PD-L1 was found to be variable in two cases, and beta-HCG was negative. In conclusion, giant cell carcinoma is a subtype of urothelial carcinoma associated with advanced clinical stage and a trend to lower survival rates., (© 2024. The Author(s).)

The NKX3.1 immunohistochemical stain is widely recognized as a highly sensitive and specific marker for prostate adenocarcinoma. Nevertheless, its expression has been documented in various nonprostatic tissues and malignancies. This review aims to provide an overview of NKX3.1 expression in diverse tumor types, with a specific focus on its aberrant expression in esophageal/gastroesophageal adenocarcinoma (E/GE-ADC). In our investigation, we explored the expression of NKX3.1 in a series of E/GE-ADC to shed light on its prevalence in this tumor category. A total of 50 samples, comprising primary and metastatic E/GE-ADC specimens from 34 patients, were subjected to immunohistochemical analysis. Stained sections were scored based on the intensity and distribution-categorized as negative, weak, moderate, or strong in either a focal or diffuse pattern. Strong staining corresponds to the intensity observed in normal prostate controls, while focal and diffuse staining denote <50% and ≥50% of tumor nuclei staining positive, respectively. Our semiquantitative scoring revealed that 6 (12%) of the primary and metastatic E/GE-ADC specimens exhibited variable positivity for NKX3.1. This finding suggests that E/GE-ADC can sporadically stain positive for NKX3.1, introducing potential challenges in definitively determining the primary site of origin in certain clinical scenarios. Along with a literature review of NKX3.1 expression in other tumor types, our study provides additional important information about the extent to which this immunostain can be seen in E/GE-ADCs, which, to our knowledge, has not been reported., Competing Interests: ​Funding for this study is provided by the NorthShore University HealthSystem, Department of Pathology and Laboratory Medicine. The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Most cystic renal tumors after resection (Boniak IIF to IV cysts) have an indolent course despite the significantly higher proportion of malignant [ie, renal cell carcinoma (RCC)] diagnosis. Most cystic renal tumors have clear cell histology that include cystic clear cell RCC and multilocular cystic renal neoplasm of low malignant potential (MCNLMP). There is growing evidence to suggest that MCNLMP, cystic clear cell RCC, and noncystic clear cell RCC form a cystic-to-solid biological spectrum with MCNLMP representing the most indolent form and with cystic clear cell RCC behaving better than noncystic (solid) clear cell RCC. Extensively (>75%) cystic clear cell RCC also has an excellent outcome similar to MCNLMP stressing the need to reevaluate the histologic criteria that separate these 2 cystic clear cell tumors. Other tumors with clear cells that can be extensively cystic such as the recently reclassified noncancerous clear cell papillary renal tumor and the newly described MED15::TFE3 RCC also have indolent course and may mimic MCNLMP. Cystic features occur also in renal tumors with nonclear cell histology including tumors capable of metastasis such as acquired cystic disease-associated, tubulocystic, fumarate hydratase-deficient, and eosinophilic solid and cystic RCCs. Cystic imaging presentation of some renal tumors such as papillary RCC can be attributed in part to pseudocystic necrosis and hemorrhage. It is important to know that tubulocystic RCC may have a lower Bosniak class presentation that overlaps with benign renal cysts (Bosniak I to IIF) that are managed conservatively. This review highlights the cystic renal tumors with clear cell and nonclear cell morphologies including some novel RCC subtypes that may have cystic features. The presence of cystic features and their extent may aid in the classification and prognostication of renal neoplasms underscoring its increasing importance in the pathologic diagnosis and reporting of renal neoplasia., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: American men of African ancestry (AA) have higher prostate cancer incidence and mortality rates compared with American men of European ancestry (EA). Differences in genetic susceptibility mechanisms may contribute to this disparity., Methods: To gain insights into the regulatory mechanisms of prostate cancer susceptibility variants, we tested the association between SNPs and DNA methylation (DNAm) at nearby CpG sites across the genome in benign and cancer prostate tissue from 74 AA and 74 EA men. Genome-wide SNP data (from benign tissue) and DNAm were generated using Illumina arrays., Results: Among AA men, we identified 6,298 and 2,641 cis-methylation QTLs (meQTL; FDR of 0.05) in benign and tumor tissue, respectively, with 6,960 and 1,700 detected in EA men. We leveraged genome-wide association study (GWAS) summary statistics to identify previously reported prostate cancer GWAS signals likely to share a common causal variant with a detected meQTL. We identified nine GWAS-meQTL pairs with strong evidence of colocalization (four in EA benign, three in EA tumor, two in AA benign, and three in AA tumor). Among these colocalized GWAS-meQTL pairs, we identified colocalizing expression quantitative trait loci (eQTL) impacting four eGenes with known roles in tumorigenesis., Conclusions: These findings highlight epigenetic regulatory mechanisms by which prostate cancer-risk SNPs can modify local DNAm and/or gene expression in prostate tissue., Impact: Overall, our findings showed general consistency in the meQTL landscape of AA and EA men, but meQTLs often differ by tissue type (normal vs. cancer). Ancestry-based linkage disequilibrium differences and lack of AA representation in GWAS decrease statistical power to detect colocalization for some regions., (©2024 American Association for Cancer Research.)

Glandular lesions in the urinary tract or their associated pathologies can pose a diagnostic challenge. There is a variety of benign alterations and tumor types that need to be taken into account in differential diagnostic considerations. In recent times, efforts for better defining these alterations or lesions both on the histopathological and molecular levels have been undertaken. This article will provide an update on current diagnostic and molecular considerations of these lesions., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The 2022 International Society of Urological Pathology (ISUP) Consensus Conference on Urinary Bladder Cancer Working Group 2 was tasked to provide evidence-based proposals on the applications of grading in noninvasive urothelial carcinoma with mixed grades, invasive urothelial carcinoma including subtypes (variants) and divergent differentiations, and in pure non-urothelial carcinomas. Studies suggested that predominantly low-grade noninvasive papillary urothelial carcinoma with focal high-grade component has intermediate outcome between low- and high-grade tumors. However, no consensus was reached on how to define a focal high-grade component. By 2004 WHO grading, the vast majority of lamina propria-invasive (T1) urothelial carcinomas are high-grade, and the rare invasive low-grade tumors show only limited superficial invasion. While by 1973 WHO grading, the vast majority of T1 urothelial carcinomas are G2 and G3 and show significant differences in outcome based on tumor grade. No consensus was reached if T1 tumors should be graded either by the 2004 WHO system or by the 1973 WHO system. Because of the concern for underdiagnosis and underreporting with potential undertreatment, participants unanimously recommended that the presence of urothelial carcinoma subtypes and divergent differentiations should be reported. There was consensus that the extent of these subtypes and divergent differentiations should also be documented in biopsy, transurethral resection, and cystectomy specimens. Any distinct subtype and divergent differentiation should be diagnosed without a threshold cutoff, and each type should be enumerated in tumors with combined morphologies. The participants agreed that all subtypes and divergent differentiations should be considered high-grade according to the 2004 WHO grading system. However, participants strongly acknowledged that subtypes and divergent differentiations should not be considered as a homogenous group in terms of behavior. Thus, future studies should focus on individual subtypes and divergent differentiations rather than lumping these different entities into a single clinicopathological group. Likewise, clinical recommendations should pay attention to the potential heterogeneity of subtypes and divergent differentiations in terms of behavior and response to therapy. There was consensus that invasive pure squamous cell carcinoma and pure adenocarcinoma of the bladder should be graded according to the degree of differentiation. In conclusion, this summary of the International Society of Urological Pathology Working Group 2 proceedings addresses some of the issues on grading beyond its traditional application, including for papillary urothelial carcinomas with mixed grades and with invasive components. Reporting of subtypes and divergent differentiation is also addressed in detail, acknowledging their role in risk stratification. This report could serve as a guide for best practices and may advise future research and proposals on the prognostication of these tumors., Competing Interests: Conflicts of Interest and Source of 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.)

Large Language Models are forms of artificial intelligence that use deep learning algorithms to decipher large amounts of text and exhibit strong capabilities like question answering and translation. Recently, an influx of Large Language Models has emerged in the medical and academic discussion, given their potential widespread application to improve patient care and provider workflow. One application that has gained notable recognition in the literature is ChatGPT, which is a natural language processing "chatbot" technology developed by the artificial intelligence development software company OpenAI. It learns from large amounts of text data to generate automated responses to inquiries in seconds. In health care and academia, chatbot systems like ChatGPT have gained much recognition recently, given their potential to become functional, reliable virtual assistants. However, much research is required to determine the accuracy, validity, and ethical concerns of the integration of ChatGPT and other chatbots into everyday practice. One such field where little information and research on the matter currently exists is pathology. Herein, we present a literature review of pertinent articles regarding the current status and understanding of ChatGPT and its potential application in routine diagnostic pathology. In this review, we address the promises, possible pitfalls, and future potential of this application. We provide examples of actual conversations conducted with the chatbot technology that mimic hypothetical but practical diagnostic pathology scenarios that may be encountered in routine clinical practice. On the basis of this experience, we observe that ChatGPT and other chatbots already have a remarkable ability to distill and summarize, within seconds, vast amounts of publicly available data and information to assist in laying a foundation of knowledge on a specific topic. We emphasize that, at this time, any use of such knowledge at the patient care level in clinical medicine must be carefully vetted through established sources of medical information and expertise. We suggest and anticipate that with the ever-expanding knowledge base required to reliably practice personalized, precision anatomic pathology, improved technologies like future versions of ChatGPT (and other chatbots) enabled by expanded access to reliable, diverse data, might serve as a key ally to the diagnostician. Such technology has real potential to further empower the time-honored paradigm of histopathologic diagnoses based on the integrative cognitive assessment of clinical, gross, and microscopic findings and ancillary immunohistochemical and molecular studies at a time of exploding biomedical knowledge., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Grade Group 1 (GG1) prostate cancer should be managed with active surveillance (AS). Global uptake of AS remains disappointingly slow and heterogeneous. Removal of cancer labels has been proposed to reduce GG1 overtreatment. We sought to determine the impact of GG1 disease terminology on individual's perceptions and decision making., Methods: Discrete choice experiments were conducted on 3 cohorts: healthy men, canonical partners (partners), and patients with GG1 (patients). Participants reported preferences in a series of vignettes with 2 scenarios each, permuting key opinion leader-endorsed descriptors: biopsy (adenocarcinoma, acinar neoplasm, prostatic acinar neoplasm of low malignant potential [PAN-LMP], prostatic acinar neoplasm of uncertain malignant potential), disease (cancer, neoplasm, tumor, growth), management decision (treatment, AS), and recurrence risk (6%, 3%, 1%, <1%). Influence on scenario selection were estimated by conditional logit models and marginal rates of substitution. Two additional validation vignettes with scenarios portraying identical descriptors except the management options were embedded into the discrete choice experiments., Results: Across cohorts (194 healthy men, 159 partners, and 159 patients), noncancer labels PAN-LMP or prostatic acinar neoplasm of uncertain malignant potential and neoplasm, tumor, or growth were favored over adenocarcinoma and cancer (P < .01), respectively. Switching adenocarcinoma and cancer labels to PAN-LMP and growth, respectively, increased AS choice by up to 17%: healthy men (15%, 95% confidence interval [CI] = 10% to 20%, from 76% to 91%, P < .001), partners (17%, 95% CI = 12% to 24%, from 65% to 82%, P < .001), and patients (7%, 95% CI = 4% to 12%, from 75% to 82%, P = .063). The main limitation is the theoretical nature of questions perhaps leading to less realistic choices., Conclusions: "Cancer" labels negatively affect perceptions and decision making regarding GG1. Relabeling (ie, avoiding word "cancer") increases proclivity for AS and would likely improve public health., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Despite its low-risk nature, grade group 1 (GG 1) prostate cancer (PCa) remains overtreated. This suggests a disconnect between daily physician practice and the standard of care. We hypothesized that GG 1 disease is overtreated because of common misconceptions regarding its true natural history., Objective: To survey physicians worldwide to better understand their approach to management of GG 1 PCa., Design, Setting, and Participants: A 17-question survey was sent to urology, radiation oncology, and pathology societies on six continents, and was posted on Twitter. Responses were collected and analyzed., Outcome Measurements and Statistical Analysis: Pearson's χ 2 test was used to assess correlation between physician-related variables and the perception of active surveillance (AS) for GG 1 PCa. Logistic regression was used for multivariable analysis. Statistical analysis was performed using SPSS version 21., Results and Limitations: Among 1303 participants, 55% were urologists, 47% had completed fellowship, and 49% practice in an academic setting. Among the clinicians, 724 (83%) routinely recommend AS for GG 1 PCa and have never/rarely regretted it, while 18 (2%) "often" regretted it. Routine AS was more common among physicians aged <40 yr, those in practice for <10 yr, and those living in North America, Europe, or Australia/New Zealand. More than one-third of the respondents practicing in nonacademic settings reported 15-yr PCa mortality in low-risk PCa of >3%. Regarding reclassification of GG 1 to a precancerous lesion, 428 (39%) felt that this is a good idea, 340 (31%) disagreed, and 323 (30%) were uncertain. Those in support were more likely to be aged <40 yr (p = 0.001), in practice for <5 yr (p = 0.005), urologists (p < 0.001), and fellows trained in urologic oncology (p < 0.001). Opposition was common among pathologists (61%). Among terminologies proposed to replace "cancer" for GG 1 are neoplasm of low malignant potential (51% approval), indolent neoplasm rarely requiring treatment (23%), and indolent lesion of epithelial origin (8%)., Conclusions: AS is more commonly recommended by physicians who are younger, are fellowship-trained in urologic oncology, practice in academic settings, and are based in North America, Europe, or Australia/New Zealand. Misconceptions regarding AS outcomes may hinder its adoption. Frequent use of AS is associated with support for changing the "cancer" nomenclature., Patient Summary: In this study, we found that active surveillance remains underused in the management of low-risk prostate cancer because of incorrect perceptions regarding cancer outcomes. Omitting the word "cancer" for low-risk lesions is a challenging but promising effort that is favored by many clinicians, particularly by those who advocate for active surveillance., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Despite the innovations made to enhance smarter screening and conservative management for low-grade prostate cancer, overdiagnosis, and overtreatment remains a major health care problem. Driven by the primary goal of reducing harm to the patients, relabeling of nonlethal grade group 1 (GG 1) prostate cancer has been proposed but faced varying degrees of support and objection from clinicians and pathologists. GG 1 tumor exhibits histologic (invasive) and molecular features of cancer but paradoxically, if pure, is unable to metastasize, rarely extends out of the prostate, and if resected, has a cancer-specific survival approaching 100%. Most of the arguments against relabeling GG 1 relate to concerns of missing a higher-grade component through the unsampled area at biopsy. However, the designation of tumor benignity or malignancy should not be based on the shortcomings of a diagnostic procedure and sampling errors. This review explores possible solutions, mainly the feasibility of renaming GG 1 in radical prostatectomy (RP) with ramifications in biopsy diagnosis, acceptable for both pathologists and clinicians. One workable approach is to rename GG 1 in RP with a cautious neutral or nonbenign non-cancer term (eg, acinar neoplasm) using "defined criteria" that will stop the indiscriminate reporting of every GG 1 in biopsy as carcinoma including eventual insignificant microtumors in RPs. Use of a corresponding noncommittal term at biopsy while commenting on the possibility of an undersampled nonindolent cancer, might reduce the pathologist's concerns about upgrading. Dropping the word "carcinoma" in biopsy preempts the negative consequences of labeling the patient with cancer, including unnecessary definitive therapy (the root cause of overtreatment). Renaming should retain the status quo of contemporary grading and risk stratifications for management algorithms while trying to minimize overtreatment. However, the optimal approach to find answers to this issue is through multidisciplinary discussions of key stakeholders with a specific focus on patient-centered concerns and their ramifications in our practices. GG 1 renaming has been brought up in the past and came up again despite the continued counterarguments, and if not addressed more comprehensively will likely continue to reemerge as overdiagnosis, overtreatment, and patient's sufferings persist., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate how blood levels of prostate-specific antigen (PSA) relate to prostate volume of benign tissue, Gleason pattern 3 (GP3) and Gleason pattern 4 (GP4) cancer., Methods: The cohort included 2209 consecutive men undergoing radical prostatectomy at 2 academic institutions with pT2N0, Grade Group 1-4 prostate cancer and an undetectable postoperative PSA. Volume of benign, GP3, and GP4 were estimated. The primary analysis evaluated the association between PSA and volume of each type of tissue using multivariable linear regression. R 2 , a measure of explained variation, was calculated using a multivariable model., Results: Estimated contribution to PSA was 0.04/0.06 ng/mL/cc for benign, 0.08/0.14 ng/mL/cc for GP3, and 0.62/0.80 ng/ml/cc for GP4 for the 2 independent cohorts, respectively. GP4 was associated with 6 to 8-fold more PSA per cc compared to GP3 and 15-fold higher compared to benign tissue. We did not observe a difference between PSA per cc for GP3 vs. benign tissue (P = 0.2). R 2 decreased only slightly when removing age (0.006/0.018), volume of benign tissue (0.051/0.054) or GP3 (0.014/0.023) from the model. When GP4 was removed, R 2 decreased 0.051/0.310. PSA density (PSA divided by prostate volume) was associated with volume of GP4 but not GP3, after adjustment for benign volume., Conclusion: Gleason pattern 4 cancer contributes considerably more to PSA and PSA density per unit volume compared to GP3 and benign tissue. Contributions from GP3 and benign are similar. Further research should examine the utility of determining clinical management recommendations by absolute volume of GP4 rather than the ratio of GP3 to GP4., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Classification of the putative flat preneoplastic and neoplastic lesions of the urothelium with features subthreshold for urothelial carcinoma in situ remains a challenging, indeed, vexing problem in diagnostic surgical pathology. This area, subtending lesions including flat urothelial hyperplasia, urothelial dysplasia, and atypia of unknown significance, has struggled under evolving classifications, changing criteria, and limited clinical actionability, all confounded by the recognized lack of diagnostic reproducibility. Herein, we review the state of the literature around these lesions, reviewing contemporary criteria and definitions, assessing the arguments in favor and against of retaining hyperplasia, dysplasia, and atypia of unknown significance as diagnostic entities. We clarify the intent of the original definitions for dysplasia as a lesion felt to be clearly neoplastic but with morphologic features that fall short of the threshold of urothelial carcinoma in situ. While several pathologists, including some experts in the field, conflate the term dysplasia with urothelial atypia of unknown significance, the latter is defined as a descriptive diagnosis term to express diagnostic uncertainty of a lesion of whether it is clearly reactive or neoplastic. Both molecular studies and clinical needs are considered, as we outline our approach on diagnosing each of these lesions in clinical practice. Recommendations are made to guide consistency and interoperability in future scholarship, and the place of these lesions in context of evolving trends in the field is considered., (© 2022. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Background: Diffusion-weighted imaging (DWI) is commonly used to detect prostate cancer, and a major clinical challenge is differentiating aggressive from indolent disease., Purpose: To compare 14 site-specific parametric fitting implementations applied to the same dataset of whole-mount pathologically validated DWI to test the hypothesis that cancer differentiation varies with different fitting algorithms., Study Type: Prospective., Population: Thirty-three patients prospectively imaged prior to prostatectomy., Field Strength/sequence: 3 T, field-of-view optimized and constrained undistorted single-shot DWI sequence., Assessment: Datasets, including a noise-free digital reference object (DRO), were distributed to the 14 teams, where locally implemented DWI parameter maps were calculated, including mono-exponential apparent diffusion coefficient (MEADC), kurtosis (K), diffusion kurtosis (DK), bi-exponential diffusion (BID), pseudo-diffusion (BID*), and perfusion fraction (F). The resulting parametric maps were centrally analyzed, where differentiation of benign from cancerous tissue was compared between DWI parameters and the fitting algorithms with a receiver operating characteristic area under the curve (ROC AUC)., Statistical Test: Levene's test, P < 0.05 corrected for multiple comparisons was considered statistically significant., Results: The DRO results indicated minimal discordance between sites. Comparison across sites indicated that K, DK, and MEADC had significantly higher prostate cancer detection capability (AUC range = 0.72-0.76, 0.76-0.81, and 0.76-0.80 respectively) as compared to bi-exponential parameters (BID, BID*, F) which had lower AUC and greater between site variation (AUC range = 0.53-0.80, 0.51-0.81, and 0.52-0.80 respectively). Post-processing parameters also affected the resulting AUC, moving from, for example, 0.75 to 0.87 for MEADC varying cluster size., Data Conclusion: We found that conventional diffusion models had consistent performance at differentiating prostate cancer from benign tissue. Our results also indicated that post-processing decisions on DWI data can affect sensitivity and specificity when applied to radiological-pathological studies in prostate cancer., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 3., (© 2021 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

The World Health Organization (WHO) recommends grading of clear cell renal cell carcinoma (RCC) and papillary RCC using the WHO/International Society of Urological Pathology (ISUP) grade, which is primarily based on nuclear features. As the spectrum of RCC continues to evolve, with more recently described subtypes in the past decade, literature evidence on grading these subtypes is limited or not available for some tumor types. Herein, we outline a pragmatic approach to the topic of grading RCC, dividing the contemporarily described RCC subtypes into 7 categories based on the potential clinical applicability of grading as a useful prognostic parameter: (1) RCC subtypes that are reasonably validated and recommended for WHO/ISUP grading; (2) RCC subtypes where WHO/ISUP is not applicable; (3) RCC subtypes where WHO/ISUP grading is potentially clinically useful; (4) inherently aggressive RCC subtypes where histologic classification itself confers an aggressive biologic potential; (5) renal epithelial tumors where WHO/ISUP grading provides potentially misleading prognostic implication; (6) renal epithelial neoplasms where low WHO/ISUP grade features are a prerequisite for accurate histologic classification; and (7) renal epithelial neoplasms with no or limited data on grading or incomplete understanding of the biologic potential. Our aim in outlining this approach is 2-fold: (a) identify the gaps in understanding and application of grading in RCC subtypes so that researchers in the field may perform additional studies on the basis of which the important pathologic function of assignment of grade may be recommended to be performed as a meaningful exercise across a wider spectrum of RCC; and (b) to provide guidance in the interim to surgical pathologists in terms of providing clinically useful grading information in RCC based on currently available clinicopathologic information., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

A unique subtype of biphasic renal cell carcinoma (RCC) was recently described and termed biphasic hyalinizing psammomatous RCC (BHPRCC). This tumor shows a dual population of larger cells and small cells surrounding basement membrane-like materials and invariably has papillary features, hyalinized stroma, and psammoma calcifications. The biphasic pattern in BHPRCC may resemble that of RCC associated with TFEB gene fusion or t (6;11) RCC. However, all reported BHPRCCs had no TFEB alterations and all were associated with neurofibromin 2 (NF2) mutations. Herein, we present three biphasic RCCs encompassing the reported BHPRCC morphologies. One RCC showed solid, nested, papillary, and tubular growths, with biphasic pattern of larger cells surrounding clusters of smaller cells arranged around basement membrane-like materials, and harbored NF2 mutation consistent with BHPRCC. This patient developed bone metastasis 59 months after surgery. The two other biphasic RCCs showed morphologic overlap to BHPRCC, but in addition had other features not seen in BHPRCC, such as lack of papillary pattern, having large tubules containing mucinous to collagenous spherules (mucicarmine and collagen IV positive) bordered by a single layer of small cells with occasional central targetoid psammoma bodies, and with widespread nuclear grooves. Interestingly, these two tumors also did not show alterations in NF2 or TFEB including translocation or amplification. In conclusion, we report another example of the novel BHPRCC that had metastasized and two biphasic RCCs not associated with NF2 or TFEB alterations; the latter two shared additional distinct morphological features and may represent a unique biphasic RCC distinct from the novel BHPRCC., (Copyright © 2021 Elsevier Inc. All rights reserved.)

New strategies are needed to predict and overcome metastatic progression and therapy resistance in prostate cancer. One potential clinical target is the stem cell transcription factor SOX2, which has a critical role in prostate development and cancer. We thus investigated the impact of SOX2 expression on patient outcomes and its function within prostate cancer cells. Analyses of SOX2 expression among a case-control cohort of 1028 annotated tumor specimens demonstrated that SOX2 expression confers a more rapid time to metastasis and decreased patient survival after biochemical recurrence. SOX2 ChIP-Seq analyses revealed SOX2-binding sites within prostate cancer cells which differ significantly from canonical embryonic SOX2 gene targets, and prostate-specific SOX2 gene targets are associated with multiple oncogenic pathways. Interestingly, phenotypic and gene expression analyses after CRISPR-mediated deletion of SOX2 in castration-resistant prostate cancer cells, as well as ectopic SOX2 expression in androgen-sensitive prostate cancer cells, demonstrated that SOX2 promotes changes in multiple metabolic pathways and metabolites. SOX2 expression in prostate cancer cell lines confers increased glycolysis and glycolytic capacity, as well as increased basal and maximal oxidative respiration and increased spare respiratory capacity. Further, SOX2 expression was associated with increased quantities of mitochondria, and metabolomic analyses revealed SOX2-associated changes in the metabolism of purines, pyrimidines, amino acids and sugars, and the pentose phosphate pathway. Analyses of SOX2 gene targets with central functions metabolism (CERK, ECHS1, HS6SDT1, LPCAT4, PFKP, SLC16A3, SLC46A1, and TST) document significant expression correlation with SOX2 among RNA-Seq datasets derived from patient tumors and metastases. These data support a key role for SOX2 in metabolic reprogramming of prostate cancer cells and reveal new mechanisms to understand how SOX2 enables metastatic progression, lineage plasticity, and therapy resistance. Further, our data suggest clinical opportunities to exploit SOX2 as a biomarker for staging and imaging, as well as a potential pharmacologic target., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: To validate prostate tissue composition measured using hybrid multi-dimensional MRI (HM-MRI) by comparing with reference standard (ground truth) results from pathologists' interpretation of clinical histopathology slides following whole mount prostatectomy., Materials and Methods: 36 prospective participants with biopsy-confirmed prostate cancer underwent 3 T MRI prior to radical prostatectomy. Axial HM-MRI was acquired with all combinations of echo times of 57, 70, 150, 200 ms and b-values of 0, 150, 750, 1500 s/mm 2 and data were fitted using a 3-compartment signal model using custom software to generate volumes for each tissue component (stroma, epithelium, lumen). Three experienced genitourinary pathologists independently as well as in consensus reviewed each histology image and provide an estimate of percentage of epithelium and lumen for regions-of-interest corresponding to MRI (n = 165; 64 prostate cancers and 101 benign tissue). Agreement statistics using total deviation index (TDI 0.9 ) was performed for tissue composition measured using HM-MRI and reference standard results from pathologists' consensus., Results: Based on the initial results showing typical variation among pathologists TDI 0.9  = 25%, we determined we will declare acceptable agreement if the 95% one-sided upper confident limit of TDI 0.9 is less than 30%. The results of tissue composition measurement from HM-MRI compared to ground truth results from the consensus of 3 pathologists, reveal that ninety percent of absolute paired differences (TDI 0.9 ) were within 18.8% and 22.4% in measuring epithelium and lumen, respectively. We are 95% confident that 90% of absolute paired differences were within 20.6% and 24.2% in measuring epithelium and lumen, respectively. These were less than our criterion of 30% and inter-pathologists' agreement (22.3% for epithelium and 24.2% for lumen) and therefore we accept the agreement performance of HM-MRI. The results revealed excellent area under the ROC curve for differentiating cancer from benign tissue based on epithelium (HM-MRI: 0.87, pathologists: 0.97) and lumen volume (HM-MRI: 0.85, pathologists: 0.77)., Conclusion: The agreement in tissue composition measurement using hybrid multidimensional MRI and consensus of pathologists is on par with the inter-raters (pathologists) agreement., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: ISUP Grade Group 1 prostate cancer is the lowest histologic grade of prostate cancer with a clinically indolent course. Removal of the term 'cancer' has been proposed and has historical precedent both in urothelial and thyroid carcinoma., Methods: Evidence-based review identifying arguments for and against Grade Group 1 being referred to as cancer., Results: Grade Group 1 has histologic evidence of tissue microinvasion and 0.3-3% rate of extraprostatic extension. Genomic evaluation suggests overlap of a minority of Grade Group 1 cancers with those of Grade Group 2. Conversely, Grade Group 1 tumors appear to have distinct genetic and genomic profiles from Grade Group 3 or higher tumors. Grade Group 1 has no documented ability for regional or distant metastasis and long-term follow up after treatment or active surveillance is safe with excellent oncologic outcomes., Discussion: Grade Group 1 prostate cancer, while showing evidence of neoplasia on histology has a remarkably indolent natural history more akin to non-neoplastic precursor lesions. Consideration should be given to renaming Grade Group 1 prostate cancer, which has the potential to minimize overtreatment, treatment-related side effects, patient anxiety, and financial burden on the healthcare system., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Lower incidence and mortality rates from prostate cancer (PCa) have been shown in Asian men in general compared to Westerners. This is the first study detailing the clinicopathologic features of resected prostate cancer in Filipino men living in the Philippines (PH). This study investigated the supposed "lower risk" Filipino and "higher risk" American PCa patients from the PH and the United States of America (USA), respectively. We examined 348 (176 from PH, 172 from USA) radical prostatectomy cases. The clinicopathologic features of both groups (age at time of diagnosis, preoperative prostate-specific antigen [pre-op PSA] level, Gleason score [GS], Grade groups [GG], margin involvement, extraprostatic extension [EPE], seminal vesicle invasion [SVI], and regional lymph node [RLN] metastasis) were compared. Six of seven prognosticators examined were more strongly associated with Filipinos than with Americans. Filipinos were older at diagnosis (PH: 64.32 ± 6.56 years vs USA: 58.98 ± 8.08 years) and had higher pre-op PSA levels (PH: 21.39 ± 46.40 ng ml -1 vs USA: 7.63 ± 9.19 ng ml -1 ). Filipino men had more advanced grade, GG 2 with minor pattern 5 (PH: 6.2% vs USA: 2.9%) and GG 5 (PH: 14.8% vs USA: 3.5%). Likewise, other adverse pathological features in margin positivity (PH: 52.3% vs USA: 23.8%), focal EPE (PH: 14.2% vs USA: 2.3%), and SVI (PH: 17.1% vs USA: 5.8%) were more commonly observed in Filipinos. This study reveals the prognostic disadvantage of Filipinos versus Americans and highlights an important difference of Filipinos from other studied Asian ethnicities that have repeatedly been shown to have lower-risk PCa. This study, the first on Filipino PCa patients with RP, suggests the need to modify Western-based risk stratification when employed in other countries like the PH., Competing Interests: None

The Genitourinary Pathology Society (GUPS) undertook a critical review of the recent advances in bladder neoplasia with a focus on issues relevant to the practicing surgical pathologist for the understanding and effective reporting of bladder cancer, emphasizing particularly on the newly accumulated evidence post-2016 World Health Organization (WHO) classification. The work is presented in 2 manuscripts. Here, in the first, we revisit the nomenclature and classification system used for grading flat and papillary urothelial lesions centering on clinical relevance, and on dilemmas related to application in routine reporting. As patients of noninvasive bladder cancer frequently undergo cystoscopy and biopsy in their typically prolonged clinical course and for surveillance of disease, we discuss morphologies presented in these scenarios which may not have readily applicable diagnostic terms in the WHO classification. The topic of inverted patterns in urothelial neoplasia, particularly when prominent or exclusive, and beyond inverted papilloma has not been addressed formally in the WHO classification. Herein we provide a through review and suggest guidelines for when and how to report such lesions. In promulgating these GUPS recommendations, we aim to provide clarity on the clinical application of these not so uncommon diagnostically challenging situations encountered in routine practice, while also importantly advocating consistent terminology which would inform future work., Competing Interests: The authors have no funding or conflicts of interests to disclose relevant to this work., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The College of American Pathologists Cancer Protocols have offered guidance to pathologists for standard cancer pathology reporting for more than 35 years. The adoption of computer readable versions of these protocols by electronic health record and laboratory information system (LIS) vendors has provided a mechanism for pathologists to report within their LIS workflow, in addition to enabling standardized structured data capture and reporting to downstream consumers of these data such as the cancer surveillance community. This paper reviews the history of the Cancer Protocols and electronic Cancer Checklists, outlines the current use of these critically important cancer case reporting tools, and examines future directions, including plans to help improve the integration of the Cancer Protocols into clinical, public health, research, and other workflows.

Contemporary subspecialization of practice in prostate pathology has seen a transition to complex, nuanced reporting, where a growing number of histopathologic parameters may signal differences in patient management. In this context, the International Society of Urological Pathology (ISUP) and the Genitourinary Pathology Society (GUPS) both published proceedings papers on the grading of prostate cancer in 2019. Overall, the 2 prostate cancer grading manuscripts reached many of the same conclusions and recommendations. Yet, each consensus was conducted somewhat differently, and in a couple of key areas, each reached different conclusions and recommendations. Herein, sourced from the experience and viewpoints of members of both societies, we provide the practicing pathologist a summary of the shared recommendations, and of the discordances. It is anticipated that these 2 documents will inform future iterations of recommendations and guidelines for reporting prostate cancer by organizations such as the College of American Pathologists, the Royal College of Pathologists, and the European Society of Pathology, which will promote best practices for their respective constituents. Our goal is to provide the practicing pathologist a useful catalog of the main points of both, allowing each practitioner to make informed decisions and understand any divergent opinions as may arise between observers for individual cases.

Several molecular subtypes of bladder cancer were identified with differing clinical behavior and responses to platinum-based chemotherapy. But so far, their urothelial histomorphologic features, besides association with some variant histologies, have remained fully undefined. We sought to characterize the histological features of genomically classified bladder cancers more extensively to tumor in radical cystectomy (RC) specimens. Forty-eight bladder cancers submitted to The Cancer Genome Atlas (TCGA) were classified using the BASE47 genomic classifier into luminal subtype (LS) (14 cases), basal subtype (BS) (18 cases), and claudin-low subtype (CLS) (16 cases), and TCGA samples and the corresponding RC specimens were histologically assessed. Marked pleomorphism was more extensive in CLS tumors (87.5% had >15% extent) than in LS tumors (21.4%) (p = 0.0006), whereas the extent in BS tumors was in between LS and CLS tumors. Pleomorphism in distant carcinoma in situ appeared to correlate with that in the main tumor. Ki-67 proliferation was higher in CLS tumors (mean = 61%) than in LS tumors (mean = 29%) or BS (mean = 30%) (p < 0.001). Squamous differentiation was more extensive in BS and CLS tumors (38.2% of BS and CLS tumors versus 7.1% of LS tumors had >30% squamous, p = 0.040). Sarcomatoid change was present in BS and CLS tumors only. The micropapillary variant was identified in LS (3/14) and BS (4/18) tumors only. Histologic features associated with aggressiveness (eg, marked pleomorphism, high proliferation, and sarcomatoid change) are enriched in CLS tumors, correlating with its known poorer outcome that may provide hints in their microscopic distinction. Features more associated with BS than with LS tumors (eg, squamous, marked pleomorphism, and sarcomatoid change) are also identified or enhanced in CLS tumors, supporting the genomic findings suggesting CLS tumor as a hyperbasal form of BS tumor., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In current practice, prostate cancer staging alone is not sufficient to adequately assess the patient's prognosis and plan the management strategies. Multiple clinicopathological parameters and risk tools for prostate cancer have been developed over the past decades to better characterize the disease and provide an enhanced assessment of prognosis. Herein, we review novel prognostic biomarkers and their integration into risk assessment models for prostate cancer focusing on their capability to help avoid unnecessary imaging studies, biopsies and diagnosis of low risk prostate cancers, to help in the decision-making process between active surveillance and treatment intervention, and to predict recurrence after radical prostatectomy. There is an imperative need of reliable biomarkers to stratify prostate cancer patients that may benefit from different management approaches. The integration of biomarkers panel with risk assessment models appears to improve prostate cancer diagnosis and management. However, integration of novel genomic biomarkers in future prognostic models requires further validation in their clinical efficacy, standardization, and cost-effectiveness in routine application.

Introduction: The anatomic-based TNM classification is considered the benchmark in cancer staging and has been regularly updated since its inception. In the current era of precision medicine, the added intention for future TNM modifications is to heighten its impact in the more 'personalized' level of cancer care. In urologic cancers, this goal may be achieved by incorporating 'non-anatomic' factors into TNM, such as biomarkers (e.g. gene alterations, molecular subtypes, genomic classifiers) and risk assessment models (e.g. nomogram, look-up table), while maintaining the anatomic extent as the foundation of staging. These different prognosticators can be combined and integrated, may serve as substratifiers for T, N, or M categories, and perhaps, incorporated as elements in TNM stage groupings to enhance their prognostic capability in urologic cancers., Areas Covered: This review highlights candidate biomarkers and risk assessment models that can be explored to potentially improve TNM prognostication of bladder, prostate, kidney, and testicular cancers., Expert Opinion: Recent advances in molecular analysis have increased the understanding of the genomic, transcriptomic, and epigenetic features for biomarker use in prognostication of urologic cancers, which together with the available risk assessment models, may complement and overcome the limitations of the traditional TNM staging.

Five years after the last prostatic carcinoma grading consensus conference of the International Society of Urological Pathology (ISUP), accrual of new data and modification of clinical practice require an update of current pathologic grading guidelines. This manuscript summarizes the proceedings of the ISUP consensus meeting for grading of prostatic carcinoma held in September 2019, in Nice, France. Topics brought to consensus included the following: (1) approaches to reporting of Gleason patterns 4 and 5 quantities, and minor/tertiary patterns, (2) an agreement to report the presence of invasive cribriform carcinoma, (3) an agreement to incorporate intraductal carcinoma into grading, and (4) individual versus aggregate grading of systematic and multiparametric magnetic resonance imaging-targeted biopsies. Finally, developments in the field of artificial intelligence in the grading of prostatic carcinoma and future research perspectives were discussed.

Intraductal carcinoma of the prostate (IDC-P) has been recently recognized by the World Health Organization classification of prostatic tumors as a distinct entity, most often occurring concurrently with invasive prostatic adenocarcinoma (PCa). Whether documented admixed with PCa or in its rare pure form, numerous studies associate this entity with clinical aggressiveness. Despite increasing clinical experience and requirement of IDC-P documentation in protocols for synoptic reporting, the specifics of its potential contribution to assessment of grade group (GG) and cancer quantitation of PCa in both needle biopsies (NBx) and radical prostatectomy (RP) specimens remain unclear. Moreover, there are no standard guidelines for incorporating basal cell marker immunohistochemistry (IHC) in the diagnosis of IDC-P, either alone or as part of a cocktail with AMACR/racemase. An online survey containing 26 questions regarding diagnosis, reporting practices, and IHC resource utilization, focusing on IDC-P, was undertaken by 42 genitourinary subspecialists from 9 countries. The degree of agreement or disagreement regarding approaches to individual questions was classified as significant majority (>75%), majority (51% to 75%), minority (26% to 50%) and significant minority (≤25%). IDC-P with or without invasive cancer is considered a contraindication for active surveillance by the significant majority (95%) of respondents, although a majority (66%) also agreed that the clinical significance/behavior of IDC-P on NBx or RP with PCa required further study. The majority do not upgrade PCa based on comedonecrosis seen only in the intraductal component in NBx (62%) or RP (69%) specimens. Similarly, recognizable IDC-P with GG1 PCa was not a factor in upgrading in NBx (78%) or RP (71%) specimens. The majority (60%) of respondents include readily recognizable IDC-P in assessment of linear extent of PCa at NBx. A significant majority (78%) would use IHC to confirm or exclude intraductal carcinoma if other biopsies showed no PCa, while 60% would use it to confirm IDC-P with invasive PCa in NBx if it would change the overall GG assignment. Nearly half (48%, a minority) would use IHC to confirm IDC-P for accurate Gleason pattern 4 quantitation. A majority (57%) report the percentage of IDC-P when present, in RP specimens. When obvious Gleason pattern 4 or 5 PCa is present in RP or NBx, IHC is rarely to almost never used to confirm the presence of IDC-P by the significant majority (88% and 90%, respectively). Most genitourinary pathologists consider IDC-P to be an adverse prognostic feature independent of the PCa grade, although recommendations for standardization are needed to guide reporting of IDC-P vis a vis tumor quantitation and final GG assessment. The use of IHC varies widely and is performed for a multitude of indications, although it is used most frequently in scenarios where confirmation of IDC-P would impact the GG assigned. Further study and best practices recommendations are needed to provide guidance with regards to the most appropriate indications for IHC use in scenarios regarding IDC-P.