Upregulation of citrullination pathway: From Autoimmune to Idiopathic Lung Fibrosis

Background: Increased protein citrullination and peptidylarginine deiminases (PADIs), which catalyze the citrullination process, are central in Rheumatoid arthritis pathogenesis and probably involved in the initial steps towards autoimmunity. Approximately, 10% of RA patients develop clinically significantly ILD. A possible shared role of protein citrullination in rheumatoid arthritis associated interstitial lung disease (RA-ILD), and idiopathic pulmonary fibrosis (IPF) pathogenesis remains unclear. Methods: We evaluated PADI2 and PADI4 mRNA expression in bronchoalveolar lavage fluid (BALF) cells of 59 patients with IPF, 27 patients RA-ILD and 10 healthy controls. PADI 2 and 4 expression was analyzed by western blot and immunohistochemistry. Citrullinated protein levels were also quantified. Results: PADI4 mRNA and protein levels were higher in RA-ILD and IPF than controls. Furthermore, PADI4 mRNA levels showed an increase among smokers in RA-ILD. PADI4 expression was detected in granulocytes and macrophages in all groups, with the strongest cytoplasmic expression observed in granulocytes in RA-ILD and IPF. PADI2 mRNA and immunostaining of BAL cells, were similar in all groups among smokers. Overall, stronger staining was observed in current smokers. Citrullinated peptides were significantly increased in IPF compared to RA-ILD and controls. In RA-ILD, protein citrullination strongly correlated with PADI4 expression and anti-citrullinated protein antibodies (ACPAs). Conclusions: These results suggest that the citrullination pathway is upregulated in IPF and in RA-ILD

CD8+ PD-1+ T-cells and PD-L1+ circulating tumor cells in chemotherapy-naïve non-small cell lung cancer: towards their clinical relevance?

Background: Since tumor cells may escape from immune surveillance through the programmed cell death 1 (PD-1)/programmed death ligand (PD-L)1 axis, this study was designed in order to evaluate whether there is a correlation between the levels of PD-1+ and PD-L1+-expressing immune cells (ICs) and circulating tumor cells (CTCs) in patients with non-small cell lung cancer (NSCLC). Patients and methods: Peripheral blood was obtained from 37 chemotherapy-naïve patients with metastatic NSCLC before treatment. PD-1 and PD-L1 expression was evaluated (1) on ICs with anti-tumor function (CD4+ and CD8+ T-cells, B-cells, monocytes/dendritic cells) using flow cytometry, (2) on CTCs by immunofluorescence and (3) on cells from tumor tissues by immunohistochemistry. The levels of PD-1+ and PD-L1+-expressing ICs were correlated with progression-free survival (PFS). Results: The presence of PD-1+ CD8+ cells, with reduced interferon (IFN)-γ expression, but not other ICs, were positively correlated with PD-L1+ CTCs (p < 0.04). Increased percentages of PD-1+ CD8+ T-cells, were associated with a worse response to treatment (p = 0.032) and shorter PFS (p = 0.023) which, in multivariate analysis, was revealed as an independent predictor for decreased PFS [hazard ratio (HR): 4.1, p = 0.0007]. Conclusion: The results of the current study, for first time, provide evidence for a possible interaction between ICs and CTCs in NSCLC patients via the PD-1/PD-L1 axis and strongly support that the levels of PD-1+ CD8+ in these patients may be of clinical relevance. © The Author(s), 2019

Small Cell Ovarian Cancer in Adolescents: Report of Two Cases and Review of the Literature

Ovarian small cell carcinoma is a rare and highly malignant neoplasm carrying a poor prognosis. Although combination chemotherapy remains the cornerstone of treatment due to the rarity of these tumors, no regimen can be recommended as standard of care although in the majority of cases platinum-based regimens are used. Herein, we report two cases of small cell carcinoma of the ovaries along with a review of the relevant literature

Apocrine and eccrine hidrocystomas: A clinicopathological study

Introduction: Eccrine and apocrine hidrocystomas are uncommon, benign, cystic proliferations of the sweat glands usually located on the head and neck area. Objectives: To describe the key clinical and histopathological characteristics of a large series of hidrocystomas in Greece to improve diagnostic accuracy, and to perform a historical review of the medical term hidrocystoma. Methods: A case series of 22 hidrocystomas from 20 consecutive patients treated with surgery at University Hospital of Heraklion in Crete, Greece, from January 1, 1998 to January 1, 2020 was performed along with a comprehensive historical literature review of the term hidrocystoma and its corresponding term hydatis from ancient Greek literature to the present. Data were obtained from medical records. All patients had a histopathologically confirmed diagnosis of hidrocystoma. Formalin-fixed paraffin-embedded (FFPE) sections of 22 tumors of the 20 consecutive patients were retrieved from the pathology laboratory archive and stained for SMA, p63, and GCDFP-15 with immunochemistry and periodic acid-Schiff (PAS) histochemical stain. Results: Overall, 22 hidrocystomas (11 apocrine and 11 eccrine hidrocystomas) surgically excised from 20 patients were included in this study. Of the 20 patients, 10 (50%) were male and 10 (50%) were female, with a mean age of 56 ± 15 years. Hidrocystomas commonly occurred on the eyelids (73%), inner canthus (9%), eyebrow (4.5%), neck (4.5%), nose (4.5%), and ear (4.5%). All apocrine hidrocystomas stained positive for SMA, GCDFP-15, CAM 5.2, PAS, and PAS-D. No recurrence was observed. Conclusions: Here we have presented the clinicopathological characteristics of the largest case series of hidrocystomas in Europe and the Mediterranean region. Only apocrine hidrocystomas stained positive for SMA, GCDFP-15, CAM 5.2, PAS, and PAS-D. © 2021, Slovene Medical Society. All rights reserved