Publications by authors named "Mahul B Amin"

214 Publications

Low-grade Oncocytic Fumarate Hydratase-deficient Renal Cell Carcinoma: An Update on Biologic Potential, Morphologic Spectrum, and Differential Diagnosis With Other Low-grade Oncocytic Tumors.

Adv Anat Pathol 2021 Nov;28(6):396-407

Department of Pathology and Laboratory Medicine, University of Tennessee Health Sciences, Memphis, TN.

Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is typically considered a high-grade, aggressive subtype of RCC that frequently arises in the setting of hereditary leiomyomatosis-renal cell carcinoma (HLRCC) syndrome. Increasing experience with HLRCC-associated RCC and FH-deficient RCC has resulted in recognition of tumors with lower grade morphologic features, overlapping with those of succinate dehydrogenase-deficient RCC and other low-grade oncocytic tumors. In this review article, we report a previously unpublished case that was recently encountered in our practice and review cases in the current literature with an aim of getting a better understanding of these oncocytic tumors and their morphologic spectrum. The 13 cases reviewed were approximately equally distributed across males and females, occurred at a younger age, and were more frequently seen in the right kidney, with both unifocal and multifocal presentations. While most presented an exclusive, low-grade oncocytic morphology, in 4 cases they were associated with either separate high-grade tumors, or as a secondary pattern in an otherwise conventional high-grade FH-deficient RCC. Loss of FH and 2 succinyl cysteine (2SC) positivity by immunohistochemistry supported their diagnosis, and are recommended to be performed alongside CD117, CK7, and CK20 in to aid classification in challenging oncocytic tumors. When occurring in isolation, these tumors are distinctive from their high-grade counterparts, with no reported adverse outcomes in cases reported thus far. As such, accurate diagnosis of this low-grade pattern among FH-deficient RCCs is worthwhile not only due to its association with HLRCC and need of genetic counseling and surveillance, but also due to more favorable prognosis. Finally, increasing experience with the low-grade end of the morphologic spectrum of FH deficient RCC reiterates that not all tumors of this subtype of RCC have a uniformly aggressive outcome.
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http://dx.doi.org/10.1097/PAP.0000000000000321DOI Listing
November 2021

Updated pathology reporting standards for bladder cancer: biopsies, transurethral resections and radical cystectomies.

World J Urol 2021 Sep 23. Epub 2021 Sep 23.

Department of Pathology and Laboratory Medicine and Urology, University of Tennessee Health Science, Memphis, TN, USA.

Aim: Optimal management of bladder cancer requires an accurate, standardised and timely pathological diagnosis, and close communication between surgeons and pathologists. Here, we provide an update on pathology reporting standards of transurethral resections of the bladder and cystectomies.

Methods: We reviewed recent literature, focusing on developments between 2013 and 2021.

Results: Published reporting standards developed by pathology organizations have improved diagnosis and treatment. Tumor sub-staging and subtyping has gained increased attention. Lymph nodes continue to be an area of debate, and their staging has seen minor modifications. Several tasks, particularly regarding specimen preparation ("grossing"), are not yet standardized and offer opportunity for improvement. Molecular classification is rapidly evolving, but currently has only limited impact on management.

Conclusion: Pathological reporting of bladder cancer is continuously evolving and remains challenging in some areas. This review provides an overview of recent major developments, with a particular focus on published reporting standards.
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http://dx.doi.org/10.1007/s00345-021-03831-1DOI Listing
September 2021

Prognostic value of cribriform size, percentage, and intraductal carcinoma in Gleason score 7 prostate cancer with cribriform Gleason pattern 4.

Hum Pathol 2021 Sep 17;118:18-29. Epub 2021 Sep 17.

Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address:

Cribriform Gleason pattern 4 (CGP4) is an indicator of poor prognosis in Gleason Score 7 prostate cancer; however, the significance of the size and percentage of this pattern and the presence of concomitant intraductal carcinoma (IDC) in these patients is unclear. To study the significance of these parameters in radical prostatectomy specimens, 165 cases with CGP4 were identified and reviewed (2017-2019). The size and percentage cribriform pattern and presence of IDC were noted and correlated with adverse pathological features and biochemical recurrence (BCR)-free survival. On review, 156 cases had CGP4 (Grade Group 2: 87 and Grade Group 3: 69). Large cribriform pattern and cribriform percentage of >20% showed significant association with extraprostatic extension, surgical margin positivity, and presence of IDC, whereas the presence of IDC was associated with all the analyzed adverse pathological features. BCR was seen in 22 of 111 (20%) patients after a median follow-up of 11 months, and of these, 21 had large cribriform pattern. On univariate analysis, all parameters had significant predictive values for BCR-free survival except for tertiary Gleason pattern 5. On multivariate analysis, while >20% cribriform pattern was trending to be an independent predictor, only lymphovascular invasion was statistically significant. Large cribriform pattern, >20% cribriform, and presence of IDC are additional pathologic parameters of potential value in identifying patients with high risk for early BCR.
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http://dx.doi.org/10.1016/j.humpath.2021.09.005DOI Listing
September 2021

Adding Short-Term Androgen Deprivation Therapy to Radiation Therapy in Men With Localized Prostate Cancer: Long-Term Update of the NRG/RTOG 9408 Randomized Clinical Trial.

Int J Radiat Oncol Biol Phys 2021 Sep 1. Epub 2021 Sep 1.

Massachusetts General Hospital Cancer Center, Boston, Massachusetts.

Purpose: For men with localized prostate cancer, NRG Oncology/Radiation Therapy Oncology Group (RTOG) 9408 demonstrated that adding short-term androgen deprivation therapy (ADT) to radiation therapy (RT) improved the primary endpoint of overall survival (OS) and improved disease-specific mortality (DSM), biochemical failure (BF), local progression, and freedom from distant metastases (DM). This study was performed to determine whether the short-term ADT continued to improve OS, DSM, BF, and freedom from DM with longer follow-up.

Methods And Materials: From 1994 to 2001, NRG/RTOG 9408 randomized 2028 men from 212 North American institutions with T1b-T2b, N0 prostate adenocarcinoma and prostate-specific antigen (PSA) ≤20ng/mL to RT alone or RT plus short-term ADT. Patients were stratified by PSA, tumor grade, and surgical versus clinical nodal staging. ADT was flutamide with either goserelin or leuprolide for 4 months. Prostate RT (66.6 Gy) was started after 2 months. OS was calculated at the date of death from any cause or at last follow-up. Secondary endpoints were DSM, BF, local progression, and DM. Acute and late toxic effects were assessed using RTOG toxicity scales.

Results: Median follow-up in surviving patients was 14.8 years (range, 0.16-21.98). The 10-year and 18-year OS was 56% and 23%, respectively, with RT alone versus 63% and 23% with combined therapy (HR 0.94; 95% confidence interval [CI], 0.85-1.05; P = .94). The hazards were not proportional (P = .003). Estimated restricted mean survival time at 18 years was 11.8 years (95% CI, 11.4-12.1) with combined therapy versus 11.3 years with RT alone (95% CI, 10.9-11.6; P = .05). The 10-year and 18-year DSM was 7% and 14%, respectively, with RT alone versus 3% and 8% with combined therapy (HR 0.56; 95% CI, 0.41-0.75; P < .01). DM and BF favored combined therapy at 18 years. Rates of late grade ≥3 hepatic, gastrointestinal, and genitourinary toxicity were ≤1%, 3%, and 8%, respectively, with combined therapy versus ≤1%, 2%, and 5% with RT alone.

Conclusions: Further follow-up demonstrates that OS converges at approximately 15 years, by which point the administration of 4 months of ADT had conferred an estimated additional 6 months of life.
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http://dx.doi.org/10.1016/j.ijrobp.2021.08.031DOI Listing
September 2021

The Genitourinary Pathology Society Update on Classification of Variant Histologies, T1 Substaging, Molecular Taxonomy, and Immunotherapy and PD-L1 Testing Implications of Urothelial Cancers.

Adv Anat Pathol 2021 Jul;28(4):196-208

Department of Pathology, West German Cancer Center/University Hospital Essen, University of Duisburg-Essen, Duisburg.

The Genitourinary Pathology Society (GUPS) undertook a critical review of the recent advances in bladder cancer focusing on important topics of high interest for the practicing surgical pathologist and urologist. This review represents the second of 2 manuscripts ensuing from this effort. Herein, we address the effective reporting of bladder cancer, focusing particularly on newly published data since the last 2016 World Health Organization (WHO) classification. In addition, this review focuses on the importance of reporting bladder cancer with divergent differentiation and variant (subtypes of urothelial carcinoma) histologies and the potential impact on patient care. We provide new recommendations for reporting pT1 staging in diagnostic pathology. Furthermore, we explore molecular evolution and classification, emphasizing aspects that impact the understanding of important concepts relevant to reporting and management of patients.
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http://dx.doi.org/10.1097/PAP.0000000000000309DOI Listing
July 2021

The Genitourinary Pathology Society Update on Classification and Grading of Flat and Papillary Urothelial Neoplasia With New Reporting Recommendations and Approach to Lesions With Mixed and Early Patterns of Neoplasia.

Adv Anat Pathol 2021 Jul;28(4):179-195

Medicine.

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.
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http://dx.doi.org/10.1097/PAP.0000000000000308DOI Listing
July 2021

SWI/SNF-deficient neoplasms of the genitourinary tract.

Semin Diagn Pathol 2021 May 3;38(3):212-221. Epub 2021 Apr 3.

Department of Pathology and Laboratory Medicine, University of Tennessee Health Sciences, Memphis, TN, USA; Department of Urology, USC Keck School of Medicine, Los Angeles, CA, USA.

Since the discovery of association of SMARCB1 mutations with malignant rhabdoid tumors and renal medullary carcinoma, mutations in genes of the SWI/SNF chromatin remodeling complex have been increasingly identified across a diverse spectrum of neoplasms. As a group, SWI/SNF complex subunit mutations are now recognized to be the second most frequent type of mutations across tumors. SMARCB1 mutations were originally reported in malignant rhabdoid tumors of the kidney and thought to be pathognomonic for this tumor. However, more broadly, recognition of typical rhabdoid cytomorphology and SMARCB1 mutations beyond rhabdoid tumors has changed our understanding of the pathobiology of these tumors. While mutations of SWI/SNF complex are diagnostic of rhabdoid tumors and renal medullary carcinoma, their clinical relevance extends to potential prognostic and predictive utility in other tumors as well. Beyond SMARCB1, the PBRM1 and ARID1A genes are the most frequently altered members of the SWI/SNF complex in genitourinary neoplasms, especially in clear cell renal cell carcinoma and urothelial carcinoma. In this review, we provide an overview of alterations in the SWI/SNF complex encountered in genitourinary neoplasms and discuss their increasing clinical importance.
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http://dx.doi.org/10.1053/j.semdp.2021.03.007DOI Listing
May 2021

New developments in existing WHO entities and evolving molecular concepts: The Genitourinary Pathology Society (GUPS) update on renal neoplasia.

Mod Pathol 2021 07 4;34(7):1392-1424. Epub 2021 Mar 4.

Department of Pathology MD Anderson Cancer Center, Houston, TX, USA.

The Genitourinary Pathology Society (GUPS) reviewed recent advances in renal neoplasia, particularly post-2016 World Health Organization (WHO) classification, to provide an update on existing entities, including diagnostic criteria, molecular correlates, and updated nomenclature. Key prognostic features for clear cell renal cell carcinoma (RCC) remain WHO/ISUP grade, AJCC/pTNM stage, coagulative necrosis, and rhabdoid and sarcomatoid differentiation. Accrual of subclonal genetic alterations in clear cell RCC including SETD2, PBRM1, BAP1, loss of chromosome 14q and 9p are associated with variable prognosis, patterns of metastasis, and vulnerability to therapies. Recent National Comprehensive Cancer Network (NCCN) guidelines increasingly adopt immunotherapeutic agents in advanced RCC, including RCC with rhabdoid and sarcomatoid changes. Papillary RCC subtyping is no longer recommended, as WHO/ISUP grade and tumor architecture better predict outcome. New papillary RCC variants/patterns include biphasic, solid, Warthin-like, and papillary renal neoplasm with reverse polarity. For tumors with 'borderline' features between oncocytoma and chromophobe RCC, a term "oncocytic renal neoplasm of low malignant potential, not further classified" is proposed. Clear cell papillary RCC may warrant reclassification as a tumor of low malignant potential. Tubulocystic RCC should only be diagnosed when morphologically pure. MiTF family translocation RCCs exhibit varied morphologic patterns and fusion partners. TFEB-amplified RCC occurs in older patients and is associated with more aggressive behavior. Acquired cystic disease (ACD) RCC-like cysts are likely precursors of ACD-RCC. The diagnosis of renal medullary carcinoma requires a negative SMARCB1 (INI-1) expression and sickle cell trait/disease. Mucinous tubular and spindle cell carcinoma (MTSCC) can be distinguished from papillary RCC with overlapping morphology by losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22. MTSCC with adverse histologic features shows frequent CDKN2A/2B (9p) deletions. BRAF mutations unify the metanephric family of tumors. The term "fumarate hydratase deficient RCC" ("FH-deficient RCC") is preferred over "hereditary leiomyomatosis and RCC syndrome-associated RCC". A low threshold for FH, 2SC, and SDHB immunohistochemistry is recommended in difficult to classify RCCs, particularly those with eosinophilic morphology, occurring in younger patients. Current evidence does not support existence of a unique tumor subtype occurring after chemotherapy/radiation in early childhood.
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http://dx.doi.org/10.1038/s41379-021-00779-wDOI Listing
July 2021

Novel, emerging and provisional renal entities: The Genitourinary Pathology Society (GUPS) update on renal neoplasia.

Mod Pathol 2021 06 1;34(6):1167-1184. Epub 2021 Feb 1.

Department of Pathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.

The Genitourinary Pathology Society (GUPS) undertook a critical review of the recent advances in renal neoplasia, particularly focusing on the newly accumulated evidence post-2016 World Health Organization (WHO) classification. In the era of evolving histo-molecular classification of renal neoplasia, morphology is still key. However, entities (or groups of entities) are increasingly characterized by specific molecular features, often associated either with recognizable, specific morphologies or constellations of morphologies and corresponding immunohistochemical profiles. The correct diagnosis has clinical implications leading to better prognosis, potential clinical management with targeted therapies, may identify hereditary or syndromic associations, which may necessitate appropriate genetic testing. We hope that this undertaking will further facilitate the identification of these entities in practice. We also hope that this update will bring more clarity regarding the evolving classification of renal neoplasia and will further reduce the category of "unclassifiable renal carcinomas/tumors". We propose three categories of novel entities: (1) "Novel entity", validated by multiple independent studies; (2) "Emerging entity", good compelling data available from at least two or more independent studies, but additional validation is needed; and (3) "Provisional entity", limited data available from one or two studies, with more work required to validate them. For some entities initially described using different names, we propose new terminologies, to facilitate their recognition and to avoid further diagnostic dilemmas. Following these criteria, we propose as novel entities: eosinophilic solid and cystic renal cell carcinoma (ESC RCC), renal cell carcinoma with fibromyomatous stroma (RCC FMS) (formerly RCC with leiomyomatous or smooth muscle stroma), and anaplastic lymphoma kinase rearrangement-associated renal cell carcinoma (ALK-RCC). Emerging entities include: eosinophilic vacuolated tumor (EVT) and thyroid-like follicular renal cell carcinoma (TLFRCC). Finally, as provisional entities, we propose low-grade oncocytic tumor (LOT), atrophic kidney-like lesion (AKLL), and biphasic hyalinizing psammomatous renal cell carcinoma (BHP RCC).
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http://dx.doi.org/10.1038/s41379-021-00737-6DOI Listing
June 2021

Mesonephric (Wolffian-derived) Adenocarcinoma of the Female Urethra.

Am J Surg Pathol 2021 04;45(4):543-549

Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN.

The current World Health Organization (WHO) classification of adenocarcinoma of the urinary tract including the urethra includes uncommon Müllerian-derived carcinomas such as clear cell and endometrioid adenocarcinomas. The concept of primary mesonephric (Wolffian-derived) adenocarcinoma (MA) in the urethra (and urinary tract in general) is currently regarded as controversial as the term "mesonephric" had been also inaccurately applied in the past to label Müllerian-derived carcinomas, particularly clear cell adenocarcinoma. Further, pathologically well-documented or bona fide urethral MAs have not yet to be reported. Herein, we describe 2 examples of MA in elderly females that primarily presented in the urethra and manifested clinically with obstructive lower urinary tract symptoms. Both tumors exhibited histology similar to those in MAs of the female genital tract including the distinctive tubular proliferations with luminal eosinophilic materials. The first case, in addition, showed a variety of patterns including ductal (glandular), solid, fused/sieve-like tubules, dilated tubules, and spindled cells. The second case also showed a transition to the more irregular and poorly formed tubular proliferation of cells with greater nuclear atypia and with a desmoplastic response. Both tumors showed positivity for PAX8, GATA3, and luminal CD10, and 1 tumor analyzed harbored KRAS and ARID1A mutations. One patient received neoadjuvant chemotherapy and underwent resection but had local tumor recurrence and metastasis to the lungs and lumbar spine 12 months after presentation. In conclusion, MA, similar to those occurring in the female genital tract and distinct from the recognized Müllerian-derived carcinomas, may present primarily as urethral tumors. MA in the urethra probably shares a common pathogenesis with vaginal MA as both may originate from the same caudal loci of mesonephric remnants along the closely apposed anterior vaginal and posterior urethral walls. MA should be considered in future classifications for urethral tumors and we recommend that the confusing term "mesonephroid adenocarcinoma" should no longer be used.
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http://dx.doi.org/10.1097/PAS.0000000000001635DOI Listing
April 2021

Similarities and Differences in the 2019 ISUP and GUPS Recommendations on Prostate Cancer Grading: A Guide for Practicing Pathologists.

Adv Anat Pathol 2021 Jan;28(1):1-7

Urology, University of Tennessee Health Sciences Center, Memphis, TN.

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.
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http://dx.doi.org/10.1097/PAP.0000000000000287DOI Listing
January 2021

Practice patterns related to prostate cancer grading: results of a 2019 Genitourinary Pathology Society clinician survey.

Urol Oncol 2021 05 15;39(5):295.e1-295.e8. Epub 2020 Sep 15.

Departments of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD.

Purpose: To survey urologic clinicians regarding interpretation of and practice patterns in relation to emerging aspects of prostate cancer grading, including quantification of high-grade disease, cribriform/intraductal carcinoma, and impact of magnetic resonance imaging-targeted needle biopsy.

Materials And Methods: The Genitourinary Pathology Society distributed a survey to urology and urologic oncology-focused societies and hospital departments. Eight hundred and thirty four responses were collected and analyzed using descriptive statistics.

Results: Eighty percent of survey participants use quantity of Gleason pattern 4 on needle biopsy for clinical decisions, less frequently with higher Grade Groups. Fifty percent interpret "tertiary" grade as a minor/<5% component. Seventy percent of respondents would prefer per core grading as well as a global/overall score per set of biopsies, but 70% would consider highest Gleason score in any single core as the grade for management. Seventy five percent utilize Grade Group terminology in patient discussions. For 45%, cribriform pattern would affect management, while for 70% the presence of intraductal carcinoma would preclude active surveillance.

Conclusion: This survey of practice patterns in relationship to prostate cancer grading highlights similarities and differences between contemporary pathology reporting and its clinical application. As utilization of Gleason pattern 4 quantification, minor tertiary pattern, cribriform/intraductal carcinoma, and the incorporation of magnetic resonance imaging-based strategies evolve, these findings may serve as a basis for more nuanced communication and guide research efforts involving pathologists and clinicians.
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http://dx.doi.org/10.1016/j.urolonc.2020.08.027DOI Listing
May 2021

Primary round cell sarcomas of the urinary bladder with EWSR1 rearrangement: a multi-institutional study of thirteen cases with a review of the literature.

Hum Pathol 2020 10 14;104:84-95. Epub 2020 Aug 14.

Advanced Medical Research Institute, Bhubaneswar, 751030, India; CORE Diagnostics, Gurgaon, 122016, India. Electronic address:

Primary Ewing sarcoma (ES) of the urinary bladder is a rare and aggressive small blue round cell malignant neoplasm associated primarily with translocation involving EWSR1 and FLI1 genes located in the 22nd and 11th chromosomes, respectively. To date, 18 cases have been published in the literature as single-case reports, based chiefly on CD99 positivity (17 patients). Molecular confirmation by fluorescence in situ hybridization was performed in 9 patients, and FLI1 immunohistochemical (IHC) analysis was not performed in any of these published cases. Herein, we present thirteen patients of more comprehensive primary round cell sarcomas of the urinary bladder with EWSR1 rearrangement. Clinicopathologic parameters including demographics; clinical presentation; histopathologic, IHC, and molecular profiles; and management and follow-up data of 13 patients with primary round cell sarcomas with EWSR1 rearrangement (Ewing family of tumor) of the urinary bladder were analyzed. The studied patients (n = 13) included 6 females and 7 males; their age ranged from 4 years to 81 years (median = 30 years). The most common clinical presentation was hematuria (n = 7), followed by hydronephrosis (n = 2, one with renal failure). The tumor size ranged from 2.9 cm to 15 cm in maximum dimension. Conventional ES architecture and histology was observed in 6 cases, and diverse histology was observed in 7 cases (adamantinomatous pattern [n = 1], alveolar pattern [n = 1], ganglioneuroblastoma-like pattern [n = 2], and small cell carcinoma-like pattern [n = 3]). All the tumors were muscle invasive (invasion into the muscularis propria). IHC analysis showed that all tumors expressed FLI1, CD99, and at least one neuroendocrine marker. Focal cytokeratin staining was positive in 2 patients, and RB1 was retained in all patients. EWSR1 rearrangement was seen in 12 of 12 tumors (in 12 patients) tested. A combined multimodal approach that included surgery with chemotherapy was instituted in all patients. Follow-up was available for 11 patients (ranging from 5 to 24 months). Six patients either died of disease (n = 3) or other causes (n = 3). Five patients were alive with metastases to the liver (n = 1), liver and lung (n = 2), liver and abdominal wall (n = 1), and kidney (n = 1). Based on our experience with the largest series to date and aggregate of the published data, ES/round cell sarcomas with EWSR1 rearrangement occurring in the bladder have bimodal age distribution with poor prognosis despite aggressive therapy. Owing to its rarity and age distribution, the differential diagnosis is wide and requires a systematic approach for ruling out key age-dependent differential diagnoses aided with molecular confirmation.
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http://dx.doi.org/10.1016/j.humpath.2020.08.001DOI Listing
October 2020

Development and Validation of a Deep Learning Algorithm for Gleason Grading of Prostate Cancer From Biopsy Specimens.

JAMA Oncol 2020 09;6(9):1372-1380

Google Health, Google LLC, Mountain View, California.

Importance: For prostate cancer, Gleason grading of the biopsy specimen plays a pivotal role in determining case management. However, Gleason grading is associated with substantial interobserver variability, resulting in a need for decision support tools to improve the reproducibility of Gleason grading in routine clinical practice.

Objective: To evaluate the ability of a deep learning system (DLS) to grade diagnostic prostate biopsy specimens.

Design, Setting, And Participants: The DLS was evaluated using 752 deidentified digitized images of formalin-fixed paraffin-embedded prostate needle core biopsy specimens obtained from 3 institutions in the United States, including 1 institution not used for DLS development. To obtain the Gleason grade group (GG), each specimen was first reviewed by 2 expert urologic subspecialists from a multi-institutional panel of 6 individuals (years of experience: mean, 25 years; range, 18-34 years). A third subspecialist reviewed discordant cases to arrive at a majority opinion. To reduce diagnostic uncertainty, all subspecialists had access to an immunohistochemical-stained section and 3 histologic sections for every biopsied specimen. Their review was conducted from December 2018 to June 2019.

Main Outcomes And Measures: The frequency of the exact agreement of the DLS with the majority opinion of the subspecialists in categorizing each tumor-containing specimen as 1 of 5 categories: nontumor, GG1, GG2, GG3, or GG4-5. For comparison, the rate of agreement of 19 general pathologists' opinions with the subspecialists' majority opinions was also evaluated.

Results: For grading tumor-containing biopsy specimens in the validation set (n = 498), the rate of agreement with subspecialists was significantly higher for the DLS (71.7%; 95% CI, 67.9%-75.3%) than for general pathologists (58.0%; 95% CI, 54.5%-61.4%) (P < .001). In subanalyses of biopsy specimens from an external validation set (n = 322), the Gleason grading performance of the DLS remained similar. For distinguishing nontumor from tumor-containing biopsy specimens (n = 752), the rate of agreement with subspecialists was 94.3% (95% CI, 92.4%-95.9%) for the DLS and similar at 94.7% (95% CI, 92.8%-96.3%) for general pathologists (P = .58).

Conclusions And Relevance: In this study, the DLS showed higher proficiency than general pathologists at Gleason grading prostate needle core biopsy specimens and generalized to an independent institution. Future research is necessary to evaluate the potential utility of using the DLS as a decision support tool in clinical workflows and to improve the quality of prostate cancer grading for therapy decisions.
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http://dx.doi.org/10.1001/jamaoncol.2020.2485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378872PMC
September 2020

Peyronie disease: a clinicopathologic study of 71 cases with emphasis on histopathologic patterns and prevalent metaplastic ossification.

Hum Pathol 2020 10 15;104:9-17. Epub 2020 Jul 15.

Department of Pathology, VCU School of Medicine, Richmond, VA, 23298, USA; Division of Urology, Department of Surgery, VCU School of Medicine, Richmond, VA, 23298, USA.

Peyronie disease (PD) is a benign, superficial fibromatosis involving the fascial structures of the penis, causing deformity, pain, and loss of function, for which there are few contemporary studies of the histopathology. We performed a multi-institutional review of 74 routine and consultation specimens submitted with clinical concern for PD. Of these, three non-PD lesions were identified and excluded (a myointimoma, a mammary-type myofibroblastoma, and fibrocalcific atherosclerosis). Of the 71 confirmed to be PD, the majority of patients were white (83%), with a median age of 55 years (range: 26-88). The dorsal aspect of the penis was the most common site involved (78%), followed by lateral (12%) and ventral (10%) aspects. The median degree of curvature was 70° (range: 20-360°). On review, three overall histologic patterns characterized the lesions resected: dense fibrotic plaque (61%), dense fibrotic plaque with focal or patchy metaplastic ossification (35%), and plaque composed predominantly of metaplastic ossification (4%). The fibrotic component was predominantly nodular (18%), hyalinized/lamellar (46%), or mixed (32%), excepting two cases consisting entirely of metaplastic bone. Chronic inflammation, when present, was most often focal and perivascular in distribution. In one case, an excision after collagenase treatment showed myxoid change and increased stromal cellularity. Overall, these findings define the range of PD histology, particularly emphasizing that the calcification noted clinically nearly always represents bona fide metaplastic ossification. Such context will be of value in evaluating specimens prospectively, in light of changing practices and the use of new technologies for treatment.
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http://dx.doi.org/10.1016/j.humpath.2020.07.013DOI Listing
October 2020

Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial.

Lancet Oncol 2020 06 29;21(6):776-785. Epub 2020 Apr 29.

UroGen Pharma, New York, NY, USA.

Background: Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel.

Methods: In this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5-15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score >40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4-6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in >15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with ClinicalTrials.gov, NCT02793128.

Findings: Between April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47-71; p<0·0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11·0 months (IQR 5·1-12·4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment.

Interpretation: Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients.

Funding: UroGen Pharma.
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http://dx.doi.org/10.1016/S1470-2045(20)30147-9DOI Listing
June 2020

Genital verruciform xanthoma: lessons from a contemporary multi-institutional series.

Histopathology 2020 Nov 15;77(5):841-846. Epub 2020 Sep 15.

Department of Pathology, VCU School of Medicine, Richmond, VA, USA.

Aims: Verruciform xanthoma (VX) is an uncommon lesion, seen in the oral mucosa and rarely occurring at cutaneous genital sites. Reports of exceptional VX presentations dominate the literature; herein, we assess the clinical and histological features of a cohort of routine, consecutive cases.

Methods And Results: Clinicopathological features of genital VXs from four academic centres were reviewed. A cohort of 25 lesions from 24 patients (22 male, two female; median age = 62 years), occurred on the scrotum (84%), penis (8%) and perineum/vulva (8%). VX was never suspected clinically; considerations ranged from fibroepithelial polyps to squamous cell carcinoma. Classic diagnostic criteria were present at least focally in each lesion, including verrucous architecture, prominent wedge-shaped parakeratosis extending between exophytic epidermal projections and neutrophils in the stratum corneum. Xanthomatous cells were present in all cases, but scattered to rare in 24%.

Conclusions: Consecutive genital VXs reliably exhibited classic histopathological features, although the essential finding of xanthomatous cells may be scarce. Our comparison to meta-analyses of published cases found relatively fewer penile and vulvar examples. Additionally, the median age was older than in published series, which have emphasised syndromic associations.
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http://dx.doi.org/10.1111/his.14198DOI Listing
November 2020

The 2019 Genitourinary Pathology Society (GUPS) White Paper on Contemporary Grading of Prostate Cancer.

Arch Pathol Lab Med 2021 04;145(4):461-493

Douglass Hanly Moir Pathology, Faculty of Medicine and Health Sciences Macquarie University, North Ryde, Australia (Maclean).

Context.—: Controversies and uncertainty persist in prostate cancer grading.

Objective.—: To update grading recommendations.

Data Sources.—: Critical review of the literature along with pathology and clinician surveys.

Conclusions.—: Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace "tertiary grade pattern" in radical prostatectomy (RP) with "minor tertiary pattern 5 (TP5)," and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)-targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDC-P) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (>50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) "atypical intraductal proliferation (AIP)" is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice.
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http://dx.doi.org/10.5858/arpa.2020-0015-RADOI Listing
April 2021

Convergence of Digital Pathology and Artificial Intelligence Tools in Anatomic Pathology Practice: Current Landscape and Future Directions.

Adv Anat Pathol 2020 07;27(4):221-226

Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN.

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http://dx.doi.org/10.1097/PAP.0000000000000271DOI Listing
July 2020

CK20 versus AMACR and p53 immunostains in evaluation of Urothelial Carcinoma in Situ and Reactive Atypia.

Diagn Pathol 2020 May 26;15(1):61. Epub 2020 May 26.

Department of Pathology, Virginia Commonwealth University School of Medicine, PO Box 980662, Richmond, VA, 23298, USA.

Ancillary testing with immunohistochemistry has shown recent promise in the workup of equivocal bladder lesions. We read with interest the recent findings of Alston et al., who assessed the diagnostic utility of alpha-methylacyl-CoA racemase (AMACR) in comparison to cytokeratin 20 (CK20) in evaluation of atypia in challenging flat urothelial lesions in the differential between carcinoma in situ (CIS) and reactive atypia. AMACR was reported to be a somewhat more specific but less sensitive marker for CIS than CK20, though showing weaker intensity. Spurred by their report, with the knowledge that we had consistently and consecutively performed AMACR, CK20, and p53 on flat urothelial lesions challenging enough to reach intradepartmental consensus, we performed a retrospective review. Similarly, we found that AMACR was less sensitive (80%) and more specific (100%) than CK20, with the same caveat of less staining intensity. Additionally, our p53 review identified a significant rate (~ 27%) of equivocal/non-informative findings. Taken together, our experience in this consecutive cohort confirms the impression of Alston et al. regarding the utility and challenges of AMACR use, while highlighting challenges with p53, which we plan to use more sparingly prospectively.
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http://dx.doi.org/10.1186/s13000-020-00984-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251721PMC
May 2020

CD34 positive tubular basement membrane in testicular germ cell tumours: a potential staging pitfall.

Histopathology 2020 08 4;77(2):331-333. Epub 2020 Jul 4.

Department of Pathology, VCU School of Medicine, Richmond, VA, USA.

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http://dx.doi.org/10.1111/his.14131DOI Listing
August 2020

Comprehensive Clinicopathologic Analyses of Acquired Cystic Disease-associated Renal Cell Carcinoma With Focus on Adverse Prognostic Factors and Metastatic Lesions.

Am J Surg Pathol 2020 08;44(8):1031-1039

Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN.

Acquired cystic disease of kidney-associated renal cell carcinoma (ACD-RCC) is a distinct subtype of renal cell carcinoma with unique morphologic and clinicopathologic features. Generally, ACD-RCC is regarded as an indolent tumor; however, prognostic and outcomes data have been conflicted by the limited and relatively low number of cases with patient follow-up or adverse events. In this study, we focused on the histology of metastatic lesions and identifying prognostic factors associated with metastatic progression. From 32 cases in the cohort, 9 patients had metastasis [ACD-RCC (M+)] and 23 patients were without metastasis [ACD-RCC (M-)]. The median age of patients was 52 years; right side, n=10; left side, n=18; bilateral, n=4; median tumor size=2.6 cm; median hemodialysis duration=17 y; and the median duration of follow-up was 50 mo. Immunohistochemistry showed ACD-RCC to be racemase positive and CK7 negative to focally positive within tumor cells, with consistent positivity for renal histogenesis-associated markers (PAX8 and RCC antigen); S100A1 was a less reliable marker at metastatic sites. All metastatic ACD-RCC except 2 cases involved lymph nodes (para-aortic, renal hilar, subclavicular). Overall, 6/9 (67%) had visceral metastasis to sites including lung (n=3), liver (n=3), bone (n=5), stomach (n=1), and brain (n=1). In total, 5/9 (56%) metastatic tumors had distinctive cystic growth pattern at the metastatic site; intriguingly metastatic tumors had intrametastatic oxalate crystal deposition, a pathognomonic feature associated with primary tumors. Four of nine (44%) patients with ACD-RCC (M+) had fatal outcomes due to metastatic disease. Clinically significant adverse prognostic features associated with metastasis [median follow-up 47 mo, ACD-RCC (M+) vs. ACD-RCC (M-), 50 mo] included: duration of hemodialysis (≥20 vs. <20 y, P=0.0085) and tumor necrosis (P=0.049). Because of sufficient overlap between these parameters, the study was not able to identify parameters that would be reliable in further management strategies, in clinical settings. Our data indicate that ACD-RCC is a tumor which has distinct metastatic potential with nodal and visceral tropism and proclivity for cystic morphology at metastatic sites; this is the first report of the presence of oxalate crystals in metastatic tumors. Our data suggest that ACD-RCC patients with prolonged hemodialysis and tumoral coagulative necrosis require additional surveillance in view of the association of these parameters with metastatic progression.
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http://dx.doi.org/10.1097/PAS.0000000000001482DOI Listing
August 2020

Reporting Practices and Resource Utilization in the Era of Intraductal Carcinoma of the Prostate: A Survey of Genitourinary Subspecialists.

Am J Surg Pathol 2020 05;44(5):673-680

Cleveland Clinic, Cleveland, OH.

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.
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http://dx.doi.org/10.1097/PAS.0000000000001417DOI Listing
May 2020

Urothelial Proliferation of Unknown Malignant Potential Involving the Bladder: Histopathologic Features and Risk of Progression in De Novo Cases and Cases With Prior Neoplasia.

Arch Pathol Lab Med 2020 07;144(7):853-862

From the Department of Pathology (Drs Lowenthal and Hansel) and the Department of Computer Science and Engineering (Dr Sahoo), University of California, San Diego, La Jolla; and the Department of Pathology, University of Tennessee Health Sciences Center, Memphis (Dr Amin). Dr Lowenthal is now with Kaiser Permanente, San Diego, California. Dr Hansel is now with the Department of Pathology, Oregon Health & Science University, Portland.

Context.—: Urothelial proliferation of unknown malignant potential (UPUMP) is a 2016 World Health Organization classifier that encompasses prior categories of flat and papillary urothelial hyperplasia. In addition, UPUMP occurs in settings of both de novo and prior bladder neoplasia.

Objective.—: To identify UPUMP features associated with subsequent neoplastic development.

Design.—: Sixty-eight patients were identified from the archives, including 26 patients with de novo and 42 patients with prior bladder neoplasia. Patient slides and clinical course were reviewed.

Results.—: Patients with de novo UPUMP were detected through clinical findings (26/26; 100%), whereas surveillance cystoscopy primarily detected UPUMP in patients with prior neoplasia (29/42; 69%). Histopathologic criteria evaluated included urothelial hyperplasia, urothelial cytology, vascular ingrowth, denudation, inflammation, edema, and fibrosis. Mean clinical follow-up was 68.9 months in patients with de novo neoplasia and 69.5 months in patients with prior neoplasia. Subsequent neoplasia developed in 4 of 26 (15.4%) of patients with de novo UPUMP and was associated with cystoscopic papillary appearance (P = .02) or microscopic thin papillary ingrowths or papillations (P = .02; median time to progression, 4.1 months). Of 42 patients with prior neoplasia, 17 (40.5%) had subsequent neoplasia, significantly associated with an absence of prominent lamina propria edema (P < .001; median time to progression, 11.0 months). A higher rate of progression to high-grade disease was present in patients with a prior neoplasia versus those with de novo disease (58.9% versus 25%).

Conclusions.—: Urothelial proliferation of unknown malignant potential shows subsequent risk of neoplastic development of 17% in patients with de novo disease and 40% in patients with prior neoplasia. The greatest risk of progression is associated with early papillary formation.
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http://dx.doi.org/10.5858/arpa.2019-0005-OADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312373PMC
July 2020

MiT family translocation renal cell carcinomas: A 15th anniversary update.

Histol Histopathol 2020 Feb 6;35(2):125-136. Epub 2019 Sep 6.

Department of Pathology, University of Tennessee Health Science Center, Memphis, TN, USA.

Microphthalmia (MiT) family translocation renal cell carcinomas (RCCs) are a heterogeneous category of renal tumors which all express MiT transcription factors, typically from chromosomal translocation and rarely from gene amplification. This tumor family has two major subtypes [i.e., Xp11 translocation RCC and t(6;11) RCC] and several related neoplasms (i.e., TFEB amplification RCC and melanotic Xp11 translocation renal cancers). Increased understanding of the clinical, pathological, molecular and prognostic heterogeneity of these tumors, since their official recognition in 2004, provides the opportunity to identify prognostic biomarkers and to understand the reasons for tumor aggression. We will review the literature from the past 15 years and highlight the need for a greater understanding of the molecular mechanisms underpinning heterogeneous tumor behavior.
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http://dx.doi.org/10.14670/HH-18-159DOI Listing
February 2020

Amyloidosis of the bladder and association with urothelial carcinoma: report of 29 cases.

Hum Pathol 2019 11 16;93:48-53. Epub 2019 Aug 16.

Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd Suite Room 8725, Los Angeles, CA 90048, USA. Electronic address:

The association of amyloidosis with certain neoplastic processes is well known. Amyloid uncommonly occurs in relationship with other epithelial neoplasms including urothelial carcinoma. Herein, we report 29 cases of amyloidosis in the bladder, 14 of which were found in relationship to urothelial carcinoma. With institutional review board approval. We searched pathology archives for cases of amyloidosis in the bladder. Clinical, laboratory, and surgical pathology records were reviewed, and data were recorded for all cases. Diagnosis of amyloid was made by Congo red stain showing apple-green birefringence on polarization microscopy and special studies in some cases. Twenty-nine cases of amyloid were identified in bladder specimens. Presentation as a mass lesion was the most common (n = 18). Immunohistochemical subtyping done in 17 cases showed transthyretin-type (n = 10), AL (n = 3), AA (n = 1), amyloid P (n = 1), and undetermined (n = 2) types of amyloid. Eighteen (62%) cases were classified as localized primary amyloidosis and 11 (38%) as secondary manifestation of systemic amyloidosis. In 14 (48%) cases, there was an associated urothelial carcinoma: 5 urothelial carcinoma in situ, 4 low-grade noninvasive papillary urothelial carcinoma, 2 high-grade noninvasive papillary urothelial carcinoma, and 3 high-grade invasive urothelial carcinoma. Associated urothelial carcinoma was present in 4 of 7 patients with systemic amyloidosis and 10 of 18 patients with localized amyloidosis, with the difference not being statistically significant (P = .45). Amyloidosis of the bladder is rare and presents as a mucosal mass or hematuria that may mimic urothelial carcinoma. In this study, we found urothelial carcinoma occurring in 48% of the cases in association with amyloidosis, a finding not previously reported. The relationship of amyloid in the bladder and urothelial carcinoma, although likely not causal, appears to be a unique finding not frequently seen with other solid tumors.
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http://dx.doi.org/10.1016/j.humpath.2019.08.011DOI Listing
November 2019

Similar image search for histopathology: SMILY.

NPJ Digit Med 2019 21;2:56. Epub 2019 Jun 21.

Google AI Healthcare, Mountain View, CA 94043 USA.

The increasing availability of large institutional and public histopathology image datasets is enabling the searching of these datasets for diagnosis, research, and education. Although these datasets typically have associated metadata such as diagnosis or clinical notes, even carefully curated datasets rarely contain annotations of the location of regions of interest on each image. As pathology images are extremely large (up to 100,000 pixels in each dimension), further laborious visual search of each image may be needed to find the feature of interest. In this paper, we introduce a deep-learning-based reverse image search tool for histopathology images: Similar Medical Images Like Yours (SMILY). We assessed SMILY's ability to retrieve search results in two ways: using pathologist-provided annotations, and via prospective studies where pathologists evaluated the quality of SMILY search results. As a negative control in the second evaluation, pathologists were blinded to whether search results were retrieved by SMILY or randomly. In both types of assessments, SMILY was able to retrieve search results with similar histologic features, organ site, and prostate cancer Gleason grade compared with the original query. SMILY may be a useful general-purpose tool in the pathologist's arsenal, to improve the efficiency of searching large archives of histopathology images, without the need to develop and implement specific tools for each application.
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http://dx.doi.org/10.1038/s41746-019-0131-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588631PMC
June 2019

Development and validation of a deep learning algorithm for improving Gleason scoring of prostate cancer.

NPJ Digit Med 2019 7;2:48. Epub 2019 Jun 7.

Present Address: AI and Data Science, Tempus Labs Inc, Chicago, United States.

For prostate cancer patients, the Gleason score is one of the most important prognostic factors, potentially determining treatment independent of the stage. However, Gleason scoring is based on subjective microscopic examination of tumor morphology and suffers from poor reproducibility. Here we present a deep learning system (DLS) for Gleason scoring whole-slide images of prostatectomies. Our system was developed using 112 million pathologist-annotated image patches from 1226 slides, and evaluated on an independent validation dataset of 331 slides. Compared to a reference standard provided by genitourinary pathology experts, the mean accuracy among 29 general pathologists was 0.61 on the validation set. The DLS achieved a significantly higher diagnostic accuracy of 0.70 ( = 0.002) and trended towards better patient risk stratification in correlations to clinical follow-up data. Our approach could improve the accuracy of Gleason scoring and subsequent therapy decisions, particularly where specialist expertise is unavailable. The DLS also goes beyond the current Gleason system to more finely characterize and quantitate tumor morphology, providing opportunities for refinement of the Gleason system itself.
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http://dx.doi.org/10.1038/s41746-019-0112-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555810PMC
June 2019
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