PD-L1 expression in the microenvironment and the response to checkpoint inhibitors in head and neck squamous cell carcinoma.

In head and neck squamous cell carcinoma (HNSCC), data from studies using checkpoint-inhibiting antibodies that target programmed death 1 (PD-1) or its ligand the programmed death ligand 1 (PD-L1) demonstrated outstanding clinical activity. Translational investigations also suggested some correlations between therapeutic response and PD-L1 expression in tumor tissue. We comprehensively summarize results that have evaluated PD-L1 expression in HNSCC. We discuss flaws and strength of current PD-1/PD-L1 detection, quantification methods and the evaluation of PD-L1 as a prognostic and theragnostic biomarker. Understanding tumor microenvironment may help understanding resistance to checkpoint inhibitors, designing clinical trials that can exploit drug combinations.

Overexpression of gastric leptin precedes adipocyte leptin during high-fat diet and is linked to 5HT-containing enterochromaffin cells.

OBJECTIVES: In obesity, while hyperleptinemia highly correlates with excess fat mass, the status of gastric leptin remains unknown. Here, we investigated the expression of leptin in stomach biopsies of obese humans and analyzed the temporal changes of gastric leptin expression in response to diet-induced obesity and its impact on 5-hydroxytryptamine (5HT)-producing cells. METHODS: Enterochromaffin (EC) cells and expression of leptin, PAX4 (critical factor for EC specification), tryptophane hydroxylase-1 (TPH1, the peripheral rate-limiting enzyme for 5HT) and 5HT were examined by immunofluorescence, quantitative real-time PCR, radioimmunoassay, respectively, in stomach and duodenum biopsies from 19 obese and 14 normo-weighed individuals, and in mucosa scrapings from C57Bl6/J diet-induced obese mice, leptin-deficient ob/ob mice and intestine-specific leptin receptor isoform B-deficient mice. RESULTS: Gastric mucosa of obese subjects displays an increased expression of leptin (LEP mRNA by fivefold and protein by twofold, P<0.01), TPH1 ((1.75-2.73, 95% confidence interval (CI)) vs (0.38-0.67, 95% CI); P<0.01) and PAX4 ((1.33-2.11, 95%CI) vs (0.62-0.81, 95% CI); P<0.01) as compared with normo-weighed individuals. In diet-induced obese mice, the overexpressions of gastric leptin, antral Pax4, Tph1 and increased EC cell number occurred before the onset of obesity and hyperleptinemia (reflect of adipocyte leptin production). In addition, leptin deficiency was associated with reduced Pax4 mRNA, whereas oral leptin treatment enhanced both Tph1 and Pax4 mRNA. Finally, mice with an intestine-specific deletion of leptin signaling exhibit significant decrease in duodenal mucosa 5HT content. CONCLUSIONS: These data demonstrate that gastric leptin is upregulated in obese individuals. RESULTS from high-fat diet mice showed that overexpression of gastric leptin that is linked to gut '5HT pathway' occurred before the onset of obesity and expansion of fat mass. This may be relevant in the pathophysiology of obesity.

Production and significance of CCAAT enhancer binding proteins alpha and beta in sinonasal inverted papilloma.

Sinonasal inverted papilloma (SIP) is a rare benign tumor featuring increased cell proliferation, a tendency toward squamous differentiation, recurrence and malignant transformation. The CCAAT enhancer binding proteins, C/EBPs, are transcription factors regulating the proliferation and differentiation of various types of cells, including epithelial cells. We prospectively investigated the production of these transcription factors and the related proliferation and differentiation targets, keratin-10, keratin-15 and cyclin-D1, in 26 SIP patients and 8 sinonasal polyposis cases suspected for SIP. Ten of these patients had one or more recurrences over follow-up periods of one to eight years. C/EBP-alpha and C/EBP-beta proteins were not found in normal-looking sinonasal epithelial cells. The proteins and RNAs were detected in SIP and, occasionally, in polyposis tissues. The production of these factors was not significantly correlated with age, sex, site, tumor size or medical history. By contrast, correlations were found between the levels of C/EBP-alpha and keratin-10 levels and between those of C/EBP-beta and keratin-15. C/EBP-alpha levels were also significantly correlated with cyclin-D1 levels. These data suggested that the C/EBPs are implicated in the regulation of cell proliferation and differentiation in SIP. Finally, recurrent SIP produced significantly larger amounts of C/EBP-alpha than non- recurrent tumors. These results implicate CCAAT enhancer binding proteins in the pathogenesis of SIP and highlight the role of C/EBP-alpha as a candidate marker for tumor recurrence.

[Nodular amyloidoma associated with primary pulmonary Malt lymphoma]. / Amyloïdome associé à un lymphome du Malt pulmonaire primitif.

INTRODUCTION: Pulmonary amyloïdoma is a nodular formation containing amyloid deposits, which can mimick a pulmonary carcinoma. Its etiologic diagnosis require the search of an underlying infectious disease, a connective tissue disorder or a lymphoma. CASE REPORT: We report the case of a 73 year old woman, asymptomatic, presenting an incidental pulmonary opacity in the left upper lobe, associated with hilar lymphadenopathies, positive on PET scan. The patient underwent a left superior lobectomy with mediastinal lymphadenectomy. Histologically, the nodule was composed of amylodosis deposits. It was surrounded by a dense lymphoïd infiltrate. The phenotype (CD20+, CD5-, CD3-, CD23-) of the lymphoïd cells, like the demonstration of a lambda light chain restriction permited to pose the diagnostic of pulmonary Malt lymphoma and to characterize the AL lambda type of the amyloïdosis CONCLUSION: Association of amyloïdoma and Malt lymphoma is a rare condition. The histologic diagnosis of lymphoma may be difficult in this case, the lymphomatous process being concealed by the volume of the amyloïd mass. Therefore it is necessary in case of amyloïdoma to search histological signs of Malt lymphoma and to confirm diagnosis by demonstrating a B clonality and a immunoglobulin light chains restriction.

Herpetic salpingitis and fallopian tube prolapse.

AIM: We describe the unusual association of fallopian tubal prolapse and herpetic infection, an occurrence not previously reported to our knowledge. METHODS AND RESULTS: A 37-year-old woman presented with a small polypoid mass of the vaginal vault, 3 months after abdominal hysterectomy and abdominoplasty. The vaginal mass proved to be the fimbriated end of a fallopian tube, herniated into the vagina. Reintervention 3 months later with resection of a small vaginal 'polyp' revealed a residual portion of fallopian tube, with superimposed herpes simplex virus (HSV) infection and marked cytological atypia of surface epithelial cells. HSV-2 immunostaining of viral nuclear inclusions and of atypical cells confirmed the herpetic nature of the infection. CONCLUSION: Involvement of the genito-urinary tract by HSV may occur via an ascending infection from the cervix, but the fallopian tube, deeply located in the pelvis, is generally spared from herpetic infection. In the setting of fallopian tubal prolapse, direct exposure of the herniated fallopian tube to various pathogens in the vagina provides an unique clinical model for salpingitis. In herpetic tubal infections, special attention must be paid to cytological atypia of probable viral cytopathogenic origin, to avoid a misdiagnosis of malignancy.