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Poroma is a benign skin tumor exhibiting terminal sweat gland duct differentiation. The present study aimed to explore the potential role of gene fusions in the tumorigenesis of poromas. RNA sequencing and reverse transcription PCR identified highly recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poromas (92/104 lesions, 88.5%) and their rare malignant counterpart, porocarcinomas (7/11 lesions, 63.6%). A WWTR1-NUTM1 fusion was identified in a single lesion of poroma. Fluorescent in-situ hybridization confirmed genomic rearrangements involving these genetic loci. Immunohistochemical staining could readily identify the YAP1 fusion products as nuclear expression of the N-terminal portion of YAP1 with a lack of the C-terminal portion. YAP1 and WWTR1, also known as YAP and TAZ, respectively, encode paralogous transcriptional activators of TEAD, which are negatively regulated by the Hippo signaling pathway. The YAP1 and WWTR1 fusions strongly transactivated a TEAD reporter and promoted anchorage-independent growth, confirming their tumorigenic roles. Our results demonstrate the frequent presence of transforming YAP1 fusions in poromas and porocarcinomas and suggest YAP1/TEAD-dependent transcription as a candidate therapeutic target against porocarcinoma.

The Cancer Genome Atlas (TCGA) network has clarified that ~50% of high‐grade serous ovarian cancers show homologous recombination deficiency (HRD). However, the frequency of HRD in Japanese patients with ovarian cancer remains unclear. We aimed to identify the frequency of HR‐associated gene mutations in Japanese patients with ovarian cancer. The JGOG3025 study is a multicenter collaborative prospective observational study involving 65 study sites throughout Japan. We recruited 996 patients who were clinically diagnosed with ovarian cancer before surgery from March 2017 to March 2019, and 701 patients were eligible according to the criteria. We used frozen tumor tissues to extract DNA and performed next‐generation sequencing for 51 targeted genes (including 29 HR‐associated genes) in 701 ovarian cancers (298 high‐grade serous cases, 189 clear cell cases, 135 endometrioid cases, 12 mucinous cases, 3 low‐grade serous cases, and 64 others). HRD was defined as positive when at least one HR‐associated gene was mutated. The frequencies of HRD and tumor BRCA1/2 mutations were 45.2% (317/701) and 18.5% (130/701), respectively, in the full analysis set. Next, we performed multivariate Cox proportional hazards regression analysis for progression‐free survival (PFS) and overall survival (OS). Advanced‐stage ovarian cancer patients with HRD had adjusted hazard ratios of 0.72 (95% CI, 0.55–0.94) and 0.57 (95% CI, 0.38–0.86) for PFS and OS, respectively, compared with those without HRD (p = 0.016 and 0.007). Our study demonstrated that mutations in HR‐associated genes were associated with prognosis. Further studies are needed to investigate the prognostic impact of each HR‐associated gene in ovarian cancer. Ovarian cancers with HR‐associated gene mutations show platinum sensitivity, leading to better outcomes. In particular, advanced‐stage clear cell carcinoma harboring HR‐associated gene mutations demonstrated longer PFS and OS.

Background A previous report showed that a glucagon-like peptide-1 receptor (GLP-1R) agonist (exenatide) induced apoptosis in endometrial cancer cells. However, the pathophysiological role of GLP-1R in endometrial cancer has not been fully elucidated. Here, we investigated the effects of the GLP-1R agonist liraglutide in endometrial cancer cells and examined the association between GLP-1R expression and clinicopathological characteristics in endometrial cancer patients. Methods Human Ishikawa endometrial cancer cells were treated with different concentrations of liraglutide. To assess the effects of liraglutide, cell viability, colony formation, flow cytometry, Western blotting, and immunofluorescence assays were performed. Autophagy induction was examined by analyzing LC3 and p62 expression and autophagosome accumulation. Moreover, using a tissue microarray, we analyzed GLP-1R expression in 154 endometrial cancer tissue samples by immunohistochemistry. Results In accordance with the previous report, liraglutide inhibited Ishikawa cell growth in a dose-dependent manner. Liraglutide significantly induced autophagy, and phosphorylated AMPK expression was elevated. Immunohistochemical analysis revealed that GLP-1R expression was associated with positive estrogen receptor and progesterone receptor status, and higher GLP-1R expression was significantly correlated with better progression-free survival. Conclusions The use of liraglutide to target autophagy in endometrial cancer cells may be a novel potential treatment for endometrial cancer. Furthermore, higher GLP-1R expression may be associated with better prognosis in endometrial cancer patients.

More specific screening systems for cervical cancer may become necessary as the human papillomavirus (HPV) vaccine becomes more widespread. Although p16/Ki-67 dual-staining cytology has several advantages, it requires advanced diagnostic skills. Here, we developed an automated on-chip immunostaining method using a microfluidic device. An electroactive microwell array (EMA) microfluidic device with patterned thin-film electrodes at the bottom of each microwell was used for single-cell capture by dielectrophoresis. Immunostaining and dual staining for p16/Ki-67 were performed on diagnosed liquid cytology samples using the EMA device. The numbers of p16/Ki-67 dual-stained cells captured by the EMA device were determined and compared among the cervical intraepithelial neoplasia (CIN) lesion samples. Seven normal, fifteen CIN grade 3, and seven CIN grade 2 samples were examined. The percentage of dual-positive cells was 18.6% in the CIN grade 2 samples and 23.6% in the CIN grade 3 samples. The percentages of dual-positive staining increased significantly as the severity of the cervical lesions increased. p16/Ki67 dual immunostaining using the EMA device is as sensitive as the conventional method of confirming the histopathological diagnosis of cervical samples. This system enables a quantified parallel analysis at the individual cell level.

Background Tumor-to-tumor metastasis is a rare phenomenon in which primary tumor cells metastasize hematogenously into another tumor. Herein, we report an extremely rare case of a renal cell carcinoma metastasis into a pancreatic neuroendocrine tumor exhibiting a tumor-to-tumor metastasis. Ours is the third reported case worldwide. Case presentation The patient, a 72-year-old male, was referred to our hospital for further examination and treatment due to high levels of prostate-specific antigen. A left renal tumor and pancreatic head tumor were revealed incidentally on screening computed tomography. There were suspected to be a renal cell carcinoma and primary pancreatic neuroendocrine tumor or pancreatic metastasis from the renal cell carcinoma according to preoperative examination. The left nephrectomy and subtotal stomach-preserving pancreaticoduodenectomy were performed because of the pancreatic tumor indicated for operation in either case of diagnosis. Postoperative pathological examination showed a diagnosis of clear cell renal cell carcinoma for the left renal tumor. The pancreatic tumor was diagnosed with clear cell renal cell carcinoma metastasis into the pancreatic neuroendocrine tumor, that is to say tumor-to-tumor metastasis. Conclusion In some cases, conservative approach is selected for pancreatic neuroendocrine tumor patients who meet some requirements. However, if such patients exhibit tumor-to-tumor metastasis which combines with renal cell carcinoma and pancreatic neuroendocrine tumor as this case, conservative approach leads to progression of renal cell carcinoma. Therefore, conceiving the possibility of tumor-to-tumor metastasis, it is necessary to carefully choose a treatment plan for pancreatic neuroendocrine tumor patients associated with renal cell carcinoma, not easily choosing conservative approach.

Forgotten childhood foreign body aspiration may present in adulthood as chronic bronchial obstruction, creating substantial diagnostic challenges. A 45‐year‐old man with a history of recurrent pneumonia in childhood had an abnormal chest shadow on routine examination without recollection of choking episodes. Chest computed tomography demonstrated complete obstruction of the right basal bronchus with atelectasis. Bronchoscopy revealed inflammatory changes and an occluded bronchus with viscous secretions. Differential diagnosis included pulmonary sequestration, bronchial atresia, and malignancy. Right middle and lower bilobectomy was performed because malignancy could not be excluded. Pathological examination unexpectedly identified a 12‐mm plastic air pistol pellet encapsulated by thick fibrous tissue, indicating retention exceeding 30 years. Foreign body aspiration should remain in the differential diagnosis of chronic bronchial obstruction even when patient history and all preoperative diagnostic modalities fail to suggest this aetiology, particularly in patients with childhood respiratory illness. We report a highly unusual case in which none of the conventional diagnostic modalities could identify a bronchial FB preoperatively, and the diagnosis was established only through pathological examination after surgical resection. This case underscores the substantial diagnostic challenges posed by long‐standing occult FBA and highlights the importance of considering FBA in the differential diagnosis of chronic bronchial obstruction, even when clinical and radiological findings strongly suggest alternative aetiologies.

Background Interval debulking surgery (IDS) following neoadjuvant chemotherapy is a treatment option for advanced ovarian cancer. Optimal surgery is required for better survival; however, while peritoneal washing cytology (PWC) has been identified as a prognostic factor, its comprehensive assessment during IDS remains unexplored. Therefore, we aimed to evaluate PWC efficacy during IDS, alongside other factors including residual disease and the modeled cancer antigen 125 (CA-125) ELIMination rate constant K (KELIM), by retrospectively reviewing the medical records of 25 patients with advanced ovarian cancer underwent neoadjuvant chemotherapy and IDS between January 2017 to June 2023. Results Twelve (48.0%) patients were PWC-positive, and the remainder were PWC-negative. PWC was performed at laparotomy during IDS, after which five (41.7%) PWC-positive and four (30.8%) PWC-negative patients received bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, for maintenance treatment. Four (33.3%) PWC-positive and 10 (76.9%) PWC-negative patients received poly adenosine diphosphate (ADP)-ribose polymerase inhibitors. In patients who received bevacizumab and poly ADP-ribose polymerase inhibitors, overall survival and progression-free survival did not significantly differ between those who were PWC-positive and PWC-negative ( p  = 0.27 and 0.20, respectively). Progression-free survival significantly differed between those with favorable and unfavorable CA-125 KELIM ( p  = 0.02). Multivariate analysis indicated that optimal surgery and favorable CA-125 KELIM were associated with better progression-free survival ( p  < 0.01 and 0.02, respectively), with only optimal surgery associated with better overall survival ( p  = 0.04). Conclusions A positive PWC at IDS was not associated with survival in advanced ovarian cancer. Our findings indicate that although PWC status at IDS should be one of the factors determining survival in patients with advanced ovarian cancer, recent improvements in maintenance therapy may make the combination of CA-125 KELIM and PWC status a more useful prognostic factor in selecting treatment after IDS. Further studies are needed to validate these results, highlighting the potential importance of maintenance treatment after IDS and the need for further research to validate the clinical significance of a positive PWC.

Six years prior to the current admission, the patient had presented with fever, joint pain, epididymitis, mononeuritis multiplex, sinusitis, and erythema, and his blood tests had revealed a positive result for myeloperoxidase- antineutrophil cytoplasmic antibody (MPO-ANCA) (61 U/ml; reference range, 0-19) and elevated C-reactive protein (CRP) level (124.2 mg/l; reference range, 0-3.0). [...]the patient had been diagnosed with ANCA-associated vasculitis, specifically GPA, due to the presence of epididymitis. [...]intravenous cyclophosphamide was discontinued 3 years before the current admission, and infliximab (IFX) therapy was initiated because rituximab and azathioprine had not been approved for GPA in our country at that time. [...]he was prescribed minodronic acid hydrate (50 mg every 4 weeks) and alfacalcidol (5 µg/day).

Background Nipple–areola complex (NAC) necrosis, which is caused by local ischemia, remains one of the complications associated with nipple-sparing mastectomy. Obesity, smoking, diabetes mellitus, and immediate breast reconstruction have been identified as risk factors of NAC necrosis. The current study examined the correlation between NAC necrosis and nipple volume. Materials and methods A total of 83 patients who underwent NSM for primary breast cancer from January 2016 to December 2019 were retrospectively analyzed. Nipple volume was determined using the formula: volume (mm 3 ) = length × width × height (mm), with measurements determined using contrast-enhanced magnetic resonance imaging. Total and partial NAC necrosis was defined as full-thickness necrosis requiring surgical procedures and epidermal necrosis managing local wound care, respectively. Results NAC necrosis was observed in 30 patients (36%), with 3 and 27 patients having total and partial necrosis, respectively. Large nipple volume (56% vs. 24%, p  = 0.006), as well as smoking and immediate breast reconstruction (57 vs. 28%, p  = 0.017; 48% vs. 20%, p = 0.009, respectively), were significantly correlated with NAC necrosis. Multivariate analysis identified nipple volume as an independent risk factor for NAC necrosis (OR, 3.75; 95% CI, 1.23–11.44; p  = 0.02). Smoking (OR, 4.68; 95% CI, 1.37–15.94; p  = 0.014) and immediate breast reconstruction (OR, 3.43; 95% CI, 1.05–11.23; p  = 0.042) were also independently associated with NAC necrosis. Conclusions This study suggested that a large nipple volume could be one of the risk factors for NAC necrosis following NSM.