Pathology International最新文献

High-grade gliomas (HGGs) in pediatric and adolescent/young adult (AYA) patients are biologically heterogeneous. Most exhibit pediatric-type molecular features, but a subset shows adult-type DNA methylation profiles with distinct diagnostic and therapeutic implications. We retrospectively analyzed 60 consecutive HGG, NOS cases in patients aged 0-39 years. Genome-wide DNA methylation profiling was performed using two independent brain tumor classifiers, with parallel copy-number analysis, and final diagnoses were reached by integrating epigenetic signatures with histopathology; targeted next-generation sequencing was undertaken in selected tumors. Adult-type molecular profiles were identified in 14 of 60 cases (23.3%), comprising 11 glioblastomas, IDH-wildtype (GBM RTK I, RTK II, and mesenchymal) and 3 adult-type diffuse high-grade gliomas, IDH-wildtype, subtype B, with 35.7% (5/14) occurring in patients ≤ 18 years. Recurrent alterations included NF1 (87.5%), PTEN (62.5%), and TERT promoter mutations (25%), with a single BRAF V600E-mutant tumor, while the classical +7/ - 10 signature was infrequent and MGMT promoter methylation was largely absent in GBM, IDH-wildtype. This study demonstrates that a substantial subset of pediatric and AYA HGGs harbor molecularly adult-type signatures, revealing the limitations of conventional histopathology and immunohistochemistry, challenging age-based diagnostic paradigms, and highlights the value of methylation profiling for diagnostic refinement, detection of targetable alterations in younger patients.

Reported herein is an extremely rare case of combined LCNEC with enteric-type adenocarcinoma of the lung (EAL) in a 72-year-old male. The LCNEC component was further divided into two subcomponents, based on cohesiveness and immunohistochemical characteristics. Overall, the heterogeneity of this tumor demonstrated an unusual histologic pattern of combined LCNEC.

CD109 is a glycosylphosphatidylinositol-anchored glycoprotein that is upregulated in various human cancers and exhibits tumor-promoting effects. In this study, we investigated the role of CD109 in gallbladder adenocarcinoma (GBAC). CD109 expression in 77 resected GBAC samples was immunohistochemically evaluated. CD109 expression in tumor cells correlated with TNM stage, N factor, histological grade, lymphatic invasion, and perineural invasion and was associated with reduced disease-free survival (DFS) and overall survival (OS). Stromal CD109 expression was detected in several cases, similar to that of α-SMA and FAP, suggesting its presence in cancer-associated fibroblasts. Stromal expression was also correlated with TNM stage, N factor, perineural invasion, and reduced DFS. Combined analysis of CD109 expression in tumor and stromal cells further stratified patients by prognosis. CD109 overexpression in GBAC cell lines induced the expression of the epithelial-to-mesenchymal transition (EMT) markers. Analyses using a public database revealed the association between CD109 and EMT-related gene expression in biliary tract cancer cell lines. Moreover, CD109 depletion promoted enhanced transforming growth factor-β1/Smad3 signaling and attenuated epidermal growth factor/AKT signaling in GBAC cells in a cell type-dependent manner. Collectively, these findings suggest that CD109 may serve as a prognostic biomarker of tumor progression and outcome in GBAC.

Lung is a common site of metastasis for squamous cell carcinoma (SqCC), and distinguishing primary lung SqCC from pulmonary metastatic SqCC is critical for clinical decision-making, including treatment planning. However, no practical histological criteria have been established for routine diagnosis. This study aimed to develop histopathological criteria to differentiate lung SqCC and pulmonary metastatic SqCC. A total of 85 surgical cases (48 primary and 37 metastatic) were collected with clinical background data. Seven histological features were evaluated. Six [morphological heterogeneity, dilated airway, interstitial fibrosis (IF), squamous dysplasia (SD), emphysema, RB macrophage] were presented as primary-associated features, while stromal infarction was proposed as metastatic. Seven pathologists scored these features. Primary-associated findings showed significantly higher score in primary cases. Tumor size (size) was significantly larger in the primary group (median: primary, 30 mm; metastatic, 14 mm; p < 0.001). A multivariate analysis incorporating size produced the "pathological primary formula" based on parameter estimates: 0.70・IF + 0.36・SD + 0.09・size, with an AUC of 0.86, sensitivity of 89.5%, and specificity of 70.2%. These results suggest that the extracted histologic features may provide reproducible criteria for distinguishing primary lung SqCC from pulmonary metastatic SqCC, offering insight into potential diagnostic applications.

Immune checkpoint inhibitors (ICIs) were approved in Japan in 2021 for the initial treatment of pleural mesothelioma (PM), offering anticipated prognostic benefits. However, reports of atypical responses exist. We report the case of an 80-year-old man with PM who, despite primary tumor shrinkage on ICI treatment, died of small intestinal perforation resulting from rapid, multiorgan metastasis. This case provided an opportunity to examine the histological changes in PM post-ICI treatment. The rapid clinical course was suggestive of hyperprogressive disease (HPD), a pattern of unexpectedly accelerated progression. Atypical response patterns remain rare in PM, and it is noteworthy that in this case fulminant metastatic progression occurred concurrently with marked regression of the primary pleural lesion. We believe this is a significant case worthy of presentation.

A 64-year-old female presenting with multiple cystic lesions in bilateral parotid glands was clinically considered to be benign. The surgically resected specimen revealed that the lesions met the diagnostic criteria of lymphoepithelial cysts (LECs). What's unique is that Langerhans cell histiocytosis (LCH) were identified in the LECs by immunohistochemistry (IHC) and molecular test. The inconspicuous LCH cells distributed along and mimicked the epithelial lining of cyst walls and were possibly to be missed in diagnosis. To date, there has no documented report of primary LCH originating within LECs. This study presents for the first time of a unique growth pattern. In addition, we reviewed published articles and attempt to make tentative discussion on pathogenesis.

Although rare, thyroid follicular nodular disease (TFND) may exhibit a nodule-in-nodule (NN) appearance with solid/trabecular (ST) components (STc). While the STc has histologically aggressive features compared to the outer nodule (Out-N) in TFND, its pathological significance remains unclear. We present a case of TFND with STc in a 63-year-old man who developed skin implantation and lung metastases 3 years after lobectomy. Histologically, the skin tumor resembled STc with high mitotic activity. Molecular analysis revealed EZH1 mutations in both the Out-N and STc of TFND, while KRAS and TERT promoter mutations were restricted to STc and the skin tumor. These findings suggest that the STc of NN may be a precursor to poorly differentiated thyroid carcinoma arising from well-differentiated components through stepwise mutations. This case highlights the malignant potential of certain Noninvasive TFNDs and suggests the need for further analyses to clarify this hypothesis and reconsider their classification and management.

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.