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Bronchiolar adenoma (BA) is a rare benign lung tumor that shows proliferation of bland bronchiolar‐type epithelium containing a continuous layer of basal cells. This tumor entity has been newly added to the recent World Health Organization (WHO) classification 5th edition. This entity encompasses a spectrum of lesions: the classic ciliated muconodular papillary tumor (CMPT) and the non‐classic CMPT. Although BA is reported to have driver mutations including BRAF V600E, EGFR, and KRAS, the molecular profile of BA is still incompletely understood. Five resected BAs at our institutions were analyzed. The BA lesions were subdivided into two groups: three proximal‐type BAs and two distal‐type BAs. NRAS codon 12/13 mutation and EML4 exon 20‐ALK exon 20 fusion were found in two of the three proximal‐types. BRAF V600E mutation was found in one of the two distal‐types. Two cases coexisted with lung adenocarcinoma, with EGFR exon 19 deletion and KRAS mutation, respectively. No recurrence was observed at a median of 12 months (range 2–84 months) of follow‐up. BA has uncommon variants of mutation seen in lung adenocarcinoma. NRAS mutation and ALK fusion partner has not been reported previously. The present cases may reinforce the distinctive biology of BA from lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

• Prognostic impact of STAS in pulmonary metastasis from colorectal cancer is unknown. • STAS was related to a poor prognosis in pulmonary metastasis from colorectal cancer. • Distance between main tumor and STAS was related to surgical margin relapse. Surgical resection for pulmonary metastases from colorectal cancer could provide long-term survival in selected patients, and it is commonly performed in practice. However, surgical margin relapse sometimes occurs and is a problematic issue to resolve. Spread through air spaces (STAS) is one of the invasion forms in primary lung cancer and is associated with local recurrence and a poor prognosis. The aim of this study was to evaluate the prognostic significance of STAS for pulmonary metastases from colorectal cancer and to assess the predictability of STAS with preoperative clinical information. A total of 96 pulmonary metastatic lesions from colorectal cancer in 37 patients who underwent metastasectomy at our institution from January 2008 to December 2013 were retrospectively analyzed. STAS was identified in 41.6 % of the 96 lesions. Surgical margin relapse was found in 8 lesions (8.3 %) from 7 patients (18.9 %). The distance of STAS was identified as an independent risk factor for surgical margin relapse on multivariable analysis (p = 0.033). The patients with STAS showed significantly worse overall survival than those without (5-year overall survival rate: 30.3 % vs. 76.9 %; p = 0.002). On multivariable analysis, patients with STAS had a significantly higher risk of death than those without (p = 0.019). An elevated pre-metastasectomy serum carcinoembryonic antigen level was independently correlated with STAS on multivariable analysis (p = 0.049). STAS was related to a poor prognosis and surgical margin relapse in pulmonary metastases from colorectal cancer. [ABSTRACT FROM AUTHOR]

Background The pathological criteria of early-stage mucinous adenocarcinoma of the lung have recently been defined; however, its characteristic radiologic imaging findings are still poorly understood. Thus, this study aimed to clarify the radiologic and pathological findings of early-stage mucinous adenocarcinoma. Materials and methods In this study, we clinicopathologically reviewed 22 cases of surgically resected mucinous adenocarcinoma in situ (AIS) and minimal invasive adenocarcinoma (MIA), and attempted to elucidate the characteristic radiologic features of early mucinous adenocarcinomas using high-resolution computed tomography (HRCT). Results Radiologically, the mean value of the maximum diameter of 22 tumours was 2.1 cm (range, 1.0–2.9 cm). Based on the HRCT findings, the tumours were divided into part-solid ground glass nodules ( n = 11) and solid nodules ( n = 11). The mean CT attenuation value was 25.7 HU (range, 17–35 HU). All tumours, except 3 tumours pathologically diagnosed as AIS, showed air-containing features. According to the preoperative CT findings, 7 (35%) cases were diagnosed as inflammatory nodules. Of these, 4 cases had lobular-bounded margins, and 3 showed vaguely outlined ground glass shadows. Conclusion The characteristic HRCT findings of mucinous AIS and MIA were solid or part-solid nodules with air-containing spaces. However, some AIS and MIA nodules showed lobular-bounded margins or marginally vaguely outlined ground glass shadows, and were difficult to differentiate from inflammatory nodules. [ABSTRACT FROM AUTHOR]

Abstract: Pharmacological modulation of IgE-mediated mast cell activation is important to the development of anti-allergic reagents. In this study, we investigated the effects of parthenolide (PTL) on high-affinity IgE receptor (FcεRI)-induced degranulation in mast cells. PTL dose-dependently inhibited degranulation induced by IgE·antigen stimulation in RBL-2H3 cells and BMMCs. Although PTL is a potent NF-κB inhibitor by targeting IκB kinase complex, NF-κB inhibition by other IκB kinase inhibitors did not inhibit degranulation in mast cells. IgE·antigen-induced microtubule formation is well known to be critical for degranulation in mast cells. Immunocytochemical study with anti-α-tubulin antibody revealed that PTL significantly inhibited IgE·antigen-induced microtubule formation. However, PTL, as well as nocodazol, had no significant effects on degranulation in the fyn-deficient BMMCs, suggesting that inhibitory effects of PTL in the microtubule formation are fyn dependent. We further demonstrated that in vivo administration of PTL in mice strongly inhibited passive cutaneous anaphylaxis reaction. The present study provides a possibility to develop potent reagents against mast cell activation based on an inhibition of microtubule formation. [Copyright &y& Elsevier]

Background: The mechanism by which tumors escape the immune system has been actively investigated and is partly explained by the programmed death-1 (PD-1) and its ligand (PD-L1) pathway. This study is aimed at clarifying the prognostic significance of PD-L1 expression in patients with surgically resected pulmonary metastases of head and neck squamous cell carcinoma (HNSCC). Patients and methods: A retrospective review was conducted of 26 HNSCC patients who underwent complete resection of pulmonary metastases. PD-L1 expression in both the primary and metastatic tumors was evaluated using immunohistochemistry (anti-PD-L1 antibody, clone SP263). High PD-L1 expression was defined as ≥50% of tumor cells with positive staining. Survival and prognostic impacts following pulmonary metastasectomy were analyzed based on the PD-L1 expression level. Results: The patients included 23 men and 3 women, with a median age of 65 years. Six (23%) of the pulmonary metastatic cases showed high PD-L1 expression, while their corresponding primary lesions had low PD-L1 expression. The 5-year overall survival rate after pulmonary metastasectomy was 57.6% in all cases. The 5-year overall survival rates were 72.5% and 16.7% in the low and high PD-L1 groups, respectively (p < 0.001). Multivariate analysis demonstrated that high PD-L1 expression and older age (>65 years) correlated independently with a shorter overall survival (p < 0.001). Conclusions: High PD-L1 expression in pulmonary metastases could be an independent predictor of poor outcome in HNSCC patients undergoing pulmonary metastasectomy. This is the first report evaluating the prognostic implication of PD-L1 expression in metastatic HNSCC. [ABSTRACT FROM AUTHOR]

Abstract: Protein kinase D (PKD) is a serine–threonine kinase involved in the activation of a variety of cells. In mast cells, activation of PKD by cross-linking of high affinity receptor for IgE (FcεRI) has been reported, but little is known for its effects on cytokine production. We investigated the roles of PKD on FcεRI-induced activator protein-1 (AP-1) activation and proinflammatory cytokine productions in mast cells. Pharmacological inhibition of PKD strongly inhibited production of interleukin (IL)-13 and tumor necrosis factor (TNF)-α induced by FcεRI stimulation, and the overexpression of PKD significantly increased the IL-13 and TNF-α production. Reporter assay revealed that the overexpression of PKD enhanced FcεRI-induced IL-13 promoter activation, and that the 5′-flanking region of IL-13 gene from positions −110 to −52 was under the regulation of PKD. The overexpression of PKD enhanced the induction of AP-1 luciferase activity by FcεRI stimulation, while it had no effect on luciferase activities dependent upon NF-κB and NF-AT activated by FcεRI stimulation. In EMSA, c-Jun and c-Fos appear to be the major components of AP-1 complexes activated by FcεRI stimulation. Moreover the overexpression of PKD strongly enhanced the phosphorylation of both c-Jun and c-Fos following FcεRI stimulation. Although stress-activated protein kinase/c-Jun N-terminal kinase (JNK) is known to be an important regulator for c-Jun phosphorylation and AP-1 activation, overexpression and inhibition of PKD had no effects on JNK phosphorylation. These results suggest that PKD may play a pivotal role in FcεRI-induced cytokine production in mast cells through the activation of c-Jun, c-Fos, and AP-1. [Copyright &y& Elsevier]