Pathology International最新文献

Limited resection has recently emerged as a standard procedure for small peripheral squamous cell carcinoma (SqCC) of the lung, emphasizing the need for accurate prognostic prediction. We retrospectively analyzed 53 peripheral SqCCs at pathological stage IA. Hematoxylin and eosin (H&E)-stained and immunohistochemically stained sections for TTF-1 and p40 were reviewed to assess peripheral tumor growth patterns and intra-tumoral alveolar remnants. Three peripheral growth patterns were identified: alveolar filling peripheral growth (AFPG) in 32.1%, lepidic-like peripheral growth (LpPG) in 26.4%, and destructive invasive peripheral growth (DIPG) in 52.8%. Intra-tumoral alveolar remnants, defined as consecutive TTF-1-positive non-neoplastic alveolar cells, were classified as expanded alveolar remnants (EAR) in 81.1%, collapsed alveolar remnants (CAR) in 71.7%, or no alveolar remnants (NAR) in 17.0%. Logistic regression analysis demonstrated significant associations: AFPG with EAR and LpPG with CAR. The frequency of NAR in the recurrence group was significantly higher than in the non-recurrence group. Kaplan-Meier analysis showed that NAR was associated with significantly worse overall survival compared with EAR or CAR. These findings indicate that peripheral growth patterns reflect intra-tumoral alveolar remnants and that absence of alveolar remnants is a strong negative prognostic factor in small peripheral SqCCs at stage IA.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by alveolar epithelial injury and fibrosis. Alveolar epithelial type 2 cells (AEC2s) transdifferentiate into basal cells via intermediate states, contributing to disease progression. Long non-coding RNAs (lncRNAs) regulate various cellular processes and gene expression, presenting potential therapeutic targets, but their role in inflammation-induced alveolar injury remains unclear. This study aimed to investigate the expression of lncRNAs in alveolar epithelial injury models relevant to IPF. Using human alveolar epithelial organoids, we identified the lncRNA HAGLR as highly expressed in normal epithelium but markedly reduced following inflammatory stimulation. This downregulation was confirmed in vitro and in IPF lung tissues. NT5E, an immune-regulatory gene, was identified as a downstream target negatively regulated by HAGLR. HAGLR knockdown increased NT5E expression, while overexpression reversed it. NT5E was elevated in fibrotic regions of IPF lungs, where HAGLR was diminished, suggesting an inverse regulatory relationship. These findings indicate that HAGLR modulates alveolar injury responses via NT5E and may serve as a therapeutic target. Targeting the HAGLR-NT5E axis could offer a novel strategy to mitigate fibrosis and respiratory decline in IPF.

We report a case of pancreatic ductal adenocarcinoma (PDAC) in a 51-year-old woman with PRSS1-associated hereditary pancreatitis (HP) and a history of chronic alcohol and tobacco use. Following neoadjuvant chemotherapy, she underwent total pancreatectomy. Histological analysis of the entire pancreas revealed no high-grade PanINs and scattered low-grade PanINs, with and without KRAS mutations, indicating molecular heterogeneity. Genomic profiling identified multiple driver alterations, comprising both clonal and subclonal events, including mutations in KRAS, CDKN2A/B, SMAD4, ATRX, MSH3, and the TERT promoter. Immunohistochemistry showed strong nuclear p53 overexpression despite the absence of TP53 mutation, suggesting a chromosomal instability phenotype. These findings support the hypothesis of a chromothripsis-like catastrophic genomic event contributing to rapid oncogenesis, bypassing the conventional PanIN sequence. The background of chronic inflammation, advanced lipomatous atrophy, and environmental exposures may have facilitated this transformation. This case underscores the need to consider alternative, nonlinear pathways of PDAC development in genetically predisposed individuals and highlights the potential utility of molecular surveillance for early detection and risk stratification.

Germinomas constitute two-thirds of intracranial germ cell neoplasms, with a woman: male ratio of 8:22. A characteristic of this tumor is its adequate vascularity, which has not been previously studied with markers such as Nestin, YAP and CD15, and which can provide valuable information about the biology of this tumor. These markers were analyzed by immunohistochemistry, showing tumor blood vessels cytoplasmic staining for nestin and for CD15, demonstrating angiogenesis as an important mechanism in germinomas.

Kawasaki disease presents dilation and occlusion of one or more coronary arteries in patients with early to late phases. Here we present the case of a 41-year-old Japanese male who underwent heart transplantation due to Kawasaki disease which was diagnosed at 3 years of age. The coronary arteries of the explanted heart showed pathological variations such as vascular remodeling, including aneurysm, intimal thickening, recanalization of occludes parts, and neovascularization of all vessels, especially developed vasa vasorum in the distal segments. Continuous vascular remodeling of coronary arteries may have developed progressive left ventricular dysfunction during the very late phase of Kawasaki disease.

Macrophage activation markers, specifically CD163 and CD169, play pivotal roles in the modulation of immune responses within the tumor microenvironment (TME), influencing the outcome of various cancers. These markers delineate the activation states of macrophages, with CD163 associated with the protumoral phenotype and CD169 with activation of tumor immunity. This review comprehensively explores the dualistic roles of these markers in cancer progression and immune suppression, and discusses the mechanisms through which these markers influence macrophage behavior, the impact of their expression on cancer progression, and the therapeutic potential of targeting these pathways to reprogram the TME toward enhancing antitumor immunity. This review aims to underscore the therapeutic potential of macrophage activation markers as targets for cancer treatment, highlighting emerging strategies and future directions in cancer immunotherapy.