FOXA1 repression drives lineage plasticity and immune heterogeneity in bladder cancers with squamous differentiation.

Cancers arising from the bladder urothelium often exhibit lineage plasticity with regions of urothelial carcinoma adjacent to or admixed with regions of divergent histomorphology, most commonly squamous differentiation. To define the biologic basis for and clinical significance of this morphologic heterogeneity, here we perform integrated genomic analyses of mixed histology bladder cancers with separable regions of urothelial and squamous differentiation. We find that squamous differentiation is a marker of intratumoral genomic and immunologic heterogeneity in patients with bladder cancer and a biomarker of intrinsic immunotherapy resistance.

Pathological characterization and clinical outcome of penile intraepithelial neoplasia variants: a North American series.

Penile intraepithelial neoplasia (PeIN) is classified as human papillomavirus (HPV)- and non-HPV-related. This classification is associated with distinct morphologic subtypes. The natural history and prognosis of PeIN subtypes are not well known.

Targeted Mutational Analysis of Cortisol-Producing Adenomas.

Context: Somatic gene mutations have been identified in only about half of cortisol-producing adenomas (CPAs). Affected genes include PRKACA, GNAS, PRKAR1A, and CTNNB1.

Objective: This work aims to expand our understanding of the prevalence of somatic mutations in CPAs from patients with overt Cushing syndrome (OCS) and "subclinical" mild autonomous cortisol excess (MACE), with an immunohistochemistry (IHC)‒guided targeted amplicon sequencing approach using formalin-fixed paraffin-embedded (FFPE) tissue.

Development of multiple adrenal myelolipomas after trauma-induced adrenal haemorrhage.

Adrenal myelolipomas represent a benign neoplasm with known associations with many chronic diseases, 21-hydroxylase deficiency and cancer. However, the aetiology of adrenal myelolipomas remains unknown. Here, we present a case of a patient with image-proven bilateral adrenal haemorrhages caused by trauma with the subsequent development of bilateral adrenal myelolipomas several years later.

Genetic Characteristics of Aldosterone-Producing Adenomas in Blacks.

Somatic mutations have been identified in aldosterone-producing adenomas (APAs) in genes that include KCNJ5, ATP1A1, ATP2B3, and CACNA1D. Based on independent studies, there appears to be racial differences in the prevalence of somatic KCNJ5 mutations, particularly between East Asians and Europeans. Despite the high cardiovascular disease mortality of blacks, there have been no studies focusing on somatic mutations in APAs in this population.

Case of reversible diabetes mellitus in the setting of benign Pheochromocytoma.

Pheochromocytomas have been shown to impair glucose tolerance and, rarely, to precipitate overt diabetes mellitus. We report here a case of a large pheochromocytoma in a woman with a recent diagnosis of diabetes mellitus that proved difficult to control despite high-dose insulin therapy who had complete resolution of her hyperglycemia following adrenalectomy. Her dramatic presentation demonstrates the need to consider this etiology in patients with new-onset insulin resistance and hypertension.

MAGI2 is an independent predictor of biochemical recurrence in prostate cancer.

Background: Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2) promotes the activity of phosphatase and tensin homolog (PTEN). Recent studies suggest that dysregulation of this signaling pathway has a role in prostate carcinogenesis. Our study aims to determine the prognostic significance of MAGI2 expression in prostate cancer.

TPX2 as a prognostic indicator and potential therapeutic target in clear cell renal cell carcinoma.

Objectives: Our aims were to determine if targeting protein for Xklp2 (TPX2) is correlated with clear cell renal cell carcinoma (ccRCC) histology and oncologic outcomes using The Cancer Genome Atlas (TCGA) and an institutional tissue microarray (TMA).

Methods: Clinicopathological data obtained from the TCGA consisted of 415 samples diagnosed with ccRCC. A TMA was constructed from tumors of 207 patients who underwent radical nephrectomy for ccRCC.

Core Needle Biopsy and Fine Needle Aspiration Alone or in Combination: Diagnostic Accuracy and Impact on Management of Renal Masses.

Purpose: Fine needle aspiration with and without concurrent core needle biopsy is a minimally invasive method to diagnose and assist in management of renal masses. We assessed the pathological accuracy of fine needle aspiration compared to and associated with core needle biopsy and the impact on management.

Materials And Methods: We performed a single institution, retrospective study of 342 cases from 2001 to 2015 with small and large renal masses (4 or less and greater than 4 cm, respectively).

New and Emerging Diagnostic and Prognostic Immunohistochemical Biomarkers in Prostate Pathology.

The diagnosis of minimal prostatic adenocarcinoma can be challenging on prostate needle biopsy, and immunohistochemistry may be used to support the diagnosis of cancer. The International Society of Urologic Pathology currently recommends the use of the basal cell markers high-molecular-weight cytokeraratin and p63, and α-methylacyl-coenzyme-A racemase. However, there are caveats associated with the interpretation of these markers, particularly with benign mimickers.

Primary Carcinoid Tumor of the Renal Pelvis Arising From Intestinal Metaplasia: An Unusual Histogenetic Pathway?

Objectives: Primary carcinoid tumor of the renal pelvis is a rare neoplasm with few cases reported in the literature. Here we present the clinical and histopathologic findings of a primary carcinoid tumor arising in the left renal pelvis of a horseshoe kidney in a 61-year-old female patient.

Materials And Methods: Pathologic features were evaluated with standard hematoxylin and eosin sections and immunohistochemical studies.

MAGI-2 Is a Sensitive and Specific Marker of Prostatic Adenocarcinoma: A Comparison With AMACR.

Objectives: We compared the utility of membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI-2) and α-methylacyl CoA (AMACR) by immunohistochemistry in diagnosing prostatic adenocarcinoma.

Methods: Seventy-eight radical prostatectomies were used to construct three tissue microarrays with 512 cores, including benign prostatic tissue, benign prostatic hyperplasia, high-grade prostatic intraepithelial neoplasia (HGPIN), and adenocarcinoma. AMACR and MAGI-2 immunohistochemistry were evaluated by visual and image analysis.

MAGI-2 in prostate cancer: an immunohistochemical study.

Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI-2) is a scaffolding protein that links cell adhesion molecules, receptors, and signaling molecules to the cytoskeleton and maintains the architecture of cell junctions. MAGI-2 gene rearrangements have recently been described in prostate cancer. We studied the immunohistochemical expression of MAGI-2 protein in prostate tissue.

Pediatric cystic nephromas: distinctive features and frequent DICER1 mutations.

Cystic nephromas (CNs) are uncommon benign renal neoplasms that present with a bimodal age distribution, affecting either infants/young children or adult females. Although differences between these age groups have been suggested, large studies of pediatric CN have not been conducted. As a result, the nomenclature and diagnostic criteria for these lesions remain controversial.

A collision tumor of papillary renal cell carcinoma and oncocytoma: case report and literature review.

Objectives: The most common renal neoplasms include clear cell, chromophobe, and papillary renal cell carcinomas (PRCCs) and oncocytomas. While lesions containing hybrid features of different tumor types, such as hybrid oncocytic tumors, have been well documented in the literature, the finding of a collision tumor of two distinct tumor types- PRCC and oncocytoma-is extremely rare.

Methods: We present a case of PRCC associated with an oncocytoma.

Urothelial carcinoma with squamous differentiation--the pathologists׳ perspective.

Squamous differentiation is the most common variant histology in urothelial carcinoma and may have effects on clinical outcome. Inconsistencies in reporting variant histologies in urothelial carcinoma are well documented. Immunohistochemical and molecular markers may help identify tumors with squamous differentiation beyond light microscopy.

Loss of FOXA1 Drives Sexually Dimorphic Changes in Urothelial Differentiation and Is an Independent Predictor of Poor Prognosis in Bladder Cancer.

We previously found loss of forkhead box A1 (FOXA1) expression to be associated with aggressive urothelial carcinoma of the bladder, as well as increased tumor proliferation and invasion. These initial findings were substantiated by The Cancer Genome Atlas, which identified FOXA1 mutations in a subset of bladder cancers. However, the prognostic significance of FOXA1 inactivation and the effect of FOXA1 loss on urothelial differentiation remain unknown.

The diagnostic accuracy of percutaneous renal needle core biopsy and its potential impact on the clinical management of renal cortical neoplasms.

Context: While biopsies are now increasingly being performed for the diagnosis of renal cortical neoplasms, the influence of the rendered pathological diagnoses on the clinical management is only rarely documented.

Objectives: To report our experience with consecutively performed renal biopsies and the potential impact of the diagnosis on subsequent clinical management.

Design: Material from needle biopsies performed consecutively at our institution between 2006 and 2011 was reviewed.

Lack of P16ink4a over expression in penile squamous cell carcinoma is associated with recurrence after lymph node dissection.

Purpose: There have been conflicting data in studies on the prognostic role of high risk human papillomavirus in penile squamous cell carcinoma. Using P16(ink4a) over expression as a surrogate marker for high risk human papillomavirus, we evaluated high risk human papillomavirus status with respect to various clinical features, including recurrence and overall survival, among others.

Materials And Methods: P16(ink4a) over expression was evaluated by immunohistochemistry for 119 consecutive patients with penile squamous cell carcinoma.

Epithelial and stromal expression of miRNAs during prostate cancer progression.

Global microRNA (miRNA) profile may predict prostate cancer (PCa) behaviors. In this study, we examined global miRNA expression by miRNA profiling as well as specific miRNA expression levels in PCa epithelium and stroma by in situ hybridization (ISH) and correlated with various clinicopathological features. We first performed comprehensive miRNA profiling on 27 macrodissected cases of PCa by miRNA microarray.

Decreased expression of stromal estrogen receptor α and β in prostate cancer.

Background: Recently there has been an increased interest in the role of tumor-associated stroma in prostate tumorigenesis, but little is known about the respective roles of stomal ERα and ERβ in prostate cancer (PCa). This study characterizes the expression patterns of ERα and ERβ in tumor-associated stroma in association with various clinicopathological factors of importance in PCa prognosis and treatment.

Design: Immunohistochemistry was performed using antibodies against ERα and ERβ to characterize their expression patterns in PCa tissue.

TBLR1 as an androgen receptor (AR) coactivator selectively activates AR target genes to inhibit prostate cancer growth.

Androgen receptor (AR), a steroid hormone receptor, is critical for prostate cancer growth. However, activation of AR by androgens can also lead to growth suppression and differentiation. Transcriptional cofactors play an important role in this switch between proliferative and anti-proliferative AR target gene programs.

Phase II study of everolimus in metastatic urothelial cancer.

Unlabelled: What's known on the subject? and what does the study add?: No recent advances have been made in the treatment of patients with advanced bladder cancer and, to date, targeted therapies have not resulted in an improvement in outcome. The mammalian target of rapamycin pathway has been shown to be up-regulated in bladder cancer and represents a rational target for therapeutic intervention. In the present phase II study of everolimus, one near-complete response, one partial response and several minor responses suggest that everolimus possesses biological activity in a subset of patients with bladder cancer.

Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma: correlative analysis from a large North American cooperative group trial.

Epstein-Barr virus (EBV) is associated with Hodgkin lymphoma (HL) and can be detected by in situ hybridization (ISH) of viral nucleic acid (EBER) in tumor cells. We sought to determine whether plasma EBV-DNA could serve as a surrogate for EBER-ISH and to explore its prognostic utility in HL. Specimens from the Cancer Cooperative Intergroup Trial E2496 were used to compare pretreatment plasma EBV-DNA quantification with EBV tumor status by EBER-ISH.