Large Cell Neuroendocrine Carcinoma Research Articles

Clinical analysis of 12 cases of ovarian neuroendocrine carcinoma.

Neuroendocrine neoplasms of the female genital tract are rare. To enhance our clinical understanding of neuroendocrine carcinoma (NEC) of the ovary. A retrospective review was conducted on 12 patients diagnosed with NEC of the ovary, analyzing clinicopathological characteristics, treatment modalities, and survival status. The median age at diagnosis was 34.5 years (range: 20 to 62 years). Among the 12 cases, 9 were small cell carcinoma of the ovary and 3 were large cell NEC. Five cases were stage I tumors, one case was stage IV, and six cases were stage III. Eleven patients underwent surgery as part of their treatment. All patients received adjuvant chemotherapy. Among the 12 patients, one patient received radiotherapy, and one patient with a BRCA2 mutation was administered PARP inhibitor maintenance after chemotherapy. The median progression-free survival was 13 months, and the median overall survival was 19.5 months. Four cases remained disease-free, while eight cases experienced tumor recurrence, including three cases that resulted in death due to disease recurrence. NEC of the ovary is a rare condition that is more common in women of childbearing age and is associated with aggressive behavior and poor clinical outcomes. Surgical resection remains the mainstay of treatment, with some patients benefiting from adjuvant chemoradiation therapy.

Management of colorectal large cell neuroendocrine carcinoma: case report and literature review

Large cell neuroendocrine carcinoma (LCNEC) of the colorectum is a rare, aggressive subtype of neuroendocrine cancer with a dismal prognosis. Accounting for a mere 0.25% of colorectal cancers, LCNEC is associated with a median overall survival of 4 to 16 months, and nearly all patients succumb within a year. Pure colorectal LCNEC reports are scarce, and this review and case study presents a 40-year-old male, the youngest reported patient, diagnosed with rectal LCNEC. A comprehensive PubMed search for “large cell neuroendocrine carcinoma” and “colorectal” was conducted. Titles were meticulously screened for relevance to the nuanced management of colorectal LCNEC. Despite aggressive therapeutic interventions, including chemotherapy with carboplatin and etoposide, the patient experienced rapid disease progression, emphasizing the challenging nature of LCNEC. The paper discusses the evolving classification of NEC, morphological features, and immunophenotypic characteristics that differentiate LCNEC from other neuroendocrine tumours. Survival rates underscore the aggressive nature of colorectal NEC, and treatment options, primarily relying on retrospective studies, reveal limited efficacy. While surgery remains the preferred approach for localized disease, the optimal chemotherapy regimen for LCNEC is yet to be established. Current evidence suggests platinum-based therapy as a common first-line treatment, but the demand for more effective options persists. The paper highlights the need for additional research, including prospective trials, to elucidate the genuine benefits of adjuvant chemotherapy and to explore emerging therapies, such as immunotherapy, in the context of LCNEC.

Challenging Neurological Manifestations in Large-Cell Neuroendocrine Carcinoma (LCNEC): A Case Study of Extensive Intracranial and Intradural Metastases

Challenging Neurological Manifestations in Large-Cell Neuroendocrine Carcinoma (LCNEC): A Case Study of Extensive Intracranial and Intradural Metastases

Advances of pathological diagnosis and molecular pathology of lung neuroendocrine neoplasms

The pathological classification and diagnostic criteria for lung neuroendocrine neoplasms (NENs) in the 2021 World Health Organization (WHO) lung tumor classification are similar to the prior classifications. However, the advances on the molecular studies of lung NENs have shown that both small cell lung carcinoma and large cell neuroendocrine carcinoma are highly heterogeneous tumors with neuroendocrine characteristics and can be subclassified based on the features of genomics or transcriptomics, which are valuable in the diagnosis of lung NENs subtypes and patient treatment. In addition, it is necessary to interpret emerging concepts such as "lung neuroendocrine tumor G3" and "histological transformation" from pathological perspectives, as well as to know the novel neuroendocrine biomarkers such as INSM1 and POU2F3. This article summarized the diagnostic changes and the advances of molecular pathology of lung NENs based on the latest WHO classification and molecular research.

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

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. 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. 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. The new nomogram was developed for predicting CSS in patients with metastatic LCNEC, providing personalized risk evaluation and aiding clinical decision-making.

A prognostic nomogram based on least absolute shrinkage and selection operator Cox regression in patients with pulmonary large-cell neuroendocrine carcinoma.

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare subtype of breast cancer with a poor prognosis. Despite its rarity, it is important to gain a better understanding of the epidemiological, clinical, and prognostic features of pulmonary LCNEC. The purpose of this study was to design, construct, and validate a new nomogram for predicting overall survival (OS) in patients with pulmonary LCNEC. In total, the data of 1,864 LCNEC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, which is maintained by the National Cancer Institute in the United States and serves as a comprehensive source of cancer-related information. Of these patients, 556 served as the validation group and 1,308 served as the training cohort. We constructed a new nomogram with the training cohort that included the independent factors for OS as identified by least absolute shrinkage and selection operator Cox regression. Five independent factors were ultimately selected by the stepwise regression. Every factor of the Cox regression was included in the nomogram. Analyses of the calibration curve, decision curve, area under the curve, and concordance index (C-index) values were performed to assess the effectiveness and discriminative ability of the nomogram. Five optimal predictive factors for OS were selected and merged to construct a 3- and 5-year OS nomogram. The nomogram had C-index values of 0.716 and 0.708 in the training cohort and validation cohort, respectively. The actual OS rates and the calibration curves showing the predictions of the nomogram were in good agreement. The prognostic nomogram may be very helpful in estimating the OS of patients with pulmonary LCNEC.

Prognostic thresholds of fluorine-18 fluorodeoxyglucose-positron emission tomography mean and maximum standardized uptake values for survival and nodal involvement in lung neuroendocrine neoplasms.

The mean standardized uptake value (SUVmean) and maximum standardized uptake value (SUVmax) on fluorine-18 fluorodeoxyglucose-positron emission tomography are prognostic biomarkers for survival and nodal involvement in non-small-cell lung cancer but their prognostic value in lung neuroendocrine neoplasms (NENs) remains unexplored. In this study, we aimed to examine whether they are also prognostic biomarkers for survival and nodal involvement in lung NENs. We retrospectively studied patients with typical carcinoid, atypical carcinoid or large cell neuroendocrine carcinoma who had been radically resected at our institution between 2008 and 2020. We measured SUVmean and SUVmax on all primary tumours and lymph nodes that were clinically and/or pathologically involved. We dichotomized the patients into groups of high or low SUVmean and SUVmax of the primary tumour using time-dependent receiver operating characteristic curves and compared their overall survival using Kaplan-Meier curves and Cox models. Lastly, we predicted the patients' pathological nodal status with SUVmean and SUVmax of the lymph nodes using binomial logistic models. The study included 245 patients. Patients died earlier if their SUVmean of the primary tumour exceeded 3.9 [hazard ratio 1.97, 95% confidence interval (CI) 1.27-3.04, P = 0.002] or SUVmax exceeded 5.3 (hazard ratio 1.85, 95% CI 1.20-2.87, P = 0.006). Likewise, patients had a higher risk of pathological nodal involvement if their SUVmean of the lymph nodes exceeded 3.3 (odds ratio 10.00, 95% CI 2.59-51.01, P = 0.002) or SUVmax exceeded 4.2 (odds ratio 4.00, 95% CI 1.20-14.65, P = 0.028). The fluorine-18 fluorodeoxyglucose-positron emission tomography SUVmean and SUVmax are strong prognostic biomarkers for survival and nodal involvement in lung NENs and could be important guides for making treatment decisions.

Clinical efficacy of lurbinectedin in metastatic neuroendocrine carcinomas of the genitourinary tract: Multi-institutional real-world experience.

601 Background: Neuroendocrine carcinomas (NEC) of the genitourinary (GU) tract, including small cell (SC) NEC and large cell (LC) NEC, are rare aggressive malignancies. Although highly sensitive to cisplatin-based chemotherapy, GU metastatic NEC (mNEC) have limited data to support next therapies. Lurbinectedin, a marine-derived alkylating drug and a selective inhibitor of oncogenic transcription and DNA repair pathways, is FDA-approved for small cell lung cancer (SCLC) after progression on frontline platinum-based therapy, with a disease control rate (DCR) of 68.6%. It is unknown whether DCR is similar in SCLC and GU mNEC. Methods: We report the first multi-institutional series (n=14) of lurbinectedin in GU mNEC. Imaging-based best overall responses (BOR) were noted as complete (CR), partial (PR), stable (SD), progressive (PD) or non-evaluable (NE). DCR includes CR, PR, and SD. We use the Kaplan-Meier method for overall survival (OS) and progression-free survival (PFS) from lurbinectedin start date. We define duration of response (DoR) from response date to progression or last contact date for patients (pts) with CR or PR. Results: Most pts had a median age at metastasis of 70.5 years (ICR: 64-74.5) [Table]. Primary locations were bladder (7/14, 50%), prostate (5/14, 35.7%) and ureter (2/14, 12.3%). Histology at diagnosis mostly consisted of mixed or pure SCNEC, with one exception of LCNEC. Most pts had visceral disease, prior immunotherapy and at least 2 prior lines of therapy for mNEC before lurbinectedin (8/14, 57.1%). DCR was 6/14 (42.8%), including 5 bladder pts and 1 prostate pt. Among bladder pts, BOR included one CR (1/7, 14.3%) for the LCNEC case, 2 PR (2/7, 28.6%), 2 SD (2/7, 28.6%) and 2 PD (2/7, 28.6%). Most prostate and ureteral pts either progressed on lurbinectedin or were NE (Prostate: 1 PR, 2 PD, and 2 NE; Ureteral: 1 PD and 1 NE). For all 14 pts, median OS was 11.47 months (95% CI: 2.17-13.63) and median PFS was 2.8 mo (1.4-10.9). Median DoR was 7.38 mo (2.3-9.53) for 4 responding pts (CR or PR). Treatment was stopped due to progression (9/14, 64.3%), three adverse events [thrombocytopenia, electrolyte abnormalities, cerebrovascular accident] (3/14, 21.4%), and pt preference (1/14, 7.1%). Conclusions: Lurbinectedin offers encouraging responses (DCR: 5/7, 71.4%) close to those in SCLC, in previously treated bladder mNEC. One CR was noted for a bladder pt with LCNEC. Responses were less appreciated in prostate and ureteral mNEC due to NE responses and limited number. Larger cohorts are needed to confirm survival benefit and genetic analyses are warranted to identify characteristics of responders. [Table: see text]

Efficacy of immune checkpoint inhibitors in advanced large cell neuroendocrine carcinoma of the lung: A single‑institution experience.

Large cell neuroendocrine carcinoma (LCNEC) is a rare and highly invasive lung cancer subtype with an overall poor prognosis. Due to its low incidence rate and unusual pathological features, the clinical management of LCNEC remains controversial. The present study aimed to assess the effect of immune checkpoint inhibitors (ICIs) on treatment response and survival outcomes in patients with advanced LCNEC. The clinical data from 148 patients with LCNEC treated with ICIs at The First Affiliated Hospital of Zhengzhou University (Zhengzhou, China) between January 2019 and September 2021 were retrospectively analyzed. Kaplan-Meier and multivariable Cox regression analyses were used to evaluate associations between clinicopathological variables and patient outcomes. Patients treated with ICIs demonstrated extended median overall survival (mOS) times [23.5 months; 95% confidence interval (CI), 18.524-28.476] compared with patients who did not receive ICIs (11.2 months; 95% CI, 4.530-18.930) (P<0.001). Univariate analysis revealed that histological subtype (P=0.043), lymph node metastases (P=0.032) and number of metastatic organs (P=0.009) were associated with a poor prognosis. The heterogeneity of pathological components was associated with prognosis, and the mOS time was shorter for mixed LCNEC than that for pure LCNEC (P=0.043). The median progression-free survival (mPFS) (9.78 vs. 9.37 months; P=0.82) and mOS (20.70 vs. 25.79 months; P=0.181) times showed no significant association with regard to different regimens of immuno-based combination therapy (chemotherapy combined with ICIs vs. anti-angiogenic agents combined with ICIs). Poor Eastern Cooperative Oncology Group performance status score (P=0.04), multiple organ metastases (P=0.02) and high cancer antigen 125 levels (P=0.01) were independent risk factors of a poor prognosis. The present findings offer valuable insights into potential prognostic markers and highlight the favorable impact of ICIs on OS in advanced LCNEC. Prospective clinical studies are required to validate the therapeutic value of ICIs in LCNEC.

Prognostic scores in pulmonary large cell neuroendocrine carcinoma: A retrospective cohort study

IntroductionPulmonary large cell neuroendocrine carcinoma (PLCNEC) is a rare but aggressive subtype of lung cancer with an incidence of approximately 3 %. Identifying effective prognostic indicators is crucial for guiding treatments. This study examined the relationship between inflammatory markers and PLCNEC patient overall survival (OS) and sought to determine their prognostic significance in PLCNEC. MethodsPatients diagnosed with PLCNEC between 2007 and 2022 at the oncology center, were retrospectively included. Patients who underwent surgery were pathologically re-staged post-surgery. Potential prognostic parameters (neutrophil/lymphocyte ratio, platelet/lymphocyte ratio [PLR], panimmune inflammatory value, prognostic nutritional index and modified Glasgow prognostic score [mGPS]) were calculated at that time of diagnosis. ResultsSixty patients were included. The median follow-up was 23 months. Thirty-eight patients initially diagnosed with early or locally advanced. The mGPS was identified as a poor prognostic factor that influenced disease free survival (DFS) fourfold (p = 0.03). All patients' median OS was 45 months. Evaluating factors affecting OS in all patients, statistically significant relationships were observed between OS and the prognostic nutritional index (p = 0.001), neutrophil/lymphocyte ratio (p = 0.03), platelet/lymphocyte ratio (p = 0.002), and pan-immunoinflammatory value (p = 0.005). Upon multivariate analysis, the platelet/lymphocyte ratio was identified as an independent poor prognostic factor for OS, increasing the mortality risk by 5.4 times (p = 0.002). ConclusionmGPS was significantly linked with prognosis in non-metastatic PLCNEC, with patients with higher mGPS exhibiting poorer long-term DFS. This finding contributes to the evolving understanding of PLCNEC. The multivariable predictive model we employed suggests that PLR is an independent predictor of OS at all stages. A lower PLR was correlated with worse overall survival. Thus, PLR can be a readily accessible and cost-effective prognostic factor in PLCNEC patients.

Strengths and challenges in current lung cancer care: Timeliness and diagnostic procedures in six Dutch hospitals

ObjectivesTimely diagnosis of lung cancer (LC) is crucial to achieve optimal patient care and outcome. Moreover, the number of procedures required to obtain a definitive diagnosis can have a large influence on the life expectancy of a patient. Here, adherence with existing Dutch guidelines for timeliness and type and number of invasive and imaging procedures was assessed. Materials and methods1096 patients with suspected LC were enrolled in this multicenter prospective study (NL9146). The overall survival, time from referral to the first appointment with the pulmonologist, time to diagnosis and treatment, and the number of imaging and invasive procedures were evaluated. Patients were divided into different diagnostic groupsearly- and advanced stage non-small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC), large cell neuroendocrine carcinoma of the lung (LCNEC), patients without LC and patients without a definitive diagnosis. ResultsThe majority of patients (66 %) received a definitive diagnosis within 5 weeks, although the time to diagnosis of early-stage LC patients and patients without LC was significantly longer comparted to advanced stage LC. An increase in invasive procedures was seen for early-stage LC compared to advanced stage LC and for 13 % of the advanced stage non-squamous NSCLC patients up to three additional invasive procedures were performed solely to obtain sufficient material for NGS. For patients without a definitive diagnosis, 50 % did undergo at least one invasive procedure, while 11 % did not wish to undergo any invasive procedures. ConclusionThese insights could aid in improved LC diagnostics and efficient implementation of new techniques like liquid biopsy and artificial intelligence. This may lead to more timely LC care, a decreased number of invasive procedures, less variability between the diagnostic trajectory of different patients and aid in obtaining a definitive diagnosis for all patients.

Phase 1/2 trial of vesicular stomatitis virus expressing human interferon-β and NIS (VSV-IFNβ-NIS), with ipilimumab and nivolumab, in patients with neuroendocrine carcinoma.

TPS602 Background: Poorly differentiated neuroendocrine carcinoma (NEC) is an aggressive malignancy comprising both pulmonary and extrapulmonary primary sites. NEC includes both small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), as well as other neuroendocrine carcinomas arising from any primary organ. A substantial portion (~40%) of NEC arises from gastrointestinal primary sites. The optimal systemic therapy beyond first line platinum and etoposide is not established. There is a critical need to improve upon the median survival in the second line, as most patients do not survive more than 6 months. The efficacy of dual immune checkpoint inhibitor (ICIs) therapy in NEC shows some promise, but most tumors do not respond. One possible explanation for this is that the tumor microenvironment in NEC is non-inflamed. VSV-IFNβ-NIS is a vesicular stomatitis virus (VSV)-based oncolytic virus being tested in multiple early phase clinical trials. Preliminary studies of immune responses in patients receiving VSV-IFNβ-NIS therapy suggest some patients develop T cell responses to viral antigens and known tumor antigens. We hypothesize that VSV-IFNβ-NIS therapy may convert a non-inflamed or immune-excluded phenotype in NEC to a highly inflamed phenotype that sensitizes the tumor to ICIs. Methods: This is a phase 1-2 safety run-in study designed to determine the safety and efficacy of VSV-IFNβ-NIS in combination with dual ICI therapy, ipilimumab and nivolumab, followed by dose expansion in patients with refractory non-small cell lung cancer (NSCLC) or NEC. After a safety run-in, we will be testing the recommended phase 2 dose (RP2D) of VSV-IFNβ-NIS in an expansion cohort of patients with SCLC or NEC of any primary site. Patients must have previously progressed on at least one line of systemic therapy. Prior treatment with checkpoint inhibitors is permitted. Patients are treated with ipilimumab and nivolumab on day 1, followed by one RP2D of 1.0x10^11 TCID50 VSV-IFNβ-NIS on day 4, followed by nivolumab every 3 weeks and ipilimumab every 6 weeks until progression, up to 2 years. The primary objective is to estimate the response rate by RECIST 1.1. Secondary objectives include estimation of disease-control rate, duration or response, progression-free survival, overall survival, and safety signals. The NEC expansion cohort will seek to enroll 10 patients. If at least one objective response is observed, and safety is confirmed, the regimen will be considered for future study. Clinical trial information: NCT03647163 .

Spread Through Air Spaces in Stage I Pulmonary Large Cell Neuroendocrine Carcinoma

BackgroundPulmonary large cell neuroendocrine carcinoma (LCNEC) represents an exceptionally aggressive and infrequent variant within the realm of non-small cell lung cancer, necessitating surgical intervention as the primary therapeutic approach. However, the postoperative management strategy for early-stage patients continues to be a subject of intense debate and uncertainty. MethodsA retrospective analysis was conducted on a cohort of patients diagnosed with LCNEC who underwent surgical resection at Shanghai Pulmonary Hospital between July 2018 and June 2022. Comprehensive assessments, encompassing univariate and multivariate analyses, were performed to evaluate the prognostic significance of these indicators in patient clinical profiles, overall survival (OS), and disease-free survival (DFS). ResultsA comprehensive screening effort identified 171 patients with LCNEC, with 70 stage I patients meeting the criteria for inclusion in the final cohort. Of these, 11 patients (15.7%) presented with combined LCNEC, and 59 (84.3%) exhibited pure LCNEC. Univariate and multivariate analyses both unveiled that spread through air spaces (STAS) status emerged as an independent prognostic determinant for both DFS (P = .003) and OS (P = .013), whereas histologic subtype independently predicted OS (P = .011). Subgroup survival analyses further underscored that the advantageous effects of postoperative chemotherapy were significantly pronounced exclusively among STAS-positive patients, showcasing a statistically significant enhancement in DFS (P = .047) and OS (P = .018). ConclusionsSTAS may serve as an adverse prognostic factor in stage I LCNEC patients, potentially offering guidance for postoperative chemotherapy decisions.

Misleading wheeze in a case of atypical large cell neuroendocrine carcinoma of lung - A deadly variety

Neuroendocrine tumors are neoplasms arising from cells of endocrine and nervous system containing special secretory granules with biogenic amines and polypeptide hormones. One of the varieties that occurs commonly in the lung is large cell neuro endocrine carcinoma. The replicative potential of these neuroendocrine malignancies is so rapid that the patients usually present with metastatic disease. We describe a case of 29-year-old-male presented with nocturnal wheeze which led on to a misdiagnosis of bronchial asthma and finally found to be LCNEC with endobronchial obstruction. They are usually peripherally located lesions, mostly in the upper lung zones of an elderly male smoker. But he had a hilar mass with right lower lobe collapse due to endobronchial obstruction. Hence careful examination of wheeze whether unilateral or bilateral, monophonic or polyphonic, random or fixed, inspiratory or expiratory or biphasic may help in early identification of the endobronchial lesions.

Multi-omic dataset of patient-derived tumor organoids of neuroendocrine neoplasms.

Organoids are 3-dimensional experimental models that summarize the anatomical and functional structure of an organ. Although a promising experimental model for precision medicine, patient-derived tumor organoids (PDTOs) have currently been developed only for a fraction of tumor types. We have generated the first multi-omic dataset (whole-genome sequencing [WGS] and RNA-sequencing [RNA-seq]) of PDTOs from the rare and understudied pulmonary neuroendocrine tumors (n = 12; 6 grade 1, 6 grade 2) and provide data from other rare neuroendocrine neoplasms: small intestine (ileal) neuroendocrine tumors (n = 6; 2 grade 1 and 4 grade 2) and large-cell neuroendocrine carcinoma (n = 5; 1 pancreatic and 4 pulmonary). This dataset includes a matched sample from the parental sample (primary tumor or metastasis) for a majority of samples (21/23) and longitudinal sampling of the PDTOs (1 to 2 time points), for a total of n = 47 RNA-seq and n = 33 WGS. We here provide quality control for each technique and the raw and processed data as well as all scripts for genomic analyses to ensure an optimal reuse of the data. In addition, we report gene expression data and somatic small variant calls and describe how they were generated, in particular how we used WGS somatic calls to train a random forest classifier to detect variants in tumor-only RNA-seq. We also report all histopathological images used for medical diagnosis: hematoxylin and eosin-stained slides, brightfield images, and immunohistochemistry images of protein markers of clinical relevance. This dataset will be critical to future studies relying on this PDTO biobank, such as drug screens for novel therapies and experiments investigating the mechanisms of carcinogenesis in these understudied diseases.

The outcomes of different regimens depend on the molecular subtypes of pulmonary large-cell neuroendocrine carcinoma: A retrospective study in China.

The optimal systemic treatment for pulmonary large-cell neuroendocrine carcinoma (LCNEC) remains controversial, and recent advances in LCNEC molecular subtype classification have provided potential strategies for assisting in treatment decisions. Our study aimed to investigate the impact of treatment regimens, molecular subtypes and their concordance on clinical outcomes of patients diagnosed with LCNEC. All patients diagnosed with advanced pulmonary LCNEC in Peking Union Medical College Hospital (PUMCH) between January 2000 and October 2021 were enrolled in this retrospective study. The tumor samples were collected and sequenced using a tumor-specific gene panel, while clinical information was retrieved from the medical records system. The survival and therapeutic response were analyzed and compared between different subgroups classified by treatment regimen (SCLC or NSCLC-based), molecular subtype (type I or II) or the combination. In univariate subgroup analysis categorized only by treatment regimen or molecular subtype, there were no differences identified in DCR, ORR, PFS, or OS. Nevertheless, the group with consistent treatment regimen and molecular subtype exhibited significantly longer OS than that of the inconsistent group (median OS 37.7 vs. 8.3 months; p = 0.046). Particularly, the OS of patients with type II LCNEC treated with SCLC-based regimen was significantly prolonged than that of others (median 37.7 vs. 10.5 months; p = 0.039). Collectively, our study revealed the clinical outcomes of different treatment regimens for LCNEC patients highly depend on their molecular subtypes, highlighting the need for sequencing-guided therapy.

Advances in genetic profile and therapeutic strategy of pulmonary large cell neuroendocrine carcinoma.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine carcinoma (HGNEC) accounting for 3% of primary lung cancer, and characterized by strong invasion, high heterogeneity, and extremely poor prognosis. At present, the diagnosis and treatment of LCNEC remains controversial and refer to therapeutic strategy of small cell lung cancer (SCLC), lacking precise therapy. Recently, the genetic analysis and clinical trials of LCNEC gradually emerged, providing more evidence for precise diagnosis and treatment. Here, we review the diagnosis, molecular characteristics, and treatment of LCNEC based on the existing research and frontier progress to provide a potential direction for future diagnosis and treatment of LCNEC.

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.

Clinicopathological and Immunohistochemical Analysis of Lung Cancer Biopsies at a Tertiary Care Centre in Central Gujarat, India

Introduction: Lung biopsy is a reliable and highly accurate tool for diagnosing and subtyping lung lesions. Two-thirds of lung cancer patients present with advanced disease, and small biopsies remain the main diagnostic tool. Histopathological and immunohistochemical examination of lung biopsies plays an important role in accurately diagnosing lung malignancies. Aim: The aim of present study was to analyse the clinicopathological and immunohistochemical features of lung cancer. Materials and Methods: This cross-sectional study was conducted in the Department of Pathology, Medical College, Baroda, over a period of two years and three months, from March 2019 to May 2021. A total of 53 cases of malignant lung cancer biopsies were included in this study. Clinical parameters, such as patient age, complaints, smoking history, clinical presentation, radiological findings, histopathology reports, and IHC findings, were retrieved. All cases underwent histopathological examination, and tumour typing was done according to the WHO classification 2021 of lung tumours. Immunohistochemistry (IHC) markers like CK5/6, CK7, TTF1, P63, synaptophysin, chromogranin, and pankeratin were used for further subtyping. Data analysis was done by Microsoft Excel 2019 spreadsheet. Results: A total of 53 cases of malignant lung cancer were included in this study. Of these, 38 (71.69%) cases were male, and 15 (28.30%) cases were female. 43 (81.13%) cases were over 50 years old, with a mean age of 61 years. After IHC, adenocarcinoma was seen in 27 cases (50.9%), followed by Squamous Cell Carcinoma (SCC) in 19 cases (35.8%), five cases of small cell carcinoma, one case of large cell neuroendocrine carcinoma, and one case of Non Small Cell Carcinoma-Not Otherwise Specified (NSCC-NOS). In adenocarcinoma, positivity for CK7, TTF1, and p63 was 100%, 74.07%, and 16.6%, respectively. In squamous cell carcinoma, positivity for CK5/6 and p63 was 100% and 78.94%, respectively. Conclusion: In the present study, the majority of cases were males. Adenocarcinoma was the most common subtype of Non Small Cell Lung Cancer (NSCLC). A panel of IHC markers is helpful in differentiating NSCLC into adenocarcinoma and squamous cell carcinoma on small true-cut lung biopsies. CK5/6 and p63 aid in detecting squamous cell carcinoma, while CK7 and TTF-1 help in detecting adenocarcinoma. The recommended immunohistochemical profile for NSCLC includes TTF1, CK5/6, CK7, and p63.

Effect of Ki-67 proliferation index on survival in large cell neuroendocrine carcinoma of the lung.

Large cell neuroendocrine carcinoma of the lung is a rare type of lung cancer. There is a limited number of studies on clinical and histopathological characteristics that are effective in survival. The aim of this study was to investigate the relationship between histopathological and clinical characteristics, mainly Ki-67 proliferation index, and survival in patients diagnosed with large cell neuroendocrine carcinoma of the lung. The data of 38 patients followed up with the diagnosis of large cell neuroendocrine carcinoma of the lung were evaluated. The mean Ki-67 value was determined to be 65.8% (±20.8). The patients' clinical characteristics and survival times were compared according to the cut-off value determined for Ki-67 index. When median overall survival times were compared, it was seen that overall survival was numerically lower in patients aged 65 years and over, in tumors located on the right side, in cases who were in the metastatic stage at diagnosis, whose Ki-67 index was 65% and above, who did not receive chemotherapy, who did not undergo curative surgery, and in patients with chronic diseases (p>0.05). In the Kaplan-Meier analysis, the median overall survival was determined to be 22.2 months (95%CI 21.7-22.7) in the patients with Ki-67<65%, while it was found to be 20.3 months (95%CI 4.5-36.2) in the patients with Ki-67≥65% (p=0.351). Our study identified subgroups with decreased survival in large cell neuroendocrine carcinoma of lung patients. Studies including a larger number of patients are needed to identify the prognostic importance of these clinical and histopathological characteristics.