Synchronous Penile Squamous Cell Carcinoma, Bladder Urothelial Carcinoma and Prostate Adenocarcinoma Diagnosed in One Procedure.

BACKGROUND: The synchronous diagnoses of three primary malignancies in a patient is rare and represents a difficult treatment challenge. We report a rare case of an 81-year-old male with synchronous triple urogenital cancers including penile squamous cell carcinoma, bladder papillary urothelial carcinoma, and prostate adenocarcinoma. CASE REPORT: The patients presented with a penile lesion with blood draining through the foreskin. Further examination with cystoscopy during the biopsy procedure revealed a 1.5-cm tumor along the left lateral bladder wall and a firm prostate in bilateral lobes. Diagnosis of penile squamous cell carcinoma was confirmed by biopsies of the penile lesions and glans as confirmed by cystoscopy and histological evaluation of the tissue obtained by transurethral resection of the bladder. Biopsies of the prostatic urethra confirmed a diagnosis of prostate adenocarcinoma. All biopsies were performed in a single procedure. Pathology findings revealed moderately differentiated squamous cell carcinoma (p16+) invading the lamina propria of the glans penis, noninvasive low-grade papillary urothelial carcinoma of the bladder, and high-grade prostatic adenocarcinoma (Gleason score 5+5=10) within the prostatic stroma. CONCLUSION: Review of the English literature through PubMed search suggests that this specific combination of synchronous triple urogenital cancer is the first documented case of its kind. Incidence, diagnosis, and treatment for the combination of these cancer types are discussed with consideration for concurrent management of three primary cancers.

Thyroid Follicular Cell-derived Carcinomas in a Background of Multiple Adenomatous Nodules Leading to a Diagnosis of PTEN Hamartoma Tumor Syndrome in an Adult Patient With a Novel RECQL4 Mutation.

BACKGROUND: Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a complex disorder. Carriers develop hamartomatous tumors, with an increased risk for developing malignant tumors in multiple organs. Surveillance to facilitate the early detection and treatment of malignancies is extremely important. CASE REPORT: A 31-year-old male presented with a 10 cm left lobe thyroid gland mass. After fine needle aspiration a left hemithyroidectomy was performed, which demonstrated a minimally invasive follicular thyroid carcinoma (FTC, stage pT3a) and microscopic classical papillary thyroid carcinoma (PTC) in the background of about 50 separate adenomatous nodules (0.2-5 mm). Immunostaining showed loss of PTEN protein in the minimally invasive FTC and in all of the nodules tested, with uninvolved parenchyma serving as an internal control. Kaiser Permanente Northern California (KPNC) Hereditary Cancer Panel, testing for 62 genes, was performed and showed germline mutations in PTEN and RecQ like helicase 4 (RECQL4) genes. Completion thyroidectomy subsequently performed demonstrated about 60 follicular cell-derived adenomatous nodules (0.3-10 mm). Genetic counseling and evaluation documented Cowden syndrome (CS) in the family. Thus, PHTS was confirmed. CONCLUSION: This report documents synchronous FTC and PTC in a background of multiple follicular adenomatous nodules with a novel RECQL4 mutation in an adult patient with PHTS. As such, documented the loss of PTEN protein in a thyroid gland affected by multiple adenomatous nodules aided in diagnosing PHTS.

Common Diagnostic Challenges and Pitfalls in Genitourinary Organs, With Emphasis on Immunohistochemical and Molecular Updates.

CONTEXT.­: Lesions in the genitourinary (GU) organs, both benign and malignant, can demonstrate overlapping morphology, and practicing surgical pathologists should be aware of these potential pitfalls and consider a broad differential diagnosis for each specific type of lesion involving the GU organs. The following summary of the contents presented at the 6th Annual Chinese American Pathologists Association (CAPA) Diagnostic Course (October 10-11, 2020), supplemented with relevant literature review, exemplifies the common diagnostic challenges and pitfalls for mass lesions of the GU system of adults, including adrenal gland, with emphasis on immunohistochemical and molecular updates when relevant. OBJECTIVE.­: To describe the common mass lesions in the GU system of adults, including adrenal gland, with emphasis on the diagnostic challenges and pitfalls that may arise in the pathologic assessment, and to highlight immunohistochemical workups and emerging molecular findings when relevant. DATA SOURCES.­: The contents presented at the course and literature search comprise our data sources. CONCLUSIONS.­: The diagnostic challenges and pitfalls that arise in the pathologic assessment of the mass lesions in the GU system of adults, including adrenal gland, are common. We summarize the contents presented at the course, supplemented with relevant literature review, and hope to provide a diagnostic framework to evaluate these lesions in routine clinical practice.

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

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.

EGFR Mutated Lung Adenocarcinoma Metastasis to the Pancreas Mimicking Primary Pancreatic Ductal Carcinoma.

BACKGROUND: The occurrence of lung adenocarcinoma metastasizing to the pancreas is overall rare and can histologically imitate primary pancreatic ductal carcinoma (PDAC). CASE REPORT: This is a case report of a 70-year-old female with a history of surgically resected right lung adenocarcinoma presenting for routine follow up without symptoms. CT scans revealed a pancreatic cystic mass with ductal dilatation that was sampled via endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and thought to be a primary pancreatic mucinous neoplasm with high grade dysplasia suspicious for carcinoma based on smear cytology. On repeat EUS-FNA and biopsy (FNB) with additional immunohistochemical testing for lung adenocarcinoma markers thyroid transcription factor (TTF1) and Napsin A and molecular testing, the lesion was identified as a metastasis of lung adenocarcinoma with an epidermal growth factor receptor (EGFR L858R) mutation; subsequently, the patient underwent targeted therapy that yielded an almost complete response. CONCLUSION: To the best of our knowledge, this is the first documented case in English literature of a lung adenocarcinoma metastasis to the pancreas mimicking a pancreatic primary neoplasm and highlights the potential pitfalls of EUS-FNA for the diagnosis of certain metastases to the pancreas.

Atypical Intraductal Cribriform Proliferations of the Prostate Exhibit Similar Molecular and Clinicopathologic Characteristics as Intraductal Carcinoma of the Prostate.

Atypical intraductal cribriform proliferations of the prostate (AIP) are loose cribriform proliferations of luminal cells that exhibit greater architectural complexity and/or nuclear atypia than high-grade prostatic intraepithelial neoplasia (HGPIN), but lack the diagnostic criteria for intraductal carcinoma (IDC). The significance of AIP has not been formally established. We compared the clinical, morphologic, and immunohistochemical characteristics of AIP with classic IDC in 310 radical prostatectomy specimens that were received over an 18-month period. Of the 310 cases, 46 cases had AIP only (n=10), IDC only (n=6), or AIP coexisting with IDC (n=30). The ERG status of all 46 AIP/IDC cases was identical to the nearby acinar carcinoma, contrasted to just 3 cases of HGPIN (7%, P<0.01). The degree of uniform phosphatase and tensin homolog (PTEN) loss in 34 selected cases was identical in AIP and IDC (66.7%). No foci of HGPIN showed uniform PTEN loss; there was only 38% concordance of PTEN expression pattern between HGPIN and the nearby acinar carcinoma, unlike AIP and IDC (77% and 81%, respectively, P<0.01). AIP-associated and/or IDC-associated carcinoma (n=46) showed a higher stage and grade compared with acinar-only carcinoma (n=264, P<0.01). AIP-associated carcinoma had similar clinicopathologic features as IDC-associated carcinoma, including preoperative prostate-specific antigen, Gleason score, extraprostatic extension, seminal vesicle invasion, and lymph node metastasis (n=36, P>0.05). In conclusion, AIP shares similar ERG/PTEN immunoprofiles and exhibits similar clinical behavior as IDC, warranting immediate repeat biopsy when AIP is identified on biopsy, as is recommended in the most recent WHO Classification of Tumours of the Urinary System and Male Genital Organs, 2016.

Dynamic contrast-enhanced MRI of the prostate: An intraindividual assessment of the effect of temporal resolution on qualitative detection and quantitative analysis of histopathologically proven prostate cancer.

PURPOSE: To assess the effects of temporal resolution (RT ) in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) on qualitative tumor detection and quantitative pharmacokinetic parameters in prostate cancer. MATERIALS AND METHODS: This retrospective Institutional Review Board (IRB)-approved study included 58 men (64 ± 7 years). They underwent 3T prostate MRI showing dominant peripheral zone (PZ) tumors (24 with Gleason ≥ 4 + 3), prior to prostatectomy. Continuously acquired DCE utilizing GRASP (Golden-angle RAdial Sparse Parallel) was retrospectively reconstructed at RT of 1.4 sec, 3.7 sec, 6.0 sec, 9.7 sec, and 14.9 sec. A reader placed volumes-of-interest on dominant tumors and benign PZ, generating quantitative pharmacokinetic parameters (ktrans , ve ) at each RT . Two blinded readers assessed each RT for lesion presence, location, conspicuity, and reader confidence on a 5-point scale. Data were assessed by mixed-model analysis of variance (ANOVA), generalized estimating equation (GEE), and receiver operating characteristic (ROC) analysis. RESULTS: RT did not affect sensitivity (R1all : 69.0%-72.4%, all Padj = 1.000; R1GS≥4 + 3 : 83.3-91.7%, all Padj = 1.000; R2all : 60.3-69.0%, all Padj = 1.000; R2GS≥4 + 3 : 58.3%-79.2%, all Padj = 1.000). R1 reported greater conspicuity of GS ≥ 4 + 3 tumors at RT of 1.4 sec vs. 14.9 sec (4.29 ± 1.23 vs. 3.46 ± 1.44; Padj = 0.029). No other tumor conspicuity pairwise comparison reached significance (R1all : 2.98-3.43, all Padj ≥ 0.205; R2all : 2.57-3.19, all Padj ≥ 0.059; R1GS≥4 + 3 : 3.46-4.29, all other Padj ≥ 0.156; R2GS≥4 + 3 : 2.92-3.71, all Padj ≥ 0.439). There was no effect of RT on reader confidence (R1all : 3.17-3.34, all Padj = 1.000; R2all : 2.83-3.19, all Padj ≥ 0.801; R1GS≥4 + 3 : 3.79-4.21, all Padj = 1.000; R2GS≥4 + 3 : 3.13-3.79, all Padj = 1.000). ktrans and ve of tumor and benign tissue did not differ across RT (all adjusted P values [Padj ] = 1.000). RT did not significantly affect area under the curve (AUC) of Ktrans or ve for differentiating tumor from benign (all Padj = 1.000). CONCLUSION: Current PI-RADS recommendations for RT of 10 seconds may be sufficient, with further reduction to the stated PI-RADS preference of RT ≤ 7 seconds offering no benefit in tumor detection or quantitative analysis. LEVEL OF EVIDENCE: 3 J. MAGN. RESON. IMAGING 2017;45:1464-1475.

Incidence of intraductal carcinoma, multifocality and bilateral significant disease in radical prostatectomy specimens from Japan and United States.

Significant differences, including epidemiologic, clinical, pathologic and genetic, exist between Asian and Caucasian prostate cancer. Detailed pathologic data are, however, scarce. We studied in detail and compared the pathological features of prostate cancer in radical prostatectomy specimens in 228 patients (117 Japan, 111 US). Japanese prostate cancer had a higher Gleason grade group (mean 2.67 vs. 2.42 US, P < 0.05), but lower pathological stage (72 % pT2 and 28 % pT3 vs 55 % pT2 and 45 % pT3 US, P < 0.05). Japanese cancer showed significantly more tumor foci (3.8 vs 2.9 US, P < 0.05), and higher incidence of bilateral significant disease (81.3 % vs. 66.7 % US, P < 0.05). The dominant tumor nodules in Japanese cases had higher Gleason grade group (mean 2.73 vs. 2.40 US, P < 0.05). The incidence of intraductal carcinoma was significantly higher in Japanese patients (35.3 % vs. 12.6 % US, P < 0.01), which was independent of Gleason score (7: 30.9 % Japan vs 11.8 % US, P < 0.01; ≥ 8: 87.5 % Japan vs 28.6 % US, P < 0.01) and tumor stage (pT2: 24.1 % Japan vs 6.6 % US, P < 0.01; pT3: 62.9 % Japan vs 20 % US, P < 0.01). These findings demonstrate distinct pathological features in prostate cancer between Japanese and Caucasian patients, and may have important diagnostic and therapeutic implications.

Prediction of prostate cancer recurrence using quantitative phase imaging: Validation on a general population.

Prediction of biochemical recurrence risk of prostate cancer following radical prostatectomy is critical for determining whether the patient would benefit from adjuvant treatments. Various nomograms exist today for identifying individuals at higher risk for recurrence; however, an optimistic under-estimation of recurrence risk is a common problem associated with these methods. We previously showed that anisotropy of light scattering measured using quantitative phase imaging, in the stromal layer adjacent to cancerous glands, is predictive of recurrence. That nested-case controlled study consisted of specimens specifically chosen such that the current prognostic methods fail. Here we report on validating the utility of optical anisotropy for prediction of prostate cancer recurrence in a general population of 192 patients, with 17% probability of recurrence. Our results show that our method can identify recurrent cases with 73% sensitivity and 72% specificity, which is comparable to that of CAPRA-S, a current state of the art method, in the same population. However, our results show that optical anisotropy outperforms CAPRA-S for patients with Gleason grades 7-10. In essence, we demonstrate that anisotropy is a better biomarker for identifying high-risk cases, while Gleason grade is better suited for selecting non-recurrence. Therefore, we propose that anisotropy and current techniques be used together to maximize prediction accuracy.

Association Between Progranulin and Gaucher Disease.

BACKGROUND: Gaucher disease (GD) is a genetic disease caused by mutations in the GBA1 gene which result in reduced enzymatic activity of ß-glucocerebrosidase (GCase). This study identified the progranulin (PGRN) gene (GRN) as another gene associated with GD. METHODS: Serum levels of PGRN were measured from 115 GD patients and 99 healthy controls, whole GRN gene from 40 GD patients was sequenced, and the genotyping of 4 SNPs identified in GD patients was performed in 161 GD and 142 healthy control samples. Development of GD in PGRN-deficient mice was characterized, and the therapeutic effect of rPGRN on GD analyzed. FINDINGS: Serum PGRN levels were significantly lower in GD patients (96.65±53.45ng/ml) than those in healthy controls of the general population (164.99±43.16ng/ml, p<0.0001) and of Ashkenazi Jews (150.64±33.99ng/ml, p<0.0001). Four GRN gene SNPs, including rs4792937, rs78403836, rs850713, and rs5848, and three point mutations, were identified in a full-length GRN gene sequencing in 40 GD patients. Large scale SNP genotyping in 161 GD and 142 healthy controls was conducted and the four SNP sites have significantly higher frequency in GD patients. In addition, "aged" and challenged adult PGRN null mice develop GD-like phenotypes, including typical Gaucher-like cells in lung, spleen, and bone marrow. Moreover, lysosomes in PGRN KO mice exhibit a tubular-like appearance. PGRN is required for the lysosomal appearance of GCase and its deficiency leads to GCase accumulation in the cytoplasm. More importantly, recombinant PGRN is therapeutic in various animal models of GD and human fibroblasts from GD patients. INTERPRETATION: Our data demonstrates an unknown association between PGRN and GD and identifies PGRN as an essential factor for GCase's lysosomal localization. These findings not only provide new insight into the pathogenesis of GD, but may also have implications for diagnosis and alternative targeted therapies for GD.

Modification of the pT2 substage classification in prostate adenocarcinoma.

The current substage classification of pT2 prostate cancer (AJCC, 7th edition, 2010) into pT2a (unilateral tumors <1/2 of lobe), pT2b (unilateral tumors ≥1/2 of lobe), and pT2c (bilateral tumors) is of questionable relevance. Many studies show no difference in prognosis between substages, and incidence of pT2b prostate cancer is low. Other classification systems have been proposed based on tumor volume, as measured by dominant nodule size or tumor percentage. We characterized pT2b tumors and assessed the utility of current pT2 substaging in predicting biochemical recurrence-free survival after radical prostatectomy and compared them with different substaging methods based on tumor volume. Patients with pT2 tumors were selected among patients who underwent radical prostatectomy from 1998 to 2008. Dominant nodule size was dichotomized as <1.6 cm versus ≥1.6 cm. Tumor percentage was dichotomized as ≤25% versus >25%. Kaplan-Meier analysis and multivariate Cox proportional hazard regression models were used to evaluate pathological parameters predictive of biochemical recurrence-free survival. Of 785 patients who met criteria, 145 (18.5%) were pT2a, 15 (1.9%) were pT2b, and 625 (79.6%) were pT2c. The pT2 substages were not significant predictors of biochemical recurrence-free survival on univariate or multivariate analysis. In a multivariate model, tumor percentage >25% (P=.002) was associated with decreased biochemical recurrence-free survival. In patients with stage pT2 prostate cancer, the current substaging method lacks predictive value for biochemical recurrence-free survival after accounting for other pathologic and clinical predictors. However, tumor percentage (≤25% versus >25%) is a promising approach to substaging of pT2 prostate cancer based on its prognostic significance.

Prostate Cancer Detection Using Computed Very High b-value Diffusion-weighted Imaging: How High Should We Go?

RATIONALE AND OBJECTIVES: The aim of this study was to assess prostate cancer detection using a broad range of computed b-values up to 5000 s/mm(2). MATERIALS AND METHODS: This retrospective Health Insurance Portability and Accountability Act-compliant study was approved by an institutional review board with consent waiver. Forty-nine patients (63 ± 8 years) underwent 3T prostate magnetic resonance imaging before prostatectomy. Examinations included diffusion-weighted imaging (DWI) with b-values of 50 and 1000 s/mm(2). Seven computed DWI image sets (b-values: 1000, 1500, 2000, 2500, 3000, 4000, and 5000 s/mm(2)) were generated by mono-exponential fit. Two blinded radiologists (R1 [attending], R2 [fellow]) independently evaluated diffusion weighted image sets for image quality and dominant lesion location. A separate unblinded radiologist placed regions of interest to measure tumor-to-peripheral zone (PZ) contrast. Pathologic findings from prostatectomy served as reference standard. Measures were compared between b-values using the Jonckheere-Terpstra trend test, Spearman correlation coefficient, and generalized estimating equations based on logistic regression for correlated data. RESULTS: As b-value increased, tumor-to-PZ contrast and benign prostate suppression for both readers increased (r = +0.65 to +0.71, P ≤ 0.001), whereas anatomic clarity, visualization of the capsule, and visualization of peripheral-transition zone edge decreased (r = -0.69 to -0.75, P ≤ 0.003). Sensitivity for tumor was highest for R1 at b1500-3000 (84%-88%) and for R2 at b1500-2500 (70%-76%). Sensitivities for both pathologic outcomes were lower for both readers at both b1000 and the highest computed b-values. Sensitivity for Gleason >6 tumor was highest for R1 at b1500-3000 (90%-93%) and for R2 at 1500-2500 (78%-80%). The positive predictive value for tumor for R1 was similar from b1000 to 4000 (93%-98%) and for R2 was similar from b1500 to 4000 (88%-94%). CONCLUSIONS: Computed b-values in the range of 1500-2500 s/mm(2) (but not higher) were optimal for prostate cancer detection; b-values of 1000 or 3000-5000 exhibited overall lower performance.

Length of capsular contact for diagnosing extraprostatic extension on prostate MRI: Assessment at an optimal threshold.

PURPOSE: To evaluate the length of capsular contact of dominant lesions on multiparametric prostate magnetic resonance imaging (MRI) for predicting extraprostatic extension (EPE) and to determine a threshold value to apply in clinical practice. MATERIALS AND METHODS: Ninety patients undergoing 3T prostate MRI before prostatectomy were included. Two independent readers (R1, R2) recorded for each lobe the presence or absence of capsular irregularity on T2 -weighted imaging (T2 WI) and of overt measurable EPE. Readers also recorded the length of capsular contact of each lobe's dominant lesion for T2 WI and the apparent diffusion coefficient (ADC) map. Based on prostatectomy specimens, EPE was recorded for each lobe and classified as focal (single focus ≤0.5 mm in depth) vs. established. Receiver operating characteristic analysis, logistic regression, and kappa coefficients were used to assess interpretive approaches on a side-specific basis. RESULTS: The optimal thresholds were 6 mm and 7 mm of contact using T2 WI and ADC for any EPE, and 10 mm and 7 mm using T2 WI and ADC for nonfocal EPE (AUCs 81.0-82.5%). Capsular contact had higher sensitivity, yet lower specificity, than subjective interpretations for any EPE and for nonfocal EPE (all P ≤ 0.018, aside from any EPE for R2 using ADC). Length of contact exhibited more substantial gains in sensitivity (9-20% for any EPE; 34-41% for nonfocal EPE) than losses in specificity (6-13% for any EPE; 17-27% for nonfocal EPE) compared with subjective interpretations. Interreader agreement: 0.70 for assessments based on length of contact; 0.49-0.59 for subjective assessments. CONCLUSION: Length of capsular contact of dominant lesions can improve interreader agreement and sensitivity for EPE compared with subjective features, with relatively mild specificity loss.

Prognostic factors in myoepithelial carcinoma of salivary glands: a clinicopathologic study of 48 cases.

Myoepithelial carcinoma (MECA) is an underrecognized rare tumor with a diverse clinical behavior. The histologic features of this tumor are not well characterized, much less its grading, which is controversial. The objective of this study is to provide a better characterization of MECA and its prognostic factors. A total of 48 cases were retrieved from the pathology files. The cases were subjected to a detailed histopathologic, immunohistochemical, statistical, and clinical analysis. Tumors were classified as de novo MECA in 22 cases (46%) and carcinoma ex-pleomorphic adenoma (CA ex-PA) in 26 cases (54%). Tumor necrosis, high mitotic count (≥6/10 high-power fields), and severe pleomorphism were identified in 38%, 33%, and 21%, respectively. Perineural invasion, vascular invasion, and positive margins were noted in 10%, 12%, and 47%, respectively. Median follow-up was 38 months. Four patients had lymph node metastasis at presentation, 9 developed local recurrences, and 12 had distant metastases with the lung being the most common site (83%). The presence of CA ex-PA, necrosis, and vascular invasion correlated significantly with disease-free survival (P=0.02, 0.01, 0.03, respectively). No distant recurrence was noted in all 23 patients lacking necrosis in their neoplasms (median follow-up: 44 mo). MECA is a relatively aggressive tumor that is associated with a high rate of distant metastasis (27%). Compared with de novo MECA, CA ex-PA correlates with worse clinical outcome. A grading system based on the presence of tumor necrosis should be used to identify high-grade MECA and predict its clinical behavior.

Papillary or pseudopapillary tumors of the kidney.

Papillary architecture is one of the most common morphological patterns in renal cell neoplasms. Many renal cell neoplasms can also exhibit, diffusely or focally, papillary growth pattern. This article reviews all the renal cell neoplasms with papillary or pseudopapillary architecture, with an emphasis on recently described new histological types. New insights into the "old" entities, including their immunohistochemical and genetic features, will also be discussed.

Gleason score 3 + 4=7 prostate cancer with minimal quantity of gleason pattern 4 on needle biopsy is associated with low-risk tumor in radical prostatectomy specimen.

A modified Gleason grading system as proposed in the 2005 International Society of Urological Pathology (ISUP) consensus meeting is the current grading system for prostate cancer. With this modified ISUP Gleason grading system, many Gleason score (GS) 6 cancers by the old grading system are upgraded to GS7 cancers on biopsy diagnosis even with minimal quantity (≤5%) of Gleason pattern 4 (GP4) component (GS7miniGP4). However, grade concordance between the core needle biopsy of GS7miniGP4 and the corresponding radical prostatectomy (RP) specimens has not been studied. In this study, we analyzed the pathologic features of 256 consecutive needle biopsies and their corresponding RP specimens. The quantity of GP4 was calculated as the percentage of total cancer for GS7 cancer in the biopsy. Of 256 biopsies, 88 (34.4%), 107 (41.8%), and 61 (23.8%) had a GS of 6, 3+4=7, and 4+3=7, respectively. Of 107 biopsies with GS 3+4=7, 22 (20.6%) are GS7miniGP4. Ten of 22 cases of G7miniGP4 in the biopsies (45%) had pathologically insignificant tumor in the RP. The quantity of GP4 in the GS7 biopsy significantly correlated with GS, pathologic stage, and total tumor volume in the corresponding RP. The GS, pathologic stages, total tumor volume, and insignificant tumor rate in RP were not significantly different between the biopsy groups of GS 3+3=6 and GS7miniGP4, whereas those parameters were significantly different between biopsy groups of GS 3+3=6 and GS 3+4=7 with GP4 6% to 50% and between biopsy groups of GS7miniGP4 and GS7 with GP4 6% to 50%. Our data demonstrate that pathologic parameters in the RP are similar between the biopsy groups of GS7miniGP4 and GS6, and the grading of cases with biopsy GS7miniGP4 is often downgraded in RP specimens. The clinical significance of minimal quantity (≤5%) of GP4 in biopsies with GS7 prostate cancer needs to be further evaluated, particularly because of its potential impact on clinical decisions between active surveillance versus surgery.

Re-evaluating the concept of "dominant/index tumor nodule" in multifocal prostate cancer.

Prostate cancer (PCa) often presents as a multifocal disease with heterogeneity in Gleason score (GS) and genetic alterations. Dominant/index tumor nodule (DN), the largest nodule in a multifocal disease, is presumed to harbor the most aggressive biological behavior and therefore dictate the overall clinical behavior of PCa. In this study, we examined the pathological features of DN and re-evaluated the validity of the "DN" concept in multifocal PCa. A total of 201 consecutive radical prostatectomy specimens were totally submitted and examined. All independent cancer foci were recorded with prognostically important pathological parameters. Unifocal and multifocal disease was present in 25 (12.4 %) and 176 (87.6 %) cases, respectively. In 20 (11.3 %) multifocal cases, the highest GS, the largest tumor volume (TV), and extraprostatic extension (EPE) did not concur in the same tumor nodules. Non-DNs had a higher GS and EPE in 13 cases each and had both the highest GS and EPE in 5 cases. In the majority of multifocal prostate cancer (88.7 %), DNs have the highest GS and EPE. In these cases, DN is still a valid concept and can be used for assigning overall GS and procuring tissue for research. However, in a significant number of cases (11.3 %), the largest TV, the highest GS, and EPE did not concur in the same tumor nodules. In these cases, pathologists should de-emphasize the concept of DN. Instead, they should place the emphasis on the multifocal nature of the disease and document the pathological features of all independent tumor foci that have the largest TV, the highest GS, and EPE.

Effect of soy protein isolate supplementation on biochemical recurrence of prostate cancer after radical prostatectomy: a randomized trial.

IMPORTANCE: Soy consumption has been suggested to reduce risk or recurrence of prostate cancer, but this has not been tested in a randomized trial with prostate cancer as the end point. OBJECTIVE: To determine whether daily consumption of a soy protein isolate supplement for 2 years reduces the rate of biochemical recurrence of prostate cancer after radical prostatectomy or delays such recurrence. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind trial conducted from July 1997 to May 2010 at 7 US centers comparing daily consumption of a soy protein supplement vs placebo in 177 men at high risk of recurrence after radical prostatectomy for prostate cancer. Supplement intervention was started within 4 months after surgery and continued for up to 2 years, with prostate-specific antigen (PSA) measurements made at 2-month intervals in the first year and every 3 months thereafter. INTERVENTION: Participants were randomized to receive a daily serving of a beverage powder containing 20 g of protein in the form of either soy protein isolate (n=87) or, as placebo, calcium caseinate (n=90). MAIN OUTCOMES AND MEASURES: Biochemical recurrence rate of prostate cancer (defined as development of a PSA level of ≥0.07 ng/mL) over the first 2 years following randomization and time to recurrence. RESULTS: The trial was stopped early for lack of treatment effects at a planned interim analysis with 81 evaluable participants in the intervention group and 78 in the placebo group. Overall, 28.3% of participants developed biochemical recurrence within 2 years of entering the trial (close to the a priori predicted recurrence rate of 30%). Among these, 22 (27.2%) occurred in the intervention group and 23 (29.5%) in the placebo group. The resulting hazard ratio for active treatment was 0.96 (95% CI, 0.53-1.72; log-rank P = .89). Adherence was greater than 90% and there were no apparent adverse events related to supplementation. CONCLUSION AND RELEVANCE: Daily consumption of a beverage powder supplement containing soy protein isolate for 2 years following radical prostatectomy did not reduce biochemical recurrence of prostate cancer in men at high risk of PSA failure. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00765479.

Histopathologic and clinical features of vesical diverticula.

OBJECTIVE: To study the histopathology changes and clinical features of vesical diverticula, focusing on the neoplastic entities. MATERIALS AND METHODS: We retrieved data for 108 patients with vesical diverticula from the archives of our institute during the past 15 years (1998 to 2012) and reviewed their clinical and pathologic characteristics. RESULTS: Diverticula most often involved the lateral wall, followed by the posterolateral and posterior walls of the urinary bladder. Nonneoplastic processes were found in 70 of 108 patients (65%), including inflammation, metaplasia, and urothelial hyperplasia, with or without atypia/dysplasia. Primary carcinomas arising within the diverticula were found in 36 patients (33.3%), of which 33 were urothelial carcinoma, including 5 with divergent differentiation, 2 with squamous carcinoma, and 1 with adenocarcinoma. Patient follow-up for neoplastic diverticula (mean, 59 months; range, 1-108 months) showed that no patients died of disease progression. Concurrent or subsequent urothelial carcinoma was present in the nondiverticular bladder in 19 of 36 patients (53%). Four patients with subsequent extradiverticular urothelial carcinoma showed progression, with pathology upstaging. CONCLUSION: Inflammation, metaplasia, and dysplasia are commonly seen in vesical diverticula. In our series, which includes patients who underwent endoscopic or surgical intervention and microscopic examination, those with vesical diverticula appeared to have a significantly higher risk for development of urothelial carcinoma, which can occur synchronously or precede carcinoma of the nondiverticular bladder. Compared with their non-diverticulum-associated counterparts, a significantly higher percentage of diverticulum-associated bladder carcinomas are high-grade and invasive. Conservative approaches are suggested for tumors confined within diverticula, after extensive investigation of the nondiverticular bladder.

Bilateral tubulocystic renal cell carcinomas in diabetic end-stage renal disease: first case report with cytogenetic and ultrastructural studies.

Tubulocystic renal cell carcinoma (TC-RCC) is a rare renal tumor composed of well-differentiated tubules and cysts lined by neoplastic cells with eosinophilic cytoplasm and prominent nucleoli. The origin of the tumor cells is still controversial. TC-RCC typically arises unilaterally. Involvement of both kidneys by multifocal TC-RCC has not been reported. In this study we report the first case of bilateral and multifocal TC-RCC. Immunohistochemical, cytogenetic and ultrastructural studies suggest TC-RCC is closely related to papillary RCC.