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Background/Aim: The development of treatment-related neuroendocrine prostate cancer (t-NEPC) is an increasing clinical concern. The objectives were to clarify the clinical features of t-NEPC. Patients and Methods: A total of 9 patients with histologically confirmed t-NEPC were reviewed. Results: Of these 9 patients, 2 patients were diagnosed with t-NEPC by a histological examination without elevation in blood tumor marker levels. Immunohistochemistry revealed an acquired Rb loss in 5 patients. All patients were treated with platinum-based chemotherapy as first-line treatment and 6 patients received concurrent radiation therapy (RT). The median cancer-specific survival was 14.4 months, and 7 patients achieved an objective response. Patients with tumor-infiltrating CD8+ lymphocyte (CD8+-TILs) showed better response than those without CD8+-TILs. Conclusion: We described the clinical features of histologically confirmed t-NEPC. In addition to the importance of biopsy, we showed that platinum-based chemotherapy plus RT had a favorable cytoreductive effect. Further clinical recognition and studies are needed.

Ultrathin bronchoscopy has been reported to have a higher diagnostic yield than thin bronchoscopy for small peripheral lung lesions in transbronchial biopsy under radial endobronchial ultrasonography (EBUS). However, data comparing the number of tumor cells in non-small cell lung cancer (NSCLC) are limited. We retrospectively compared the number of NSCLC tumor cells in peripheral lung lesions obtained using an ultrathin bronchoscope and a thin bronchoscope with radial EBUS between April 2020 and October 2021. In all patients, we used virtual bronchoscopic navigation (VBN) software, and guide sheaths were used in thin bronchoscopy cases. A total of 175 patients were enrolled in this study. Ultrathin bronchoscopy cases (n = 69) had lesions with a smaller diameter that are more peripherally located compared to thin bronchoscopy cases (n = 106) (median, 25.0 vs. 26.5 mm, mean bronchial generations accessed by bronchoscopy; 4.4±1.2 vs. 3.8±1.0, respectively; p<0.010). There were no significant differences in the overall diagnostic yield (ultrathin vs. thin bronchoscopy cases, 68.1% vs. 72.6%, p = 0.610) or diagnostic yield in only lung cancer cases (78.6% vs. 78.5%, p = 1.000). In histologically NSCLC cases (n = 102), the maximum number of tumor cells per slide as the primary endpoint was similar (average, 307.6±246.7 vs. 328.7±314.9, p = 0.710). The success rate of the Oncomine™ analysis did not differ significantly (80.0% vs. 55.6%, p = 0.247). The yield of NSCLC tumor cells was not different between the samples obtained by the ultrathin bronchoscope and those obtained by the thin bronchoscope.

Malignant pleural mesothelioma (MPM), associated with unfavorable outcomes, is closely associated with asbestos exposure. Early detection and treatment are critical to prolong survival of patients with MPM because of the rapid progression and resistance to treatment. The recently defined malignant mesothelioma in situ (MIS) has been gaining increasing attention with advances in genome-based methods including fluorescence in situ hybridization (FISH) as well as immunohistochemistry. We herein report the case of a MIS in a 73-year-old male with a history of asbestos exposure presenting with massive pleural effusion in the right thoracic cavity. Video-assisted thoracoscopic surgery with pleural biopsy of the right side revealed a single layer of atypical mesothelial cells without invasive lesions by hematoxylin and eosin staining. However, these mesothelial cells exhibited a loss of methylthioadenosine phosphorylase (MTAP) by immunohistochemistry and homozygous deletion of CDKN2A (p16) by FISH, leading to the diagnosis of MIS.

We herein describe soft tissue tumor arising in the lower extremity of a pediatric patient. The tumor displayed a unique and wide range of histological features, sheet-like and cohesive growth pattern consisting of enlarged round to epithelioid atypical cells with a large alveolar and pseudopapillary histological architecture, focally mimicking alveolar soft part sarcoma and MiT family translocation renal cell carcinoma. Tumor cells were focally immunoreactive for cytokeratin, S-100, and EMA. RNA sequencing identified a novel in-frame NR1D1 (exon 5)-MAML1 (exon 2) gene rearrangement resulting in the formation of a putative chimeric protein containing the N-terminal C4-type zing finger domains of NR1D1 and the C-terminal MAML1 protein, which was confirmed by subsequent RT-PCR, Sanger sequencing, and FISH assay. To the best of our knowledge, NR1D1-MAML1 fusion has not yet been described in any neoplasms, suggesting the emergence of a novel tumor entity.

 High-grade neuroendocrine carcinoma (HGNEC) with dominant POU2F3 expression exhibits non-neuroendocrine features. However, clinical data regarding this subset of pulmonary HGNECs are scarce, and its clinical characteristics remain unclear.  Clinicopathological data from 109 patients who underwent surgery for HGNEC were collected and analyzed based on transcription factor expression. Patients were divided into a POU2F3-dominant group (HGNEC-P) and a non-dominant group (HGNEC-non-P) according to immunohistochemical analysis. The clinicopathological characteristics of the two groups were compared, and univariate and multivariate analyses were conducted to identify prognostic factors.  The HGNEC-P group comprised 26 patients, while the HGNEC-non-P group comprised 83 patients. The HGNEC-P group showed significantly lower expression of carcinoembryonic antigen (CEA) (p < 0.001) and a lower rate of vascular invasion (p = 0.021) compared to the HGNEC-non-P group. In addition, the HGNEC-P group exhibited a unique tumor marker profile, with lower serum CEA and higher serum cytokeratin antigen (CYFRA) levels (p < 0.001 and p = 0.046, respectively). Complete resection was achieved in all HGNEC-P cases, whereas only 75.9% of HGNEC-non-P cases achieved complete resection. Multivariate analysis identified POU2F3 expression as an independent prognostic factor for recurrence-free survival (RFS) and disease-specific survival (DSS) (p = 0.037 and p = 0.038, respectively). In patients with pathological Stage I disease, the HGNEC-P group showed significantly better RFS (p = 0.010).  POU2F3-dominant HGNEC is associated with distinct clinicopathological features and favorable prognosis, particularly in early-stage disease. These findings may support the identification of this subset and inform the development of more effective treatment strategies.

Annexin A10 (ANXA10) is a member of the annexin family and a calcium-dependent phospholipid-binding protein. The aim of this study was to clarify the clinical significance of ANXA10 expression in lung adenocarcinoma. ANXA10 expression was immunohistochemically examined in surgical specimens of lung adenocarcinoma obtained from 74 consecutive patients who underwent complete resection from January 2014 to December 2014. Expression of ANXA10 was down-regulated in A549 cells via siRNA transfection and the effect of ANXA10 on cell migration was assessed by the wound healing assay. Expression of ANXA10 was examined by immunocytochemistry and polymerase chain reaction. High ANXA10 expression was significantly correlated with poor overall survival (p=0.00705). Multivariate analysis with the Cox proportional hazard model demonstrated that ANXA10 expression was an independent prognostic factor. Cell migration was suppressed in ANXA10-down-regulated A549 cell lines. ANXA10 has a role in cancer cell migration and high ANXA10 expression is a novel prognostic marker in lung adenocarcinoma.

Adequate tumor tissue is required to make the best treatment choice for non-small cell lung cancer (NSCLC). Transbronchial biopsy (TBB) by endobronchial ultrasonography with a guide sheath (EBUS-GS) is useful to diagnose peripheral lung lesions. The data of tumor cell numbers obtained by two different sizes of GSs is limited. We conducted this study to investigate the utility of a large GS kit to obtain many tumor cells in patients with NSCLC. Patients with a peripheral lung lesion and suspected of NSCLC were prospectively enrolled. They underwent TBB with a 5.9-mm diameter bronchoscope with a large GS. When the lesion was invisible in EBUS, we changed to a thinner bronchoscope and TBB was performed with a small GS. We compared the tumor cell number prospectively obtained with a large GS (prospective large GS group) and those previously obtained with a small GS (small GS cohort). The primary endpoint was the tumor cell number per sample, and we assessed characteristics of lesions that could be obtained by TBB with large GS. Biopsy with large GS was performed in 55 of 87 patients (63.2%), and 37 were diagnosed with NSCLC based on histological samples. The number of tumor cells per sample was not different between two groups (658±553 vs. 532±526, estimated difference between two groups with 95% confidence interval (CI); 125 (-125-376), p = 0.32). The sample size of the large GS group was significantly larger than that of the small GS cohort (1.75 mm2 vs. 0.83 mm2, estimated difference with 95% CI; 0.92 (0.60-1.23) mm2, p = 0.00000019). The lesion involving a third or less bronchus generation was predictive factors using large GS. The sample size obtained with large GS was significantly larger compared to that obtained with small GS, but there was no significant difference in tumor cell number. The 5.9-mm diameter bronchoscope with large GS can be used for lesions involving a third or less bronchus generation.

Diffuse low-grade glioma, MAPK pathway–altered (DLGG–MAPK), is a recently defined tumor entity characterized by genetic alterations activating the MAPK signaling cascade. While BRAF and FGFR alterations are most frequently reported, the biological and clinical significance of other MAPK-activating events remains poorly understood. We report a 25-year-old woman with a right temporal lobe tumor harboring a novel CUX1 :: MET fusion. The lesion was initially detected at age 10 during neuroimaging performed for a transient headache and subsequently followed an indolent clinical course for approximately 15 years before manifesting with acute hemorrhage. Histologically, the tumor showed diffuse infiltration with oligodendroglioma-like morphology, absence of high-grade features, and a low proliferative index. Molecular analysis identified an in-frame CUX1 :: MET fusion retaining the MET kinase domain, resulting in exon 14 skipping and activation of the MAPK pathway. Despite the presence of a MET alteration typically associated with aggressive tumors, the lesion demonstrated prolonged indolence and low-grade biological behavior. To our knowledge, this is the first case report demonstrating the presence of a CUX1 :: MET fusion in DLLG-MAPK. This case expands the molecular spectrum of DLGG–MAPK and provides novel insight into the biological heterogeneity of MET-driven gliomas, suggesting that MET fusion alone is insufficient to confer high-grade behavior in this tumor context.

Birt–Hogg–Dubé (BHD) syndrome is an autosomal dominant disease characterized by benign skin hamartomas, pulmonary cysts leading to spontaneous pneumothorax, and an increased risk of renal cancer. BHD syndrome is caused by germline mutations in the folliculin (FLCN) gene, a putative tumor suppressor, which result in loss of function of the folliculin protein and may cause cancer predisposition. In a 45-year-old woman with anemia, lymphadenopathy, and a history of recurrent spontaneous pneumothorax, 18F-FDG PET/CT detected diffuse and slight 18F-FDG accumulation in the bone marrow, enlarged spleen, and systemic multiple enlarged lymph nodes. Genetic examination identified a germline nonsense mutation [c.998C > G (p.Ser333*)] on exon 9 of FLCN. Pathological examination of the lymph node revealed a diffuse neoplastic proliferation of plasmacytoid lymphocytes. The neoplastic lymphoid cells were positive for CD20, CD138, and light chain kappa as per immunohistochemistry and mRNA in situ hybridization, and a MYD88 gene mutation [c.755T > C (p.L252P)] was identified. Accordingly, she was diagnosed with lymphoplasmacytic lymphoma concomitant with BHD syndrome. To the best of our knowledge, this is the first report describing the development of hematological malignancy in a patient with BHD syndrome. The FLCN mutation might contribute lymphomagenesis as an additional mutation cooperating with the MYD88 mutation.

Background Recent studies have revealed that serpin peptidase inhibitor clade E member 2 (SERPINE2) is associated with tumorigenesis. However, SERPINE2 expression and its role in lung adenocarcinomas are still unknown. Methods The expression levels of SERPINE2 in 74 consecutively resected lung adenocarcinomas were analyzed by using immunostaining. Inhibition of SERPINE2 expression by small interfering RNA (siRNA) was detected by quantitative PCR. Cell number assays and cell apoptosis assays were performed to clarify the cell-autonomous function of SERPINE2 in A549 and PC9 lung cancer cells. Results The overall survival of patients with high SERPINE2 expression was significantly worse than that of patients with low SERPINE2 expression (P = 0.0172). Multivariate analysis revealed that SERPINE2 expression was an independent factor associated with poor prognosis (P = 0.03237). The interference of SERPINE2 decreased cell number and increased apoptosis in A549 and PC9 cells Conclusion These results suggest that SERPINE2 can be used as a novel prognostic marker of lung adenocarcinoma.