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.

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.

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.

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.

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.