DOI： 10.1245/s10434-025-17255-3

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記述言語：英語   出版者・発行元：Medicine United States  

Rationale: Clear cell meningioma (CCM) is a rare and aggressive subtype of meningioma, classified as Grade II by the World Health Organization due to its higher recurrence risk. While CCMs predominantly arise in the cerebellopontine angle, intraspinal cases, particularly those without dural attachment, are exceedingly rare and present diagnostic and surgical challenges. Patient concerns and diagnosis: We report a case of a 66-year-old woman who presented with a one-year history of pain and numbness radiating from the right buttock to the posterior thigh, along with intermittent claudication. Physical examination showed no motor deficits or significant neurological abnormalities. Magnetic resonance imaging revealed a 32 × 16 mm intradural mass at the L5 level with iso-intensity on both T1- and T2-weighted images and uniform contrast enhancement. The lesion was diagnosed as CCM based on pathological examination following tumor resection. Interventions and outcomes: The patient underwent lumbar laminectomy and complete tumor resection. Intraoperatively, the tumor was observed to compress the cauda equina nerve but was nonadherent to the dura mater. A nerve fiber connected the tumor to surrounding neural structures, requiring partial nerve root resection for complete tumor removal. Postoperatively, the patient reported complete resolution of pain, numbness, and gait disturbance. The visual analogue scale scores for leg pain and numbness improved from 7.4 and 7.3 to 0, respectively. The Japanese Orthopaedic Association score improved from 22 to 28 (out of 29). Follow-up magnetic resonance imaging at 1 year showed no evidence of recurrence. Lessons: CCM without dural attachment is a rare variant of meningioma that presents challenges in diagnosis and surgical management. Complete resection during the first surgery led to favorable outcomes in this case. Although the recurrence rate for this subtype is lower, long-term follow-up with regular imaging is recommended.

DOI： 10.1097/MD.0000000000043193

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記述言語：英語   出版者・発行元：Annals of Surgical Oncology  

Background: DNA polymerase delta 2 (POLD2) plays a crucial role in DNA repair and replication. POLD2 is upregulated and related to poor prognosis in several types of cancer. However, the biological and clinical importance of POLD2 in lung adenocarcinoma remains unclear. Patients and Methods: We investigated the relationship between POLD2 expression and tumor malignancy in lung adenocarcinoma cell lines. Immunohistochemistry (IHC) was performed on 373 patients with completely resected lung adenocarcinoma, and the association between POLD2 expression, clinicopathological features, and prognosis was examined. Results: POLD2 knockdown decreases cell proliferation and migration, resulting in apoptosis and G1 arrest in the cell cycle in lung adenocarcinoma cells. Additionally, POLD2 knockdown attenuates MYC expression, which may decrease the expression of cyclin-dependent kinases 4 and 6, pRb, Rb, and E2F1. Furthermore, among 373 patients with completely resected lung adenocarcinoma, smoking history, advanced pathological stage, and vascular invasion were significantly more prevalent in patients with high POLD2 expression (n = 146, 39.3%) than in those with low POLD2 expression (n = 227, 60.7%). Patients with high POLD2 expression also had a significantly worse recurrence-free survival (RFS) and overall survival. In the multivariable analysis, high POLD2 expression was an independent poor prognostic factor of RFS. Conclusions: We provide the possibility of POLD2 as a potential new therapeutic target because high POLD2 expression is associated with high malignancy and poor prognosis in specimens from patients with lung adenocarcinoma and POLD2 depletion triggers the suppression of cell migration, cell cycle progression, and cell proliferation.

DOI： 10.1245/s10434-025-17118-x

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記述言語：英語   出版者・発行元：Cancer Science  

Ovarian carcinosarcoma (OCS) is a rare and aggressive tumor, and the development of its sarcomatous component is believed to be due to epithelial–mesenchymal transition (EMT). The SWIch/sucrose nonfermentable chromatin remodeling factor (CRF) is closely related to EMT; however, the relationship between CRF and EMT in OCS remains unclear. In this study, we analyzed the protein expression of CRFs, including ARID1A and SMARCA4, and their downstream mRNA expression in 28 OCS cases, two fallopian tube CS cases, and one peritoneal CS case. ARID1A and SMARCA4 exhibited a histological type-specific loss of protein expression in 5 of 11 (45%) endometrioid cases and all 5 serous/homologous OCS cases, respectively. The mRNA analysis suggested that sarcomatogenesis is induced by the transforming growth factor-β and Hippo signaling pathways, both of which regulate YAP1. Immunostaining for YAP1 suggested YAP1-associated sarcomatogenesis in the CRF-retained group, whereas YAP1-unassociated sarcomatogenesis was suggested in the CRF-reduced group. High-grade serous carcinoma cell line experiments showed that the transcriptome of the SMARCA4-knockdown group showed lower expression of the epithelial gene CDH1 and higher expression of mesenchymal genes such as VIM, ZEB1, and SNAI1 than the control group. Moreover, cell adhesion disappeared and cell morphology changed to a spindle shape, indicating sarcomatogenesis. In conclusion, this study reveals a mechanism for sarcoma development in OCS and provides novel therapeutic possibilities.

DOI： 10.1111/cas.16423

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記述言語：日本語   出版者・発行元：(公社)日本医学放射線学会  

記述言語：英語   出版者・発行元：Interdisciplinary Cardiovascular and Thoracic Surgery  

OBJECTIVES: Spread through air spaces (STAS) is considered a poor prognostic factor in patients with resected non-small lung cell cancer; however, the clinical significance of STAS extent remains unclear. We hypothesized that the further the tumour cells spread from the tumour edge, the worse the prognosis becomes. METHODS: This study retrospectively reviewed the data of 642 patients with completely resected pathological stage I-III non-small lung cell cancer between 2008 and 2018. The maximum spread distance (MSD) from the tumour edge to the farthest STAS was quantitatively evaluated, and STAS was categorized as limited (MSD ≤1000 μm) or extended (MSD >1000 μm), based on the median MSD. Recurrence-free survival (RFS) and overall survival (OS) were compared among patients stratified by STAS classification. RESULTS: Patients were classified into STAS-negative (n = 382, 59.6%), limited STAS (n = 130, 20.2%) and extended STAS (n = 130, 20.2%) groups. Extended STAS was associated with a high maximum standardized uptake value, advanced pathological stage and vascular invasion compared with limited STAS. The extended STAS group demonstrated significantly shorter RFS and OS than both the limited STAS and STAS-negative groups (both P < 0.001 for RFS; P = 0.007 and P < 0.001 for OS, respectively). Multivariable analysis showed that extended STAS was an independent prognostic factor for both RFS and OS (P < 0.001, P < 0.001, respectively). CONCLUSIONS: The distance from tumour edge to STAS affects prognosis in patients with completely resected non-small lung cell cancer.

DOI： 10.1093/icvts/ivae181

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記述言語：英語   出版者・発行元：Oncology Letters  

Ovarian high-grade serous carcinoma (OHGSC) is the most common type of ovarian cancer worldwide. Genome sequencing has identified mutations in chromatin remodeling factors (CRFs) in gynecological cancer, such as clear cell carcinoma, endometrioid carcinoma and endometrial serous carcinoma. However, to the best of our knowledge, the asso- ciation between CRFs and OHGSC remains unexplored. The present study aimed to investigate the clinicopathological and molecular characteristics of CRF dysfunction in OHGSC. CRF alterations were analyzed through numerous methods, including the analysis of public next-generation sequencing (NGS) data from 585 ovarian serous carcinoma cases from The Cancer Genome Atlas (TCGA), immunohistochemistry (IHC), and DNA copy number assays, which were performed on 203 surgically resected OHGSC samples. In the public NGS dataset, the most frequent genetic alteration was actin-like protein 6A (ACTL6A) amplification at 19.5%. Switch/sucrose non-fermentable related, matrix associated, actin dependent regulator of chromatin subfamily c member 2 (SMARCC2) amplification (3.1%) was associated with significantly decreased overall survival (OS). In addition, chromodo- main-helicase-DNA-binding protein 4 (CHD4) amplification (5.7%) exhibited unfavorable outcome trends, although not statistically significant. IHC revealed the protein expression loss of ARID1A (2.5%), SMARCA2 (2.5%) and SMARCA4 (3.9%). The protein expression levels of ACTL6A, SMARCC2 and CHD4 were evaluated using H-score. Patients with low protein expression levels of ACTL6A showed a significantly decreased OS. Copy number gain or gene amplification was demonstrated in ACTL6A (66.2%) and SMARCC2 (33.5%), while shallow deletion or deep deletion was demonstrated in CHD4 (70.7%). However, there was no statistically significant difference in protein levels of these CRFs, between the different copy number alterations (CNAs). Overall, OHGSC exhibited CNAs and protein loss, indicating possible gene alterations in CRFs. Moreover, there was a significant association between the protein expression levels of ACTL6A and poor prognosis. Based on these findings, it is suggested that CRFs could serve as prognostic markers for OHGSC.

DOI： 10.3892/ol.2024.14329

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記述言語：英語   出版者・発行元：Human Pathology  

Several high-grade pleomorphic sarcoma cases that cannot be classified into any existing established categories have been reported. These cases were provisionally classified into undifferentiated pleomorphic sarcoma (UPS). Some dedifferentiated liposarcoma (DDLS) cases may also have been classified into the UPS category due to the absence of MDM2 amplification or an atypical lipomatous tumor/well-differentiated liposarcoma component. We retrieved and reviewed 77 high-grade pleomorphic sarcoma cases, initially diagnosed as UPS in 66 cases and DDLS in 11 cases. Fluorescence in situ hybridization (FISH) analyses of DDIT3 and MDM2 were performed for available cases. Of the cases successfully subjected to DDIT3 FISH (n = 56), nine (7 UPS and 2 DDLS) showed DDIT3 amplification but no MDM2 amplification. Two UPS cases showed both telomeric (5′) and centromeric (3′) amplification of DDIT3 or low polysomy of chromosome 12, whereas 5 UPS and 2 DDLS cases showed 5′-predominant DDIT3 amplification. Histopathologically, all cases showed UPS-like proliferation of atypical pleomorphic tumor cells. Immunohistochemically, only one case showed focal nuclear positivity for DDIT3, supporting the previous finding that DDIT3 expression was not correlated with DDIT3 amplification. All three cases with focal MDM2 expression involved 5′-predominant amplification, two of which showed DDLS-like histological features. The majority of cases (7/9) showed decreased expression in p53 staining, suggesting that DDIT3 amplification regulates the expression of TP53 like MDM2. From a clinicopathological perspective, we hypothesize that DDIT3-amplified sarcoma, especially with 5′-predominant amplification, can be reclassified out of the UPS category.

DOI： 10.1016/j.humpath.2024.02.007

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記述言語：英語   出版者・発行元：Human Pathology  

Collecting duct carcinoma (CDC) is a rare subset of high-grade renal cell carcinoma (RCC). To diagnose CDC, it is necessary to rule out other renal tumors including renal medullary carcinoma and fumarate hydratase (FH)-deficient RCC. However, there is overlap in the morphology of these three tumors, which all have poor outcomes. There is also still a need to sufficiently examine the therapeutic strategies for each of these tumors. In this study, we retrospectively reclassified invasive/infiltrating high-grade RCC and investigated its pathological features. We reviewed 18 cases previously diagnosed as “CDC,” “FH-deficient RCC,” and “unclassified RCC,” which were reclassified as SMARCB1/INI1-deficient RCC, FH-deficient RCC, and CDC by SMARCB1/INI1, FH, and 2SC immunohistochemistry (IHC) and FH gene mutational status. As the result, 18 cases were reclassified into 2 cases of SMARCB1/INI1-deficient RCC, 7 cases of FH-deficient RCC, and 9 cases of CDC. The morphological features of each group overlapped, and no specific immunohistochemical expression except for SMARCB1/INI1, FH, and 2SC was detected. These results suggest that invasive/infiltrating high-grade RCC should be diagnosed by the combination of immunohistochemistry and molecular biological technique.

DOI： 10.1016/j.humpath.2022.03.002

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