Objectives: To define the characteristics of necrotizing sarcoid granulomatosis (NGS) a very rare pulmonary disease hardly recognised by pulmonologists and pathologists.Data source: PubMed was searched for the term necrotising or necrotizing sarcoid granulomatosis.Study selection: All cases reported in the English literature were included.

BackgroundCombined pulmonary fibrosis and emphysema (CPFE) is an umbrella term encompassing upper lobe emphysema and lower lobe pulmonary fibrosis with pathogenesis elusive. The aim of our study was to investigate the incidence of autoimmune markers in patients with CPFE.MethodsIn this multicenter study we retrospectively evaluated records from patients with CPFE (n=40) and IPF (n=60) without emphysema. Baseline demographic characteristics, high-resolution computed tomography (HRCT), spirometry, histopathological, treatment, serum immunologic and survival data were investigated. B cell presence was estimated with CD20 immunostaining in representative lung biopsy samples from CPFE patients and control subjects.ResultsA statistically significant increased number of CPFE patients with elevated serum ANA with or without positive p-ANCA titers compared to patients with IPF without emphysema was observed. Patients with CPFE and positive autoimmune markers exhibited improved survival compared to patients with a negative autoimmune profile. A massive infiltration of clusters of CD20+ B cells forming lymphoid follicles within the fibrotic lung in CPFE patients with positive serum immunologic profile compared to patients with negative profile, was noted and positively correlated with improved survival.ConclusionsA significant proportion of patients with CPFE may present with underlying auto-immune disorders that may reside insidiously and be associated with favorable prognosis. Early identification of these patients using a panel of auto-antibodies may lead to more targeted and effective therapeutic applications.

Introduction. Emerging evidence supports the role of epidermal growth factor-receptor (EGFR) in fibrogenesis. The aim of our study was to investigate the expression profiles of EGFR in three forms of IIPs, including idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia (COP), and nonspecific interstitial pneumonia (NSIP). Patients and Methods. Twenty newly diagnosed patients with IPF, 15 with COP, and 15 with NSIP (cellular, n = 4 and fibrotic, n = 11) were investigated. Fifteen paraffin blocks obtained from the normal part of lungs removed for benign lesions were used as controls. Immunohistochemistry was carried out using specific monoclonal antibody. Results were verified by qRT-PCR. Results. A significant EGFR upregulation, both in protein and mRNA level, was observed in IPF, COP, and fibrotic NSIP samples compared to controls. EGFR was primarily localized in the hyperplastic alveolar epithelium surrounding areas of fibrosis in IPF, COP, and fibrotic NSIP samples, as assessed by double immunohistochemistry analysis with surfactant protein-A. EGFR mRNA levels were positively associated with indicators of lung fibrosis (type 1 collagen mRNA levels) and negatively correlated with functional prognostic parameters. Conclusions. We conclude that EGFR is upregulated in the hyperplastic alveolar epithelium in all three fibrotic forms of IIPs indicating a potential role during abnormal reepithelization.

BackgroundSarcoidosis is a granulomatous disorder of unknown etiology. The term of immunoangiostasis has been addressed by various studies as potentially involved in the disease pathogenesis. The aim of the study was to investigate the expression of the master regulator of angiogenesis hypoxia inducible factor (HIF)-1a – vascular endothelial growth factor (VEGF)- inhibitor of growth factor 4-(ING4) - axis within sarcoid granuloma.MethodsA total of 37 patients with sarcoidosis stages II-III were recruited in our study. Tissue microarray technology coupled with immunohistochemistry analysis were applied to video-assisted thoracoscopic surgery (VATS) lung biopsy samples collected from 37 sarcoidosis patients and 24 controls underwent surgery for benign lesions of the lung. Computerized image analysis was used to quantify immunohistochemistry results. qRT-PCR was used to assess HIF-1a and ING4 expression in 10 sarcoidosis mediastinal lymph node and 10 control lung samples.ResultsHIF-1a and VEGF-ING4 expression, both in protein and mRNA level, was found to be downregulated and upregulated, respectively, in sarcoidosis samples compared to controls. Immunohistochemistry coupled with computerized image analysis revealed minimal expression of HIF-1a within sarcoid granulomas whereas an abundant staining of ING4 and VEGF in epithelioid cells was also visualized.ConclusionsOur data suggest an impairment of the HIF-1a – VEGF axis, potentialy arising by ING4 overexpression and ultimately resulting in angiostasis and monocyte recruitment within granulomas. The concept of immunoangiostasis as a possible protection mechanism against antigens of infectious origin needs further research to be verified.

Idiopathic pulmonary hemosiderosis is a very rare condition rarely affecting adults and causing recurrent episodes of diffuse alveolar haemorrhage that may lead to lung fibrosis. Due to lack of pathognomonic findings, IPH diagnosis is established upon exclusion of all other possible causes of DAH in combination with specific pathologic findings revealing bland alveolar haemorrhage with absence of vasculitis and/or accumulation of immune complexes within lung parenchyma. Here we describe a rare case of idiopathic pulmonary hemosiderosis in an otherwise healthy 27-year-old Greek male patient with relapsing episodes of fever accompanied by general fatigue and discomfort. He was at this time point a light smoker and had been hospitalised once in the past for similar symptoms. His iron deficiency anemia coupled with chest high-resolution computed tomography and bronchoalveolar lavage revealed findings compatible with diffuse alveolar hemorrhage. After excluding all other sources of bleeding through extensive gastrointestinal workup and thorough immunologic profile, video-assisted thoracic lung biopsy was performed and the diagnosis of Idiopathic Pulmonary Hemosiderosis was established. Patient was treated with high doses of oral corticosteroids, leading to clinical response. We highlight the need for vigilance by the respiratory physician for the presence of DAH, a challenging, acute condition requiring early recognition along with identification of the underlying syndrome and appropriate treatment to achieve optimal results.

Patients with IPF exhibit higher MPV values and lower platelet count. Further studies are needed to assess the clinical implications of these findings.

IntroductionWilliams–Campbell syndrome, also known as bronchomalacia, is a rare disorder characterized by a deficiency of cartilage in subsegmental bronchi, leading to distal airway collapse and bronchiectasis. There have been few reports about patients affected by saccular bronchiectasis, paracicatricial emphysema, and diminished cartilage. These are all characteristic of Williams–Campbell syndrome.Case presentationThis report presents a 57-year-old woman with progressive dyspnea, cough, sputum production, and fever. The clinical and laboratory examination revealed that the patient had a respiratory infection due to bronchiectasis caused by Williams–Campbell syndrome, which was undiagnosed in the patient until then.ConclusionAlthough a rare syndrome, when patients’ signs and symptoms include recurrent respiratory infections, bronchiectasis, productive cough, and dyspnea, Williams–Campbell syndrome should be included in the differential diagnosis.

Aim: To determine the immunoreactivity of cholecystokinin (CCK) during the development of the human fetal pancreas and pancreatic adenocarcinoma, given that, CCK positive cells were demonstrated either in its embryonic anlage or in pancreatic cancer. In order to obtain possible parallels in the expression pattern of neoplastic cells in adults (well – moderately – poorly differentiated), we investigated the pattern of CCK expression in the pancreatic tissue during the various stages of development and compared these with the proliferation of tissue assessed by proliferating cell nuclear antigen (PCNA) immunohistochemistry. Experimental design: Tissue sections from 15 pancreatic fetal specimens, and equal number of ductal adenocarcinoma specimens, were assessed using immunohistochemical methods for CCK. Results: The density of positive cells in the primitive exocrine ductal walls and outgrowing buds was significantly higher than the relevant density in the neoplastic pancreatic tissue of mixed (ductal – endocrine) and pure ductal type (p1=0.004, p2<0.0005, p3<0.0005 and p4=0.023 respectively). The above values were estimated from 20th to 22nd weeks of gestation. There was no significant difference in the density of positive cells in the islet cell epithelium from 25–30 weeks, and the neoplastic tissue of mixed (p5=0.10) and pure ductal type (p6=0.15). Conclusions: The immunostaining for CCK identifies a subgroup of pancreatic ductal adenocarcinomas with a neuroendocrine component (initially considered as pure ductal tumors), and mixed ductal-endocrine tumors. This pattern of expression in neoplasms recapitulates the normal pattern during the embryonal development of the organ, and may be important for the development of new therapeutic approaches with eventual clinical utility.