Faculty Bibliography

OBJECTIVES/OBJECTIVE:To determine the prognostic significance of the maximum allowable percentage of Gleason pattern 4 (GP4) at prostate biopsy compared with adverse pathology observed at radical prostatectomy (RP) to expand active surveillance eligibility among a cohort with intermediate risk of prostate cancer. METHODS:A retrospective study of patients with grade group (GG) 1 or 2 prostate cancer on prostate biopsy with subsequent RP was performed at our institution. A Fisher exact test was used to understand the relationship among GP4 subgroups (0%, ≤5%, 6%-10%, and 11%-49%) assigned at biopsy and adverse pathologic findings at RP. Additional analyses comparing the GP4 ≤5% cohort's prebiopsy prostate-specific antigen (PSA) level and GP4 length with adverse pathology at RP were also performed. RESULTS:No statistically significant difference in adverse pathology at RP was observed between the active surveillance-eligible control (GP4 0%) and the GP4 ≤5% subgroup. In total, 68.9% of the GP4 ≤5% cohort showed favorable pathologic outcomes. A separate analysis of the GP4 ≤5% subgroup revealed that neither prebiopsy serum PSA levels nor GP4 length showed statistical correlation with adverse pathology at RP. CONCLUSIONS:Active surveillance may be a reasonable option for management of patients in the GP4 ≤5% group until long-term follow-up data become available.

INTRODUCTION/BACKGROUND:Renal tumor biopsy requires adequate tissue sampling to aid in the investigation of small renal masses. In some centers the contemporary nondiagnostic renal mass biopsy rate may be as high as 22% and may be as high as 42% in challenging cases. Stimulated Raman Histology (SRH) is a novel microscopic technique which has created the possibility for rapid, label-free, high-resolution images of unprocessed tissue which may be viewed on standard radiology viewing platforms. The application of SRH to renal biopsy may provide the benefits of routine pathologic evaluation during the procedure, thereby reducing nondiagnostic results. We conducted a pilot feasibility study, to assess if renal cell carcinoma (RCC) subtypes may be imaged and to see if high-quality hematoxylin and eosin (H&E) could subsequently be generated. METHODS/MATERIALS/METHODS:. The cores were then processed as per routine pathologic protocols. The SRH images and hematoxylin and eosin (H&E) slides were then viewed by a genitourinary pathologist. RESULTS:The SRH microscope took 8 to 11 minutes to produce high-quality images of the renal biopsies. Total of 25 renal tumors including 1 oncocytoma, 3 chromophobe RCC, 16 clear cells RCC, 4 papillary RCC, and 1 medullary RCC were included. All renal tumor subtypes were captured, and the SRH images were easily differentiated from adjacent normal renal parenchyma. High quality H&E slides were produced from each of the renal biopsies after SRH was completed. Immunostains were performed on selected cases and the staining was not affected by the SRH image process. CONCLUSION/CONCLUSIONS:SRH produces high quality images of all renal cell subtypes that can be rapidly produced and easily interpreted to determine renal mass biopsy adequacy, and on occasion, may allow renal tumor subtype identification. Renal biopsies remained available to produce high quality H&E slides and immunostains for confirmation of diagnosis. Procedural application has promise to decrease the known rate of renal mass nondiagnostic biopsies, and application of convolutional neural network methodology may further improve diagnostic capability and increase utilization of renal mass biopsy among urologists.

BACKGROUND:Evading immune surveillance is a hallmark for the development of multiple cancer types. Whether immune evasion contributes to the pathogenesis of high-grade prostate cancer (HGPCa) remains an area of active inquiry. METHODS:Through single-cell RNA sequencing and multicolor flow cytometry of freshly isolated prostatectomy specimens and matched peripheral blood, we aimed to characterize the tumor immune microenvironment (TME) of localized prostate cancer (PCa), including HGPCa and low-grade prostate cancer (LGPCa). RESULTS: TILs. The PCa TME was infiltrated by macrophages but these did not clearly cluster by M1 and M2 markers. CONCLUSIONS:T cell exhaustion in localized PCa, a finding enriched in HGPCa relative to LGPCa. These studies suggest a possible link between the clinical-pathologic risk of PCa and the associated TME. Our results have implications for our understanding of the immunologic mechanisms of PCa pathogenesis and the implementation of immunotherapy for localized PCa.

BACKGROUND:Magnetic resonance imaging (MRI)-targeted prostate biopsy has become an increasingly common method of diagnosing prostate cancer. A previous study from our institution demonstrated that the biopsy global Grade Group (gGG, aggregate GG of all positive cores) and highest Grade Group (hGG in any core) both show substantial concordance with the Grade Group at radical prostatectomy (RPGG) while the discordance predominantly consists of upgrading in gGG and downgrading in hGG. We performed a larger cohort study focused on biopsy cases in which gGG and hGG differ, to determine their relative concordance with RPGG. METHODS:We conducted a retrospective review of radical prostatectomy specimens with prior MRI-targeted biopsies from our institution between 2016 and 2020. Separate gGG and hGG were assigned to each MRI-targeted lesion. Targeted lesions with different gGG versus hGG were segregated from those with identical gGG and hGG. The concordance of biopsy GG with RPGG was evaluated using κ coefficient analysis. RESULTS:Of the 489 lesions with MRI-targeted biopsies, 82 (17%) differed in gGG versus hGG. The gGG of 46 (56%), 33 (40%), and 3 (4%) lesions were unchanged, upgraded, and downgraded at radical prostatectomy, respectively (κ= 0.302, weighted κ = 0.334). The hGG of 24 (29%), 9 (11%), and 49 (60%) lesions were unchanged, upgraded, and downgraded at radical prostatectomy, respectively (κ = 0.040, weighted κ = 0.198). When stratified by the biopsy GG, gGG showed the highest concordance in GG2 (61%) and GG3 (54%) lesions. The hGG resulted in substantial downgrading (60%) with less optimal concordance regardless of the biopsy GG. Neither the prebiopsy prostate specific antigen level nor the PI-RADS score was predictive of upgrading of gGG. CONCLUSIONS:When gGG and hGG differ, gGG method more accurately predicts the RPGG than hGG, particularly in GG2 and GG3 lesions which comprised the majority of targeted lesions.

The most common histological type of urinary bladder cancer is urothelial carcinoma (UC). Clear cell adenocarcinoma (CCA) of the urinary bladder is a rare histologic subtype of adenocarcinoma in the urinary tract. The tumor primarily affects women and has histomorphological features resembling CCA of the female genital tract (or Müllerian origin). Clear cell adenocarcinoma consists of cells with abundant clear cytoplasm, arranged in solid, glandular, or tubulocystic patterns. Patients typically present with gross hematuria, dysuria, and discharge. In this study, we report a case of a 50-year-old male, presenting with gross hematuria, which was subsequently diagnosed with CCA at our pathology department. Furthermore, we provide a short systematic review of the literature for this rare histopathological entity and a brief discussion about its morphological and immunohistochemical (IHC) characteristics.

Introduction: The utility of The Paris System (TPS) in diagnosing low-grade urothelial neoplasm (LGUN) on urine cytology is controversial due to the strict requirement for fibrovascular cores, and low sensitivity/specificity. Many LGUNs are classified as atypical urothelial cells (AUC) on cytology, which compromises the performance and utility of TPS. Here, we studied cytomorphologic features of LGUN in urine samples to determine which features were commonly observed.
Material(s) and Method(s): Twenty-two urine cytology cases with corresponding (within 2 months) LGUN histologic diagnosis were retrieved for this pilot study and were evaluated by one cytopathologist for the presence of clusters, cercariform cells, hyperchromasia, irregular nuclear rim, papillary architecture +/-fibrovascular core, and nucleus:cytoplasm (N:C) ratio (Figure 1). Hierarchical cluster analysis (Ward's Method) was used to classify the features.
Result(s): Of the 22 urines, one was voided (4.5%) and 21 were instrumented (95.5%). Majority (77.3%) were diagnosed as AUC, 1 was suspicious for urothelial carcinoma (4.5%), 4 cases were graded as LGUN (18.2%, Table 1). Clustering analysis demonstrated that the morphologic features abundantly present in the urine specimen of LGUN included: clusters (77.3%), N:C ratio >50% (85.4%), and papillary architecture without a core (72.7%). The features that were mostly absent in LGUN specimens included: irregular nuclear rim (0%), papillary formation with a core (0%), hyperchromasia (9.1%), coarse chromatin (22.7%), and cercariform cells (36.3%). (Table 2).
Conclusion(s): Papillary formation with a fibrovascular core, the most convincing feature of LGUN, was not present in our pilot cohort of LGUN urines. However, our study describes additional cytomorphologic features that may be useful in identifying LGUN in urine cytology. Our research will continue with the evaluation of a larger cohort of LGUN cases with corresponding urine cytology in order to further investigate these findings

CONTEXT.—/UNASSIGNED:Gender-affirming surgery is part of a multidisciplinary approach in gender transitioning. Deeper histologic examination may strengthen care for transmasculine individuals and increase the understanding of the influence of hormonal therapy in specific organs. OBJECTIVE.—/UNASSIGNED:To evaluate and catalogue histologic findings of tissue obtained from gender-affirming gynecologic surgery and cervical cytology specimens. DESIGN.—/UNASSIGNED:This is an institutional review board-approved retrospective study that included transmasculine individuals who underwent gender-affirming gynecologic surgery from January 2015 to June 2020. All surgical gynecologic pathology and cervical cytology slides were reviewed by 2 pathologists. RESULTS.—/UNASSIGNED:Fifty-five patients were included, which represented 40 uteri, 35 bilateral ovaries, 15 vaginectomy specimens, and 24 cervical cytology results. The median age was 27 years (range, 18-56) and 94% (50 of 53) of patients were receiving testosterone for at least 1 year. Seventy-five percent (30 of 40) of endometria were inactive, while 25% (10 of 40) showed evidence of cycling. Transitional cell metaplasia was the most common finding in the cervix (17 of 40) and vagina (15 of 15), reflecting a high percentage (4 of 24) of unsatisfactory or ASC-US (atypical squamous cells of undetermined significance) cervical cytologies. Prostatic-type glands were identified in 20% (8 of 40) of cervices and 67% (10 of 15) of vaginectomy specimens. Multiple bilateral cystic follicles and evidence of follicular maturation were present in 57% (20 of 35) of cases. Four cases showed paratubal epididymis-like mesonephric remnant hypertrophy. CONCLUSIONS.—/UNASSIGNED:A comprehensive evaluation of tissue from gender-affirming surgery increases knowledge of the changes following androgen therapy in transmasculine individuals and may contribute to optimal patient care by raising awareness of normal histologic variations in this population.

BACKGROUND:Prostate cancer (PCa) is the most common malignant tumor found among men in the United States. Incidence rates of PCa have recently grown in Asian countries, partially due to the comprehensive implementation of early detection systems. Interestingly, a prospective cohort study showed that adopting a westernized dietary pattern was associated with a higher risk of being diagnosed with PCa among Korean and Japanese men. However, a comparison of current clinicopathological features of PCa between American and Chinese men is lacking. In this study, we report the current clinicopathological features of PCa in Chinese men and compare them to those of patients in the USA. MATERIALS AND METHODS/METHODS:Case cohorts included, in total, 871 PCa cases with prostatectomy sequentially treated since 2017, including 299 cases from USA and 572 cases from two different academic hospitals in China. The parameters, including patient's age, preoperative Prostate-Specific Antigen (PSA) level, Gleason score, Grade Group, stage and tumor focality, were collected, analyzed and compared using two sample t-test, Wilcoxon rank sum test, Pearson's Chi-squared test and Fisher's exact test. RESULTS:Significant differences were demonstrated in the mean age of patients, preoperative PSA levels, extra-prostatic extension, Gleason scores, and Grade Groups (p < 0.05). PCa patients in the Chinese group were older than patients in the USA group (67.81 vs. 63.53, p < 0.01). The preoperative PSA levels in the Chinese group were higher than those in the USA group (11.69 v.s 6.30, p < 0.01). A higher percentage of high Grade Groups (Groups 4 and 5) was observed in the Chinese group (25.7%) compared to the USA cohort (17.11%), while Grade Group 2 was more common in the USA group than in the Chinese group (51.68% vs. 32.52%, p < 0.01). CONCLUSIONS:All these data suggest that the clinicopathologic features of PCa are different between the USA and Chinese populations, which may be influenced by treatment strategies (including surgical case selection criteria).

Lymphoma of the urinary tract is relatively rare and comprises of < 5% of all primary extra nodal lymphoma. Diagnoses of these lesions at anearly stage is important as they can disseminate or transform into high grade lesion if there is a delay in the diagnoses. There are only few case series and case reports on the malignant lymphoma of the urinary tract. The aim of this study was to characterize lymphoma involving the urinary bladder and prostate. We retrospectively reviewed the clinical data and histologic findings of the malignant lymphoma involving urinary bladder and prostate at our institution. Lymphoma involving the lower urinary tract clinically presented with lower urinary tract symptoms and usually with concurrent associated urinary bladder cancer or prostatic cancer in our series. Lymphoma should be included in the differential diagnoses especially in patients with prior history of lymphoid disorders. There should be a high index of suspicion when there is any atypical lymphoid infiltrate in routine urinary bladder and prostate surgical specimens.

Background: Magnetic resonance imaging (MRI) targeted prostate biopsy has become an increasingly common method of diagnosing prostate cancer. Previous study from our institution demonstrates the biopsy global Gleason grade (gGG) and highest Gleason grade (hGG) show substantial concordance with the radical prostatectomy Gleason grade (RPGG) while the discordance predominantly comprise of upgrading in gGG and downgrading in hGG. We performed a larger cohort focused analysis on the agreement of gGG and hGG to the RPGG when they differ.
Design(s): A retrospective review of radical prostatectomy specimens between 10/2016 and 12/2020 from our institution with prior MRI-targeted biopsies was conducted. A gGG (aggregate GG of all positive cores) and a hGG (highest GG in any core) was assigned to each MRI-targeted lesion. Only cases with different gGG versus hGG were selected for further analysis. The concordance of gGG and hGG with RPGG was evaluated using kappa coefficient analyses. The power of pre-biopsy PSA and PIRADS scores to predict upgrading based on gGG was also analyzed.
Result(s): Of the 489 radical prostatectomy specimens with prior MRI-targeted biopsies, 82 cases (17%) differed in gGG versus hGG. Using the gGG, 33 cases (40%), 46 cases (56%), and 3 cases (4%) were upgraded, unchanged, and downgraded at radical prostatectomy, respectively (Kappa = 0.302, weighted Kappa = 0.334). Based on the hGG, 9 cases (11%), 24 cases (29%), and 49 cases (60%) were upgraded, unchanged, and downgraded at radical prostatectomy, respectively (Kappa = 0.040, weighted Kappa = 0.198) (Figure 1). When stratified by RPGG, gGG shows the best concordance in RPGG2 and RPGG3 lesions. The hGG resulted in substantial downgrading at RPGG4 or less and upgrading at RPGG5 (Figure 2). No significant difference in the mean PSA [H(2) = 5.89, p = 0.053] or PI-RADS score [H(2) = 4.48, p = 0.107] was found among the cases upgraded, unchanged, and downgraded based on the gGG. Neither the pre-biopsy PSA (OR = 1.92, 95% CI = 0.65-5.64, p = 0.117) nor the PI-RADS score (OR = 0.899, 95% CI = 0.31-2.607, p = 0.423) was predictive of upgrading based on gGG.
Conclusion(s): When the gGG and hGG differ, the gGG correlates better with the RPGG than the hGG in the majority of cases for RPGG2 and RPGG3 lesions (46 cases, 74%). It results in upgrading in high grade lesions (GG4 and GG5) with potentially minimal impact on clinical management. Further studies are needed to substantiate a standard GG reporting method for MRI-targeted prostate biopsies