The lack of lineage-specific markers and overlapping shape make undifferentiated round cell cancers of the oral cavity extremely difficult to diagnose. We describe a 47-year-old female patient who had a submucosal lesion affecting her mandibular gingiva and labial mucosa. Histopathological analysis showed that the stroma was infiltrated by sheets of monotonous round cells with hardly noticeable nucleoli without any epithelial involvement. The results of a comprehensive immunohistochemistry panel that included cytokeratin, CD45, S100, desmin, synaptophysin, CD99, CD117, MyoD1, CK20, TTF-1, ER, PR, and INI1 were negative, ruling out metastatic disease and epithelial, lymphoid, melanocytic, myogenic, and neuroendocrine differentiation. Certain poorly differentiated carcinomas were further ruled out by retained INI1 expression and negative NUT. A diagnosis of undifferentiated round cell sarcoma, not otherwise described, was made in the absence of an identifiable primary tumor and conclusive immunophenotype. This case thereby emphasizes the value of a methodical exclusion-based strategy and the necessity of supplementary molecular tests in the diagnosis of head and neck tumors that are difficult to diagnose.
The pathogenesis of cancer is characterized by the acceleration of tumor growth, inhibition of tumor suppression, genetic and epigenetic alteration, lubricative transformation and tumor microenvironment. Extramammary Paget’s disease (EMPD) is a rare skin cancer that originates from apocrine glands in genital and axillary area. Although the pathogenesis of EMPD is still poorly understood, increasing evidence reveals that the mechanism of EMPD progression is regulated by the acquired ability of EMPD cells and tumor microenvironment. HER2/PI3K/AKT signaling and hormone receptor pathways are activated. Whereas tumor mutation burden is low, numerous driver genes such as ERBB2 and PIK3CA are detected. Tumor evolution in EMPD is characterized by high genetic intratumor heterogeneity with shared background factors. Tumor microenvironment in EMPD promotes immune evasion through the reduction of reduced CD4 + and CD8 + T cells and the increase of Treg cells and CD163 + macrophages. Enhanced Warburg effect and S. aureus contribute to the suppression of antitumor immunity. This review focuses on the mechanism of malignant progression in EMPD (hallmarks of EMPD).
Primary biliary cholangitis (PBC) is an autoimmune-related cholestatic liver disease predominantly affecting women, yet sex-specific differences in progression remain unclear. Multicenter retrospective analysis of 289 Japanese PBC patients compared sex disparities in demographics, laboratory parameters, histopathology, and prognostic scores. Males tended to be older at diagnosis, although this difference did not reach statistical significance. At diagnosis, significant laboratory differences were observed in total bilirubin and γGT, both higher in males (p < 0.05), consistent with a slightly higher ALBI score in males (p = 0.046), suggesting worse liver functional reserve. Males also had worse outcomes according to UK‑PBC Risk Scores and GLOBE score (p < 0.05). Histologically, at comparable bile duct loss, males tended to exhibit higher orcein‑positive granule deposition scores than females, suggesting chronic cholestasis resulting from bile duct loss tends to be more pronounced in males. Furthermore, positive correlations between fibrosis and bile duct loss, and between fibrosis and orcein‑positive granule deposition, were observed in females but not in males. Among mild‑fibrosis patients, males exhibited greater orcein-positive granule deposition. This study demonstrates sex differences in PBC progression and suggests that males may exhibit more pronounced chronic cholestatic changes, as reflected by greater orcein‑positive granule deposition, particularly in mild fibrosis.
Zinc transporters, including ZIP6 (SLC39A6, also known as LIV-1) and ZIP10 (SLC39A10), are reportedly involved in breast cancer progression and metastasis. We aimed to clarify the association of the expression of zinc transporters with clinicopathological features and prognosis in breast cancer. We retrospectively included 200 patients who underwent surgery for invasive ductal carcinoma of the breast (invasive diameter ≥ 10 mm) at our institution between January 1, 2010 and June 30, 2023. Immunohistochemical staining for ZIP6 and ZIP10 was performed, and their expression levels were evaluated. Survival analyses were performed by stratifying patients into four groups based on combined ZIP6 and ZIP10 expression (high/low). We found that the expression levels of ZIP6 and ZIP10 showed a statistically significant positive correlation. Low ZIP6 expression was associated with aggressive clinicopathological features, including a higher Ki-67 labeling index, higher histological grade, and larger tumor size. Although survival differences did not reach statistical significance, combined evaluation of ZIP6 and ZIP10 expression revealed distinct survival tendencies among the expression groups. These findings suggest that combined assessment of ZIP6 and ZIP10 expression may provide additional prognostic information beyond ZIP6 expression alone. Future studies with larger cohorts and longer follow-up are warranted to validate these findings.
Neutrophil extracellular traps (NETs) are web-like chromatin structures released by neutrophils that play dual roles in host defense and tissue injury. In liver diseases, NETs have emerged as key pathogenic mediators. This narrative review synthesizes current evidence on the involvement of NETs in alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), viral hepatitis, hepatic ischemia–reperfusion injury (HIRI), hepatocellular carcinoma (HCC), and intrahepatic cholangiocarcinoma (iCCA). Mechanistically, NETs amplify sterile inflammation, promote hepatocyte death, activate hepatic stellate cells to drive fibrosis. NETs also promote malignant transformation, sustain an aggressive phenotype, attenuate immunotherapy responses, mediate resistance to targeted therapies, and contribute to poor prognosis in primary liver cancers. Preclinical studies targeting NET formation or degrading existing NETs have shown therapeutic benefits across these liver diseases. Despite promising results, clinical translation remains limited, with challenges including a lack of standardized biomarkers, optimal timing of intervention, and the need for liver-specific delivery. This review highlights NETs as a druggable target in liver diseases, and underscores future directions toward biomarker development and targeted therapies.
