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Pulmonary large cell carcinoma (LCC) is an undifferentiated neoplasm lacking morphological, histochemical, and immunohistochemical features of small cell lung cancer, adenocarcinoma (ADC), or squamous cell carcinoma (SCC). The available molecular information on this rare disease is limited. This study aimed to provide an integrated molecular overview of 16 cases evaluating the mutational asset of 409 genes and the transcriptomic profiles of 20,815 genes. Our data showed that TP53 was the most frequently inactivated gene (15/16; 93.7%) followed by RB1 (5/16; 31.3%) and KEAP1 (4/16; 25%), while CRKL and MYB genes were each amplified in 4/16 (25%) cases and MYC in 3/16 (18.8%) cases; transcriptomic analysis identified two molecular subtypes including a Pure-LCC and an adenocarcinoma like-LCC (ADLike-LCC) characterized by different activated pathways and cell of origin. In the Pure-LCC group, POU2F3 and FOXI1 were distinctive overexpressed markers. A tuft cell-like profile and the enrichment of a replication stress signature, particularly involving ATR, was related to this profile. Differently, the ADLike-LCC were characterized by an alveolar-cell transcriptomic profile and association with AIM2 inflammasome complex signature. In conclusion, our study split the histological marker-null LCC into two different transcriptomic entities, with POU2F3, FOXI1, and AIM2 genes as differential expression markers that might be probed by immunohistochemistry for the differential diagnosis between Pure-LCC and ADLike-LCC. Finally, the identification of several signatures linked to replication stress in Pure-LCC and inflammasome complex in ADLike-LCC could be useful for designing new potential therapeutic approaches for these subtypes. [ABSTRACT FROM AUTHOR]

Introduction: Carcinoma of the gallbladder is extremely rare, papillary adenocarcinoma comprises 90% of these cases. Although neuroendocrine neoplasms (NENs) comprise 0.5% of the cases of gallbladder cancer, the incidence is rising. NEN is classified into a well-differentiated neuroendocrine tumor and poorly differentiated neuroendocrine cancer (NEC). Histologically, NEC is small-cell or large-cell carcinoma. We present the extremely rare case, 15th in the literature to be precise, of large cell neuroendocrine carcinoma of the gallbladder. Case Presentation: A 72-year-old male presented to the emergency department with constipation and right upper quadrant pain for 3 months. Computed tomography scan of the abdomen demonstrated an ill-defined 7.2 × 4.9 cm hypodense lesion in the gallbladder fossa with extension into the liver. Histopathological and immunohistochemical analysis of the biopsy specimen confirmed the diagnosis of large cell neuroendocrine carcinoma of the gallbladder. He was started on palliative chemotherapy. Conclusion: The plethora of tumors present in the gallbladder necessitates a search for risk factors for gallbladder neoplasia, and underscores the need to more carefully examine the nature of “asymptomatic gallstones.” Further studies may reveal subclasses of cholelithiasis, gallbladder morphology, or imaging to define which patients should be followed more carefully, and may clarify additional risk factors for cancer of the gallbladder.

Background. Neuroendocrine differentiation in the prostate gland ranges from clinically insignificant neuroendocrine differentiation detected with markers in an otherwise conventional prostatic adenocarcinoma to a lethal high-grade small/large cell neuroendocrine carcinoma. The concept of neuroendocrine differentiation in prostatic adenocarcinoma has gained considerable importance due to its prognostic and therapeutic ramifications and pathologists play a pivotal role in its recognition. However, its awareness, reporting, and resource utilization practice patterns among pathologists are largely unknown. Methods. Representative examples of different spectrums of neuroendocrine differentiation along with a detailed questionnaire were shared among 39 urologic pathologists using the survey monkey software. Participants were specifically questioned about the use and awareness of the 2016 WHO classification of neuroendocrine tumors of the prostate, understanding of the clinical significance of each entity, and use of different immunohistochemical (IHC) markers. De-identified respondent data were analyzed. Results. A vast majority (90%) of the participants utilize IHC markers to confirm the diagnosis of small cell neuroendocrine carcinoma. A majority (87%) of the respondents were in agreement regarding the utilization of type of IHC markers for small cell neuroendocrine carcinoma for which 85% of the pathologists agreed that determination of the site of origin of a high-grade neuroendocrine carcinoma is not critical, as these are treated similarly. In the setting of mixed carcinomas, 62% of respondents indicated that they provide quantification and grading of the acinar component. There were varied responses regarding the prognostic implication of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and for Paneth cell-like differentiation. The classification of large cell neuroendocrine carcinoma was highly varied, with only 38% agreement in the illustrated case. Finally, despite the recommendation not to perform neuroendocrine markers in the absence of morphologic evidence of neuroendocrine differentiation, 62% would routinely utilize IHC in the work-up of a Gleason score 5 + 5 = 10 acinar adenocarcinoma and its differentiation from high-grade neuroendocrine carcinoma. Conclusion. There is a disparity in the practice utilization patterns among the urologic pathologists with regard to diagnosing high-grade neuroendocrine carcinoma and in understanding the clinical significance of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and Paneth cell-like neuroendocrine differentiation. There seems to have a trend towards overutilization of IHC to determine neuroendocrine differentiation in the absence of neuroendocrine features on morphology. The survey results suggest a need for further refinement and development of standardized guidelines for the classification and reporting of neuroendocrine differentiation in the prostate gland. [ABSTRACT FROM AUTHOR]

Abstract Background Neuroendocrine carcinomas are extremely rare in the esophagus as they represent less than 0.04% of all neuroendocrine tumors. To date, only 14 cases of poorly differentiated, high-grade esophageal NEC have been described in the literature. The majority of these patients presented with typical dysphagia symptoms. Due to its rarity, no standardized guidelines have been proposed to treat esophageal neuroendocrine carcinoma, although general recommendations suggest surgery with adjuvant chemoradiotherapy as the treatment of choice. Case presentation A 67-year-old previously healthy White male presented with a year-long intermittent nonspecific retrosternal discomfort, with the absence of any other symptoms. Esophagogastroduodenoscopy revealed an ulcerative mass in his lower esophagus, with concern of malignancy. Endoscopic ultrasound-guided biopsy revealed poorly differentiated neuroendocrine carcinoma of the esophagus with metastasis to a diaphragmatic lymph node. He was treated with neoadjuvant chemoradiation followed by surgery, and he has been in remission for over 5 years. Conclusion Here, we review the literature and report a unique case of a patient with a vague presentation of esophageal neuroendocrine carcinoma as he enters his sixth year of survival following neoadjuvant chemoradiotherapy.

Abstract Background Patients with pulmonary large cell carcinoma (LCC) have a high incidence of synchronous brain metastases (SBM) and a poor prognosis. Our study was to evaluate the predictive and prognostic value of the clinical characteristics of pulmonary LCC patients with SBM at initial diagnosis by utilizing the Surveillance, Epidemiology, and End Results (SEER) database. Methods LCC patients, diagnosed from 2010 to 2019, were identified from the latest SEER database which was released in April 2022. Logistic regression and Cox regression were used to identify the predictive and prognostic factors for LCC patients with SBM. Propensity score matching (PSM) and Kaplan–Meier analyses were applied to assess different therapy modalities. Results A total of 1375 LCC patients were enrolled in this study and 216 (15.7%) of them had SBM at the initial diagnosis. The median overall survival (OS) of LCC patients with SBM was 4 months. Multivariate Cox regression identified age 60–79 (OR 0.57; 95% CI 0.41–0.78; p

Introduction Prostatic large‐cell neuroendocrine carcinoma is poorly studied. Although several case reports are available, information on the clinicopathological characteristics of this disease is limited, particularly for the de novo (hormone‐naive) type. Herein, we report an extremely rare de novo case of this disease with a good prognosis despite a multi‐metastatic status. Case presentation An 83‐year‐old male patient presented with a high serum prostate‐specific antigen level and was found to have de novo prostatic large‐cell neuroendocrine carcinoma with an adenocarcinoma component upon pathological examination. Diagnosed with stage pT4cN1cM1c, he underwent chemo‐hormonal therapy using a luteinizing hormone‐releasing hormone antagonist and combined etoposide and cisplatin, which achieved a partial response. The patient has survived for 20 months without progression. Conclusion Although prostatic large‐cell neuroendocrine carcinoma is known for its aggressive clinical behavior, the de novo type with an adenocarcinoma component may be sensitive to hormonal therapy and achieve a good prognosis.

Background: To review the outcomes of surgically resected lung neuroendocrine neoplasms (LNEN) at a tertiary referral centre and to validate a previously published LNEN‐specific staging system (NETL). Methods: All patients who were identified on histopathology to have LNEN were included. Pre‐, intra‐ and post‐operative outcomes were collected, including long‐term survival. Patients were staged by both the TNM (seventh and eighth edition) and NETL staging (seventh and eighth edition definitions). Kaplan–Meier (KM) survival analysis was performed according to histopathology and stage, along with uni‐ and multivariate analyses. Result: A total of 132 patients were included in the study, with a median age of 65 years; 55% were female. Typical carcinoid (TC) was the most common pathology (53.4%) followed by large cell neuroendocrine carcinoma (LCNEC – 23.5%), atypical carcinoid (AC – 20.5%) and small cell carcinoma (3.0%). The most common operation performed was a lobectomy (55.3%). Overall survival at 5 years was 80% (100% TC, 78.2% AC, LCNEC 40.9%) and 5‐year disease free survival was 76.8% (TC 94.3%, AC 56.8%, LCNEC 56.4%). KM curves showed a trend towards NETL performing better than TNM, however, in multivariate analysis only the histological subtype was found to be significant in our study. Conclusion: This is the largest known Australian series of LNEN to date, showing survival comparable to international outcomes. We have demonstrated large variations in outcome, driven by histological grade. The TNM system does not correlate with survival and we have not been able to show that currently proposed NETL staging is superior. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most commonly diagnosed cancer types. Studying the molecular changes that occur in lung cancer is important to understand tumor formation and identify new therapeutic targets and early markers of the disease to decrease mortality. Glycosaminoglycan chains play important roles in various signaling events in the tumor microenvironment. Therefore, we have determined the quantity and sulfation characteristics of chondroitin sulfate and heparan sulfate in formalin-fixed paraffin-embedded human lung tissue samples belonging to different lung cancer types as well as tumor adjacent normal areas. Glycosaminoglycan disaccharide analysis was performed using HPLC-MS following on-surface lyase digestion. Significant changes were identified predominantly in the case of chondroitin sulfate; for example, the total amount was higher in tumor tissue compared to the adjacent normal tissue. We also observed differences in the degree of sulfation and relative proportions of individual chondroitin sulfate disaccharides between lung cancer types and adjacent normal tissue. Furthermore, the differences in the 6-O-/4-O-sulfation ratio of chondroitin sulfate were different between the lung cancer types. Our pilot study revealed that further investigation of the role of chondroitin sulfate chains and enzymes involved in their biosynthesis is an important aspect of lung cancer research. [ABSTRACT FROM AUTHOR]

Background: Neuroendocrine carcinomas are extremely rare in the esophagus as they represent less than 0.04% of all neuroendocrine tumors. To date, only 14 cases of poorly differentiated, high-grade esophageal NEC have been described in the literature. The majority of these patients presented with typical dysphagia symptoms. Due to its rarity, no standardized guidelines have been proposed to treat esophageal neuroendocrine carcinoma, although general recommendations suggest surgery with adjuvant chemoradiotherapy as the treatment of choice. Case presentation: A 67-year-old previously healthy White male presented with a year-long intermittent nonspecific retrosternal discomfort, with the absence of any other symptoms. Esophagogastroduodenoscopy revealed an ulcerative mass in his lower esophagus, with concern of malignancy. Endoscopic ultrasound-guided biopsy revealed poorly differentiated neuroendocrine carcinoma of the esophagus with metastasis to a diaphragmatic lymph node. He was treated with neoadjuvant chemoradiation followed by surgery, and he has been in remission for over 5 years. Conclusion: Here, we review the literature and report a unique case of a patient with a vague presentation of esophageal neuroendocrine carcinoma as he enters his sixth year of survival following neoadjuvant chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the most frequent form of lung cancer and represents a set of histological entities that have an ominous long-term prognosis, for example, adenocarcinoma, squamous carcinoma and large cell carcinoma. Both small cell and non-small cell lung cancer are the main causes of oncological death and the oncological diseases with the highest incidence worldwide. With regard to clinical approaches for NSCLC, several advances have been achieved in diagnosis and treatment; the analysis of different molecular markers has led to the development of new targeted therapies that have improved the prognosis for selected patients. Despite this, most patients are diagnosed in an advanced stage, presenting a limited life expectancy with an ominous short-term prognosis. Numerous molecular alterations have been described in recent years, allowing for the development of therapies directed against specific therapeutic targets. The correct identification of the expression of different molecular markers has allowed for the individualization of treatment throughout the disease course, expanding the available therapeutic arsenal. The purpose of this article is to summarize the main characteristics of NSCLC and the advances that have occurred in the use of targeted therapies, thus explaining the limitations that have been observed in the management of this disease. [ABSTRACT FROM AUTHOR]

Neuroendocrine (NE) tumors of the bladder are infrequent. Among them, large cell NE tumor has been outlined only in case reports and short case series, which describes them as aggressive malignancies with dismal prognosis requiring a multidisciplinary approach. The case of an 82-year-old patient with muscle-invasive large cell NE carcinoma of the bladder associated with urothelial carcinoma in situ is presented. Despite combined treatment modality, relapse with metastatic disease was detected 12.5 months after the initial diagnosis. Thereafter, we review several published cases, and results of the collected data are compared with the largest studies published on this topic.

Abstract Background Large cell neuroendocrine carcinoma (LCNEC) is a high-grade malignant pulmonary neuroendocrine tumour. The distinction of pulmonary large cell carcinoma (LCC) and LCNEC is based on the presence of neuroendocrine morphology and the expression of at least one neuroendocrine marker in at least 10% of tumour cells in the latter. According to the current classification, LCC with neuroendocrine morphology and without neuroendocrine marker expression is classified as LCC. This subgroup we have named LCNEC-null and aimed to analyze its characteristics. Methods 31 surgical samples resected in West China Hospital of Sichuan University between 2017 to 2021 were collected, including 7 traditional LCCs, 11 LCNEC-nulls and 13 LCNECs. Each case was conducted to immunohistochemistry and 425-panel-NGS. Results Compared to other LCCs, detailed analysis of LCNEC-nulls revealed biological features similar to those of LCNECs, especially for immunohistochemistry and molecular analysis: 1. diffusive, coarse granular and high expression of Pan-CK; 2. rare PD-L1 expression; 3. High rate of p53 expression and Rb deficiency 4. abundant genetic alterations are similar to LCNEC. All characteristics above deviated from traditional LCC, indicating they have the same origin as LCNEC. Furthermore, LCNEC could be genetically divided into two subtypes when we reclassified LCNEC-null as LCNEC, and the mutational type and prognosis differed significantly. Conclusions We consider that LCNEC-null should be reclassified as LCNEC based on analysis above. In addition, two genetic types of LCNEC with different prognosis also indicate two mechanism of tumour formation.

Background: Patients with pulmonary large cell carcinoma (LCC) have a high incidence of synchronous brain metastases (SBM) and a poor prognosis. Our study was to evaluate the predictive and prognostic value of the clinical characteristics of pulmonary LCC patients with SBM at initial diagnosis by utilizing the Surveillance, Epidemiology, and End Results (SEER) database. Methods: LCC patients, diagnosed from 2010 to 2019, were identified from the latest SEER database which was released in April 2022. Logistic regression and Cox regression were used to identify the predictive and prognostic factors for LCC patients with SBM. Propensity score matching (PSM) and Kaplan–Meier analyses were applied to assess different therapy modalities. Results: A total of 1375 LCC patients were enrolled in this study and 216 (15.7%) of them had SBM at the initial diagnosis. The median overall survival (OS) of LCC patients with SBM was 4 months. Multivariate Cox regression identified age 60–79 (OR 0.57; 95% CI 0.41–0.78; p < 0.001), age ≥ 80 (OR 0.23; 95% CI 0.12–0.45; p < 0.001) and bone metastases (OR 1.75; 95% CI 1.22–2.51; p < 0.001) as significant independent predictors for developing SBM. Multivariable Cox regression revealed that age 60–79, T stage, bone metastases and chemotherapy were independent prognostic factor for OS. The surgery combined with chemotherapy and radiotherapy group, in which all patients were N0 stage and had no other site-specific metastases, exhibited the best median OS of 15 months. Conclusions: LCC patients with age < 60 or bone metastases were more likely to have SBM at initial diagnosis. Age, T stage, bone metastases and chemotherapy were independent prognostic factors for OS of LCC patients with SBM. Highly selected patients might achieve the best survival benefit from surgery combined with chemotherapy and radiotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Pulmonary large cell carcinoma (LCC) represents a kind of rare and highly malignant tumors with significantly worse survival outcomes compared to other types of NSCLC. Our study mainly demonstrated that for LCC patients ≥65 years old, radiation after surgery had the optimal therapeutic effect to improve survival outcomes compared to other sequences of radiation with surgery. Our research provided significant advice on the appropriate choice of radiation sequences with surgery for advanced LCC patients with age ≥65 years old. Background: Pulmonary large cell carcinoma, a type of non-small cell lung cancer (NSCLC), is a rare neoplasm with poor prognosis. In this study, our aim was to investigate the impact of radiation sequences with surgery for stage III/IV LCC patients between different age groups, especially in the elderly patients. Patients and Methods: The patients with LCC and other types of NSCLC in the Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2015 were retrospectively analyzed. Then we divided the LCC patients into two age groups: <65 years old group and ≥65 years old group. Propensity score method (PSM) was used to control potential differences between different groups. The overall survival (OS) of LCC patients and other types of NSCLC patients were evaluated by Kaplan–Meier analysis. Univariate and multivariate Cox regression analysis were employed to explore the independent risk factors of OS. The forest plots of HRs for OS were generated to show the above outcomes more visually. Results: In total, 11,349 LCC patients and 129,118 other types of NSCLC patients were enrolled in this study. We divided LCC patients into <65 years old group (4300) and ≥65 years old group (7049). LCC patients was more common in whites (81.4%), males (58.3%), elderly (≥65 years old: 62.1%), east regions (52.7%), upper lobe (51.6%), right-origin of primary (55.4%), with advanced grade (54.2%) or stage (76.7%). After PSM, Kaplan–Meier analysis and multivariate Cox analysis showed significantly worse survival prognosis for LCC patients compared to other types of NSCLC, especially in the group ≥65 years old (HR: 1.230; 95% CI: 1.171–1.291; p < 0.001). For LCC patients, there were some risk survival factors including whites, males, not upper lobe, advanced stage, elder age at diagnosis, bone metastasis, liver metastasis, singled status, no lymphadenectomy, no surgery, and no chemotherapy (p < 0.05). In LCC patients ≥65 years old, radiation after surgery had significantly better impact on overall survival outcomes (HR: 0.863, 95% CI: 0.765–0.973, p = 0.016), whereas radiation prior to surgery (HR: 1.425, 95% CI: 1.059–1.916, p = 0.019) had significantly worse impact on prognosis of patients. In LCC patients <65 years old, radiation sequences with surgery had no significant impact on the OS of patients (p = 0.580), but ≥4 LNRs had significantly survival benefits to prognosis (HR:0.707, 95% CI: 0.584–0.855). Elderly LCC patients had worse malignant tumors than young patients, of which the majority were diagnosed as stage III/IV tumors. Conclusions: Postoperative radiotherapy may achieve a better prognosis for stage III/IV LCC patients older than 65 years old compared to other radiation sequences with surgery. [ABSTRACT FROM AUTHOR]

Large Cell Carcinoma (LCC) observed in low-dose computed tomography (LDCT) screening trials typically presented as a single solid peripheral nodule or mass, often with lobulated margins (panels A-D), and exhibited a fast growth (panels E-F and G-H). The 5-year survival (panel I) reflected the stage at diagnosis and was fair (15/20 alive) for stages I-II (dashed line) and poor (1/10 alive) (continuous line) for stages III-IV. [Display omitted] • LDCT screening enables the definition of early radiological features of LCC. • LCC was diagnosed in 30 (4%) of 750 subjects with LDCT screen-detected lung cancers. • LCC appeared as a peripheral solid nodule/mass often (43%) with lobulated margins. • 5 years after diagnosis, 5/20 stages I-II and 9/10 stages III-IV subjects had died of LCC. • Survival of screen-detected LCC depends on the stage at diagnosis. To investigate the early radiological features and survival of Large Cell Carcinoma (LCC) cases diagnosed in low-dose computed tomography (LDCT) screening trials. Two radiologists jointly reviewed the radiological features of screen-detected LCCs observed in NLST, ITALUNG, and LUSI trials between 2002 and 2016, comprising a total of 29,744 subjects who underwent 3–5 annual screening LDCT examinations. Survival or causes of death were established according to the mortality registries extending more than 12 years since randomization. LCC was diagnosed in 30 (4 %) of 750 subjects with screen-detected lung cancer (LC), including 15 prevalent and 15 incident cases. Three additional LCCs occurred as interval cancers during the screening period. LDCT images were available for 29 cases of screen-detected LCCs, and 28 showed a single, peripheral, and well-defined solid nodule or mass with regularly smooth (39 %), lobulated (43 %), or spiculated (18 %) margins. One case presented as hilar mass. In 9 incident LCCs, smaller solid nodules were identified in prior LDCT examinations, allowing us to calculate a mean Volume Doubling Time (VDT) of 98.7 ± 47.8 days. The overall five-year survival rate was 50 %, with a significant (p = 0.0001) difference between stages I-II (75 % alive) and stages III-IV (10 % alive). LCC is a fast-growing neoplasm that can escape detection by annual LDCT screening. LCC typically presents as a single solid peripheral nodule or mass, often with lobulated margins, and exhibits a short VDT. The 5-year survival reflects the stage at diagnosis. [ABSTRACT FROM AUTHOR]

This paper presents a novel approach that merges a lightweight parallel depth-wise separable convolutional neural network (LPDCNN) with a ridge regression extreme learning machine (Ridge-ELM) for precise classification of three lung cancer types alongside normal lung tissue (adenocarcinoma, large cell carcinoma, normal, and squamous cell carcinoma) using CT images. The proposed methodology combines contrast-limited adaptive histogram equalization (CLAHE) and Gaussian blur to enhance image quality, reduce noise, and improve visual clarity. The LPDCNN extracts discriminant features while minimizing computational complexity (0.53 million parameters and 9 layers). The Ridge-ELM model was developed to enhance classification performance, replacing the traditional pseudoinverse in the ELM approach. Through comprehensive evaluation against state-of-the-art models, the framework achieves remarkable average recall and accuracy values of 98.25 ± 1.031 % and 98.40 ± 0.822 %, respectively, through rigorous five-fold cross-validation for four-class classifications. In binary classifications, outstanding results are obtained with recall and accuracy values of 99.70 ± 0.671 % and 99.70 ± 0.447 %%, respectively. Notably, the framework exhibits exceptional efficiency, with a testing time of only 0.003 s. Additionally, integrating the SHAP (Shapley Additive Explanations) in the proposed framework enhances Explain-ability, providing insights into decision-making and boosting confidence in real-world lung cancer diagnoses. [ABSTRACT FROM AUTHOR]

The aim of the present study was to integrate the available data published in the literature on oral and maxillofacial neuroendocrine carcinomas concerning the demographic, clinical and histopathological features of this condition. An electronic search with no publication date restriction was undertaken in April 2021 in four databases. Eligibility criteria included reports published in English having enough data to confirm a definite diagnosis, always showing a neuroendocrine marker. Cases originating in the oropharynx, including base of the tongue and tonsils, were excluded. Outcomes were evaluated by the Kaplan–Meier method along with Cox regression. Twenty-five articles (29 cases) from nine different countries were detected. Mean patient age was 56.3 (± 17.5) years, with a slight male predilection. Symptomatology was present in 72.2% of informed cases. Regarding clinical presentation, a non-ulcerated nodule located in the gingiva with a mean size of 3.4 (± 2.0) cm was most frequently reported. Concomitant metastasis was identified in seven individuals. Histopathologically, most neoplasms were of the small cell type, and immunohistochemistry for both epithelial and neuroendocrine differentiation was used in 65.5% cases. Radical surgery was the treatment of choice in almost all cases, with or without adjuvant therapy. Mean follow-up was 20.5 (± 21.2) months, and only four patients developed recurrences. Eleven (44.0%) individuals died due to the disease. Ulcerated lesions were a prognostic factor. This study provides knowledge that can assist surgeons, oncologists, and oral and maxillofacial pathologists with the diagnosis and management of neuroendocrine carcinomas. Our findings demonstrated that the long-term prognosis of this lesion continues to be poor. [ABSTRACT FROM AUTHOR]

Background: Large cell neuroendocrine carcinoma (LCNEC) is a high-grade malignant pulmonary neuroendocrine tumour. The distinction of pulmonary large cell carcinoma (LCC) and LCNEC is based on the presence of neuroendocrine morphology and the expression of at least one neuroendocrine marker in at least 10% of tumour cells in the latter. According to the current classification, LCC with neuroendocrine morphology and without neuroendocrine marker expression is classified as LCC. This subgroup we have named LCNEC-null and aimed to analyze its characteristics. Methods: 31 surgical samples resected in West China Hospital of Sichuan University between 2017 to 2021 were collected, including 7 traditional LCCs, 11 LCNEC-nulls and 13 LCNECs. Each case was conducted to immunohistochemistry and 425-panel-NGS. Results: Compared to other LCCs, detailed analysis of LCNEC-nulls revealed biological features similar to those of LCNECs, especially for immunohistochemistry and molecular analysis: 1. diffusive, coarse granular and high expression of Pan-CK; 2. rare PD-L1 expression; 3. High rate of p53 expression and Rb deficiency 4. abundant genetic alterations are similar to LCNEC. All characteristics above deviated from traditional LCC, indicating they have the same origin as LCNEC. Furthermore, LCNEC could be genetically divided into two subtypes when we reclassified LCNEC-null as LCNEC, and the mutational type and prognosis differed significantly. Conclusions: We consider that LCNEC-null should be reclassified as LCNEC based on analysis above. In addition, two genetic types of LCNEC with different prognosis also indicate two mechanism of tumour formation. [ABSTRACT FROM AUTHOR]

Herein, we summarize two rare cases of salivary neuroendocrine carcinoma arising in the parotid gland. The patients were a 54-year-old Japanese female and a 74-year-old Japanese male. In the first case, the tumor presented as a typical small cell carcinoma with extensive crush artifacts and nuclear molding, but metastatic foci of the lymph node revealed characteristic ribbon-like trabecular arrangements or sheet-like solid growths of tumor cells with moderate amounts of pale eosinophilic cytoplasm intermingled with bizarre giant or multinucleated cells. In the second case, the tumor was initially diagnosed as a small cell neuroendocrine carcinoma, but a retrospective review revealed that the large cell component was dominant and that it should be strictly considered a mixed large and small cell neuroendocrine carcinoma. The difference in prognoses between these two salivary subtypes remains unknown, and distinction between the small and large cell subtypes of neuroendocrine carcinomas seems merely simple and convenient in the salivary glands.

PurposeLarge cell neuroendocrine carcinoma (LCNEC) and classic large cell carcinoma (LCC) are two distinct entities with different histological and biological characteristics. However, the mutational profiles and the clinical behavior of the two subtypes of lung cancer remain to be explored.Patients and MethodsPathological diagnoses of all screened patients were finally confirmed by three or four experienced pathologists. Patients with uncertain pathological diagnoses were excluded. Finally, we genetically profiled ten patients with LCNEC and seven with LCC. ALL patients were subjected to next-generation sequencing (NGS) test, which included nine patients sequenced with a 139-gene panel and eight patients with a 425-gene panel. Including only intersected mutations from these two panels, survival analysis was further conducted.ResultsBoth LCNEC and LCC showed high prevalence in male patients, with no clear association with smoking history. Potential targetable mutations in KRAS and RET were detected in the study cohort. However, LCNEC and LCC showed distinct mutational profiles with an enrichment of RB1/TP53 co-mutations in a subset of LCNEC patients. SMARCA4 and KEAP1 mutations were exclusively found in LCC patients, and RICTOR, BRAF, ROS1 and TET2 mutations were only detected in LCNEC. LCC patients in the cohort had shorter survival compared to LCNEC patients (p=0.006). Survival analysis revealed an association between SMARCA4 mutations and poor outcome in the study cohort and in the LCC subset. Mutations in BRAF were associated with a trend of increased survival in the study cohort, as well as in the LCNEC subset. Finally, TET2 mutations were associated with poor outcome in the LCNEC cohort.ConclusionLCC and LCNEC were both heterogeneous diseases with limited treatment options. Our study identified potential targetable mutations and prognostic biomarkers that might provide more therapeutic options and improve individualized patient care.

Purpose: Large cell neuroendocrine carcinoma (LCNEC) and classic large cell carcinoma (LCC) are two distinct entities with different histological and biological characteristics. However, the mutational profiles and the clinical behavior of the two subtypes of lung cancer remain to be explored. Patients and Methods: Pathological diagnoses of all screened patients were finally confirmed by three or four experienced pathologists. Patients with uncertain pathological diagnoses were excluded. Finally, we genetically profiled ten patients with LCNEC and seven with LCC. ALL patients were subjected to next-generation sequencing (NGS) test, which included nine patients sequenced with a 139-gene panel and eight patients with a 425-gene panel. Including only intersected mutations from these two panels, survival analysis was further conducted. Results: Both LCNEC and LCC showed high prevalence in male patients, with no clear association with smoking history. Potential targetable mutations in KRAS and RET were detected in the study cohort. However, LCNEC and LCC showed distinct mutational profiles with an enrichment of RB1 / TP53 co-mutations in a subset of LCNEC patients. SMARCA4 and KEAP1 mutations were exclusively found in LCC patients, and RICTOR , BRAF , ROS1 and TET2 mutations were only detected in LCNEC. LCC patients in the cohort had shorter survival compared to LCNEC patients (p=0.006). Survival analysis revealed an association between SMARCA4 mutations and poor outcome in the study cohort and in the LCC subset. Mutations in BRAF were associated with a trend of increased survival in the study cohort, as well as in the LCNEC subset. Finally, TET2 mutations were associated with poor outcome in the LCNEC cohort. Conclusion: LCC and LCNEC were both heterogeneous diseases with limited treatment options. Our study identified potential targetable mutations and prognostic biomarkers that might provide more therapeutic options and improve individualized patient care. [ABSTRACT FROM AUTHOR]

Neuroendocrine (NE) tumors of the bladder are infrequent. Among them, large cell NE tumor has been outlined only in case reports and short case series, which describes them as aggressive malignancies with dismal prognosis requiring a multidisciplinary approach. The case of an 82-year-old patient with muscle-invasive large cell NE carcinoma of the bladder associated with urothelial carcinoma in situ is presented. Despite combined treatment modality, relapse with metastatic disease was detected 12.5 months after the initial diagnosis. Thereafter, we review several published cases, and results of the collected data are compared with the largest studies published on this topic. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy (neoCTX) has been recommended as the optimal strategy in surgically resectable neuroendocrine carcinoma (NEC) of the urinary tract (NEC-URO)., Objective: To determine the systemic therapy regimen and timing, which are most active against NEC-URO., Design, Setting, and Participants: We used our institutional historical clinical and pathological database to study 203 patients (cT2, 74%; cT3/4a, 22%; and cTx, 4%) with surgically resectable NEC-URO between November 1985 and May 2020. A total of 141 patients received neoCTX and 62 underwent initial radical surgery, 24 of whom received adjuvant CTX (adjCTX)., Intervention: Neoadjuvant CTX with etoposide/cisplatin (EP), an alternating doublet of ifosfamide/doxorubicin (IA) and EP, dose-dense methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), gemcitabine/cisplatin (GC), or others., Outcome Measurements and Statistical Analysis: Overall survival (OS), downstaging rate, and pathological complete response using a multivariable model adjusting for tumor- and patient-related factors., Results and Limitations: Downstaging rate was significantly improved with neoCTX versus initial surgery (49.6% vs 14.5%, p < 0.0001), stage cT2N0 versus cT3/4N0 (44% vs 25%, p = 0.01), or presence of carcinoma in situ (47% vs 28%, p = 0.01). Downstaging was greatest with IA/EP (65%) versus EP (39%), MVAC/GC (27%), or others (36%, p = 0.04). After adjusting for age and Eastern Cooperative Oncology Group performance status, IA/EP was still associated with improved downstaging (odds ratio = 3.7 [1.3-10.2], p = 0.01). At a median follow-up of 59.7 mo, 5-yr OS rates for neoCTX followed by surgery, surgery alone, and surgery followed by adjCTX were 57%, 22%, and 30%, respectively. An NEC regimen (IA/EP or EP) versus a urothelial regimen (MVAC/GC or others) was associated with improved survival (145.4 vs 42.5 mo, hazard ratio = 0.49, 95% confidence interval: 0.25-0.94)., Conclusions: Neoadjuvant CTX remains the standard-of-care treatment for NEC-URO with an advantage for NEC regimens over traditional urothelial regimens. IA/EP improves pathological downstaging at the time of surgery compared with EP, but is reserved for younger and higher function patients., Patient Summary: In this report, we looked at the outcomes from invasive neuroendocrine carcinoma of the urinary tract in a large US population. We found that the outcomes varied with treatment strategy. We conclude that the best outcomes are seen in patients treated with chemotherapy prior to surgery and regimens tailored to histology and tolerance., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Large-cell neuroendocrine carcinoma (NEC) is an uncommon type of tumor that can occur in the endometrium. This aggressive cancer requires definitive management. Here, we describe the clinical characteristics and treatment of a postmenopausal woman with large cell NEC of the endometrium., Case Summary: A 55-year-old Asian female presented with a 1-year history of postmenopausal vaginal bleeding. Transvaginal ultrasound revealed a thickened endometrium (30.2 mm) and a hypervascular tumor. Computed tomography revealed that the tumor had invaded more than half of the myometrium and spread to the pelvic lymph nodes. The tumor marker, carcinoembryonic antigen, was elevated (3.65 ng/mL). Endocervical biopsy revealed high-grade endometrial carcinoma. She underwent radical hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and bilateral pelvic and para-aortic lymph node dissection. Pathological examination revealed mixed neuroendocrine and endometrioid adenocarcinoma, pT2N0M0, grade 3, and International Federation of Gynecology and Obstetrics stage 2. Immunohistochemistry showed moderate estrogen and progesterone receptor expressions (20% and 1%, respectively), focal CD56 expression (NEC marker), positive staining for vimentin, p53 (wild type), and ki67 (90%), and loss of expression of PMS2 (Lynch syndrome marker). The patient received five cycles of cisplatin and etoposide after surgery. No recurrence was noted after 5 mo., Conclusion: We report the characteristics and successful management of a rare case of large-cell endometrial NEC concomitant with Lynch syndrome., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)