Strong PD-L1 expression in granulomatous prostatitis.

BACKGROUND: The expression of programmed cell death ligand protein (PD-L1) is weakly investigated in non-tumoral and inflammatory prostatic pathology. The diagnosis of granulomatous prostatitis (GP) rests on the recognition of localized or diffuse epithelioid granulomatous inflammation in prostatic tissue which is frequently difficult by conventional histological observation alone. PD-L1 expression in GP is not well studied so far. METHODS: We studied PD-L1 expression in 17 GP cases (9 nonspecific GP, 5 Bacillus Calmette-Guérin induced prostatitis, 1 prostatic tuberculosis, and 3 cases of postsurgical prostatic granulomas). The control group included 10 radical prostatectomies of patients with high Gleason score prostate adenocarcinoma (PCa) and National Institutes of Health-category IV prostatitis (high-grade histologic prostatitis; HG-HP). RESULTS: All of the GP cases showed easily visible strong membranous PD-L1 expression (high levels of combined positive score) in localized and diffuse epithelioid granulomatous prostatic inflammation. None of the control cases showed the presence of significant PD-L1 expression in inflammatory infiltrates in HG-HP, tumor parenchyma, and stroma in PCa. CONCLUSIONS: The study presents the first attempt to examine PD-L1 expression in GP. Granulomatous inflammation in GP is easily identified when stained with PD-L1.

Machine Learning Model for Chest Radiographs: Using Local Data to Enhance Performance.

PURPOSE: To develop and assess the performance of a machine learning model which screens chest radiographs for 14 labels, and to determine whether fine-tuning the model on local data improves its performance. Generalizability at different institutions has been an obstacle to machine learning model implementation. We hypothesized that the performance of a model trained on an open-source dataset will improve at our local institution after being fine-tuned on local data. METHODS: In this retrospective, institutional review board approved study, an ensemble of neural networks was trained on open-source datasets of chest radiographs for the detection of 14 labels. This model was then fine-tuned using 4510 local radiograph studies, using radiologists' reports as the gold standard to evaluate model performance. Both the open-source and fine-tuned models' accuracy were tested on 802 local radiographs. Receiver-operator characteristic curves were calculated, and statistical analysis was completed using DeLong's method and Wilcoxon signed-rank test. RESULTS: The fine-tuned model identified 12 of 14 pathology labels with area under the curves greater than .75. After fine-tuning with local data, the model performed statistically significantly better overall, and specifically in detecting six pathology labels (P < .01). CONCLUSIONS: A machine learning model able to accurately detect 14 labels simultaneously on chest radiographs was developed using open-source data, and its performance was improved after fine-tuning on local site data. This simple method of fine-tuning existing models on local data could improve the generalizability of existing models across different institutions to further improve their local performance.

Expression of MUC1 in eosinophilic metaplasia of the prostate.

BACKGROUND: Eosinophilic metaplasia (EM) in the prostate is characterized by the presence of eosinophilic cytoplasmic granules in benign prostatic epithelium. These granules show exocrine-type morphology and positive expression for prostate specific antigen (PSA) and some lysosomal markers. The nature and the full immunohistochemical profile of the granules of EM have not been studied in detail yet. AIM: The aim of the current study is to investigate the expression of epithelial mucins (MUCs) in prostatic epithelium with EM. METHODS: Twenty specimens from transurethral resection of the prostate (TURP) were reviewed for the presence of EM and were stained with Periodic acid-Schiff's procedure with diastase digestion (PAS.D) and immunostained with PSA and MUCs: MUC1, MUC2, MUC5AC, and MUC6. RESULTS: The EM-foci of all prostate glands are PAS.D, PSA positive and show constant immunoreactivity for MUC1. The expression of MUC1 is with membranous and cytoplasmic localization: predominantly apical with membranous accentuation in the cases of EM with large eosinophilic granules, and perinuclear in EM with small eosinophilic granules. There is no expression of other MUCs (MUC2, MUC5AC, and MUC6) in prostatic EM. CONCLUSION: We report for the first time that eosinophilic cytoplasmic granules in prostatic EM are MUC1 positive and can vary in size. Based on our immunohistochemical study we suggest that EM of the prostate is not a form of mucinous metaplasia. The present results enrich the available information about the immunophenotype of EM. We assume that MUC1 might serve as a reliable and constant, although nonspecific, immunohistochemical marker of benign EM-phenotype.

Adenovirus E1A targets the DREF nuclear factor to regulate virus gene expression, DNA replication, and growth.

UNLABELLED: The adenovirus E1A gene is the first gene expressed upon viral infection. E1A remodels the cellular environment to maximize permissivity for viral replication. E1A is also the major transactivator of viral early gene expression and a coregulator of a large number of cellular genes. E1A carries out its functions predominantly by binding to cellular regulatory proteins and altering their activities. The unstructured nature of E1A enables it to bind to a large variety of cellular proteins and form new molecular complexes with novel functions. The C terminus of E1A is the least-characterized region of the protein, with few known binding partners. Here we report the identification of cellular factor DREF (ZBED1) as a novel and direct binding partner of E1A. Our studies identify a dual role for DREF in the viral life cycle. DREF contributes to activation of gene expression from all viral promoters early in infection. Unexpectedly, it also functions as a growth restriction factor for adenovirus as knockdown of DREF enhances virus growth and increases viral genome copy number late in the infection. We also identify DREF as a component of viral replication centers. E1A affects the subcellular distribution of DREF within PML bodies and enhances DREF SUMOylation. Our findings identify DREF as a novel E1A C terminus binding partner and provide evidence supporting a role for DREF in viral replication. IMPORTANCE: This work identifies the putative transcription factor DREF as a new target of the E1A oncoproteins of human adenovirus. DREF was found to primarily localize with PML nuclear bodies in uninfected cells and to relocalize into virus replication centers during infection. DREF was also found to be SUMOylated, and this was enhanced in the presence of E1A. Knockdown of DREF reduced the levels of viral transcripts detected at 20 h, but not at 40 h, postinfection, increased overall virus yield, and enhanced viral DNA replication. DREF was also found to localize to viral promoters during infection together with E1A. These results suggest that DREF contributes to activation of viral gene expression. However, like several other PML-associated proteins, DREF also appears to function as a growth restriction factor for adenovirus infection.

Leiomyosarcoma of the esophagus, arising from lamina muscularis mucosae, in a combination with microinvasive squamous cell carcinoma-A case report.

ABSTRACT: Leiomyosarcoma of the esophagus is a very rare disease, accounting for less than 0.5% of malignant esophageal tumors. Esophageal leiomyosarcoma combined with squamous cell carcinoma is even rarer than solitary leiomyosarcoma. To our knowledge, there are less than ten cases of simultaneously diagnosed leiomyosarcoma and squamous cell carcinoma of the esophagus. A 66-year-old male was admitted to our hospital suffering from epigastric pain, asthenia, weight loss, and difficulties when feeding with solid food which had been present for 2 weeks. A computed tomography scan showed a large tumor tissue mass in the mid-to-distal part of the esophagus. The patient underwent robot-assisted surgery-an esophagectomy with esophagogastrostomy. Histologically, the tumor consisted of highly pleomorphic spindle cells with multiple atypical mitosis and necrotic areas. An immunohistochemical examination was performed to distinguish leiomyosarcoma from spindle cell squamous carcinoma or malignant GIST. Tumor cells stained diffusely positive for smooth muscle actin, but negative for p63, CD117, and CKAE1/AE3. Tumor invasion involved mucosa and submucosa, without tunica muscularis propria. Microinvasive well-differentiated squamous cell carcinoma was also noted in the mucosa at the borders between the tumor and the healthy part of the esophagus. The aim of the manuscript is to present an extremely rare case of combined polypoid leiomyosarcoma and microinvasive squamous cell carcinoma of the esophagus, cured by robot-assisted surgical intervention and to emphasize that such cases should be examined carefully, including additional diagnostic tests such as Immunohistochemistry (IHC) in order to define the correct diagnosis.

Diagnostic benefits of 18F-FDG PET/CT in cases of prosthetic infective endocarditis.

Infective endocarditis (IE) is a difficult-to-diagnose provocative disease that causes significant morbidity and mortality. The first-line imaging test for the diagnosis of IE is echocardiography. However, in cases of prosthetic IE or IE associated with intracardiac devices, its sensitivity is limited. A new diagnostic tool, 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT), improves diagnosis in these difficult cases. The most recent European guidelines for IE (2015) include this imaging modality as a primary diagnostic criterion. We present a case of culture-negative prosthetic IE diagnosed with 18F-FDG PET/CT.

PD-L1 positive lympho-epithelial lesions in inflammatory prostate.

OBJECTIVES: Ductal epithelial changes (lympho-epithelial lesions-LEL) in prostatic chronic inflammation (CI) are not well studied so far. AIM: to investigate LEL immediately adjacent to prostatic CI. METHODS: We studied LEL in 144 prostatic surgical and autopsy specimens in various types of prostatic CI: NIH-category IV prostatitis (histologic prostatitis-HP), nonspecific granulomatous prostatitis (NSGP), and the reactive lymphoid infiltrates in the vicinity of benign prostatic hyperplasia (BPH) and prostate adenocarcinoma (PCa). CI is scored as low and high grade (LG, HG) according to the severity of inflammation. RESULTS: LEL was identified in all types of prostatic specimens and in all types of prostatic CI: in 70.9% of patients with HP; in 100% of cases with NSGP; in 68.7% and in 80% adjacent to BPH and PCa respectively. Statistical analysis showed a significant correlation of the presence of LEL with HG CI (p<0.001). LEL showed strong membranous PD-L1 expression. CONCLUSIONS: The study presents the first attempt to examine LEL in inflammatory human prostate. PD-L1 positive LEL have no diagnostic organ specificity, although they are a constant histological finding in HG prostatic CI. LEL, inducible after birth by CI, are an integral part of prostate-associated lymphoid tissue (PALT) and of the inflammatory prostatic microenvironment.

Eosinophilic metaplasia in transurethral resection of the prostate.

BACKGROUND: To investigate prostatic eosinophilic metaplasia (EM) in a large series of cases and their relationship with the basic prostate pathology in TURP-material: benign prostatic hyperplasia (BPH), National Institutes of Health category IV prostatitis (also called histologic prostatitis or HP), and prostatic adenocarcinoma (PCa). AIM: The relation between EM and basic prostate pathology: BPH, PCa, and HP. MATERIALS AND METHODS: Around 61 consecutive TURP-specimens were reviewed for the presence of EM. The tissue sections were stained routinely with hematoxylin-eosin (HE), hematoxylin-phloxine-saffron (HPS), and periodic acid-Schiff's procedure. Simultaneously BPH, HP, and PCa were evaluated. RESULTS: We found EM in 55.7% of TURP-specimens. EM is located more often in the ductal epithelium (58.8%) and is usually focal (73.5%) and in small groups (88.2%) of secretory luminal cells. They are associated with BPH and with a variable degree of HP in all cases. However, there is no association with PCa. Eosinophilic cytoplasmic granules in EM are better visualized with HPS. Zones induced by tissue electrocoagulation which mimic EM, are seen in the periphery of TURP-fragments. CONCLUSION: EM in prostate is presented by the presence of eosinophilic cytoplasmic granules in benign secretory epithelium. The study presents the first attempt to investigate EM in a large series of patients. Our results enrich the available information about the histoepidemiology of prostatic EM. Moreover, EM is more common in a focal lesion, found in small groups of ductal secretory epithelial cells while EM in TURP-specimens is associated with BPH and HP in all the cases.

Histopathology of nonspecific granulomatous prostatitis with special reference to eosinophilic epithelial metaplasia: Pathophysiologic, diagnostic and differential diagnostic correlations.

BACKGROUND: Recently, we publish two case reports about association of nonspecific granulomatous prostatitis (NSGP) and eosinophilic metaplasia (EM) in benign prostatic epithelium. There is no investigation of large series of this association in medical literature. Aim of the current study is to investigate the frequency of association of NSGP and prostatic EM in a large series of cases and their relationship with the basic prostate pathology: benign prostatic hyperplasia (BPH), National Institutes of Health-category IV prostatitis (so-called histologic prostatitis (HP)), and prostatic adenocarcinoma (PCa). MATERIALS AND METHODS: A retrospective record review for NSGP was performed on a total of 2366 prostatic specimens of all types of material. All cases of NSGP were reviewed for the presence of EM, BPH, and HP. NSGP with EM-cases and control cases with high grade PCa with endocrine differentiation (so-called Paneth cell-like changes) were evaluated immunohistochemically. RESULTS: NSGP was found in nine cases (0.38%). EM was detected in benign perigranulomatous secretory epithelial cells in 100% of cases with NSGP and were closely associated with BPH and HP. Immunohistochemically, in 55.5% of cases with EM, there was weak focal apical false-positive staining for p504s. CONCLUSION: EM is a very common lesion in NSGP and reflects histologically a nonspecific cellular response, connected with repeated inflammation, in close relation with BPH and HP. We speculate that EM might serve as a morphological precursor of the immunologic phase of NSGP. This constant morphological finding could facilitate the histopathological differential diagnosis of NSGP with other types of granulomatous prostatitis and high grade PCa with or without endocrine differentiation.

Nonspecific granulomatous prostatitis in association with eosinophilic epithelial metaplasia and prostatic adenocarcinoma.

We present the first case of nonspecific granulomatous prostatitis (NSGP) associated with both eosinophilic epithelial metaplasia (EM) in benign glands and prostatic adenocarcinoma (PCa). The patient was a 68-year old man with a history of obstructive prostatic syndrome. After a transurethral resection of the prostate, the histologic analysis revealed NSGP and PCa. EM was seen in benign peri-granulomatous secretory epithelial cells as PAS Diastase positive granular eosinophilic transformation of the apical cell cytoplasm. This unusual cell appearance closely simulated the Paneth cell-like changes found in PCa. Negative chromogranin expression and weakly positive P504S immune staining in the foci of EM, surrounded by P63 positive basal cells confirmed the benign EM - phenotype. The combination of NSGP with both EM and PCa has not been reported in medical literature so far. Some observations concerning their differential diagnosis are suggested.