Pathology International最新文献

Recent studies suggest that lung adenocarcinoma cells are closely associated with the tumorigenesis of large-cell neuroendocrine carcinoma via cellular transformation. However, morphological evidence, along with genetic abnormalities before, during, and after transformation, is quite limited. We present here a case of combined large-cell neuroendocrine carcinoma and adenocarcinoma exhibiting acinar and solid patterns. Adenocarcinoma cells with abundant mucin, exhibiting positivity for both napsin-A and neuroendocrine markers, were partially found in the acinar adenocarcinoma component and extensively observed in the solid adenocarcinoma component. Next-generation sequencing using extracted genomic DNA from the three components revealed homozygous TP53 (missense) and STK11 (nonsense) mutations in all three components, suggesting monoclonal origin. Furthermore, MYC gene amplification, recently presumed to be a pivotal driver in neuroendocrine transformation, was observed in both the solid adenocarcinoma and large-cell neuroendocrine carcinoma components. These genetic findings corresponded to pre- and post-transformation morphology, providing compelling evidence that some kinds of adenocarcinomas may serve as a precursor of large-cell neuroendocrine carcinoma.

Prostate cancer (PCa) is the second most common cancer in men globally. Its growth is driven by oxidative stress associated with inflammation, aging, and environmental factors, including diet and lifestyle. These factors contribute to multiple stages of PCa progression, including progression to castration-resistant prostate cancer (CRPC). Therefore, oxidative stress represents an intriguing target for PCa chemoprevention and treatment. In vivo experimental models are crucial for understanding the mechanisms of PCa development, validating chemopreventive and therapeutic approaches, and translating preclinical results into clinical applications. We established a transgenic rat for adenocarcinoma of the prostate (TRAP) model, a transgenic rat that efficiently develops androgen-dependent adenocarcinoma, pathologically and biologically mimicking human PCa progression, to clarify the mechanisms of tumor progression, including the involvement of oxidative stress, and established a system for screening the chemopreventive effects of agents against PCa. Additionally, we derived a CRPC model from the TRAP model and developed a distant metastasis model, providing a comprehensive multistage rat model of prostate carcinogenesis. This review presents findings on the molecular mechanisms of PCa and the chemopreventive effects of natural compounds with antioxidant properties, such as polyphenols. We additionally described the potential for repositioning existing drugs with antiandrogenic activity for PCa chemoprevention.

A male in his seventies presented with lung cancer in the right lower lobe. The surgically resected specimen revealed a pleomorphic carcinoma featuring an adenocarcinoma component with lepidic, acinar, and papillary patterns, alongside a spindle cell component spreading along the pulmonary artery wall, resembling intimal sarcoma. The spindle tumor cells were positive for keratins, TTF-1, napsin A, and vimentin, but negative for p40, CK14, desmin, alpha-smooth muscle actin, CDK4, and MDM2. This profile indicates that the spindle cells originated from the adenocarcinoma cells via epithelial-mesenchymal transition. The vascular spread of pleomorphic carcinoma, mimicking pulmonary artery intimal sarcoma, represents an extremely rare mode of tumor invasion, which could be termed "arterial carcinomatosis". Immunohistochemical analysis is crucial for distinguishing pleomorphic carcinoma from coexisting intimal sarcoma, as the latter's prognosis is markedly poor.

Brown adipose tissue (BAT) is an energy-consuming organ, and its functional dysregulation contributes to the development of metabolic diseases and obesity. BAT function is regulated by the sympathetic nervous system but declines with age, which is partly caused by reduced sympathetic nerve fibers innervating BAT. Thus far, the role of mesenchymal stromal/stem cells in age-related BAT dysfunction remains unknown. Here, we show that BAT dysfunction may be induced by a defect in the antioxidant capacity of stromal cells that localize in and around the nerve fibers (perineurial cells) of BAT. These cells express Meflin, a marker of mesenchymal stromal/stem cells. Specific deletion of the antioxidant enzyme superoxide dismutase 2 in Meflin-lineage cells caused sympathetic denervation and whitening of BAT and its functional impairment, as exemplified by a decline in the fat oxidation rate during the daytime. This phenotype was accompanied by overexpression of the neurorepulsive factor semaphorin 3A in perineurial cells. Notably, Meflin-deficient mice exhibited resistance to doxorubicin-induced BAT dysfunction. These results highlight the role of Meflin⁺ stromal cells, including perineurial cells, in maintaining BAT function and suggest that targeting BAT stromal cells provides a new avenue for improving BAT function.

Fusobacterium nucleatum is implicated in esophageal cancer; however, its distribution in esophageal cancer tissues remains unknown. This study aimed to clarify the presence and distribution of F. nucleatum in esophageal cancer tissues using fluorescence in situ hybridization (FISH). Tissues collected from 70 patients with esophageal squamous cell carcinoma were examined using FISH. Corresponding normal epithelium and metastatic lymph nodes were assessed. F. nucleatum was identified more frequently in esophageal cancer tissues than in the normal epithelium. F. nucleatum also showed significant correlation with factors associated with tumor progression, such as pT factor and tumor size. As tumor progression advanced, the area occupied by F. nucleatum gradually became larger. F. nucleatum positivity was observed around the deep edge of the tumor nest (border-dense type) or identified diffusely in the tumor nest (diffuse distributed type). Furthermore, F. nucleatum was observed in metastatic lymph nodes, lesions of venous invasion, and walls of veins in normal epithelium. In conclusion, we visualized F. nucleatum using FISH and identified different distribution patterns of F. nucleatum, highlighting the spot density of its presence in tumor tissues. Recognizing this quantitative change is pivotal for establishing F. nucleatum as a reliable biomarker.