Some undesirable traps which can mislead the pathologist.

In clinical laboratories, the diagnosis of parasite diseases can sometimes be challenging for non-expert microbiologists. Indeed, in spite of the advent of the molecular biology, macroscopic and microscopic examinations still remain essential. Nonetheless, it is usually not automated and requires great skills to complete the correct diagnosis. It is not infrequent that inert elements mislead to erroneous diagnoses. Through three different concrete examples, this article aims at underscoring the actual risk of parasite misidentification and at highlighting the systematic approach to be conducted in order to enable reliable diagnosis.

Early Results of Unilateral Prostatic Artery Embolization as a Focal Therapy in Patients with Prostate Cancer under Active Surveillance: Cancer Prostate Embolisation, a Pilot Study.

PURPOSE: To evaluate the feasibility of prostatic artery embolization in patients with low-risk prostate cancer (PC) under active surveillance (AS). METHODS: This monocentric prospective pilot study, running from June 2018 to June 2019, included 10 patients with low-risk PC under AS, median age 72 years (range, 62-77 years), with a unilateral focal lesion visible on magnetic resonance (MR) imaging, with Prostate Imaging Reporting and Data System v2 score ≥3/5 confirmed by multiparametric MR imaging-targeted biopsy and Gleason score 6. The patients underwent unilateral prostatic artery embolization with 300-500 µm Embospheres in the affected prostatic lobe. The primary endpoint was technical feasibility (prostate and no off-target ischemia in the imaging). The secondary endpoints included safety, negative biopsies/MR imaging response/functional outcomes at 6 months, and oncologic efficacy at 1 year. RESULTS: Embolization was successfully achieved in all patients; prostate ischemia was confirmed on multiparametric MR imaging, and no off-target ischemia was reported. No major complications were reported. Four patients (40%) presented with both negative targeted and systematic biopsies at 6 months. No lesions were seen on the MR imaging in 30% of patients. The mean International Prostate Symptom Score and International Index of Erectile Function score were 7 and 19 and 5 and 20 at baseline and 6 months, respectively, with no significant difference. Nine patients (90%) were still under AS at 1 year. One patient (10%) had PC progression outside the target lesion and was switched over to curative radiotherapy. CONCLUSIONS: Prostatic artery embolization is feasible and appears safe for prostate cancer patients under AS, with no impact on erectile function or continence status. These results justify the pursuit of further studies.

Characterisation of tumour microenvironment and immune checkpoints in primary central nervous system diffuse large B cell lymphomas.

Primary central nervous system diffuse large B cell lymphoma (PCNS-DLBCL) is a rare and aggressive entity of diffuse large B cell lymphoma (DLBCL). Elements of the tumour microenvironment (TME) including tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) have been associated with survival in DLBCL but their composition and prognostic impact in PCNS-DLBCL are unknown. Programmed cell death-1 (PD1)/programmed death-ligand 1 (PD-L1) immune checkpoint may represent a therapeutic option. Here, we aimed to characterise PD1/PDL1 immune checkpoints and the composition of the TME in PCNS-DLBCL. We collected tumour tissue and clinical data from 57 PCNS-DLBCL and used immunohistochemistry to examine TAMs (CD68, CD163), TILs (CD3, CD4, CD8, PD1) and tumour B cells (PAX5/PDL1 double stains, PDL1). The PDL1 gene was evaluated by fluorescence in situ hybridization (FISH). PAX5/PDL1 identified PDL1 expression by tumour B cells in 10/57 cases (17.5%). PDL1 gene translocation was a recurrent cytogenetic alteration in PNCS-DLBCL (8/47.17%) and was correlated with PDL1 positive expression in tumour B cells. The TME consisted predominantly of CD163 (+) M2 TAMs and CD8 (+) TILs. Most TAMs expressed PDL1 and most TILs expressed PD1. The density of TAMs and TILs did not associate with outcome. We showed that expression of PD1 on TILs and PDL1 on TAMs, but not the expression of PDL1 on tumour B cells was correlated with better prognosis. These findings support a significant role of TME composition and PD1/PDL1 crosstalk in PCNS-DLBCL pathogenesis and bring new insights to the targeted therapy of this aggressive lymphoma.

Systemic, primary cutaneous, and breast implant-associated ALK-negative anaplastic large-cell lymphomas present similar biologic features despite distinct clinical behavior.

Despite distinct clinical presentation and outcome, systemic, primary cutaneous, and breast implant-associated anaplastic large cell lymphomas (S-, PC-, BI-ALCL) ALK-negative (ALK-) show similar histopathological features including the presence of the "hallmark" cells with horseshoe-shaped nuclei and CD30 protein expression. The purpose was to better characterize these three entities using immunohistochemistry and FISH (Fluorescent in situ hybridization) to identify biomarkers differently expressed and that might be involved in their pathogenesis. Twenty-two S-ALCL ALK-, 13 PC-ALCL, and 2 BI-ALCL were included. Cases were tested for P53, P63, MUM1, MYC, GATA3, p-STAT3, PD1, and PDL1 protein expression and DUP22, TP53, TP63, MYC, and PDL1 chromosomal aberrations. As expected, S-ALCL ALK- patients had adverse outcome compare to PC and BI-ALCL. No difference was observed between the three groups concerning protein expression except for MUM1 that was significantly more frequently expressed in S-ALCL ALK- compared to PC-ALCL. In particular, constitutive activation of the STAT3 pathway and PDL1/PD1 immune-checkpoint expression was present in the three entities. TP53 deletion and PDL1 gene amplification were the commonest cytogenetic alterations and were present in the three entities. None of the studied biological parameters was associated with prognosis. Despite distinct clinical behavior, S-ALCL ALK-, PC-ALCL, and BI-ALCL share similar biological features. Larger series should be investigated with the current approach to determine more precisely the activity and the prognostic value of these biomarkers and pathways in each group.

Natural history of eosinophilic gastroenteritis.

BACKGROUND & AIMS: Eosinophilic gastroenteritis (EGE) is a rare gastrointestinal disorder; little is known about its natural history. We determined the clinical features and long-term outcomes of patients with EGE. METHODS: We reviewed files from 43 patients diagnosed with EGE who were followed from January 1988 to April 2009. The diagnosis was made according to standard criteria after other eosinophilic gastrointestinal disorders were excluded. We analyzed data on initial clinical presentation and long-term outcomes. RESULTS: EGE was classified as mucosal, subserosal, or muscular in 44%, 39%, and 12% of cases, respectively. Disease location was mostly duodenal (62%), ileal (72%), or colonic (88%); it was less frequently esophageal (30%) or gastric (38%). Blood eosinophilia (numbers >500/mm(3)) was observed in 74% of cases. Spontaneous remission occurred in 40% of patients; the majority of treated patients (74%) received oral corticosteroids, which were effective in most cases. After a median follow-up period of 13 years (0.8-29 years), we identified 3 different courses of disease progression: 18 patients (42%; 9 with subserosal disease) had an initial flare of the disease without relapse, 16 (37%) had multiple flares that were separated by periods of full remission (recurring disease), and 9 (21%) had chronic disease. CONCLUSIONS: The clinical presentation of EGE is heterogeneous and varies in histologic pattern; about 40% of patients resolve the disease spontaneously, without relapse. Approximately 50% have a more complex disease, which is characterized by unpredictable relapses and a chronic course.

Autocrine proliferative effects of hGH are maintained in primary cultures of human mammary carcinoma cells.

CONTEXT: Empirical evidence suggests that autocrine human GH (hGH) may possess a proliferative and oncogenic role in human mammary carcinoma. However, this concept is largely derived from studies using cultured human mammary carcinoma cell (HMCC) lines. OBJECTIVE: We investigated the expression and functionality of hGH and the hGH receptor in isolated cultures of primary HMCC. DESIGN: Epithelial cell adhesion molecule-positive primary HMCC were isolated from surgical biopsies of patients with mammary carcinoma and cultured in vitro. Expression of hGH and hGH receptor was determined by RT-PCR, immunofluorescence microscopy, and ELISA. The proliferative response of the cultured primary HMCC to hGH stimulation or hGH inhibition with a hGH antagonist was determined. RESULTS: One hundred percent of cultured primary HMCC expressed the hGH receptor, and 52% expressed hGH at the mRNA level. hGH-positive primary HMCC produced hGH protein within the cell and secreted hGH to the media. Both hGH-negative and hGH-positive HMCC responded to hGH stimulation with large increases in cell number. hGH-positive HMCC responded to inhibition of hGH by a hGH antagonist with a decrease in cell number, whereas hGH-negative HMCC did not. CONCLUSION: Primary HMCC proliferate in response to hGH, and the proliferation of hGH-positive HMCC is inhibited by hGH antagonism. Inhibition of hGH in patients with mammary carcinoma may therefore limit tumor growth.

Prognostic value of combined p53 and survivin in pT1G3 urothelial carcinoma of the bladder.

pT1G3 bladder tumors have a high tendency to recur and progress. We evaluated the prognostic values of the depth of submucosal invasion and immunostaining with survivin and p53 in 30 pT1G3 urothelial carcinomas at the first endoscopic resection. The depth of invasion was evaluated toward the muscularis mucosa and measured using a micrometer. Survivin and p53 immunostaining were performed using an automated immunostainer. Of the patients, 19 (63%) had tumor recurrence, 11 (37%) had tumor progression, 10 (33%) had metastatic spread, and 10 (33%) died of the disease. Infiltration of deep lamina propria (pT1b) and a micrometric measure of 1.5 mm or more were associated with an increased risk of tumor local and/or metastatic progression (P = .03 and P = .02, respectively). A combined high expression of survivin (

Lipoid-cell variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of five cases.

Invasive urothelial carcinoma may present with many deceptive morphologic variants. We report the clinicopathologic and immunohistochemical features of 5 cases of the so-called lipid-cell variant of urothelial carcinoma. The tumors occurred in 4 men and 1 women aged from 56 to 80 years. Four cases were developed in the bladder and 1 case in the renal pelvis. All cases were revealed by a macroscopic hematuria. The tumors were composed of sheets and nests of large epithelial cells with an abundant clear multivacuolated cytoplasm mimicking lipoblasts. Nuclei were irregular, hyperchromatic, eccentric, and frequently indented by cytoplasmic vacuoles. Mucin stains (PAS, Alcian Blue) were negative. Tumor cells were strongly stained with cytokeratin 7, cytokeratin 20, and EMA but were negative with S-100 protein. In all cases, a usual high-grade urothelial carcinoma component was admixed with lipoid tumor cells. Two tumors infiltrated the bladder muscle, 2 cases invaded the bladder submucosa, and 1 case invaded the renal parenchyma. In the follow-up, despite appropriate surgical treatment, 4 patients died of the disease and 1 patient is alive without recurrence. Because of its rarity and the tumor cells' appearance, the lipoid-cell variant may be misdiagnosed and must be distinguished from liposarcoma or signet-ring cell carcinoma. In the present series, the lipoid-cell variant of urothelial carcinoma was associated with an aggressive behavior and a poor prognosis.