First-line selpercatinib for a patient with RET fusion-positive pulmonary large cell neuroendocrine carcinoma.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is an uncommon variant of non-small cell lung cancer (NSCLC), known for its aggressive behavior. This includes rapid progression, widespread metastases, and resistance to conventional chemotherapy, all of which contribute to a dismal prognosis. Consequently, managing pulmonary LCNEC remains a significant challenge. In this case report, we describe the successful use of selpercatinib, RET (rearranged during transfection) kinase inhibitor, as a first-line treatment in a patient with advanced pulmonary LCNEC harboring a RET fusion gene. Although RET fusion genes are exceedingly rare in pulmonary LCNEC, this case underscores the importance of early genetic testing in patients with pulmonary LCNEC to tailor targeted therapies effectively.

Large-cell neuroendocrine carcinoma of the bladder: A case report.

BACKGROUND: Bladder neuroendocrine tumors are few and exhibit a high degree of aggressiveness. The bladder is characterized by four distinct forms of neuroendocrine tumors. Among them, large-cell neuroendocrine carcinoma is the least prevalent, but has the highest level of aggressiveness. The 5-year survival rate for large-cell neuroendocrine carcinoma of the bladder is exceedingly poor. To date, only a few dozen cases have been reported. CASE SUMMARY: Here, we report the case of a 65-year-old man with large-cell neuroendocrine carcinoma of the bladder. The patient presented to the Department of Urology at our hospital due to the presence of painless hematuria without any identifiable etiology. During hospitalization, abdominal computed tomography revealed the presence of an irregular mass on the right anterior wall of the bladder. A cystoscopic non-radical resection of the bladder lesion was performed. The postoperative pathological examination revealed large-cell neuroendocrine bladder cancer. Previous reports on cases of large-cell neuroendocrine carcinoma cases were retrieved from PubMed, and the present paper discusses the currently recognized best diagnostic and treatment options for large-cell neuroendocrine carcinoma based on the latest research progress. CONCLUSION: Large-cell neuroendocrine carcinoma of the bladder is an uncommon malignancy with a highly unfavorable prognosis. Despite ongoing efforts to prolong patient survival through multidisciplinary therapy, the prognosis remains unfavorable. Large-cell neuroendocrine carcinoma continues to be a subject of uncertainty.

Tarlatamab for Large Cell Neuroendocrine Carcinoma in a Young Adult: A Case Report.

A 20-year-old man with metastatic large cell neuroendocrine carcinoma of the lung was treated with the delta-like ligand 3-targeting bispecific T cell engager, tarlatamab. Treatment was complicated by transient cytokine release syndrome but resulted in a partial response. Bispecific T cell engagers may offer a novel treatment approach for large cell neuroendocrine carcinoma of the lung.

The prognostic analysis and a machine-learning based disease-specific survival state model in pulmonary large-cell neuroendocrine carcinomas.

Background: Pulmonary large-cell neuroendocrine carcinoma (PLCNEC) is a rare and highly malignant lung cancer. Due to the paucity of data from clinical studies, its clinical characteristics and treatment remain controversial. The present study explored factors influencing the prognosis and survival outcomes of patients with PLCNEC and developed a dependable prognostic model using machine learning. Methods: The clinical data of PLCNEC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2020. A total of 2,897 PLCNEC patients were enrolled and univariate and multivariate Cox regression analyses were performed to explore independent prognostic factors for disease-specific survival (DSS). Ten machine learning algorithms were utilized to predict the 2-year survival. The clinicopathological data collected from The First Affiliated Hospital of Sun Yat-sen University between 2010 and 2022 were used to test the trained machine. Results: Sex [hazard ratio (HR) 1.168, 95% confidence interval (CI): 1.063-1.284], age (HR 1.262, 95% CI: 1.144-1.391), surgery (HR 0.481, 95% CI: 0.413-0.559), chemotherapy (HR 0.450, 95% CI: 0.404-0.501), bone metastasis (HR 1.284, 95% CI: 1.124-1.466), brain metastasis (HR 1.167, 95% CI: 1.023-1.331), liver metastasis (HR 1.223, 95% CI: 1.069-1.399), American Joint Committee on Cancer-Node (AJCC-N), and tumor stage were independent prognostic factors. The gradient boosting decision tree (GBDT) performed better than other models, with an F1-score of 0.791 and an area under the curve of 0.831. Conclusions: Male, age ≥65 years, distant metastasis to the bone, liver, and brain are associated with a worse prognosis in PLCNEC patients, while surgery and chemotherapy are associated with improved prognosis. GBDT showed promising performance in predicting 2-year survival, which can serve as a valuable reference for clinical diagnosis and treatment of PLCNEC.

Perioperative serplulimab­based chemoimmunotherapy in stage IV large cell neuroendocrine carcinoma of the lung: A case report.

Large cell neuroendocrine carcinoma (LCNEC) is a rare and enigmatic tumor, characterized by neuroendocrine features and a poor prognosis similar to small cell lung cancer (SCLC). The present report details the case of a 45-year-old male with oligometastatic stage IV LCNEC who achieved clinical cure after undergoing perioperative immunochemotherapy. Despite the typical non-recommendation of surgery for stage IV cases, based on the insistence of the patient, the present study initiated three cycles of neoadjuvant therapy combining serplulimab (a programmed cell death protein 1 inhibitor) with chemotherapy, resulting in the radiological disappearance of the tumor. Pathological complete response was confirmed following resection of the primary tumor. The treatment continued with three cycles of adjuvant therapy using serplulimab and chemotherapy, followed by maintenance therapy with serplulimab alone. After 17 cycles of maintenance therapy, a positron emission tomography-computed tomography scan revealed a complete metabolic response of the metastasis, and radiological scans revealed no visible tumor or distant metastasis, indicating a clinical cure. Event-free survival has exceeded 11 months, and overall survival has exceeded 14 months. The present case highlights the efficacy of immunochemotherapy in treating advanced LCNEC.

Isolated Splenic Metastasis From Large-Cell Neuroendocrine Carcinoma of Lung: A Case Report.

Splenic malignancies are mostly primary and lymphocytic. Metastases to the spleen are rare and imply tumor dissemination. Limited cases were reporting isolated splenic metastasis from non-small cell cancer of the lung (NSCLC). We report the case of a 68-year-old male with mixed large-cell neuroendocrine carcinoma (LCNEC) and adenocarcinoma of the lung who presented with asymptomatic, synchronous, and isolated splenic metastasis. The patient refused adjuvant or neoadjuvant therapies. Surgical removal of both primary and metastatic lesions was achieved separately. In the scenario of isolated splenic metastasis, local consolidative therapy such as splenectomy appears to benefit survival by alleviating tumor burden. The patient is currently disease-free after one year of postoperative follow-up.

Bronchoscopic Interventional Therapy Combined With Pembrolizumab in the Treatment of Pulmonary Large Cell Neuroendocrine Carcinoma: A Case Report.

This study reports a significant clinical outcome following the use of bronchoscopic interventional therapy combined with pembrolizumab for treating pulmonary large cell neuroendocrine carcinoma (LCNEC), showcasing a novel approach in managing this aggressive cancer.

Neuroendocrine neoplasms of the thymus.

Neuroendocrine neoplasms of the thymus (tNENs), including typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma, are rare tumors with scarce clinical and pathological data available in the literature. They share many common features with neuroendocrine neoplasms in other organs, such as those in the lungs, while demonstrating some distinct clinical and pathological features. This review aims to give an updated overview of each category of tNENs, focusing primarily on the pathologic diagnosis and differential diagnosis of these tumors.

Implementing machine learning to predict survival outcomes in patients with resected pulmonary large cell neuroendocrine carcinoma.

BACKGROUND: The post-surgical prognosis for Pulmonary Large Cell Neuroendocrine Carcinoma (PLCNEC) patients remains largely unexplored. Developing a precise prognostic model is vital to assist clinicians in patient counseling and creating effective treatment strategies. RESEARCH DESIGN AND METHODS: This retrospective study utilized the Surveillance, Epidemiology, and End Results database from 2000 to 2018 to identify key prognostic features for Overall Survival (OS) in PLCNEC using Boruta analysis. Predictive models employing XGBoost, Random Forest, Decision Trees, Elastic Net, and Support Vector Machine were constructed and evaluated based on Area Under the Receiver Operating Characteristic Curve (AUC), calibration plots, Brier scores, and Decision Curve Analysis (DCA). RESULTS: Analysis of 604 patients revealed eight significant predictors of OS. The Random Forest model outperformed others, with AUC values of 0.765 and 0.756 for 3 and 5-year survival predictions in the training set, and 0.739 and 0.706 in the validation set, respectively. Its superior validation cohort performance was confirmed by its AUC, calibration, and DCA metrics. CONCLUSIONS: This study introduces a novel machine learning-based prognostic model with a supportive web-based platform, offering valuable tools for healthcare professionals. These advancements facilitate more personalized clinical decision-making for PLCNEC patients following primary tumor resection.

[Advances of Treatment of Pulmonary Large Cell Neuroendocrine Carcinoma].

Large cell neuroendocrine carcinoma (LCNEC) of lung is a rare neuroendocrine carcinoma subtype with difficulty in early diagnosis and poor prognosis which is treated with standard strategies of small cell lung cancer and non-small cell lung cancer. In recent years, the precise types of LCNEC and its response to therapy have been identified by next-generation sequencing. Some researches have also found the correlation between different subtypes of LCNEC and the efficacy of chemotherapy regimens. However, there is no consensual agreement of its therapy. Recently, immune checkpoint inhibitors (ICIs) has provided a new option for LCNEC patients based on some retrospective research data and case reports. In this review, we aimed to summarize the epidemiological characteristics, standard therapy, the advances of molecular subtypes and clinical applications of ICIs of LCNEC, so as to provide optimal systemic clinical decision-making for LCNEC patients.
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Unusual Association of Large Cell Neuroendocrine Carcinoma of the Bladder and Prostatic Adenocarcinoma Within a 76-Year-Old Man.

Large cell neuroendocrine carcinoma (LCNEC) is one of the rarest types of bladder cancer, with an aggressive course and a poor prognosis. We report a case of LCNEC of the bladder associated with a prostatic adenocarcinoma. A very rare association, to our knowledge, is described for the first time in the literature. The patient was a 76-year-old non-smoker male, who presented with intermittent hematuria and dysuria. Cystoscopy revealed a lesion on the right lateral bladder wall. Biopsy was in favor of a LCNEC with muscle invasion. The CT scan showed the presence of a second lesion in the prostate, confirmed by histological examination. The patient was treated by neoadjuvant chemotherapy of the cisplatin-etoposide type for large-cell bladder neuroendocrine carcinoma, and hormone therapy with luteinizing hormone-releasing hormone (LH-RH) analogs for prostatic adenocarcinoma, followed by radical surgery. Given the rarity of this tumor, LCNEC treatment lacks precision. Many cases are published with different therapeutic strategies. A literature review would be interesting to codify the therapeutic strategy for this rare tumor.

Metabolomic Profiling of Pulmonary Neuroendocrine Neoplasms.

BACKGROUND/OBJECTIVES: Pulmonary neuroendocrine neoplasms (NENs) account for 20% of malignant lung tumors. Their management is challenging due to their diverse clinical features and aggressive nature. Currently, metabolomics offers a range of potential cancer biomarkers for diagnosis, monitoring tumor progression, and assessing therapeutic response. However, a specific metabolomic profile for early diagnosis of lung NENs has yet to be identified. This study aims to identify specific metabolomic profiles that can serve as biomarkers for early diagnosis of lung NENs. METHODS: We measured 153 metabolites using liquid chromatography combined with mass spectrometry (LC-MS) in the plasma of 120 NEN patients and compared them with those of 71 healthy individuals. Additionally, we compared these profiles with those of 466 patients with non-small-cell lung cancers (NSCLCs) to ensure clinical relevance. RESULTS: We identified 21 metabolites with consistently altered plasma concentrations in NENs. Compared to healthy controls, 18 metabolites were specific to carcinoid tumors, 5 to small-cell lung carcinomas (SCLCs), and 10 to large-cell neuroendocrine carcinomas (LCNECs). These findings revealed alterations in various metabolic pathways, such as fatty acid biosynthesis and beta-oxidation, the Warburg effect, and the citric acid cycle. CONCLUSIONS: Our study identified biomarker metabolites in the plasma of patients with each subtype of lung NENs and demonstrated significant alterations in several metabolic pathways. These metabolomic profiles could potentially serve as biomarkers for early diagnosis and better management of lung NENs.

Pure large-cell neuroendocrine carcinoma of the ovary with a somatic BRCA1 mutation: The first reported case and the review of the literature.

Pure large-cell neuroendocrine carcinomas of the ovary are extremely rare, so there is a lack of molecular information on this type of cancer. Herein, we presented a pure primary large-cell neuroendocrine carcinomas of the ovary in a 72-year-old female with a pathogenic somatic mutation at the c.5332+1g>a splice site of the BRCA1 gene and with no TP53 mutation. She was uneventful 32 months after the operation and chemotherapies. To the best of our knowledge, this is the first report of a BRCA1 somatic mutation in the ovary large-cell neuroendocrine carcinomas. Testing BRCA1/2 mutations in patients with large ovarian cell neuroendocrine carcinomas might provide an opportunity for their future target treatments. It would expand our understanding.

Combined large­cell neuroendocrine carcinoma and small­cell lung cancer: A case report.

Combined large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) is extremely rare, with only a few reports available in the literature. An accurate diagnosis is difficult to make due to the overlapping clinical features between LCNEC and SCLC, and a standardized treatment option is lacking. A 53-year-old female patient was admitted to Xiaoshan Affiliated Hospital of Wenzhou Medical University (Hangzhou, China) due to symptoms of dyspnea and phlegm, with blood in the sputum. Computed tomography revealed a 52×32×26-mm irregular soft-tissue mass in the left upper lung. Pathological examination of the biopsy specimen showed a poorly differentiated neuroendocrine carcinoma with compression injury, consistent with a mixed type of large and small cell carcinoma. The patient was administered chemotherapy, radiotherapy and targeted therapy, and as of October 2023, the patient had a survival period of 29 months. LCNEC combined with SCLC is a sporadic tumor with a high potential for malignancy. Multidisciplinary treatment and close follow-up are recommended. The multidisciplinary treatment strategy used in the present study is expected to help inform future therapeutic decisions.

Mixed glandular neuroendocrine carcinoma of the endometrium with hypercalcemic crisis.

OBJECTIVE: To explore the ideas and research progress in diagnosing and treating hypercalcemic crisis in patients with cancer. METHODS: We reviewed the clinical data, diagnosis and treatment of hypercalcemic crisis in a patient with mixed glandular neuroendocrine carcinoma of the endometrium. RESULTS: The patient had gastrointestinal symptoms and acute renal impairment as the main manifestations, and the blood biochemical indexes suggested a hypercalcemic crisis with elevated parathyroid hormone (PTH). No lesions were seen in the parathyroid glands on imaging and nuclide imaging, but an abnormal pelvic mass was seen in the pelvis and the biopsy of the uterine cervix tissue suggested that it was an adenocarcinoma. Surgery was performed to remove the mass, and postoperative findings suggested endometrial large-cell neuroendocrine carcinoma with endometrioid adenocarcinoma. The calcium and PTH decreased to normal after surgery and chemotherapy. CONCLUSIONS: The condition of the hypercalcemia crisis is dangerous, so it is necessary to think from different aspects of the clinical diagnosis and treatment.

Establishment and Validation of Prognostic Nomograms for Patients with Metastatic Pulmonary Large Cell Neuroendocrine Carcinoma.

PURPOSE: Metastatic pulmonary large cell neuroendocrine carcinoma (LCNEC) is an aggressive cancer with generally poor outcomes. Effective methods for predicting survival in patients with metastatic LCNEC are needed. This study aimed to identify independent survival predictors and develop nomograms for predicting survival in patients with metastatic LCNEC. PATIENTS AND METHODS: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database, identifying patients with metastatic LCNEC diagnosed between 2010 and 2017. To find independent predictors of cancer-specific survival (CSS), we performed Cox regression analysis. A nomogram was developed to predict the 6-, 12-, and 18-month CSS rates of patients with metastatic LCNEC. The concordance index (C-index), area under the receiver operating characteristic (ROC) curves (AUC), and calibration curves were adopted with the aim of assessing whether the model can be discriminative and reliable. Decision curve analyses (DCAs) were used to assess the model's utility and benefits from a clinical perspective. RESULTS: This study enrolled a total of 616 patients, of whom 432 were allocated to the training cohort and 184 to the validation cohort. Age, T staging, N staging, metastatic sites, radiotherapy, and chemotherapy were identified as independent prognostic factors for patients with metastatic LCNEC based on multivariable Cox regression analysis results. The nomogram showed strong performance with C-index values of 0.733 and 0.728 for the training and validation cohorts, respectively. ROC curves indicated good predictive performance of the model, with AUC values of 0.796, 0.735, and 0.736 for predicting the 6-, 12-, and 18-month CSS rates of patients with metastatic LCNEC in the training cohort, and 0.795, 0.801, and 0.780 in the validation cohort, respectively. Calibration curves and DCAs confirmed the nomogram's reliability and clinical utility. CONCLUSION: The new nomogram was developed for predicting CSS in patients with metastatic LCNEC, providing personalized risk evaluation and aiding clinical decision-making.

Prognostic Nomogram Predicting Survival and Propensity Score Matching with Demographics and Comparative Analysis of Prostate Small Cell and Large Cell Neuroendocrine Carcinoma.

Background: This retrospective study aims to examine the patient demographics, survival rates, and treatment methods for small-cell neuroendocrine carcinoma (SCNEC) and large-cell neuroendocrine carcinoma (LCNEC) of prostate origin while also identifying the main differences between common types of prostate cancer with comparative analysis for survival. Methods: Our analysis utilized the Surveillance, Epidemiology, and End Results database (SEER), and data was collected from 2000-2020. Cox proportional hazards and chi-squared analysis were used for statistical analysis. Results: A total of 718 cases of prostate small and large neuroendocrine carcinoma were identified. The median age was 71.5 years, and the median follow-up was 11.0 years (95% confidence interval (95% CI) = 9.2-12.8). Most patients were over the age of 80 years (33.8%) and Caucasian (74.4%). The overall 5-year survival was 8.0% (95% CI = 6.8-9.2). The 5-year OS for Caucasians was 7.3% (95% C.I. 6.0-8.3). For Black Americans, the 5-year OS was 11.9% (95% C.I. 7.3-16.5). For Hispanics, the 5-year OS was 12.2% (95% C.I. 7.7-16.7). The 5-year cause-specific survival (CSS) was 16.2% (95% CI = 14.3-18.1). For treatment modality, the five-year survival for each were as follows: chemotherapy, 3.5% (95% CI = 2.1-4.9); surgery, 18.2% (95% CI = 13.6-22.8); multimodality therapy (surgery and chemotherapy), 4.8% (95% CI = 1.7-7.9); and combination (chemoradiation with surgery), 5.0% (95% CI = 1.0-9.0). The prognostic nomogram created to predict patient survivability matched the findings from the statistical analysis with a statistical difference found in race, income, housing, stage, and nodal status. The nomogram also indicated a slight increase in mortality with tumors of greater size. This analysis showed a slight increase in mortality for patients of Asian race. In addition, there was a significant increase in death for patients with stage 3 tumors, as well as patients who underwent surgery and radiation. Furthermore, we performed propensity score matching for survival differences, and no survival difference was found between SCNEC and LCNEC. Conclusions: Asian patients, larger tumor size, and distant disease were associated with worse long-term clinical outcomes. By leveraging insights from registry-based studies, clinicians can better strategize treatment options, improving patient outcomes in this challenging oncology arena.

Primary large cell neuroendocrine carcinoma of the bladder: A case report.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the bladder is a rare non-urothelial tumor of the bladder. The treatment of LCNEC of the bladder is different from that of urothelial carcinoma (UC); therefore, early and accurate diagnosis is particularly important. As LCNEC of the bladder is rare and its clinical symptoms and radiographic features are similar to those of urothelial tumors, the clinical diagnosis of the disease remains challenging. CASE SUMMARY: We report a 72-year-old female patient who presented with gross hematuria for 3 mo. A solitary tumor located in the anterior wall of the bladder was found by cystoscopy. Pathological examination after biopsy suggested UC of the bladder in the absence of immunohistochemical assessment. The patient underwent partial cystectomy and was finally diagnosed with LCNEC (pT2bN0M0) based on the results of postoperative immunohistochemical examination. During the 10-mo follow-up, no signs of tumor recurrence or metastasis were found. CONCLUSION: Immunohistochemical examination is essential for diagnosing LCNEC of the bladder. Accurate diagnosis and multidisciplinary treatment in the early stage of the disease are crucial for improving the prognosis.

An elderly case of paraneoplastic anti-NMDA receptor encephalitis associated with large cell neuroendocrine carcinoma of the lung.

BACKGROUND: Recent studies have suggested that N-methyl-D-aspartate (NMDA) receptors are involved in the cell proliferation in several tumors. However, there have been no reports demonstrating the expression of NR1 subunit of the NMDA receptor in large cell neuroendocrine carcinoma (LCNEC). CASE PRESENTATION: Here, we report the first elderly case of paraneoplastic anti-NMDA receptor encephalitis associated with LCNEC of the lung with NR1 expression. Of note, NR1 subunit expression in the tumor cells of the present case was confirmed by immunohistochemistry (IHC). Radiation therapy and immunotherapies, such as corticosteroids and intravenous immunoglobulin (IVIG), shrank the tumors and improved neurological symptoms in the present case. Additionally, we also confirmed the expression of NR1 in the tumor cells obtained from three other cases with LCNEC of the lung at our hospital by IHC. CONCLUSION: Our IHC results indicate that LCNEC generally expresses NR1 subunit and NMDA receptor may be involved in the tumor development and growth.

Endometrial large cell neuroendocrine carcinoma: A case report and literature review.

Endometrial large cell neuroendocrine carcinoma (LCNEC) is a highly malignant tumor that presents with neuroendocrine function. It is difficult to diagnose at an early stage. Moreover, the diagnosis depends on the pathological and immunohistochemical findings. It is also prone to distant metastasis, but is difficult to treat and shows poor prognosis. Presently, there exists no unified treatment plan, and the prognosis of this disease is also poor. We reported here an analysis and literature review of a case of endometrial LCNEC to facilitate the comprehension of this disease and provide help toward clinical diagnosis and treatment.