Distinctive Phenotypic and Microenvironmental Characteristics of Neuroendocrine Carcinoma and Adenocarcinoma Components in Gastric Mixed Adenoneuroendocrine Carcinoma.

This study aimed to conduct an in-depth examination of gene expression and microenvironmental profiles of gastric neuroendocrine carcinoma (NEC) and mixed adeno-NEC (MANEC). Tissue microarrays from 55 patients with gastric MANEC (N = 32) or NEC (N = 23) were analyzed using digital spatial profiling (GeoMx DSP, NanoString Technologies). Representative regions of interest were selected from the adenocarcinoma (ADC) portion (ADC-MANEC) and the NEC portion (NEC-MANEC) of the MANEC cores, and pure NEC (pNEC) cores. All regions of interest were separated into epithelial components and stromal components using the masking procedure in the GeoMx platform, followed by transcriptome analysis. Comparison of gene expression between ADC-MANEC and NEC-MANEC/pNEC identified several differentially expressed genes in the epithelial (including PEG10, MAP1B, STMN3, and AKT3) and stromal (FN1, COL1A1, SPARC, and BGN) components. Gene set enrichment analysis revealed that pathways related to the E2F target and G2M checkpoint were more enriched in NEC-MANEC and pNEC than in ADC-MANEC. Deconvolution analysis showed that the microenvironmental profile varied according to histologic differentiation. In ADC-MANEC, intraepithelial infiltrating immune cells were relatively more numerous, whereas fibroblasts in the stroma were more abundant in NEC-MANEC and pNEC. This study confirmed the distinct expression profile of each histologic component of MANEC according to its tumor vs stromal compartment using the DSP platform. Although each component of MANEC shares the same genetic origin, distinctive phenotypes should not be overlooked when managing patients with MANEC. This study provides a useful validation data set for future studies.

Goblet cell adenocarcinoma.

Appendix, considered a vestigial and disposable organ, has been long neglected as a source of abdominal tumors. Among the appendiceal tumors, goblet cell adenocarcinoma (GCA) is a rare primary epithelial neoplasm which has undergone multiple name changes and classifications in recent years, adding to confusion surrounding this unique amphicrine tumor. This entity was previously known as goblet cell carcinoid and adenocarcinoma ex goblet cell carcinoid. This review article provides an update on pathology, nomenclature, and recent classification systems with emphasis on 2019 World Health Organization Classification of Tumors, 3-tiered grading system.1.

MiNEN of base of tongue - first case report in literature.

INTRODUCTION: Mixed neuroendocrine and non-neuroendocrine neoplasms (MiNENs) refer to a heterogenous group of rare neoplasms which is usually composed of a neuroendocrine population which is either well differentiated and more frequently poorly differentiated along with a non-neuroendocrine component, each of the above accounting for at least 30% of the tumour population. It is most commonly seen in the gastro-entero-pancreatic tract. MiNENs have an aggressive behaviour due to its high grade neuroendocrine component and have poor prognosis. This is the first case reported in literature of a MiNEN in the oropharynx. CASE REPORT: 69 year old male patient with no co morbidities presented to the outpatient department with complains of odynophagia for 1 month. He had history of neoadjuvant chemotherapy followed by transoral robotic surgery (TORS) with right selective neck dissection (SND) done in 2019 for carcinoma base of tongue. On flexible laryngoscopy, an ulcerative lesion was noted over the left base of tongue. Although PET scan done showed no significant abnormalities. Biopsy from the lesion showed features of poorly differentiated carcinoma along with morphological features of poorly differentiated neuroendocrine carcinoma (small cell carcinoma). He was planned for upfront surgery (TORS with left SND). Post operatively recovery was uneventful and patient was on ryles tube feed for 12 days. Final histopathology report showed features of mixed neuroendocrine non neuroendocrine neoplasm. He has been on follow up for 1 year with no features of recurrence. CONCLUSION: MiNEN is an aggressive tumour which has poor prognosis and is most commonly located in the gastrointestinal tract. This is the first case reported in oropharynx who has been successfully treated and has been on follow up.

Mixed adenoneuroendocrine carcinoma originating from the appendix and colorectum: a comparative analysis of a large population-based database.

PURPOSE: As a rare gastrointestinal neoplasm, the demographic, clinicopathological, and prognostic characteristics of mixed adenoneuroendocrine carcinoma (MANEC) remain unclear. The purpose of this study was to evaluate its biological features, survival outcome, and prognostic factors. METHODS: From the Surveillance, Epidemiology, and End Results (SEER) database, we retrospectively reviewed clinicopathological and survival data of 513 patients who were histopathologically diagnosed with MANEC of the appendix and colorectum bettween 2004 and 2015. The clinicopathological features and survival outcomes of MANEC located at different anatomical locations were compared, and predictive factors for cancer-specific survival (CSS) and overall survival (OS) were assessed. RESULTS: In terms of anatomical distribution of MANEC, the appendix (64.5%, 331/513) was more frequently involved, followed by colon (28.1%, 144/513) and rectum (7.4%, 38/513). The MANEC at different anatomical locations had a distinct clinicopathological characteristic, and colorectal MANEC was significantly associated with more aggressive biological features. The survival outcomes of appendiceal MANEC were significantly better than that of colorectal MANEC (3-year CSS rate 73.8% vs 59.4%, P = 0.010; 3-year OS 69.2% vs 48.3%, P < 0.001). In addition, hemicolectomy had a better survival benefit than appendicectomy for patients with appendiceal MANEC, regardless of lymph node metastasis (P < 0.05). Tumor location, histology grade III, tumor size > 2 cm, T3-T4 stage, lymph node metastasis, and distant metastasis were independent prognostic factors for patients with MANEC. CONCLUSIONS: Tumor location had an important prognostic significance for MANEC. As an uncommon clinical entity, colorectal MANEC had more aggressive biological features and worse prognosis than its appendiceal counterpart. The standard surgical procedure and clinical management strategy for MANEC need to be established.

Mixed adenoneuroendocrine carcinoma of the non-ampullary duodenum with mismatch repair deficiency: a rare case report.

A non-ampullary duodenal mixed adenoneuroendocrine carcinoma (MANEC), consisting of a conventional adenocarcinoma and a neuroendocrine carcinoma (NEC), is exceedingly rare. Moreover, mismatch repair (MMR) deficient tumors have recently attracted attention. The patient, a 75-year-old woman with epigastric pain and nausea, was found to have a type 2 tumor of the duodenum, which was diagnosed on biopsy as a poorly differentiated carcinoma. A pancreaticoduodenectomy specimen showed a well-defined 50 × 48 mm tumor in the duodenal bulb, which was morphologically composed of glandular, sheet-like, and pleomorphic components. The glandular component was a tubular adenocarcinoma, showing a MUC5AC-positive gastric type. The sheet-like component consisted of homogenous tumor cells, with chromogranin A and synaptophysin diffusely positive, and a Ki-67 index of 72.8%. The pleomorphic component was diverse and prominent atypical tumor cells proliferated, focally positive for chromogranin A, diffusely positive for synaptophysin, and the Ki-67 index was 67.1%. The sheet-like and pleomorphic components were considered NEC, showing aberrant expression of p53, retinoblastoma, and p16. Notably, all three components were deficient in MLH1 and PMS2. We diagnosed a non-ampullary duodenal MANEC with MMR deficiency. This tumor has a unique morphology and immunohistochemical profile, and is valuable for clarifying the tumorigenesis mechanism of a non-ampullary duodenal MANEC.

Multi-institutional development and validation of a nomogram to predict recurrence after curative resection of gastric neuroendocrine/mixed adenoneuroendocrine carcinoma.

OBJECTIVE: To establish a novel nomogram to predict individual 1, 3, and 5 years disease-free survival (DFS) of patients with gastric neuroendocrine carcinoma/mixed adenoneuroendocrine carcinoma [(MA)NEC]. BACKGROUND: Among patients undergoing radical resection of gastric (MA)NEC, there is still a high tendency for relapse. METHODS: A retrospective analysis of 777 patients with gastric (MA)NEC at 23 centers in China from 2004 to 2015 was performed. Based on the established nomogram, which included age, ASA, pT, pN and Ki67, the overall patients were divided into low-risk group (LRG) and high-risk group (HRG). RESULTS: The median follow-up time was 40 months (1-169 months). The C-index, AUC and time-ROC of the nomogram were significantly higher than that of the 8th edition AJCC and ENETS TNM staging systems. The 3-year DFS of patients in HRG generated by the nomogram was significantly lower than that in LRG (all patients: 35% vs 66.9%, p < 0.001), and there were still significant differences in stratified analysis of the TNM staging systems. The local recurrence rate (10.5% vs 2.6%) and distant recurrence rate (45.1% vs 22.6%) in HRG were significantly higher than those in LRG, especially in anastomotic recurrence (6.3% vs 2%), liver recurrence (20.7% vs 13.4%) and peritoneal metastasis (12.7% vs 2.6%). CONCLUSIONS: Compared with AJCC and ENETS TNM staging systems, the established novel validated nomogram had a significantly better prediction ability for DFS and recurrence patterns in patients with gastric (MA)NEC. It can also compensate for the shortcomings of existing AJCC and ENETS TNM staging in predicting individual recurrence risk.

Comparison of Clinicopathological Features of Biliary Neuroendocrine Carcinoma with Adenocarcinoma.

OBJECTIVE: This study aimed to demonstrate the clinical features and postoperative outcomes of extrahepatic bile duct (EHBD) neuroendocrine carcinoma (NEC) and compared with those of adenocarcinoma. METHODS: We retrospectively analyzed patients with EHBD cancer operated in our institution between 1995 and 2015. RESULTS: Of 475 patients, 468 had adenocarcinoma, while 7 had NEC/mixed adenoneuroendocrine carcinoma (MANEC) in this study. There were no notable preoperative and pathological features in patients with NEC/MANEC. However, patients with NEC/MANEC had a higher recurrence rate (51.8 vs. 100%, p = 0.016), poorer relapse-free survival (RFS) time (the median RFS time: 35 vs. 12 months, p = 0.006), and poorer overall survival (OS) time (the median OS time: 60 vs. 19 months, p = 0.078) than those with adenocarcinoma. Furthermore, patients with NEC/MANEC had higher rates of liver metastasis (11.9 vs. 85.7%, p < 0.001) than those with adenocarcinoma. In multivariable regression analysis, pathological type with NEC/MANEC was a risk factor for poorer RFS (p = 0.022, hazard ratio: 6.09). CONCLUSIONS: Patients with NEC/MANEC have high malignant potential and poor outcomes. It is necessary to develop an effective approach and postoperative adjuvant treatment for patients with NEC/MANEC.

Gastrointestinal mixed adenoneuroendocrine carcinoma: a population level analysis of epidemiological trends.

BACKGROUND: The rise in incidence and mortality of gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC) has not been well focused. The aim of our study was to examine epidemiological trends in incidence and incidence-based (IB) mortality of gastrointestinal MANEC at a population level. METHODS: The incidence and IB mortality of gastrointestinal MANEC as well as data on affected patients from 2000 to 2016 were obtained from the Surveillance, Epidemiology, and End Results database. Trends in incidence and IB mortality were assessed using Joinpoint regression. The Kaplan-Meier method and log-rank test were used for survival analysis. Cox proportional hazards regression was used to identify independent predictors of mortality. RESULTS: 581 patients diagnosed with gastrointestinal MANEC were enrolled. Gastrointestinal MANEC incidence was 0.23 cases per 1,000,000 individuals in 2000 and 1.16 cases per 1,000,000 individuals in 2016, with an annual percent change (APC) of 8.0% (95% CI 5.7-10.3%, P < 0.05). IB mortality also showed a sustained increase (APC 12.9%, 95% CI 9.0-16.8%, P < 0.05). In Cox regression analysis, age at diagnosis, tumor grade and stage, lymph node metastasis, surgery, and tumor size were independently associated with mortality. Median survival was 75 months (95% CI 60-128 months). Median survival of appendiceal MANEC was significantly longer than that of cecal MANEC (115 vs. 31 months; P < 0.001). CONCLUSIONS: We found a sustained and rapid increase both in incidence and IB mortality of gastrointestinal MANEC, manifesting that there has been no significant improvement in patient outcomes, nor progress in prevention and treatment. Additional resources should be devoted to gastrointestinal MANEC research.

Mixed adenoneuroendocrine carcinoma of the hepatic bile duct: a case report and review of the literature.

BACKGROUND: The World Health Organization's updated classification of digestive system neuroendocrine tumors in 2010 first proposed the classification of mixed adenoneuroendocrine carcinoma (MANEC). The incidence of biliary malignant tumors with neuroendocrine tumors accounts for less than 1% of all neuroendocrine tumors. Moreover, the incidence of hilar bile duct with MANEC is very rare. CASE PRESENTATION: A 65-year-old female patient came to our hospital for repeated abdominal pain for more than 4 months and skin sclera yellow staining for 1 week. Contrast-enhanced computed tomography imaging and magnetic resonance results suggested a hilar tumor for Bismuth-Corlette Type II. The patient underwent radical surgery for hilar cholangiocarcinoma. Finally, the patient was diagnosed with hilar bile duct MANEC, staged 1 (pT1N0M0) based on the eighth edition of the AJCC. Histopathology showed that the tumor was a biliary tumor with both adenocarcinoma and neuroendocrine carcinoma. No evidence of recurrence and metastasis after 20 months of follow-up. CONCLUSIONS: We first reported a MANEC that originated in the hilar bile duct. As far as we known, there were few reports of biliary MANEC, and the overall prognosis was poor. We also found that the higher the Ki-67 index, the worse the prognosis of this type of patient. Radical surgery is the most effective treatment.

Goblet cell tumors of the appendix: A review.

Goblet cell tumors are rare tumors of the appendix that exhibit both neuroendocrine and mucinous differentiation. This dual differentiation has led to a controversy regarding the proper classification of these neoplasms as to whether they should be considered neuroendocrine tumors or adenocarcinomas. Multiple grading systems have been proposed that were able to segregate these tumors into prognostically significant groups. Many of these grading systems rely on identifying and/or quantifying the carcinomatous growth pattern. Goblet cell tumors show patchy and focal expression of neuroendocrine markers and are characterized by a mutational profile that is different from both appendiceal adenocarcinomas and neuroendocrine tumors. They exhibit a more aggressive behavior than neuroendocrine tumors, and as such, many authors recommend that they be approached and treated as adenocarcinomas.

Retrospective analysis of seven cases of pancreatic mixed adenoneuroendocrine carcinoma from a high-volume center and review of the literature.

BACKGROUNDS: The clinicopathologic features and biological behaviors of pancreatic mixed adenoneuroendocrine carcinoma (pMANEC) and its impacts on survival are poorly known. METHODS: We retrospectively reviewed seven pMANEC cases from a single institution from September 2010 to January 2017 along with twenty-one previously reported cases from the literature. Survival and prognostic analyses were conducted using Kaplan-Meier estimates and Cox regression, respectively. RESULTS: Seven pMANEC cases were identified during the study interval. Among the six patients who underwent operations, five reached R0 resections, one experienced postoperative pancreatic fistula, and two suffered other complications. The median progression-free survival (PFS) and disease-specific survival (DSS) were 7.5 months (2 to 36 months) and 15 months (6 to 36 months), respectively. A total analysis of twenty-eight pMANEC cases showed that patients were mostly older (median age, 59.5 years) and male (64.3%). The two most common symptoms were abdominal pain (53.6%) and obstructive jaundice (35.7%). The majority of pMANECs were non-functional (89.3%) and located in the pancreatic head (64.3%). The median diameter of pMANEC was 3.0 cm, with a wide range (0.5 to 19.0 cm). Lymph node metastasis (P = 0.015) was associated with decreased DSS, while age (P = 0.414), sex (P = 0.125), tumor size (P = 0.392), location (P = 0.913), functional status (P = 0.313), CA19-9 level (P = 0.608), and liver metastasis (P = 0.935) did not show significant prognoses on DSS. CONCLUSIONS: We reported seven pMANEC cases and outlined their clinical behaviors and prognoses with a review of twenty-one cases from the literature. Lymph node metastasis was found to be a negative prognostic factor of DSS based on the present study.

Prognostic factors for survival after curative resection of gastric mixed adenoneuroendocrine carcinoma: a series of 80 patients.

BACKGROUND: To assess the prognostic factors and investigate the optimal treatment of gastric mixed adenoneuroendocrine tumors. METHODS: We retrospectively analyzed clinical data from 80 patients with gastric mixed adenoneuroendocrine carcinoma that received radical resection in our department from January 2007 to December 2016. Risk factors for relapse and survival were analyzed using a multivariate Cox proportional hazards regression model. Gastric mixed adenoneuroendocrine carcinoma was divided into neuroendocrine carcinoma and adenocarcinoma based on the predominant type in the tumor. RESULTS: The 3-year overall survival was 40% in the neuroendocrine carcinoma group and 75% in the adenocarcinoma group (P = 0.006). The neuroendocrine carcinoma (NEC)-dominant tumors and a Ki-67-positive index ≥60% were independent risk factors for worse overall survival. The 3-year recurrence-free survival was 33% in the neuroendocrine carcinoma group and 68% in the adenocarcinoma group. NEC-dominant tumors and a Ki-67-positive index ≥60% were independent risk factors for gastric mixed adenoneuroendocrine carcinoma recurrence. Patients in the adenocarcinoma group that received adjuvant chemotherapy exhibited significantly better overall survival than patients that did not receive chemotherapy (median survival time 43 months vs. 13 months, P = 0.026). CONCLUSION: The NEC-dominant tumors and a Ki-67-positive index ≥60% were significantly associated with worse survival and a higher recurrence rate for gastric mixed adenoneuroendocrine carcinoma patients. Patients in the adenocarcinoma group may benefit from gastric adenocarcinoma treatments.

An extremely rare case of Epstein-Barr virus-associated gastric carcinoma with differentiation to neuroendocrine carcinoma.

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVGC) is defined as a neoplasm comprising monoclonal proliferation of EBV-infected gastric epithelial cells. Although the typical histology is gastric carcinoma with lymphoid stroma (GCLS), the histologic features of the tumor vary. We report herein the case of a 78-year-old man with multiple simultaneous EBVGCs revealing different histopathologic morphologies; one was mixed adenoneuroendocrine carcinoma (MANEC), and the other was GCLS. Both tumor types exhibited positive results for EBV in situ hybridization. To the best of our knowledge, this represents the first report of EBVGC showing neuroendocrine differentiation. Immunohistochemistry also revealed a loss of gastrointestinal features, including CDX2, MUC5AC, and MUC6 expression, among tumor cells from the neuroendocrine component of the MANEC. We describe the pathologic features of this rare neoplasm and discuss the mechanisms underlying the neuroendocrine differentiation of EBVGC cells, along with providing a brief review of the literature.

Mixed adenoneuroendocrine carcinoma of the colon and rectum.

Mixed adenoneuroendocrine carcinoma (MANEC) are rare cancers of the gastrointestinal (GI) and pancreatobiliary tract. They are characterized by the presence of a combination of epithelial and neuroendocrine elements, where each component represents at least 30% of the tumour. Review of literature and consolidation of clinicopathological data. Sixty-one cases of colorectal MANEC have been reported in literature and one seen in this centre. The median age of the patients affected was 61.9 ± 12.4 years (20-94 years). Male to female ratio is 1.0:1.2. Presentations were similar to other colorectal malignancies. 58.0% of colorectal MANECs were found in the right colon, 8.1% cases in the transverse, 16.1% in the left colon, 16.1% in the rectum. These tumours appeared invasiveness 79.1% were T3-T4. Over 90% of cases were presented with metastatic disease. The majority of patient underwent surgical resection of the primary cancer (96.6%). Of these, 10 operations (17.9%) were emergency operations due to obstruction, perforation, or bleeding. Three patients received first line palliative care. In eight cases (13.8%), patients underwent adjuvant chemotherapy. The median overall survival after diagnosis was 10 ± 2.4 months (95% CI: 5.37-14.64 months). MANECs are rare but aggressive colorectal cancers. Surgical resection of localized disease with adjuvant chemotherapy appears to significantly improve survival in small case series. Further understanding through the sharing of experiences is required.

Diagnosis, Assessment, and Therapeutic Strategy for Colorectal Mixed Adenoneuroendocrine Carcinoma.

Colorectal mixed adenoneuroendocrine carcinoma (MANEC), which acts like an aggressive tumor, is a rare clinical manifestation on which only a limited amount of literature exists. Surgical resection by regional lymphadenectomy is considered as the only curative treatment for colorectal MANEC, and adjuvant chemotherapy or radiotherapy is recommended because of its high recurrence rate. Colorectal MANEC is frequently diagnosed at an advanced stage, when it is unresectable, and chemotherapy plays a central role in its treatment. Pathological confirmation of the target lesion component is critical for regimen selection. If the lesion comprises an adenocarcinomatous component, a regimen for colorectal adenocarcinoma should be administered. For lesions comprising mainly a neuroendocrine carcinomatous component, cisplatin combined with etoposide or irinotecan has proven to be clinically appropriate. Everolimus, a mechanistic target of rapamycin pathway inhibitor, also improves survival. Sunitinib malate, another molecular targeting agent, is effective for treating neuroendocrine carcinoma; however, the evidence on its effectiveness for treating gastrointestinal neuroendocrine carcinoma is insufficient.

Gastric mixed adenoneuroendocrine carcinoma: correlation of histologic characteristics with prognosis.

Gastric mixed adenoneuroendocrine carcinomas (MANECs) are rare, with both the exocrine and neuroendocrine components exceeding 30% volume. Several classifications for MANECs have been proposed, yet they have not been clinically evaluated. The aim of this study was to evaluate the correlation between tumor grade, histologic characteristics, and prognosis of gastric MANECs. We collected eligible 14 cases in our series and 31 cases in the literature and compared the prognostic difference among gastric MANECs with different histologic characteristics. Gastric MANECs could be divided into subgroups according to tumor grade of the neuroendocrine component and adenocarcinoma types. The high grade and large proportion of neuroendocrine component correlated with aggressive behavior and a tendency of poor clinical outcome. Gastric MANECs with a poorly differentiated adenocarcinoma showed a significant lower survival rate than did MANECs with a differentiated adenocarcinoma or mucin-producing carcinoma (P = .0008). Gastric MANECs were a heterogeneous group with different tumor grades, histologic subtypes, combination patterns, and patient outcomes. Previous classifications were evaluated. This study proves that histologic characteristics correlate with clinical outcomes. Our findings are complements to the latest prognostic classification.

A case of mixed adenoneuroendocrine carcinoma of the gallbladder arising from an intracystic papillary neoplasm associated with pancreaticobiliary maljunction.

A 54-year-old Japanese woman was referred with a gallbladder tumor. Based on the results of the computed tomography scan, endoscopic retrograde cholangiopancreatography, and magnetic resonance cholangiopancreatography, a mucin-producing neoplasm of the gallbladder associated with pancreaticobiliary maljunction was diagnosed. Extended cholecystectomy, extrahepatic bile duct resection, and choledochojejunostomy were performed, and she remains free of recurrence 24 months after resection. Histopathological examination revealed that the papillary component of the lesion was an intracystic papillary neoplasm with diverse characteristics of pancreaticobiliary epithelium and intestinal epithelium including mucin. In this component, most of the papillary lesion was a high-grade intraepithelial neoplasm, but also showed slight invasion into the muscular layer. The nodular component consisted of both poorly differentiated biliary type adenocarcinoma and large cell neuroendocrine carcinoma. We report a rare case of a mixed adenoneuroendocrine carcinoma arising from an intracystic papillary neoplasm associated with pancreaticobiliary maljunction. As for the histogenesis of this tumor, based on the histopathologic appearance, transdifferentiation from poorly differentiated biliary type adenocarcinoma to large cell neuroendocrine carcinoma is considered the most possible histogenesis of this tumor.

[Mixed adenoneuroendocrine carcinoma: case report]. / Carcinoma adenoneuroendocrino mixto: reporte de caso.

Introducción: Mixed adenoneuroendocrine carcinoma is a rare tumor of the gastrointestinal tract with double differentiation into adenomatous and neuroendocrine carcinoma, each component with at least 30%. Case report: A 60-year-old female with acute abdominal pain. Surgical treatment was decided, finding a tumor at the level of the cecum and ascending colon, a right hemicolectomy and ileostomy were performed. Discussion: Mixed adenoneuroendocrine carcinoma can appear in various organs. They are highly malignant tumors, with a high risk of metastasis. Conclusions: These tumors do not present symptoms or specific radiological or laboratory findings; diagnosis depends on postoperative histopathological and immunohistochemical studies.

Introducción: El carcinoma adenoneuroendocrino mixto es un tumor raro del tracto gastrointestinal con doble diferenciación en carcinoma adenomatoso y neuroendocrino, cada componente con al menos el 30%. Caso clínico: Mujer de 60 años con cuadro de dolor abdominal agudo. Se decide tratamiento quirúrgico, encontrando un tumor a nivel de ciego y colon ascendente, y se realizan hemicolectomía derecha e ileostomía. Discusión: El carcinoma adenoneuroendocrino mixto puede aparecer en diversos órganos. Son tumores muy malignos, con alto riesgo de metástasis. Conclusiones: Estos tumores no presentan síntomas ni hallazgos radiológicos o de laboratorio específicos; el diagnóstico depende de estudios histopatológicos e inmunohistoquímicos posoperatorios.

Does the size of the neuroendocrine-carcinoma component determine the prognosis of gallbladder cancer?

Background: Gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm generally consists of a gallbladder neuroendocrine tumor and a non-neuroendocrine component. The World Health Organization (WHO) in 2019 established a guideline requiring each component, both neuroendocrine and non-neuroendocrine, to account for a minimum of 30% of the tumor mass. Methods: Patients after surgery resection and diagnosed at microscopy evaluation with pure gallbladder neuroendocrine carcinoma (GBNEC), gallbladder mixed adeno-neuroendocrine carcinoma (GBMANEC, GBNEC≥30%), and gallbladder carcinoma mixed with a small fraction of GBNEC (GBNEC <30%) between 2010 and 2022 at West China Hospital of Sichuan University were collated for the analyses. Demographic features, surgical variables, and tumor characteristics were evaluated for association with patients' overall and recurrence-free survival (OS and RFS). Results: The study included 26 GBNEC, 11 GBMANEC, 4 gallbladder squamous-cell carcinoma (GBSCC), and 7 gallbladder adenocarcinoma (GBADC) mixed with a small fraction of GBNEC. All patients had stage III or higher tumors (AJCC8th edition). The majority of included patients (79.17%) underwent curative surgical resection (R0), with only ten patients having tumoral resection margins. In the analysis comparing patients with GBNEC percentage (GBNEC≥30% vs. GBNEC<30%), the basic demographics and tumor characteristics of most patients were comparable. The prognosis of these patients was also comparable, with a median OS of 23.65 months versus 20.40 months (P=0.13) and a median RFS of 17.1 months versus 12.3 months (P=0.24). However, patients with GBADC or GBSCC mixed with GBNEC <30% had a statistically significant decreased OS and RFS (both P<0.0001)) compared with GBNEC and GBMANEC. Patients with GBNEC who exhibited advanced tumor stages and lymphovascular invasion had a higher risk of experiencing worse overall survival (OS) and recurrence-free survival (RFS). However, a 30% GBNEC component was not identified as an independent risk factor. Conclusion: Patients with GBNEC were frequently diagnosed at advanced stages and their prognosis is poor. The 30% percentage of the GBNEC component is not related to the patient's survival.