Mixed Neuroendocrine-non-neuroendocrine Neoplasms Research Articles

Clinicopathologic features and lymph node metastasis pattern of the cervical MiNEN.

Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare type of cervical tumor. Its clinicopathological features, lymph node (LN) metastatic patterns and outcomes are still unclear. We have analyzed the clinicopathological information of 26 patients with cervical MiNEN. The median age of onset for cervical MiNEN was 48 years. Macroscopically, polyps and nodules were the main types. The neuroendocrine components included small cell neuroendocrine carcinoma (SCNEC) (14/26 cases), large cell neuroendocrine carcinoma (LCNEC) (10/26 cases), and typical carcinoid (2/26 cases). Non-neuroendocrine components included adenocarcinoma (AC) (12/26, including one case of AC in situ) and squamous cell carcinoma (SC) (10/26) and adeno-squamous cell carcinoma (ASC) (4/26). Of the 16 AC cases, 15 were human papilloma virus (HPV)-associated AC and one was HPV-independent AC. Except for the case of MiNEN with HPV-independent AC, all cases were diffusely and strongly positive for p16 protein. The lympho-vascular space invasion (LVSI) was seen in 17/26 cases, and the components that invade lymphatic vessels were mainly neuroendocrine carcinomas (NECs) (15/17), followed by SC (1/17) and AC (1/17). Ten patients developed LN metastases, including six in combined SCNECs (6/14) and four in combined LCNECs (4/10); the metastatic component was pure NEC in eight cases (8/10) and SC or AC in two cases (2/10). NEC component is the key factor that determines the clinical behavior and prognosis of cervical MiNEN.

Coexistence of superficial carcinogenesis of resident epithelium besides neuroendocrine neoplasm of the digestive tract.

Background & AimsMixed neuroendocrine–non‐neuroendocrine neoplasm (MiNEN) is a rare neuroendocrine neoplasm (NEN) comprising dual neuroendocrine and non‐neuroendocrine components. Although the coexistence pattern of neuroendocrine and non‐neuroendocrine components in definitive MiNEN is thought to overlap, there may be a coexistent pattern of both components, such as superficial carcinoma adjacent to NEN. The present study evaluated the histopathological findings of the coexistence pattern of superficial carcinomas adjacent to NENs in the esophagogastrointestinal tract.MethodsFrom 2000 to 2019, 35 serial NEN resections of the esophagus (n = 9), stomach (n = 3), and large intestine (n = 23), respectively, were performed at Gunma University Hospital. Borderline areas between NEN and resident superficial epithelium were observed in the 35 serial NEN cases as well as two additional cases from affiliated hospitals.ResultsAmong the 35 serial NEN samples, squamous cell carcinomatous/dysplastic components were identified 77.8% (7/9 cases) of esophageal NENs, and adenocarcinomatous areas were seen in 66.7% (2/3 cases) of gastric NENs and 26% (6/23 cases) of colorectal NENs. Thus, all superficial carcinomatous components adjacent to NENs were observed as squamous cell carcinoma/dysplasia in esophagus and adenocarcinoma in stomach and large intestine, which showed histological characteristics as the resident epithelial pattern in each organ.ConclusionsThese findings suggested a potential “paratransformation” or “bystander effect” in resident epithelium by NENs. Thus, “bystander carcinogenesis” could be a pathogenic mechanism of resident epithelium transformation adjacent to NENs in the esophagogastrointestinal tract.

Clinicopathologic Characteristics of Gastroenteropancreatic Neuroendocrine Tumors: Experience of a National Referral Hospital in Indonesia

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have variable biological behavior although they are all malignant. This study presents the 10-year prevalence along with the clinicopathologic characteristics of GEP-NETs and their association with tumor grade at a national referral hospital in Indonesia. This is a retrospective cross-sectional study of patients with GEP-NET confirmed by histomorphology and immunohistochemistry who presented to Cipto Mangunkusumo Hospital from 2009 to 2019. Clinical characteristics included age, sex, primary site, tumor stage, metastasis, hormone status, and chief complaints. Pathological characteristics included the type of GEP-NET, specimen type, grade, and presence of lymphovascular invasion (LVI). Statistical analysis was performed to determine the association between characteristics and tumor grade. A total of 84 cases of GEP-NET from 2009 to 2019 were included; of these, 38.1% were neuroendocrine tumors (NETs), 28.6% were neuroendocrine carcinomas (NECs), and 33.3% were mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN). The mean patient age was 48.36 years, and the male to female ratio was 1. GEP-NETs predominantly originated from the rectum (21.4%) and were mostly non-functioning (90.5%) with an average tumor size of 4.77 cm. Most tumors were localized (53.6%), but metastasis was found in 28.6% cases. LVI was positive in 35.7% cases. High-grade tumors were more common (54.3%) than low-grade tumors. High-grade tumors were associated with unknown primary sites, dissemination, LVI, and larger tumor size. To conclude, GEP-NETs can arise from any site in the gastrointestinal tract and have variable clinicopathologic characteristics. Primary site, stage, LVI, and tumor size are associated with grade.

Mixed neuroendocrine-non-neuroendocrine neoplasm of the colon: case report

Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is defined as a tumor composed of cells originating from neuroendocrine cells in the embryonic intestine and elements of epithelial adenocarcinoma. To determine the differentiation grade of MiNEN, the proliferation index was used, for which at least 500 cells were examined. MiNEN is a rare neoplasm that is most frequently found in the lower gastrointestinal tract. We present a rare clinical case of surgical treatment of MiNEN of the ascending colon.

Data Set for Reporting Carcinoma of the Stomach in Gastrectomy.

A standardized detailed surgical pathology report is the cornerstone of gastric cancer management. To guide management and prognostication for patients with gastric carcinomas globally, the International Collaboration on Cancer Reporting aimed to produce an evidence-based international pathology reporting data set with a panel of globally recognized expert pathologists and clinicians. Based on published guidelines/data sets for gastric carcinomas, a working draft was developed by the chair of the expert panel of pathologists and clinicians. The draft was then circulated to the panel and discussed in a series of teleconferences and email communications until consensus was achieved. The draft data set was uploaded on the International Collaboration on Cancer Reporting Web site for public comment. The data set was reviewed in consideration of the feedback, and a final version was approved by the panel. This data set was developed for gastrectomy specimens for primary gastric carcinomas, including neuroendocrine carcinomas and mixed neuroendocrine-nonneuroendocrine neoplasms. Well-differentiated neuroendocrine tumors, nonepithelial malignancies, and secondary tumors were excluded from this data set. The final data set contains 15 core (required) elements and 8 noncore (recommended) elements. A commentary is provided for each element. The International Collaboration on Cancer Reporting has published freely available, evidence-based data sets for gastric cancer reporting. Standardized reporting has been shown to improve patient care and facilitates data exchange and analysis for quality assurance, cancer epidemiology, and clinical and basic research.

Mixed neuroendocrine-non-neuroendocrine tumour of pancreas mimicking groove pancreatitis: Case report.

IntroductionMixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare tumour of the pancreas which can mimic groove pancreatitis.Case reportWe present a 49-year-old Indian male presented with constant, dull-aching epigastric pain for last 6 months radiating to back, not associated with jaundice, gastrointestinal bleed, fever or weight loss. He also had history of alcohol abuse for last 15 years. Physical examination was unremarkable. Laboratory investigations were within normal limits. Contrast enhanced computed tomography (CT) of the abdomen was suggestive of groove pancreatitis. CA 19.9, CEA and IgG4 levels were normal. Upper gastrointestinal endoscopy revealed an oedematous mucosa with narrowing of second part of duodenum. Endoscopic ultrasound (EUS) showed bulky pancreas with ill-defined heteroechoic head with periduodenal soft tissue thickening. EUS guided fine needle aspiration revealed chronic inflammatory cells. Based on the endoscopic findings and imaging, we suspected the diagnosis to be groove pancreatitis. He underwent open Whipple's pancreaticoduodenectomy. Histopathological evaluation revealed well differentiated neuroendocrine tumour and immunohistochemistry revealed features which was consistent with mixed neuroendocrine-non-neuroendocrine tumour (MiNEN). Post-operative period was uneventful and he was discharged on post-op day 7. A PET-CT scan was done to look for any silent metastasis and it was negative. He recieved 4 cycles of cisplatin-based chemotherapy. He was symptom free and doing well on 12 months follow up with no evidence of recurrence in surveillance CT imaging.DiscussionPancreatic MiNEN is characterised by presence of two malignant tissues, adenocarcinoma and NET, with one constituent involving at least 30% of the tumour. We report the pitfalls in diagnostic work-up which can lead to misdiagnosis of this rare entity. Specially due to admixture of different kinds of tissue, radiological investigations can be misleading.ConclusionOur case highlights the fact that MiNEN of pancreas can mimic a benign condition like groove pancreatitis. If routine histopathological and immunohistochemical evaluation is not done on the resected samples, relying on radiological and fine-needle aspiration cytology evidences, the actual diagnosis could be missed.

812 PROGRAMMED CELL DEATH PROTEIN 1/PROGRAMMED DEATH LIGAND 1 AND HLA-CLASS I ARE POTENTIAL THERAPEUTIC TARGETS IN ESOPHAGEAL NEUROENDOCRINE CARCINOMA

Abstract Esophageal neuroendocrine carcinoma (NEC) is a rare and aggressive subtype with a poor prognosis. Pembrolizumab was recommended for the treatment of PD-L1 positive tumors in esophageal cancer and the combined positive score (CPS) was reported to be a better predictor of efficacy compared to the tumor proportion score (TPS). We investigated the expression profile of potential therapeutic targets (PD-L1, HLA class I, Mismatch repair (MMR) proteins) and tumor infiltrating lymphocytes (TILs) in esophageal NEC. Methods 15 NECs of the esophagus including mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) with squamous cell carcinoma (SCC) component were investigated in the study. The expression of PD-L1 (quantitatively evaluated by CPS and TPS), HLA class I, and MMR protein expression were examined immunohistochemically. TIL abundance was examined semiquantitatively by observation of H&E slides. Results Nine (60%) showed a CPS ≥ 1, five (33%) showed a CPS ≥10, and five cases showed a TPS ≥1. Survival analysis showed a significantly longer overall survival in the CPS ≥1 group than in the CPS <1 group. Deficiency of MMR protein was not observed in any cases. HLA-Class I expression was retained in 10 (67%), and loss of HLA-Class I was significantly correlated with frequent lymph node metastasis, high TNM Stage, and low TIL. Three showed both PD-L1 CPS ≥ 10 and high TIL. Conclusion In esophageal NEC, PD-L1 positivity and preserved HLA-Class I expression were frequently observed, and PD-L1 CPS ≥ 1 was significantly associated with the better prognosis of esophageal NEC. Therefore, the PD-1/PD-L1 pathway and HLA-class I are thought to be potential therapeutic targets in esophageal neuroendocrine carcinoma.

Abstracts and Case Studies for the College of American Pathologists 2021 (CAP21) Annual Meeting

Abstracts and Case Studies for the College of American Pathologists 2021 (CAP21) Annual Meeting

Neuroendocrine Neoplasms of the Larynx: A Clinicopathologic Analysis of 27 Neuroendocrine Tumors and Neuroendocrine Carcinomas.

Laryngeal neuroendocrine neoplasms (NENs) are rare and heterogeneous, encompassing well-differentiated neuroendocrine tumors (NETs; grade 1, 2, and 3), neuroendocrine carcinomas (NECs, small cell and large cell types), and mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN). We aimed to study the clinicopathologic spectrum of these neoplasms. A retrospective review of all primary laryngeal NENs diagnosed from 2005 to 2017 was undertaken. Mitotic index was divided into < 2, ≥ 2-10, and > 10 mitoses/2 mm2, with a Ki-67 labelling index of < 2%, ≥ 2-20%, and > 20% for the NET grade 1, 2 and 3 categories, respectively. A total of 27 patients were included. The median age at presentation was 60years; the male-to-female ratio was 8:1. Supraglottis (n = 22) was the most frequently affected subsite. There were 9 NETs grade 2 (G2), and 18 NECs cases. There were no NET grade 1 or 3 cases in our cohort. Among the NETs G2, the morphology was epithelioid (2), plasmacytoid (3), clear (2), oncocytic (1), and rhabdoid (1). Unique 'glomeruloid structures' (n = 5), calcification (n = 3), lymphoid aggregates (n = 5), intranuclear inclusions (n = 2), hyaline globules (n = 3), and Leisegang rings (n = 2) were identified. NECs comprised 16 small cell neuroendocrine carcinoma and 2 large cell neuroendocrine carcinoma. On immunohistochemistry, tumor cells expressed AE1/AE3 (86%), synaptophysin (100%), chromogranin (100%), INSM1 (100%), calcitonin (33.3%). In the NEC group, p53 aberrant expression (87.5%), Retinoblastoma (Rb) loss (88.2%), and diffuse p16 immunoreactivity (66.7%) were additionally observed. Lymph-node metastasis was detected in 62.5% and 85.7%, while distant metastasis in 55.6% and 76.9%, respectively in NET G2 and NEC. Laryngeal NENs are aggressive neoplasms with a high rate of nodal and distant metastasis. Awareness of the wide pathologic spectrum of laryngeal NENs and appropriate use of IHC is needed to render an accurate diagnosis. Ki67 assessment is strongly recommended for laryngeal NEN prognostication.

Clinicopathologic and Molecular Characteristics of Gastrointestinal MiNENs.

BackgroundA mixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN) is a recently defined entity that comprises a neuroendocrine tumor (NEN) component and a non-neuroendocrine tumor (nNEN) component. As MiNEN is a recently defined entity, its molecular nature is not well known. Here, we evaluated the clinicopathologic and molecular characteristics of gastrointestinal (GI) MiNENs.MethodsWe performed a genomic analysis of 31 samples from 12 GI MiNEN cases using next-generation sequencing. We examined the primary NEN and nNEN components, as well as the metastatic NENs and nNENs. The relationships between the clinical tumor features (component, location, and grade) and their molecular characteristics were examined.ResultsThe 12 MiNENs included in the study were found in the stomach (n=10), distal rectum (n=1), and anus (n=1). Primary MiNENs that had NENs as the major component showed a worse clinical outcome than those that had nNENs as the major component. All distant metastatic tumors originating from MiNENs were NENs. In addition, NENs generally carried 1.5 times more gene mutations and copy number variations than nNENs. The ATRX gene deletion and TP53 gene mutation were the most common variants in both components of GI MiNENs.ConclusionsWe have revealed the detailed clinicopathologic and molecular findings with distinguishable alterations of GI MiNENs. To our knowledge, this is the first study to report the ATRX gene deletion in GI MiNENs. The molecular characteristics of GI MiNENs could provide clues to the pathogenic origin and progression of GI MiNENs.

GNEN-1: a spontaneously immortalized cell line from gastric neuroendocrine neoplasia.

Mixed neuroendocrine-non-neuroendocrine neoplasms (MINEN) are rare tumors that consist of at least 30% of both neuroendocrine and non-neuroendocrine components. The data concerning the pathogenesis of MINEN suggest a monoclonal origin. We describe a spontaneously immortalized cell line derived from gastric MINEN called GNEN-1. Primary tumor consisted of components of high-grade neuroendocrine carcinoma and adenocarcinoma. The GNEN-1 cell line was initiated from metastatic tumor cells of peritoneal fluid and expresses a purely neuroendocrine phenotype. The GNEN-1 cell line grows as monolayers and has retained the neuroendocrine phenotype with positivity for chromogranin A in immunohistochemistry. Electron microscopy showed cytoplasmic dense core granules and axon hillocks. The karyotype revealed alterations typical of both adenocarcinoma and neuroendocrine carcinoma such as trisomy 7 and 8. GNEN-1 cells were also positive for stanniocalcin-1, a marker of poor prognosis in gastric carcinomas. Expression of several markers related to neuroendocrine tumors was found. There have been only a few studies on the pathogenesis of MINEN and management of the disease due to the rarity of this tumor type. Here we describe for the first time an immortalized cell line derived from mixed gastric NEN. The GNEN-1 line offers a tool for future research on gastric NEN.

Mixed Neuroendocrine/Non-neuroendocrine Neoplasm (MiNEN) of the Ovary Arising from Endometriosis: Molecular Pathology Analysis in Support of a Pathogenetic Paradigm

Primary ovarian neuroendocrine neoplasms (Ov-NENs) are infrequent and mainly represented by well-differentiated forms (neuroendocrine tumors — NETs — or carcinoids). Poorly differentiated neuroendocrine carcinomas (Ov-NECs) are exceedingly rare and only few cases have been reported in the literature. A subset of Ov-NECs are admixed with non-neuroendocrine carcinomas, as it occurs in other female genital organs, as well (mostly endometrium and uterine cervix), and may be assimilated to mixed neuroendocrine/non-neuroendocrine neoplasms (MiNENs) described in digestive and extra-digestive sites. Here, we present a case of large cell Ov-NEC admixed with an endometrioid carcinoma of the ovary, arising in the context of ovarian endometriosis, associated with a uterine endometrial atypical hyperplasia (EAH). We performed targeted next-generation sequencing analysis, along with a comprehensive immunohistochemical study and FISH analysis for TP53 locus, separately on the four morphologically distinct lesions (Ov-NEC, endometrioid carcinoma, endometriosis, and EAH). The results of our study identified molecular alterations of cancer-related genes (PIK3CA, CTNNB1, TP53, RB1, ARID1A, and p16), which were present with an increasing gradient from preneoplastic lesions to malignant proliferations, both neuroendocrine and non-neuroendocrine components. In conclusion, our findings underscored that the two neoplastic components of this Ov-MiNEN share a substantially identical molecular profile and they progress from a preexisting ovarian endometriotic lesion, in a patient with a coexisting preneoplastic proliferation of the endometrium, genotypically and phenotypically related to the ovarian neoplasm. Moreover, this study supports the inclusion of MiNEN in the spectrum ovarian and, possibly, of all gynecological NENs, among which they are currently not classified.

Chemotherapy in the treatment of different histological types of appendiceal cancers: a SEER based study

BackgroundDue to its rarity and high heterogeneity, neither established guidelines nor prospective data are currently available for using chemotherapy in the treatment of appendiceal cancer. This study was to determine the use of chemotherapy and its potential associations with survival in patients with different histological types of the cancer.MethodsPatients with histologically different appendiceal cancers diagnosed during 1998–2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The role and effect of chemotherapy were examined in the treatment of the disease. The Kaplan-Meier method was applied to construct survival curves and significance was examined by Log-rank test. Cox proportional hazard models were used to analyze the impact of chemotherapy and other variables on survival in these patients.ResultsA total of 8733 appendiceal cancer patients were identified from the database. Chemotherapy was administrated at highly variable rates in different histological types of appendiceal cancer. As high as 64.0% signet ring cell carcinoma (SRCC), 46.4% of mucinous adenocarcinomas (MAC), 40.6% of non-mucinous adenocarcinoma (NMAC) and 43.9% of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) were treated with chemotherapy, whereas only 14.7% of goblet cell carcinoma (GCC), 5% neuroendocrine tumors (NETs) and 1.6% carcinomas (NEC) received chemotherapy. In all patients combined, chemotherapy significantly improved overall survival during the entire study period and cancer-specific survival was improved during in cases from 2012–2016. Further multivariate analysis showed that both cancer-specific and overall survival was significantly improved with chemotherapy in patients with MAC, NMAC and SRCC, but not for patients with GCC, MiNENs, NETs and NECs. Number (> 12) of lymph node sampled was associated with survival of patients with most histological types of cancer under study. Other prognostic factors related to individual histological types were identified.ConclusionsChemotherapy is administrated at highly variable rates in different histological types of appendiceal cancer. Efficacy of chemotherapy in the treatment of these cancers has been improved in recent years and is significantly associated with better survival for patients with NMAC, MAC, and SRCC. Adequate lymph node sampling may result in a survival benefit for most of these patients.

Primary Intrahepatic Mixed Neuroendocrine–Non neuroendocrine Neoplasm (MiNEN)-Rare Solid Cystic Neoplasm of Liver

Mixed Neuroendocrine –Non-neuroendocrine neoplasm (MiNEN)) is a rare tumour of the gastrointestinal tract and hepato-pancreatic biliary system having both neuroendocrine and non-neuroendocrine components.

Gastric Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: A Western Center Case Series.

Background: Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) represent a rare tumor composed of adenocarcinoma and neuroendocrine carcinoma components. This study reports a case series of gastric MiNEN and discusses issues related to its diagnosis, management, and outcomes. Methods: We retrospectively analyzed data from patients with gastric MiNEN who underwent surgical resection at our service from 2009 to 2020. Patients with gastric adenocarcinoma served as a comparison group. Clinical, pathologic, and surgical characteristics were compared. Results: During the selected period, 5 gastric MiNEN patients and 597 patients with gastric adenocarcinoma were included. Among the clinical variables, age, sex, BMI, and laboratory exams were similar between the two groups. Only ASA classification was different (p = 0.015). Pathological variables such as tumor size, lymphovascular invasion, number of retrieved lymph nodes, and pTNM staging were also similar between both groups. Lastly, early surgical outcomes and long-term survival did not differ between gastric MiNEN and adenocarcinoma patients. Conclusion: A MiNEN is a rare tumor that represents less than 1% of GC patients undergoing curative treatment, and demonstrated clinicopathological characteristics and outcomes similar to gastric adenocarcinoma.

Mixed neuroendocrine-non neuroendocrine neoplasm of the colon

Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare diagnosis in which neuroendocrine component is combined with a non-neuroendocrine component, each of which is morphologically and immunohistochemically recognisable as a discrete component and constitute ≥30% of the neoplasm. This case study reports two elderly patients with MiNEN in their colon, the first presented with caecal tumour on colonoscopy and the second had an obstructing mass in hepatic flexure region. They underwent hemicolectomy which revealed similar morphological findings which showed high grade adenocarcinoma in the superficial part and poorly differentiated components with signet rings and extracellular mucin in the deeper aspects. Areas of rhabdoid differentiation is also present in the first patient. Grade 3 neuroendocrine component is well defined within the deep aspect and constitute about 30% of the tumour. These components are positive for synaptophysin and focally for chromogranin with high Ki67. Perineural and lymphovascular invasion is identified in both cases along with metastasis to regional lymph nodes. MiNEN has an aggressive biological behaviour, mostly driven by its (often high-grade) neuroendocrine component, and a dismal prognosis. In summary, we are discussing two cases of MiNEN with poorly differentiated mucin secreting adenocarcinoma and grade 3 neuroendocrine tumour. 1.Frizziero M, Chakrabarty B, Nagy B, et al. Mixed neuroendocrine non-neuroendocrine neoplasms: a systematic review of a controversial and underestimated diagnosis. J Clin Med 2020; 9: 273.2.WHO Classification of Tumours Editorial Board. WHO Classification of Tumours: Digestive System Tumours. 5th ed. Lyon: IARC, 2019.3.de Mestier L, Cros J, Neuzillet C, et al. Digestive system mixed neuroendocrine-non-neuroendocrine neoplasms. Neuroendocrinology 2017; 105: 412–25.

Clinicopathological features and lymph node and distant metastasis patterns in patients with gastroenteropancreatic mixed neuroendocrine-non-neuroendocrine neoplasm.

ObjectiveOwing to its rarity and heterogeneity, the biological behavior and optimal therapeutic management of mixed neuroendocrine‐non‐neuroendocrine neoplasm (MiNEN) have not been established. Herein, we aimed to evaluate the clinicopathological characteristics and metastatic patterns of MiNEN.MethodsContinuous clinicopathological data of MiNEN patients treated at our hospital were retrospectively collected and analyzed.ResultsThis study had enrolled 169 patients since January 2010 to January 2020. Pathological components were assessed in 129 patients with MiNEN (76.3%), and a focal (non‐)neuroendocrine component was observed in 40 patients (23.7%; <30% of the tumor). Among the enrolled patients, 80 underwent surgical removal of the primary tumor and lymph nodes (LNs), and 34 with distant metastasis underwent biopsy of both primary tumor and metastatic lesions. In patients with LN metastasis, 68.8% (55/80) exhibited a pure component of either neuroendocrine (NE) or adenocarcinoma/squamous carcinoma (AS) in metastatic LNs, while 20% (16/80) showed different components in different LNs, and only 11.2% (9/80) exhibited both NE and AS components in the same LN. In patients with distant metastases, 26.5% (9/34) possessed coexisting NE and AS components in the distant metastases, 70.6% (24/34) were regarded as a pure NE component, and 2.9% (1/34) were comprised of a pure AS component.ConclusionLymph node and distant metastases exhibited distinct metastatic patterns in patients with MiNEN. The major pathological component in regional LNs may have influenced the proportion of the two components within the primary tumor, but distant metastases were dominated by the NE component.

Neuroendocrine Neoplasms of the Gallbladder: A Clinicopathological Analysis of 13 Patients and a Review of the Literature.

Objectives Mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs) are rare gallbladder neuroendocrine neoplasms (GB-NENs). This study is aimed at investigating the clinicopathological features of GB-NENs and identifying prognostic factors related to overall survival (OS) of GB-MiNENs. Methods The clinical data and pathological features of 13 patients with GB-NENs in our hospital were retrospectively reviewed. Additionally, 41 GB-MiNENs cases reported in English literature were reviewed and survival analysis was performed. Results The mean age of thirteen patients (6 males and 7 females) with GB-NENs was 57.2 years (range: 35-75 years). Two patients were diagnosed with NET grade 1 (G1), two patients with NEC (large cell/small cell = 1/1), and nine patients with MiNENs. Of these 9 patients with MiNENs, 8 had composite tumors and 1 had amphicrine carcinoma. Microscopically, the adenocarcinoma component was located in the surface mucosa, and the neuroendocrine component was in the area of deep invasion, liver infiltration, and lymph node metastasis. Total analysis of 41 GB-MiNENs showed that patients were mainly elderly women (female/male ratio, 2.4 : 1.0; median age, 60 years). Kaplan-Meier's analysis demonstrated that liver metastasis and TNM stage III-IV were associated with decreased OS (P < 0.05), whereas age, sex, tumor size, grade of the neuroendocrine component, lymph node metastasis, and adjuvant chemotherapy were not significantly prognostic indicators of OS. Multivariate analysis identified liver metastasis (hazard ratio = 4.262, 95%confidence interval = 1.066‐17.044, P = 0.040) as an independent unfavorable prognostic factor. Conclusions GB-MiNENs were the most common type of GB-NENs in our case series, and neuroendocrine components exhibited more aggressive lymph node metastasis and local invasion than adenocarcinoma. Liver metastasis was a poor prognostic indicator in GB-MiNENs patients.

Mixed adenoneuroendocrine carcinoma (MANEC) of the lower gastrointestinal tract: A systematic review with Bayesian hierarchical survival analysis

BackgroundMixed adeno-neuroendocrine carcinomas (MANEC) are a subgroup of mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) described as mixed neoplasms containing dual neuroendocrine and non-neuroendocrine components. The aim of this study was to appraise the prevalence of MANEC in the lower gastrointestinal (GI) tract and provide reliable estimates of survival. MethodA systematic review was undertaken in accordance with PRISMA guidelines using PubMed, Embase, Cochrane Library of Systematic Review, Web of Science, and Scopus databases, and a Bayesian hierarchical survival pooled analysis was performed. ResultsOf 182 unique records identified, 71 studies reporting on 752 patients met the inclusion criteria. Mean age was 64.2 ± 13.6, with a male-to-female ratio of 1.25. Overall, 60.3% of MANEC were located in the appendix, 29.3% in the colon, and 10.4% in the anorectum. More than a quarter (29%) of patients had stage IV disease at diagnosis, with higher prevalence in appendiceal than colonic and anorectal primaries. More than 80% had a high-grade (G3) endocrine component. Of the 152 patients followed up for a median of 20 months (interquartile range limits, 16.5–32), median overall survival was 12.3 months (95% credible interval [95%CrI], 11.3–13.7), with a 1.12 [95%CrI, 0.67–1.83] age-adjusted hazard ratio between metastatic and non-metastatic MANEC. Stage IV disease at diagnosis was more prognostically unfavorable in cases of colonic compared to anorectal origin. ConclusionMANEC is a clinically aggressive pathological entity. The results of this study provide new insights for the understanding of tumor location within the lower GI tract and its prognosis in terms of overall survival.

Gastric Mixed Neuroendocrine-Nonneuroendocrine Neoplasm: A rare case report

Objective: The incidence of gastric neuroendocrine neoplasms is less than 1%. They are seen as combined tumors with non-neuroendocrine neoplasms at a rate of approximately 7%. This study aims to share the case of mixed neuroendocrine and non-neuroendocrine cancer with the literature.&#x0D; Case: Endoscopic biopsies were taken from the tumoral mass detected in the gastric cardia region at endoscopy in a 60-year-old male patient that has complaints of weight loss and epigastric pain. Histopathological examination revealed malignant tumor infiltration that consisting of neuroendocrine cells with large nuclei and narrow cytoplasm in some areas and adenoid structures composed of atypical cells with pleomorphic large nuclei in some areas. Strong staining was observed in neuroendocrine areas with neuroendocrine markers such as synaptophysin and Chromogranin. Ki-67 proliferative index and mitotic activity were high in neuroendocrine neoplasm areas. The case was reported as a high-grade neuroendocrine-non neuroendocrine mixed neoplasm.&#x0D; Conclusion: Gastric Mixed Neuroendocrine-Nonneuroendocrine neoplasms are rare cases and correct diagnosis and grading are important in the treatment and patient follow-up protocol.