Large Cell Neuroendocrine Carcinoma of Gallbladder: A Case Report.

Large cell neuroendocrine carcinoma of the gallbladder is an extremely rare tumour with aggressive behaviour and a bad prognosis. Here, we report a case of a 65-year-old lady suspected of carcinoma of the gallbladder and underwent extended cholecystectomy. The histopathology report revealed neuroendocrine carcinoma of a large cell type of gall bladder infiltrating the liver and three periportal and pericholedochal lymph nodes. She had an uneventful perioperative period and was doing good till 6 months of follow-up. The only potentially curative treatment for large cell neuroendocrine carcinoma of the gallbladder is aggressive surgical resection, owing to its aggressive behaviour and bad prognosis. Keywords: carcinoma; case reports; cholecystectomy; gallbladder.

[Large cell carcinoma of the lung with null immunophenotype: Case report & brief review]. / Carcinoma de células grandes de pulmón con inmunofenotipo nulo: reporte de caso y revisión breve de la literatura.

Large cell carcinoma of the lung with null-immunophenotype (LCC-NI) is a diagnostic entity that is especially uncommon now as it does not have any type of cell differentiation or its own molecular alterations. It presents an exceptional diagnostic challenge; indeed, the diagnosis is only possible with complete surgical excision and adequate immunohistochemical and molecular studies. We report the case of a 69-year-old male, with a history of long-term smoking who presented with pleuritic pain. A tumor in the upper lobe of the right lung was detected and removed by lobectomy. Histopathology revealed a neoplasm with large cell morphology without any specific immunophenotype, molecular or genomic rearrangements through next-generation sequencing (NGS) studies, which was diagnosed as LCC-NI.

Spontaneous histological transformation of lung squamous-cell carcinoma to large cell neuroendocrine carcinoma and small cell lung cancer.

BACKGROUND: Histopathological transformation between different types of lung cancer cells has been reported following a variety of anti-tumor treatments. Examples include transformation from lung adenocarcinoma to squamous-cell carcinoma (SCC) and transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC). CASE REPORT: A patient with intermittent hemoptysis for 2 days underwent a computed tomography (CT) scan that revealed interstitial pneumonia in addition to two enlarged paratracheal lymph nodes: one on the right (4R) and one on the left (4L) measuring 10 and 7 mm in diameter, respectively (Fig. 1). There was no evidence of a lung or bronchial mass. Bronchoscopy identified an endoluminal primary mass in a superior segmental bronchus of the left lower lobe and pathological examination following surgery confirmed it to be SCC. At 15 months post operation, a CT scan detected that the 4R lymph node had increased in size from 10 to 16 mm in diameter. At the next follow-up 7 months later, a CT scan showed that the R4 lymph node had further increased in size from 16 to 40 mm in the short axis, making it difficult for a surgeon to resect it "en bloc" immediately. The maximum standardized uptake value was 7.5 on PET-CT images. One month following completion of one cycle of neoadjuvant chemotherapy with gemcitabine and nedaplatin, a further CT scan indicated that the lymph node had decreased in size from 40 to 30 mm in the short axis. A complete mediastinal lymphadenectomy via open thoracotomy was performed and the lymph node was resected. Histological examination identified a main large cell neuroendocrine carcinoma (LCNEC) component with a small fraction of small cell carcinoma, confirmed by immunohistochemical analysis and genetic evidence. CONCLUSION: Histopathological transformation from SCC to LCNEC with a small fraction of SCLC may have occurred spontaneously without any treatment.

[A Case of Long-Term Remission with Surgical Therapy and Chemoradiotherapy for a Rapidly Increasing Large Cell Neuroendocrine Carcinoma(LCNEC)].

BACKGROUND: Large cell neuroendocrine carcinoma(LCNEC)is a relatively rare disease classified as a subtype of neuroendocrine tumor. LCNEC has clinical and histological similarities to small cell lung cancer, both of which have a similarly poor prognosis. There are also unclear points regarding treatment. CASE: 43-years-old, male. He had repeated intermittent fever from 1 month before the consultation. Cough appeared 4 days before the consultation, and the family doctor pointed out an abnormal shadow in the right lung field, and the patient was referred. Blood test showed increased CRP 1.34 mg/dL and mild inflammatory response. Chest CT showed an increased tumor with a major axis of 16 cm in the right thoracic cavity compared to 6 months ago. FDG-PET showed accumulation of SUVmax 11.83 in the same area. A CT-guided needle biopsy was performed, and although tumor cell hyperplasia of like a plasma cells was suspected, but most of them were coagulative necrotic images and could not be diagnosed. After hospitalization, fever continued and the general condition became poor, so surgery was performed for the purpose of diagnostic treatment. Preoperatively, Interventional Radiology was used to embolize the tumor-feeding blood vessels. Intrathoracic tumor resection and partial upper and lower lobe resection were performed under thoracotomy. Postoperative histopathological examination revealed that large round to polyhedron tumor cells proliferated in sheet-like or intercellular binding sparsely, and synaptophysin was positive, which was a diagnosis of large cell neuroendocrine cell carcinoma. The general condition improved promptly after the operation, and the patient was discharged 14 days after the operation without any complications. After discharge, 4 courses of adjuvant chemotherapy (CDDP plus CPT-11)were performed. Six months after the operation, the disseminated nodule recurred in the right thoracic cavity. Chemotherapy(CBDCA plus PTX plus BEV)and radiation therapy were performed and the patient was in remission. It has been 5 years since the operation and has not recurred. SUMMARY: We report a case of rapidly increasing LCNEC with long-term remission by surgical treatment and chemoradiotherapy, with some review of the literature.

Different Characteristics and Survival between Surgically Resected Pure and Combined Pulmonary Large Cell Neuroendocrine Carcinoma.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) is a rare high-grade neuroendocrine carcinoma of the lung. Little is known about the differences between the pure and combined LCNEC subtypes, and thus we conducted this study to provide more comprehensive insight into LCNEC. METHODS: We reviewed 221 patients with pure LCNEC (P-LCNEC) and 120 patients with combined LCNEC (C-LCNEC) who underwent pulmonary surgery in our hospital to compare their clinical features, driven genes' status (EGFR/ALK/ROS1/KRAS/BRAF), and adjuvant chemotherapy regimens. Propensity score matching (PSM) was applied to reduce selection bias. RESULTS: The P-LCNEC group included a higher proportion of males and smokers than the C-LCNEC group. Furthermore, the C-LCNEC group had higher incidences of visceral pleural invasion (VPI), EGFR mutation and ALK rearrangement compared with the P-LCNEC group. Expression of neuroendocrine markers (CD56, CGA, and SYN) and recurrence patterns were not significantly different between the two groups. The P-LCNEC group had better disease-free survival (DFS) and overall survival (OS) compared with the C-LCNEC group (median DFS: 67.0 vs. 28.1 months, p = 0.021; median OS: 72.0 vs. 45.0 months, p = 0.001), which was further confirmed by the PSM method (p = 0.004 and p < 0.001, respectively). Adjuvant chemotherapy was also an independent factor for DFS and OS. Subgroup analysis found that regardless of whether it was for the entire LCNEC group or the P- and C-LCNEC subtypes, the small cell lung cancer (SCLC) regimens presented with superior survival compared with the non-small cell lung cancer (NSCLC) regimens. CONCLUSION: P-LCNEC was associated with more favorable prognosis compared with C-LCNEC. SCLC-based adjuvant chemotherapy was more appropriate for LCNEC patients than NSCLC-based regimens, regardless of whether they were the pure or combined LCNEC subtypes. C-LCNEC patients may be the potential beneficiary of targeted therapy.

Long-term outcomes after video-assisted thoracoscopic surgery in pulmonary large-cell neuroendocrine carcinoma.

BACKGROUND: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare subtype of lung cancer with dismal prognosis. Long-term outcomes after primarily video-assisted thoracoscopic surgery (VATS) have not yet been described in LCNEC. This study aims to determine overall survival and recurrence-free survival after VATS as well as to identify prognostic factors for survival and recurrence. METHODS: Data were obtained from a prospective institutional database. Kaplan-Meier estimates of overall survival and recurrence-free survival were determined and compared across prognostic factors using log-rank analysis and the Cox proportional hazards model. RESULTS: Data from 82 consecutive patients undergoing surgical resection from 2009 to 2020 were included. All patients underwent surgical resection with curative intent, of whom 96.3% were by a VATS approach. Morbidity was low without any conversions or 30-day mortality. Lobectomy was performed in 87.8% of patients, followed by wedge resection in 4.9% and segmentectomy in 3.7%. No pneumonectomies were performed. Radical resection (R0) was achieved in 97.6%. Thirty-four patients (41.5%) had adjuvant platinum-based chemotherapy and high proportion completed at least four series (76.7%). The mean follow-up was 5.1 years. The 1-year, 3-year, and 5-year overall survival rates were 86%, 54%, and 45%, while the corresponding recurrence-free survival rates were 67%, 45%, and 35%. Advanced age was an independent predictor of poor overall survival (HR 2.08; 95% CI 1.04-4.17; p = 0.038). CONCLUSION: A 96.3% VATS rate was feasible in LCNEC and associated with a low morbidity rate and a high compliance with adjuvant chemotherapy. Overall survival and recurrence-free survival was comparable to previous series using thoracotomy.

Combined large cell neuroendocrine carcinoma: clinical characteristics, prognosis and postoperative management.

OBJECTIVES: Combined large cell neuroendocrine carcinoma (C-LCNEC) is pulmonary large cell neuroendocrine carcinoma (LCNEC) mixed with other components, such as adenocarcinoma (AD) and squamous cell carcinoma (SCC). This study aimed to describe the distinct features between C-LCNEC with different components and explore the treatment strategy. METHODS: We retrospectively collected data of 96 C-LCNEC patients who underwent surgical resection. Propensity score matching was used to balance baseline characteristics of LCNEC combined with AD (LCNEC/AD) and LCNEC combined with SCC (LCNEC/SCC). RESULTS: In our final cohort, 71 (74%) were LCNEC/AD, while 25 (26%) were LCNEC/SCC. LCNEC/AD was more likely to occur in female, younger adults, with visceral pleural invasion and with driver gene expression. However, there was no significant difference in disease-free survival and overall survival between the 2 groups (before matching: P = 0.79 and P = 0.85; after matching: P = 0.87 and P = 0.48), while adjuvant chemotherapy (P = 0.019 and P = 0.043) was an independent predictor. C-LCNEC patients of stage II or III receiving adjuvant chemotherapy had longer disease-free survival and overall survival (P = 0.054 and P = 0.025), and the benefit of etoposide-based chemotherapy was greater than the other regimens (P = 0.010 and P = 0.030). EGFR and ALK mutations were present in 28% (17/60) and 7% (4/60) of C-LCNEC patients, respectively, and they responded well to targeted therapy. CONCLUSIONS: LCNEC/AD was the most common type of C-LCNEC, and there were many differences between different combined components. Adjuvant chemotherapy, especially etoposide-based chemotherapy, was a beneficial option for resected C-LCNEC.Subj collection: 152.

Multiple large cell neuroendocrine carcinomas in the rectum and descending colon presented with liver metastasis: A case report.

Colorectal large cell neuroendocrine carcinoma (LCNEC) is rare and multiple LCNECs have not been previously reported. We encountered a case of multiple LCNECs in the rectum and the descending colon. A 66-year-old man presented with anal pain. Colonoscopy showed an ulcerated infiltrating tumor in the rectum, and 0.5 cm of erosion in the descending colon. A biopsy revealed LCNEC in both regions. Abdominal computed tomography revealed irregularly enhanced wall thickening at the rectum and hepatic metastases. Due to the diagnosis of LCNEC, laparoscopic abdominoperineal resection of the rectum was performed. Histopathological examination showed a poorly differentiated, LCNEC in both regions. Immunohistochemical examination demonstrated that the tumor cells were positive for chromogranin and synaptophysin. LCNEC was confirmed, and systemic chemotherapy with cisplatin/irinotecan was initiated. To our knowledge, this is the first case report that describes multiple LCNECs in the rectum and descending colon.

Management of Primary Hepatopancreatobiliary and Ampulla Large Cell Neuroendocrine Carcinoma.

Background: Large cell neuroendocrine carcinoma (LCNEC) of the liver, gallbladder, pancreas, and ampulla is rare and usually arises in case reports, and thus to date, no studies have well described the treatment options and outcomes of those patients. Methods: The data of 108 patients diagnosed as hepatopancreatobiliary and ampulla LCNEC between 2004 and 2015 were retrieved from the surveillance, epidemiology, and final results. Results: In the entire cohort, the median overall survival (OS) was 10 months. For nonmetastatic patients, the median OS was 32 months for surgery of the primary tumor alone (n = 17), 19 months for surgery of the primary tumor and adjuvant therapy (n = 19), and 1 month for nonsurgical treatment (n = 8). For metastatic patients, the median OS was 14 months for patients who received surgery of the primary tumor with and without adjuvant therapy (n = 16), 9 months for patients undergoing adjuvant treatment alone (n = 30), and 1 month for patients who had no treatment (n = 16). Multivariate analysis revealed that surgery of the primary tumor was an independent factor for improved survival. Conclusions: This disease offers a very poor prognosis despite aggressive treatment. Radical resection is the first choice for resectable tumors, whereas surgical resection of the primary tumor plus adjuvant therapy might represent a valid option for metastatic disease. However, further studies are needed to confirm this.

[Correlation Analysis of Serum LDH Concentration before and after Operation and Prognosis of Large Cell Neuroendocrine Lung Cancer Patients].

BACKGROUND: Studies have shown that elevated serum lactate dehydrogenase (LDH) concentration can lead to poor prognosis in patients with small cell lung cancer and lung adenocarcinoma, but its relationship with the prognosis of patients with lung large-cell neuroendocrine carcinoma (L-LCNEC) is not clear. This study aims to explore the influence of L-LCNEC preoperative serum LDH concentration and postoperative LDH concentration change trend on the disease-free survival (DFS) of patients after surgery, so as to judge the clinical prognosis of L-LCNEC provides new ideas. METHODS: Collected the clinical data. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value, while the Kaplan-Meier and Cox proportional hazard model were used to analyze data. RESULTS: DFS was shortened in patients with high serum LDH concentration before operation and increased LDH concentration after operation (P<0.001, P<0.001). The preoperative LDH concentration and postoperative LDH concentration change trend were independent prognostic factors for patients (P<0.001, P=0.037). CONCLUSIONS: Preoperative LDH concentration and its postoperative concentration change trend in patients with L-LCNEC are independent prognostic factors for DFS of patients.

Prognostic value of the preoperative lymphocyte-to-monocyte ratio for survival after lung cancer surgery.

BACKGROUND: The aim of this study was to assess the effect of the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio on overall survival and disease-free survival in patients with lung cancer treated with radical surgery. METHODS: We performed a retrospective review of patients with lung cancer who prospectively underwent radical resection between 2004 and 2012. Blood samples were taken as part of the preoperative workup. The inflammatory markers studied were absolute values of lymphocytes, monocytes, neutrophils and platelets, with subsequent calculation of ratios. Median follow-up was 52 months. RESULTS: Two hundred and sixty-eight patients underwent surgery, of whom 218 (81.3%) were men. Mean age was 62.9 ± 8.7 years. A lymphocyte-to-monocyte ratio ≥ 2.5 was independently associated with longer disease-free survival (hazard ratio [HR] 0.476 (0.307-0.738), p = 0.001) and longer overall survival (HR, 0.546; 95% CI: 0.352-0.846; p = 0.007), in models adjusted for age, sex, stage, and type of resection. No other systemic inflammatory marker showed a significant association. CONCLUSION: Preoperative LMR is an independent prognostic factor of overall survival and recurrence-free survival in patients with surgically-resected early stage lung cancer.

Genetic Polymorphisms in Activating Transcription Factor 3 Binding Site and the Prognosis of Early-Stage Non-Small Cell Lung Cancer.

BACKGROUND: Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery. METHODS: A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated. RESULTS: Among those SNPs, HAX1 rs11265425T>G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00-1.69, p = 0.05), and ME3 rs10400291C>A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46-0.95, p = 0.03). Regarding HAX1 rs11265425T>G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding ME3 rs10400291C>A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher HAX1 promoter activity than T allele. HAX1 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, ME3 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes. CONCLUSIONS: In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, HAX1 rs11265425T>G and ME3 rs10400291C>A are associated with the clinical outcomes of patients in surgically resected NSCLC.

Survival outcomes of surgery in patients with pulmonary large-cell neuroendocrine carcinoma: a retrospective single-institution analysis and literature review.

BACKGROUND: Pulmonary large-cell neuroendocrine carcinoma (pLCNEC) is a very rare malignancy originating from the lung and bronchus, and its biological behaviour, clinical diagnosis, treatment and prognosis are poorly understood. Thus, the clinical characteristics and surgical treatment-related prognostic factors of this rare disorder must be explored. RESULTS: The clinical data of 59 patients (48 males and 11 females) who were treated by surgery and diagnosed with pLCNEC by postoperative pathology at Peking Union Medical College Hospital from April 2004 to April 2019 were analysed retrospectively. The median patient age was 62 years (38-79 years), and the median duration of disease was 2 months (0.5-18 months). Compared with other lung malignancies, pLCNEC lacks specific clinical symptoms and imaging features, and preoperative biopsy pathology is often insufficient to confirm the diagnosis. The corresponding numbers of patients who were classified into stages I, II, III and IV according to the postoperative pathological tumour-nodal-metastasis stage were 25, 12, 15 and 7, respectively. The median overall survival was 36 months (0.9-61.1 months). The 1-year, 3-year and 5-year survival rates were 76.3%, 49% and 44.7%, respectively. The tumour stage exerted a significant effect on survival (Cox multivariate analysis p < 0.05). CONCLUSIONS: For patients with resectable pLCNEC, multidisciplinary therapy based on surgery may have good survival benefits, and tumour stage is an independent risk factor for the prognosis of pLCNEC.

Impact of waiting times on tumour growth and pathologic upstaging in patients with non-small cell lung cancer having lung resection.

OBJECTIVE: There are limited data on tumour growth or pathologic upstaging in patients with early-stage lung cancer awaiting lung resection. We aimed to evaluate whether waiting times on the current lung cancer treatment pathway were associated with significant tumour growth or pathologic upstaging. METHODS: This is a retrospective observational study of a consecutive series of patients with early-stage, non-small cell lung cancer who underwent resection for lung cancer. The difference between tumour size at diagnostic and preoperative computed tomography (CT) scans was calculated. Significant tumour growth was defined as a diameter increase of ⩾5 mm or ⩾20%. The time intervals between baseline and repeat CT (CT-int) and between baseline CT and date of surgery (Surg-int), as well as other potential clinical and pathologic prognostic factors, were compared between upstaged and nonupstaged patients. RESULTS: There were 121 patients identified. Fifty-four patients (44.6%) had tumour growth ⩾5 mm and 27 patients (22%) had tumour growth ⩾20%. Median CT-int and Surg-int were 2.4 and 2.6 months, respectively. Forty-four patients (36%) were upstaged at surgery due to new lymph node involvement (n = 19), pleural invasion (n = 12), satellite nodules (n = 4), or increase in tumour diameter (n = 9). There was a marginal, but statistically insignificant, difference in median CT intervals in patients who had tumour growth <20% vs ⩾20% at 2.4 vs 2.6 months (p = 0.06). CONCLUSION: Current cancer pathway waiting times are not associated with significant tumour growth or pathologic upstaging in this cohort.

Prognostic impact of peripheral blood neutrophil to lymphocyte ratio in advanced-stage pulmonary large cell neuroendocrine carcinoma and its association with the immune-related tumour microenvironment.

BACKGROUND: The prognostic value of the neutrophil-to-lymphocyte ratio (NLR) with large cell neuroendocrine carcinoma (LCNEC) patients remains unclear. Thus, we performed a retrospective study to examine the relationship between the pretreatment NLR and clinical outcome in advanced LCNEC patients and the impact of the immune-related tumour microenvironment (TME). METHODS: This retrospective study included 63 advanced LCNEC patients who had received chemotherapy. We collected clinical data and investigated the TME status (CD4, CD8, CD20 and FOXP3). RESULTS: The overall survival of the patients with a low NLR (<5) was significantly longer than those with a high NLR (≥5) (14.9 vs. 5.2 months; p < 0.001). A multivariate analysis identified a high NLR as a predictor of a poor prognosis (HR, 3.43; 95% CI, 1.73-6.79; p < 0.001). The NLR was inversely correlated with tumoural and stromal CD8-positive tumour-infiltrating lymphocytes (tumoural: r = -0.648, p = 0.005, stromal: r = -0.490, p = 0.046). CONCLUSIONS: A high NLR was associated with a poor prognosis in advanced LCNEC patients. Our study revealed that the NLR can reflect the TME, at least in part, suggesting that the NLR plays an important role not only as a clinical outcome predictor but also as a tumour immune status indicator.

Application of contrast-enhanced ultrasonography for large cell neuroendocrine carcinoma in the urinary bladder: a case report.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is an uncommon malignant bladder tumor, and the overall prognosis is poor. Contrast-enhanced ultrasound (CEUS) provides a new effective modality for tumor detection and diagnosis. CASE PRESENTATION: A 30-year-old man complained of repeated painless gross haematuria for half a month. Conventional ultrasound demonstrated a hypoechoic solitary lesion with hyperechoic margins measuring 3.4 × 3.1 cm in the anterior wall of the bladder. Superb microvascular imaging (SMI) showed a strong flow signal in the mass. CEUS revealed that the lesion was characterized by hyper-enhancement in the early phase and hypo-enhancement in the late phase. The entire bladder wall was disrupted by homogeneous hyper-enhanced tumor tissue on CEUS. Time-intensity curves (TICs) showed a rapid wash-in with a high maximum signal intensity (SI) and quick wash-out. Finally, partial cystectomy was performed and the pathological examination confirmed the diagnosis of LCNEC with invasion into the whole layer of the bladder wall. CONCLUSION: This case suggested that CEUS was a valuable imaging method to detect and diagnose LCNEC in the bladder, and that CEUS can provide information related to the depth of wall invasion and the microvasculature.

The role of postoperative radiotherapy (PORT) in pulmonary large cell neuroendocrine carcinoma (PLCNEC).

PURPOSE: To assess the long-term survivals and related prognostic indicators of patients with pulmonary large cell neuroendocrine carcinoma (PLCNEC), and determine the prognostic value of post-operative radiotherapy in PLCNEC. MATERIALS AND METHODS: Patients diagnosed with PLCNEC between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were included in our study. Cox proportional hazard model was used to evaluate the factors related to overall survival (OS). Propensity score matching analysis (PSM analysis) was used to balance the variables differences between postoperative radiotherapy (PORT) and non-PORT groups. RESULTS: A total of 701 postoperative cases were identified, with the median follow-up time of 23 months. The 3- and 5-year OS were 50.7%, and 41.2%, respectively. Multivariate analysis revealed that stage I (P<0.001), age <65 years old (P<0.001), chemotherapy (P<0.001) were independent favorable prognostic factors. There is no significant difference in survival between patients with or without postoperative radiotherapy (PORT) after PSM analysis (P=0.489). No survival benefit in favor of PORT were displayed, even when subgroups were deeply analyzed. CONCLUSIONS: Age, stage, and chemotherapy were significantly associated with OS of patients with resected PLCNEC. However, PORT after resection did not improve long-term outcome of PLCNEC patients.