Background The mammalian Notch family ligands delta‐like 3 (DLL3) is reported to be a potential therapeutic target for large cell neuroendocrine carcinomas (LCNEC). The effect of DLL3 expression on LCNEC prognosis has not yet been elucidated. Methods We reviewed the medical records of 70 LCNEC patients undergoing surgical resection between 2001 and 2015 using a prospectively maintained database. We performed immunohistochemistry for DLL3 and investigated the correlation between the sensitivity of LCNEC to platinum‐based adjuvant chemotherapy. Results DLL3 expression was positive in 26 (37.1%) LCNEC patients. A total of 23 patients (32.9%) received platinum‐based adjuvant chemotherapy. Among patients with DLL3 expression‐positive tumors, no difference was found in the five‐year overall survival (OS) or recurrence‐free survival (RFS) between patients with and without adjuvant chemotherapy (surgery + chemotherapy vs. surgery alone, five‐year OS: 58.3% vs. 35.7% P = 0.36, five‐year RFS: 41.7% vs. 35.7% P = 0.74). In contrast, among patients with DLL3‐negative tumors, significantly greater five‐year OS and RFS rates were observed for patients with adjuvant chemotherapy than for those without it (surgery + chemotherapy vs. surgery alone: five‐year OS: 90.0% vs. 26.9% P<0.01, five‐year RFS: 80.0% vs. 21.7% P < 0.01). A multivariate analysis for the RFS revealed that adjuvant chemotherapy was a significant independent prognostic factor among patients with DLL3‐negative tumors (hazard ratio [HR]: 0.05, 95% confidence interval [CI]: 0.01–0.41, P < 0.01), although it was not a factor among patients with DLL3‐positive tumors (HR: 0.73, 95% CI: 0.23–2.27, P = 0.58). Conclusions Our results revealed that DLL3 is a predictive marker of sensitivity to platinum‐based adjuvant chemotherapy for LCNEC. Key points Significant findings of the study DLL3 was a predictive marker of sensitivity to platinum‐based adjuvant chemotherapy for LCNEC. Among patients with DLL3 expression‐negative LCNEC, platinum‐based adjuvant chemotherapy significantly improved the OS and RFS, although it did not do so among patients with DLL3 expression‐positive LCNEC. What this study adds Our results suggest that DLL3 expression‐positive LCNEC may be better treated with other types of adjuvant chemotherapy, such as the anti‐DLL3 therapies if these effects are confirmed by ongoing clinical research.

The diagnosis of mesothelioma in situ (MIS) is challenging with conventional diagnostic approaches.Although recent advances in genomic-based assays have made it possible to diagnose MIS, the prognosis, treatment indications, and prognostic factors remain unclear. Previous reports have shown that MIS progresses to invasive mesothelioma; however, to the best of our knowledge, progression to sarcomatoid mesothelioma has not yet been reported. A 73-year-old man was diagnosed with MIS associated with methylthioadenosine phosphorylase (MTAP) loss and a CDKN2A homozygous deletion. Strikingly, pathological examination revealed that the MIS lesion had progressed to sarcomatoid mesothelioma. In analyses of previously reported cases and our case, MIS with a CDKN2A homozygous deletion or MTAP loss progressed to invasive mesothelioma earlier than that without them, indicating that a CDKN2A homozygous deletion and MTAP loss could be poor prognostic factors. Genomic analyses might be useful for predicting the prognosis of MIS and contributing to an optimal treatment.

EWSR1‐CREM gene fusions were recently discovered in several mesenchymal and epithelial tumors, including myxoid mesenchymal tumors of the central nervous system, rare cases of soft tissue clear cell sarcoma and angiomatoid fibrous histiocytoma, and hyalinizing clear cell carcinoma, which implicates the potential phenotypic diversities of tumors harboring an EWSR1‐CREM fusion. We herein present an exceedingly indolent pulmonary mesenchymal tumor showing distinctive clinicopathological features. This tumor histologically displayed a small nest and alveolar pattern consisting of monomorphic clear cells intermingled with dilated anastomosing vasculature. Immunophenotypically, tumor cells were positive for vimentin and focally positive for synaptophysin, but negative for many immunohistochemical panels including keratins, EMA, desmin, mesothelial markers, melanotic markers, smooth muscle actin, inhibin and S‐100 protein. Interestingly, RNA sequencing identified an in‐frame EWSR1‐CREM fusion, which was confirmed by subsequent real‐time/reverse transcription polymerase chain reaction and fluorescence in situ hybridization assay. Clinical follow‐up showed no evidence of recurrence and metastasis. Our pathological findings further expand the phenotypic spectrum of tumors associated with EWSR1‐CREM fusions, implying the emergence of a possible novel tumor entity.

OBJECTIVES Despite significant advances in surgical techniques, including thoracoscopic approaches and perioperative care, the morbidity rate remains high after lung resection. This study focused on a low attenuation cluster analysis, which represented the size distribution of pulmonary emphysema and assessed its utility for predicting postoperative pulmonary complications after thoracoscopic lobectomy. METHODS From April 2013 to September 2018, lung cancer patients who received spirometry and computed tomography (CT) before surgery and underwent thoracoscopic lobectomy were included. The cumulative size distribution of the low attenuation area (LAA, defined as ≤−950 Hounsfield unit on CT) clusters followed a power-law characterized by an exponent D-value, a measure of the complexity of the alveolar structure. D-value and LAA% (LAA/total lung volume) were calculated using preoperative 3-dimensional CT software. The relationship between pulmonary complications and patient characteristics, including D-value and LAA%, was investigated. RESULTS Among 471 patients, there were 61 respiratory complication cases (12.9%). Receiver operation characteristic curve analysis revealed that the best predictive cut-off value of D-value and LAA% for pulmonary complications was 2.27 and 16.5, respectively, with an area under the curve of 0.72 and 0.58, respectively. D-value was significantly correlated with % forced expiratory volume in 1 s. Per univariate analysis, gender, smoking history, forced expiratory volume in 1 s/forced vital capacity, LAA% and D-value were risk factors for predicting postoperative pulmonary complications. In the multivariate analysis, D-value remained a significant predictive factor. CONCLUSION Preoperative assessment of emphysema cluster analysis may represent the vulnerability of the operated lung and could be the novel predictor for pulmonary complications after thoracoscopic lobectomy.

OBJECTIVES Segmentectomies such as S1 + 2, S1 + 2+3 and S4 + 5 segmentectomy are used to treat patients with non-small-cell lung cancer (NSCLC) in the left upper lobe. However, the preservable lung volume and changes after such segmentectomies remain unknown. We compared the residual pulmonary function after thoracoscopic segmentectomy or lobectomy in the left upper lobe and examined the efficacy of S1 + 2 segmentectomy regarding postoperative pulmonary function. METHODS Patients with left upper lobe NSCLC who underwent thoracoscopic segmentectomy or lobectomy were included. Spirometry and computed tomography were performed before and 6 months after resection, and the ipsilateral preserved lobe volume was calculated using 3-dimensional computer tomography. The percentage of postoperative/preoperative forced expiratory volume in 1 s and actual/predicted regional forced expiratory volume in 1 s (preservation rate) in the residual lobe were compared. RESULTS Eighty-eight patients underwent lobectomy and 70 patients underwent segmentectomy (23 S1 + 2, 35 S1 + 2+3 and 12 S4 + 5 segmentectomies). The percentage of postoperative/preoperative forced expiratory volume in 1 s was 97 in S1 + 2, 82 in S1 + 2+3, 86 in S4 + 5 segmentectomy and 73 in left upper lobectomy, indicating that segmentectomy could be a meaningful approach to preserve pulmonary function. The preservation rate was 83% in S1 + 2 and 62% in S1 + 2+3 segmentectomy and was significantly higher in S1 + 2 than in S1 + 2+3 segmentectomy (P &lt; 0.001). CONCLUSIONS Postoperative pulmonary function and the preservable lung volume of the residual lobe after thoracoscopic S1 + 2 segmentectomy were well-preserved among other segmentectomies and lobectomy. Thoracoscopic S1 + 2 segmentectomy is a good alternative for preserving postoperative function.