Case Of Neuroendocrine Carcinoma Research Articles

Analysis of imaging features of rare tumors in nasal cavity and paranasal sinus

Objective:To explore the imaging features of rare tumors of nasal cavity and sinuses, and to improve the understanding of these diseases, thereby aiding clinical diagnosis and treatment. Methods:The CT and MRI findings of 79 cases of rare neoplasm of nasal cavity and sinuses confirmed by pathology were retrospectively analyzed, and the imaging features were summarized. Results:Among the 79 cases, there were 16 cases of neuroendocrine carcinoma, most showing expansive and infiltrative bone destruction without hyperosteogeny and sclerosis. The sphenoid sinus exhibited a "pigeon" shape. In 28 cases of malignant melanoma, MRI signals were diverse, typical signals were rare, but mixed signals were more common. In 12 cases of rhabdomyosarcoma, MRI enhancement mostly showed "grape-like" enhancement and partial ring enhancement; There were 10 cases of olfactory neuroblastoma, the lesions were consistent with the distribution area of olfactory mucosa, most of them were lobulated, marginal nodules, and "flower ring" enhancement, and 2 cases grew across intracranial and external, with multiple cystic lesions and surrounding flaky edema bands. In 5 cases of solitary fibrous tumor, Benign tumors had regular shape and uniform density, while malignant tumors had irregular shape and uneven density, The enhancement was obviously uneven and showed a "pattern" change. There were 2 cases of sarcomatoid carcinoma, both with lobed appearance, uneven density, lamellar low-density shadow, and osteolytic bone destruction. In 4 cases of schwannoma, the enhancement showed obvious inhomogeneous enhancement. One case showed cystic necrosis, one case showed calcification, and the surrounding structure was compressed without damage. There was 1 case of neurofibroma, with many cystic components, low signal separation and compartmentalized enhancement. One case of paraganglioma showed moderate enhancement in the arterial phase and progressive enhancement in the venous phase, accompanied by significant swelling bone destruction. Conclusion:Rare tumors of nasal cavity and paranasal sinuses have distinctive imaging features. CT and MRI can effectively show the extent of the lesions and the degree of infiltration into adjacent tissues and organs, which is helpful for early clinical diagnosis and staging. However, definitive diagnosis still depends on pathology and immunohistochemistry.

A case of metastatic HPV-related cervical small cell neuroendocrine carcinoma with varying cytomorphology found in cytological specimens of a solid organ transplant recipient.

Small cell neuroendocrine carcinoma (NEC) of the cervix is a rare gynecological malignancy, constituting 2%-5% of all such cases. As high-risk Human Papilloma Virus (HR-HPV) infections contribute to 85% of these tumors, small cell NEC poses a significant risk for solid organ transplant recipients, increasing their risk of progressive disease. We present a case of an uterine cervix small cell NEC with metastasis to the bladder and pleural cavities in a 53-year-old woman with a past medical history of kidney transplantation, who presented with abnormal uterine bleeding. The initial liquid preparation (ThinPrep) cytology stained with Papanicolaou (Pap) showed an adenocarcinoma not otherwise specified. At the time of diagnosis, the patient had diffusely metastatic disease. A subsequent uterine cervix biopsy was consistent with a small cell NEC. Despite treatment with chemotherapy, the patient's condition deteriorated, evidenced by a worsening right-sided pleural effusion one-month postdiagnosis. A pleural effusion showed a tumor with glandular features, with immunohistochemistry suggestive of metastatic adenocarcinoma. HR HPV E6/E7 RNA in situ hybridization (ISH) was positive. Bladder washing showed cytopathologic findings consistent with bladder involvement by small cell carcinoma. The patient's lesions in both urine and pleural fluids showed distinct cytomorphology. Within a year of diagnosis, the patient was declared deceased. This case highlights the existence of carcinoma admixed with NEC tumor, such as an HPV associated adenocarcinoma admixed with a NEC and underscores the elevated risk of HPV-related genital lesions in renal transplant patients. In patients with a history of solid organ transplant or other immunosuppressive conditions, there is an increased necessity for enhanced surveillance and appropriate cancer screening.

Imaging characteristics and diagnosis of primary middle mediastinal tumors

Objectives: To investigate the proportion of different histological types and CT enhanced imaging features of primary middle mediastinal lesions in order to improve the understanding of these tumors and the accuracy of preoperative diagnosis. Methods: Retrospective analysis was conducted on 84 patients with primary middle mediastinal lesions and clear histological classifications diagnosed and treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2012 to December 2022. Clinical, imaging, and pathological data were collected and classified according to tumor histological classifications. CT imaging manifestations such as tumor location, size, morphology, edge, boundary, internal components, enhancement characteristics, and surrounding tissue invasion were evaluated and recorded. Results: The histological types of the primary middle mediastinal lesions from the 84 patients included mesenchymal tumors, anterior intestinal cysts, giant lymph node hyperplasia, substernal goiter, neuroendocrine carcinoma, lymphohematopoietic system tumors, and mesothelioma, accounting for 28.6%, 27.4%, 14.3%, 3.6%, 11.9%, 9.5%, and 4.8%, respectively. Mesenchymal tumors included peripheral nerve sheath tumors, vascular tumors, adipogenic tumors, solitary fibrous tumors, and synovial sarcoma, accounting for 54.2%, 20.8%, 12.5%, 8.3%, and 4.2%, respectively. The above tumors had diverse imaging manifestations and specific imaging features. Mature fat were found in 3 cases of liposarcoma; Calcification was observed in 2 cases of thyroid nodules and 7 cases of giant lymph node hyperplasia; Enhanced scanning showed significant enhancement in 2 cases of solitary fibrous tumors, 3 cases of thyroid nodules, and 11 cases of giant lymph node hyperplasia; Mediastinal large lymph nodes was observed in 6 cases of lymphoma and 3 cases of mesothelioma; High invasiveness was observed in 4 cases of mesothelioma and 9 cases of neuroendocrine carcinoma. Conclusion: Mediastinal tumors have low incidence rate and rich histological types, and their imaging manifestations are diverse. Preoperative differential diagnosis can be made according to their specific imaging characteristics.

About a case of neuroendocrine carcinoma of the uterine cervix in peru

About a case of neuroendocrine carcinoma of the uterine cervix in peru

Gene expression profiling of pancreatic neuroendocrine carcinoma and mixed neuroendocrine-non-neuroendocrine neoplasm

Pancreatic neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) are rare pancreatic malignant tumors, and comprehensive gene analyses are scarce. In this study, six NECs and six MiNENs were collected, immunohistochemistry for synaptophysin, chromogranin A, INSM1, Ki-67, and Rb was conducted, and KRAS mutational status was examined. Among these cases, comprehensive gene expression analysis of oncogene pathways using nCounter® were performed with six NECs and four MiNENs, and those data were compared with that of three pancreatic ductal adenocarcinomas (PDACs), with that of three normal pancreatic ducts, and with each other. By dividing NEC and MiNEN cases into KRAS-mutated group and KRAS-wild group, the difference of clinicopathological data and gene expression profiling data were examined between the two groups. Compared to the data of normal pancreatic epithelium, all 13 cancer-related pathways were upregulated in PDAC, MiNEN, and NEC group with more upregulation in this order. Compared to the data of PDAC, genes of DNA Damage repair pathway was most upregulated both in NECs and MiNENs. Regarding the difference between KRAS-mutated and KRAS-wild groups, several genes were differentially expressed between the two, where MMP7 was the upregulated gene with highest p-value and NKD1 was the downregulated gene with highest p-value in KRAS-mutated group. From the extent of upregulation of 13 pathways, MiNEN was considered more progressed stage than PDAC, and NEC was considered more progressed than MiNEN. From the comparison of KRAS-mutated and KRAS-wild NECs and MiNENs, several differentially expressed genes were identified in this study.

Implication of cytoplasmic p53 expression in pulmonary neuroendocrine carcinoma using next-generation sequencinganalysis.

Cytoplasmic p53 expression indicates a high frequency of TP53 abnormalities in gynaecological carcinoma. However, the implication of this expression in pulmonary neuroendocrine carcinoma (NEC) remains unclear. Thus, our study aimed to fill this research gap. Immunohistochemistry (IHC) of p53 was performed on 146 cases of resected small-cell lung carcinoma and large-cell NEC, and next-generation sequencing was conducted on cases showing cytoplasmic and wild-type p53 expression. IHC revealed overexpression in 57% of the cases (n = 83), complete absence in 31% (n = 45), cytoplasmic expression in 8% (n = 12) and wild-type expression in 4% (n = 6) of the cases. TP53 mutations were identified in nine of the 13 cases with available genetic analysis. The TP53 mutation rates in cases with cytoplasmic and wild-type p53 expression were 88% (seven of eight) and 40% (two of five), respectively. All seven cases showing cytoplasmic expression with TP53 mutations harboured loss-of-function type mutations: four had mutations in the DNA-binding domain, two in the nuclear localisation domain and one in the tetramerisation domain. Clinically, cases with cytoplasmic p53 expression had a poor prognosis similar to that in cases with p53 overexpression or complete absence. Cytoplasmic p53 expression in patients with pulmonary NEC suggests a high TP53 mutation rate, which is associated with a poor prognosis similar to that in patients with p53 overexpression or complete absence. This cytoplasmic expression should not be misidentified as a wild-type expression. This is the first report, to our knowledge, that demonstrates the implication of cytoplasmic p53 expression in pulmonary NEC.

Diagnostic Challenges and Long-term Outcomes of Neuroendocrine Carcinoma of the Cervix: A Case Series.

Neuroendocrine carcinomas (NECs) of the cervix are rare, aggressive malignancies that are challenging to diagnose and treat. They are high-grade lesions that often share features with poorly differentiated adenocarcinoma and squamous cell carcinoma. NECs are classified into large-cell or small-cell subtypes but can often have a mixed appearance or occur concurrently with a squamous or adenocarcinoma. Diagnosis is dependent on tissue sampling, histomorphology, and immunohistochemistry. Eight cases of NEC were retrieved from the Department of Pathology at our institution from 2008 to 2022. Tumor slides were reviewed and evaluated by 2 independent pathologists. Seven of 8 patients tested positive for neuroendocrine markers, including CD56, synaptophysin, and chromogranin. We discuss the diagnostic challenges, review the histopathology, and describe the treatment courses and clinical outcomes. This case series reveals that traditional markers, such as p16, p63, and p40, may be focally positive in NEC and should not be considered a confirmation of squamous cell carcinoma. Patient outcomes can be affected by delays in diagnosis, misdiagnosis, and inadequate treatment when NEC is not considered in the initial differential diagnosis.

Neuroendocrine Carcinoma of the Hypopharynx - An Elusive Clinical Rarity.

Neuroendocrine carcinoma originating from neuroendocrine cells is typically linked to unfavourable survival rates. We are introducing an exceptional case of neuroendocrine carcinoma occurring in the hypopharynx. To date, only a handful of instances involving primary neuroendocrine carcinoma of the hypopharynx have been documented. Advanced age, being male, a history of chronic alcoholism, smoking, and previous radiation are all risk factors associated with this condition. The majority of patients present with distant metastases and are not amenable to a complete cure. As there are no guidelines for the treatment of this rare tumour, various treatment modalities have been tried. Here, we are reporting one such case which was diagnosed as small-cell neuroendocrine carcinoma of the hypopharynx on the basis of histopathological cues and received concurrent chemoradiotherapy.

The prognostic impact of a high number of peritumoral alveolar macrophages in neuroendocrine carcinoma in the lung.

Alveolar macrophages (AMs) are resident macrophages in the lungs; however, whether the number of AMs plays a role in the lung neuroendocrine tumor (NET) prognosis remains unclear. We counted the number of AMs located around the tumor (peritumoral alveolar macrophages [pAMs]) and the number of AMs located apart from the tumor (distant macrophages; dAMs). In 73 cases of neuroendocrine carcinoma (NEC: small cell lung carcinoma and large cell neuroendocrine carcinoma), the group that contained higher pAMs (≥86/μm2 ) revealed shorter recurrent-free survival (RFS) than those with lower pAMs (<86/μm2 ) (p = 0.005). Bivariate analysis showed that the number of pAMs was an independent predictor of a poor RFS. In contrast, in the carcinoid tumor cohort (n = 29), there was no statistically significant correlation between the two groups with high and low numbers of pAMs in RFS (p = 0.113). Furthermore, we examined the correlation between genomic alterations and the number of pAMs in NEC, but no significant correlation was observed. In conclusion, the number of pAMs is a prognostic factor for NEC in the lung and pAMs may contribute to tumor progression within the peritumoral microenvironment.

Neuroendocrine carcinoma of the minor papilla with pancreas divisum: a case report and review of the literature

BackgroundNeuroendocrine tumors of the minor papilla are very rare, and only 20 cases have been reported in the literature. Neuroendocrine carcinoma of the minor papilla with pancreas divisum has not been reported previously, making this the first reported case. Neuroendocrine tumors of the minor papilla have been reported in association with pancreas divisum in about 50% of cases reported in the literature. We herein present our case of neuroendocrine carcinoma of the minor papilla with pancreas divisum in a 75-year-old male with a systematic literature review of the previous 20 reports of neuroendocrine tumors of the minor papilla.Case presentationA 75-year-old Asian man was referred to our hospital for evaluation of dilation of the main pancreatic duct noted on abdominal ultrasonography. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed a dilated dorsal pancreatic duct, which was not connected to the ventral pancreatic duct; however, it opened to the minor papilla, indicating pancreas divisum. The common bile duct had no communication with the pancreatic main duct and opened to the ampulla of Vater. A contrast-enhanced computed tomography scan showed a 12-mm hypervascular mass near the ampulla of Vater. Endoscopic ultrasonography showed a defined hypoechoic mass in the minor papilla with no invasion. The biopsies performed at the previous hospital found adenocarcinoma. The patient underwent a subtotal stomach-preserving pancreaticoduodenectomy. The pathological diagnosis was neuroendocrine carcinoma. At the 15-year follow-up visit, the patient was doing well with no evidence of tumor recurrence.ConclusionIn our case, because the tumor was discovered during a medical check-up relatively early in the course of disease, the patient was doing well at the 15-year follow-up visit, with no evidence of tumor recurrence. Diagnosing a tumor of the minor papilla is very difficult because of the relatively small size and submucosal location. Carcinoids and endocrine cell micronests in the minor papilla occur more frequently than generally thought. It is very important to include neuroendocrine tumors of the minor papilla in the differential diagnosis of patients with recurrent pancreatitis or pancreatitis of unknown cause, especially for patients with pancreas divisum.

An integrative epigenomic approach identifies ELF3 as an oncogenic regulator in ASCL1-positive neuroendocrine carcinoma.

Neuroendocrine carcinoma (NEC) is a highly aggressive subtype of the neuroendocrine tumor with an extremely poor prognosis. We have previously conducted a comprehensive genomic analysis of over 100 cases of NEC of the gastrointestinal system (GIS-NEC) and unraveled its unique and organ-specific genomic drivers. However, the epigenomic features of GIS-NEC remain unexplored. In this study, we have described the epigenomic landscape of GIS-NEC and small cell lung carcinoma (SCLC) by integrating motif enrichment analysis from the assay of transposase-accessible chromatin sequencing (ATAC-seq) and enhancer profiling from a novel cleavage under targets and tagmentation (CUT&Tag) assay for H3K27ac and identified ELF3 as one of the super-enhancer-related transcriptional factors in NEC. By combining CUT&Tag and knockdown RNA sequencing for ELF3, we uncovered the transcriptional network regulated by ELF3 and defined its distinctive gene signature, including AURKA, CDC25B, CLDN4, ITGB6, and YWAHB. Furthermore, a loss-of-function assay revealed that ELF3 depletion led to poor cell viability. Finally, using gene expression of clinical samples, we successfully divided GIS-NEC patients into two subgroups according to the ELF3 signature and demonstrated that tumor-promoting pathways were activated in the ELF3 signature-high group. Our findings highlight the transcriptional regulation of ELF3 as an oncogenic transcription factor and its tumor-promoting properties in NEC.

Analysis of the Clinicopathological Characteristics, Prognosis, and Lymphocyte Infiltration of Esophageal Neuroendocrine Neoplasms: A Surgery-Based Cohort and Propensity-Score Matching Study.

Esophageal neuroendocrine neoplasms (E-NENs) are a rare and poorly reported subtype of esophageal carcinoma. We analyzed the differences in clinicopathological features, prognosis, and tumor-infiltrating lymphocytes (TILs) between E-NENs and esophageal squamous cell carcinoma (ESCC). A total of 3620 patients who underwent esophagectomy were enrolled retrospectively. The study cohort was divided into two groups (E-NENs and ESCC) through propensity-score matching, and the prognosis and TILs were compared between the two groups. The TILs were assessed using tumor specimens (including six cases of ESCC, six cases of neuroendocrine carcinomas [NECs], and six cases of mixed neuroendocrine-non-neuroendocrine neoplasms [MiNENs]). E-NENs accounted for 3.0% (107/3620) of cases, among which there were just 3 neuroendocrine tumor cases, 51 NEC cases, and 53 MiNENs cases. After matching, esophageal neuroendocrine carcinomas (E-NECs) showed both poorer 5-year overall survival (OS; 35.4% vs. 54.8%, p = 0.0019) and recurrence-free survival (RFS; 29.3% vs. 48.9%, p < 0.001) compared with ESCC. However, the differences were not prominent in the subgroup with stage I. No significant survival benefit was observed for E-NECs with multimodal therapy. Multivariate analysis demonstrated that E-NECs are an independent risk factor for OS and RFS. In the exploratory analysis, E-NECs were associated with less infiltration of immune cells compared with ESCC. E-NECs are significantly associated with a poorer prognosis than ESCC except for early-stage disease. The fewer TILs within the tumor microenvironment of E-NECs compared with ESCC results in weaker anti-tumor immunity and may lead to a poorer prognosis.

Neuroendocrine Carcinoma with Bone Marrow Metastasis: A Case Series

Neuroendocrine Neoplasms (NENs) account for 0.5% of all malignancies. Skeletal colonisation is often regarded as a rare event, and metastasis to the bone marrow occurs in the advanced stage of the disease, carrying a poor prognosis. In this report, the authors present three rare cases of Neuroendocrine Carcinomas (NEC) of the lung, diagnosed among 6766 bone marrow aspirations and biopsies performed at our institution between January 2019 and December 2022, highlighting the rarity of these cases. All three cases (63 years, 56 years and 73 years old male patients) presented to our institute at an advanced stage of the disease, with bone marrow involvement at the time of presentation. They exhibited nonspecific symptoms and had normal haematological parameters. Bone marrow aspiration and biopsy confirmed metastatic NEC. The aim of this case series was to investigate bone marrow involvement in NECs, along with their clinical and radiographic features, treatment, and follow-up. Bone marrow biopsy plays a crucial role not only in diagnosing haematological diseases but also in diagnosing and staging solid tumours. Future prospectives include adopting a multimodal approach for early diagnosis and treatment of NECs.

Neuroendocrine Carcinomas of the Uterine Cervix, Endometrium, and Ovary Show Higher Tendencies for Bone, Brain, and Liver Organotrophic Metastases.

Neuroendocrine carcinoma (NEC) of the female genital tract is a rare and aggressive subtype of cancer that is still poorly understood. Several recent studies reported that pulmonary and gastroenteropancreatic neuroendocrine neoplasms show significantly different patterns of metastasis compared to non-NECs of the same primary sites. The aim of this study was to evaluate the metastatic patterns of gynecologic NECs and to compare the metastatic patterns of NECs and non-NECs of the same primary sites. We retrieved and analyzed cervical, endometrial, and ovarian NEC cases from the Surveillance, Epidemiology, and End Results (SEER) database. To validate the results, we also retrieved and analyzed cervical NEC cases from an institutional database. Uterine cervical NEC was the most common NEC. The overall metastatic rate was significantly higher in the NEC group than in the non-NEC group for all three primary sites. All cervical, endometrial, and ovarian NECs showed a higher tendency for bone, brain, and liver organotrophic metastasis than non-NECs of the same primary sites. We demonstrated that gynecologic NECs show significantly different metastatic patterns compared to non-NECs of the same primary sites. These findings might help clinicians to better manage patients with gynecologic NECs.

Neuroendocrine Tumours of Extrahepatic Biliary Tract: Report of Four Cases with Literature Review.

Neuroendocrine tumours (NETs) originating from extrahepatic bile duct are an extremely rare entity. They are typically slow growing tumours with malignant potential. Commonly presenting as obstructive jaundice, preoperative clinico-radiologic differentiation between extrahepatic biliary tract neuroendocrine tumours and cholangiocarcinoma is difficult and the final diagnosis is usually established after surgical histopathology and immunohistochemistry examination. R0 resection offers the only curative option with good long-term outcomes for well-differentiated NETs (grade1, grade2, and grade3) while the aggressive poorly differentiated neuroendocrine carcinoma (NEC) needs multimodality approach. We present our experience of management of four cases including three cases of grade II NET and one case of NEC undergoing surgical resection at a single centre with a short review of available literature.

Case reports: chemoradiotherapy for locally advanced neuroendocrine carcinoma of the gallbladder

Neuroendocrine carcinoma (NEC) is a rare subtype of malignant gallbladder tumor. Although surgical resection is the only potentially curative therapy for gallbladder NEC, most cases are surgically unresectable because of advanced stage disease and/or biologically aggressive behavior. The standard palliative treatment for malignant gallbladder tumors is chemotherapy; however, the efficacy of chemoradiotherapy in the treatment of gallbladder tumors is controversial. Here, we report a case of gallbladder NEC that showed a durable response to chemoradiotherapy. A 68-year-old Japanese man presented with a huge gallbladder tumor with liver and duodenal invasion. Pathological findings revealed poorly differentiated NEC of the gallbladder. After seven cycles of chemotherapy comprising cisplatin and irinotecan, computed tomography (CT) revealed remarkable tumor shrinkage, but an enlarged portal lymph node. The patient was treated with 50.4 Gy in 28 fractions with two cycles of cisplatin and etoposide. After chemoradiotherapy, the enlarged lymph node also decreased in size. Maximum standardized uptake value of fluorodeoxyglucose-positron emission tomography/CT(FDG-PET/CT) changed from 8.2 to physiological accumulation. We defined this condition as a complete response on both enhanced CT and FDG-PET/CT; therefore, we did not perform systemic treatment and only observed his condition. This patient remained healthy with no recurrence at 3 years after chemoradiotherapy.

Endometrial neuroendocrine carcinoma and undifferentiated carcinoma are distinct entities with overlap in neuroendocrine marker expression.

Dedifferentiated endometrial carcinomas (DDECs)/undifferentiated endometrial carcinomas (UDECs) frequently harbour genomic activation of switch/sucrose non-fermentable (SWI/SNF)-complex proteins, and can show histological overlap with neuroendocrine carcinoma (NEC). The aim of this study was to compare the extent of the expression of neuroendocrine markers, SWI/SNF proteins and mismatch repair (MMR) proteins in DDEC/UDEC and NEC. The extent of expression of synaptophysin, chromogranin, CD56, ARID1A, ARID1B, SMARCA4, SMARCB1 and MMR proteins was evaluated by immunohistochemistry on 44 SWI/SNF-deficient DDECs/UDECs and 15 NECs. Thirty-three of 44 (75%) DDECs/UDECs showed expression of at least one neuroendocrine marker, with 18 of 44 (41%) expressing two or more neuroendocrine markers, whereas all 15 NECs showed expression of at least one neuroendocrine marker, with 14 of 15 (93%) expressing two or more neuroendocrine markers. Neuroendocrine marker expression in DDECs/UDECs was typically focal when present, with average extents of 17%, 4% and 8% for synaptophysin, chromogranin and CD56 in the positive cases, respectively, in contrast to 73%, 40% and 62% in the positive NEC cases, respectively. All 15 NECs showed intact expression of SWI/SNF-complex proteins, except for one that showed isolated loss of ARID1A. Thirty-eight of 44 DDECs/UDECs were MMR-abnormal (34 with loss of MLH1 and PMS2, and four with loss of PMS2 alone), whereas all NECs retained MMR protein expression. Our study demonstrates frequent but typically focal neuroendocrine marker expression in SWI/SNF-deficient DDECs/UDECs, whereas NECs typically express two or more neuroendocrine markers, with diffuse expression of at least one marker. ARID1B, SMARCA4 and SMARCB1 immunohistochemistry can be used to aid in the differentiation between DDEC/UDEC and NEC.

Survival According to Primary Tumor Location, Stage, and Treatment Patterns in Locoregional Gastroenteropancreatic High-grade Neuroendocrine Carcinomas.

BackgroundAlthough the gastrointestinal tract (including the pancreas, gastroenteropancreatic (GEP) is the most common site for extrapulmonary neuroendocrine carcinoma (NEC), the current treatment patterns of locoregional GEP NEC and in particular, the role of surgical resection is unclear.MethodsData from the National Cancer Database between 2004 and 2016 were used for this study.ResultsOf 2314 GEP NEC cases (stages I–III), 52.5% were stage III. Colon was the most common site (30%); 30.9% of all cases were small cell morphology. Age, morphology, stage, and primary site were associated with significant differences in treatment patterns. Management of NEC mimicked that of adenocarcinomas arising at the respective sites: colon NEC most likely to be treated with surgery and chemotherapy; anal and esophageal NEC was primarily likely to receive chemotherapy and radiation, and rectal NEC mostly likely to receive trimodality therapy. However, 25%-40% of patients did not undergo surgical resection even at sites typically managed with curative resection, and there was a trend toward lesser resection over time. The prognostic impact of surgical resection was significant across all stages and correlated with variations in survival across primary sites. Even in patients undergoing chemoradiation, surgery was the only prognostic variable that significantly affected survival in stages I–II patients (HR 0.63) and showed a strong trend in stage III (HR 0.77) patients.ConclusionsTreatment patterns in GEP NEC vary considerably according to stage and primary tumor site. Surgery significantly improved survival in stages I–II patients and showed a strong trend in stage III patients regardless of primary tumor location and other perioperative therapies.

Clinicopathological and molecular profile of grade 3 gastroenteropancreatic neuroendocrine neoplasms.

The 2019Word Health Organization (WHO) subclassified grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) into neuroendocrine carcinoma (NEC) or tumours (G3NET) based on morphology and proliferation. Yet, few data exist on molecular profiles for G3NEN. We compared clinicopathological and molecular characteristics of these two groups. We retrospectively reviewed consecutive G3 GEP NEN patients and had their tumour tissues reviewed, reclassified as per the WHO 2019, and analyzed by a next-generation sequencing (NGS) panel. Between 2000 and 2019, 43 patients had pathology revision: 29 (67%) were NEC and 14 (33%) were G3NET, with a 23% change in diagnosis. Median overal survival for G3NET and NEC patients was 55.6 and 11.9months, respectively (hazard ratio=2.78 [95% confidence interval=1.09-7.11], p=.042), which was confirmed by an adjusted analysis (hazard ratio=2.90NEC vs. G3NET; p=.03). NGS was performed in 32 cases: 21NEC and 11 G3NET. Mutations in RB1 and PTEN were exclusively encountered in NEC. Median tumour mutational burden was 5 (0-67) mutations per megabase in NEC and 4.5 (0-9) among G3NET. Microsatellite instability was found in 3 (14.3%) NEC cases. In conclusion, pathology revision is essential to estimate prognosis and therapeutic plan. G3 GEP NEN generally harbour low tumor mutation burden and fewer actionable mutations, but 14% of NEC cases were microsatellite unstable and could benefit from immune checkpoint inhibitors.

A Case of Large Cell Neuroendocrine Carcinoma in Posterior Supraglottis

Neuroendocrine carcinoma (NEC) is a rare form of hormone-secreting tumor. NECs originate from the epithelial cells of the larynx and account for less than 1% of the laryngeal neoplasm. Most cases of NECs are diagnosed by pathological confirmation after surgery. The terminology of laryngeal NEC has been a source of confusion. In 2017, World Health Organization newly categorized laryngeal NEC; as a result, the large cell type, which has been the main target of disagreement, was finally included into a subtype of poorly differentiated NEC. We report a case of a 58-year-old male with a growing granulomatous mass in the posterior supraglottis. The granuloma was removed by surgical excision when the size of the mass increased. He was diagnosed with the large cell type laryngeal NEC by pathological confirmation. He underwent postoperative radiotherapy and is currently being followed up in our outpatient clinic without evidence of recurrence.