Pathology International最新文献

Cabozantinib, a newly developed vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI), is an effective treatment for advanced renal cell carcinoma (RCC). However, the molecular mechanisms responsible for the superior effectiveness of cabozantinib to other drugs remain unclear. Since cabozantinib inhibits AXL and c-MET in addition to VEGFR, the expression of these molecules was immunohistologically examined in 110 cases of primary clear cell RCC (ccRCC) and eight of sunitinib (VEGFR-TKI)-treated primary ccRCC. AXL expression correlated with the primary tumor stage, while c-MET expression correlated with distant metastasis, the histological grade, and overall survival. Furthermore, the number of programmed death-ligand 1 (PD-L1)-positive tumor-infiltrating immune cells was higher in ccRCC tissues with high c-MET expression than in those with low c-MET expression. The expression of AXL and c-MET was higher in sunitinib-treated ccRCC tissues than in untreated tissues. These results suggest that AXL and c-MET play important roles in the progression of ccRCC and resistance to sunitinib. Furthermore, c-MET may modify the immune microenvironment by inducing PD-L1 expression in immune cells within RCC tissues. These molecular pathways may be related to responses to cabozantinib.

Placental transmogrification of the lung (PTL) is a rare cystic lesion characterized by a distinctive microscopic architecture resembling placental villi. Although its etiology remains unclear, PTL is frequently observed with emphysema, suggesting a potential association between these conditions. However, the precise nature of this relationship remains ambiguous, and whether PTL causes or results from emphysema remains unclear. This report presents an incidental finding of PTL without macroscopic emphysematous changes with detailed immunohistochemical and ultrastructural analysis. A 58-year-old man died from aspiration pneumonia due to methanol poisoning. Autopsy revealed pyothorax in the right lung cavity and hemorrhage in the bilateral putamen. Although the left lung showed no severe inflammatory changes, a white-yellowish granular lesion was observed. Histopathologically, the lesion demonstrated villi-like structures with interstitial adipocyte infiltration, without evidence of hamartomatous component, such as cartilage or smooth muscle. Thus, the lesion was diagnosed as PTL with lipomatous change. PTL is typically associated with emphysematous/cystic lesions and is often considered reactive due to these. Herein, the lesion was surrounded by microscopic emphysema, suggesting an early-stage PTL that may have contributed to the development of emphysematous changes. This report describes the PTL with detailed immunohistochemical analysis.

Gastric cancer (GC) confined to the mucosa (pT1a-GC) has a low incidence (approximately 3%) of lymph node metastasis (LNM), making it a suitable candidate for endoscopic resection. However, the current risk stratification system inadequately identifies high-risk patients. Although RhoGAP fusion has been identified as a risk factor for LNM in pT1b-GC, its role in pT1a-GC remains unclear. In the present study, medical records of 1099 surgically resected pT1a-GC cases over 12 years were reviewed, identifying 33 cases (3.0%) with LNM. A case-control study compared these cases to 99 LNM-negative cases based on clinicopathological data. Histological reviews and fluorescence In Situ hybridization assays to evaluate RhoGAP fusions, represented by CLDN18::ARHGAP26, were conducted. Univariate analysis revealed significant associations between LNM and larger tumor size (> 30 mm), mixed histological type, muscularis mucosae invasion (MMI), microtubular-mucocellular histology, and RhoGAP fusion. Multivariate analysis identified RhoGAP fusion and MMI as independent LNM predictors. Among LNM-positive cases, RhoGAP fusion was observed in 51.5% (17/33) and was associated with younger age and less frequent MMI. In conclusion, RhoGAP fusion and MMI may be significant biomarkers for LNM in pT1a-GC. Incorporating these factors could enhance risk stratification and inform clinical management strategies for pT1a-GC.

A gastric neuroendocrine tumor (NET) with pancreatic acinar cell differentiation is extremely rare. We report the case of an 87-year-old woman with a submucosal tumor in the gastric body on a background of atrophic gastritis. She also had Sjögren's syndrome. Initially 17.8 × 6.5 mm, the tumor enlarged over 10 years, leading to wedge resection. The resected mass (45 × 40 × 30 mm) was solid with a pale yellow to gray-white cut surface. Histologically, it showed trabecular or solid nests of epithelial cells with round nuclei and eosinophilic cytoplasm. Immunohistochemistry showed positivity for CKAE1/3, VMAT2, neuroendocrine markers, and pancreatic acinar markers. Ki-67 index was 11.2%. The tumor co-expressed PDX1 and ARX and showed loss of menin and ATRX. These findings support a diagnosis of gastric ECL-cell NET G2 arising in autoimmune gastritis, with secondary pancreatic acinar differentiation. This tumor may represent a variant of type 1 gastric NET.

Complete loss of nuclear SMARCB1 expression was originally described as a hallmark of malignant rhabdoid tumors, typically occurring in the kidney, soft tissue, and central nervous system (CNS). Generally, SMARCB1 deficiency is associated with malignant histopathological appearance, except for some rare tumors. Herein, we present a case of hitherto undescribed SMARCB1-deficient pulmonary mesenchymal tumor without rhabdoid features or malignant histopathology involving a 62-year-old male patient. Histologically, the tumor demonstrated a moderately cellular proliferation of monomorphic spindle cells arranged in short fascicles or a storiform pattern with intervening collagenous stroma. The mitotic activity was lower than that of typical SMARCB1-deficient tumors, and rhabdoid features and necrosis were absent. Nuclear SMARCB1 expression was lost, and a part of SMARCB1 was revealed to be homozygously deleted. DNA methylation analysis demonstrated that this case was not clustered with other well-known SMARCB1-deficient tumors.

The study investigated the clinicopathological features and characteristic immune tumor microenvironment (TME) of lung squamous cell carcinoma (SqCC) adjacent to emphysematous lesions. 184 consecutive patients with peripheral-type SqCC who had undergone complete surgical resection were enrolled. The clinicopathological differences between emphysema-adjacent SqCC (EA-SqCC) and non-emphysema-adjacent SqCC (non-EA-SqCC) were examined. The immune TME, including tumor-infiltrating lymphocytes (TILs) and PD-L1 expression, was also analyzed. EA-SqCC was detected in 132 (71.7%) of the 184 patients. Patients with EA-SqCC had shorter recurrence-free survival (RFS) [median 58.2 months vs. not Reached (NR); hazard ratio (HR) 0.47; 95% CI 0.25-0.81, p < 0.01] and tended to have shorter overall survival (NR vs. NR; HR 0.47; 95% CI 0.27-1.03, p = 0.07) compared to patients with non-EA-SqCC. Evaluation of TILs in the cancer stroma showed the number of Foxp3+ TILs in the EA-SqCC group was significantly higher than that in the non-EA-SqCC group (median number 58 vs. 43, p < 0.01). However, there were no significant differences in the number of CD8 + T cells and the PD-L1 expression between the two groups. Immunosuppressive microenvironment is a characteristic feature of EA-SqCC, which may contribute to the poor prognosis of this disease.

Reactive mesothelial cells (RMCs) are of interest for differentiating mesothelioma from benign conditions and have been discussed in cytology and biopsy; however, their behavior in the body remains poorly understood. In this study, we report an autopsy case of an older woman with a long-standing pleural effusion due to cardiac disease, providing insights into the relationship between body cavities, and lymphatic vessels (LVs), mesothelial cells (MCs), and endothelial cells. Cytological examination of pleural effusion revealed RMCs with mild atypia, multinucleation, and intercellular phagocytosis. Immunohistochemistry confirmed the mesothelial origin of these cells. Autopsy findings showed extensive involvement of RMCs in the pleura, diaphragm, peritoneum, lymph vessels, and lymph node sinuses. The visceral pleural submesothelial LVs were dilated, had small openings in the thoracic cavity, and were lined with endothelial and mesothelial cells. Large cavernous LVs with MC clusters were observed on the diaphragm. These structures resembled "stomata" or "lacunae," suggesting a mechanism by which RMCs migrate from the body cavities to the lymphatic network. This study focuses on the RMCs in LVs and shows the contiguity between body cavities and lymphatic networks, providing important insights into the flow of bodily fluids.

Air transport of FFPE cancer tissue samples led to increased DNA fragmentation, primarily due to radiation exposure rather than temperature changes or freeze-thaw cycles. While overall degradation was minor, critical samples requiring high nucleic acid integrity may benefit from local testing or research. Avoiding air transport could help mitigate potential risks and ensure reliable results.