Mixed Adenoneuroendocrine Carcinoma Research Articles

S3020 Ampullary Mixed Adenoneuroendocrine Carcinoma Surprising as Abdominal Pain

S3020 Ampullary Mixed Adenoneuroendocrine Carcinoma Surprising as Abdominal Pain

54 CLINICOPATHOLOGICAL FEATURES AND TREATMENT OUTCOMES OF ESOPHAGOGASTRIC JUNCTIONAL CARCINOMA TREATED WITH CURATIVE SURGERY

Abstract Compared to Western countries, Japanese esophagogastric junctional carcinoma (JC) demonstrates different epidemiologic backgrounds; squamous cell carcinoma is dominant over Barrett adenocarcinoma, and there is no consensus on surgical approach or dissection range of lymph node. JC is defined as the cancer, that is the center of the tumor is within 2 cm from the esophagogastric junction to the esophagus and stomach respectively by the Japanese Classification of Esophageal Cancer, 11th edition. Methods According to the definition, we examined the clinicopathological features and treatment outcomes of patients who underwent curative resection and pathologically defined as JC. From 2012 to 2019, 23 consecutive patients with JC who received with curative surgery in Shiga University of Medical Science Hospital were included. Clinicopathological classification was based on Japanese Classification of Esophageal Cancer, 11th edition. The patients consisted of 18 males and 5 females, median age was 68 (43–91) years old. Results Pathological diagnoses were 19 adenocarcinoma, 1 squamous cell carcinoma, 2 mixed adenoneuroendocrine carcinoma (MANEC) and 1 malignant melanoma. Patients with Barrett’s esophagus were 7 cases (30.4%). Surgical procedure was esophagectomy via right thoracotomy 9 cases, esophagectomy via left thoracotomy 2 case and laparotomy 12 cases. Tumor invasion was pT1:6 (26.1%), pT2:3 (13.0%), pT3:5 (21.7%) and pT4:9 (39.1%). Lymph node metastases were observed in 16 cases (69.6%) and #1,2,3:15 cases (93.8%), #4,5: 3 cases (18.8%), #7,8a,9: 6 cases (37.5%), #19,20: 3 cases (18.8%) and #105–110: 5 cases (31.3%). Among 7 recurrence patients, peritonitis carcinomatosa was 4 cases. Conclusion In most positive lymph node metastasis cases, metastasis was observed in #1, 2 and 3 lymph nodes, but metastasis to the cervical lymph node was not observed. In the G, GE cases, right thoracotomy was not performed because there were no metastases to the upper mediastinal lymph nodes. These results suggested that surgical operation could be reduced to proximal gastrectomy for early G, GE cases. Future studies are necessary to further evaluate this result.

Risk Factors and Predictive Score Model for Early Recurrence After Curative Surgery in Patients With Poorly Differentiated Gastrointestinal Neuroendocrine Neoplasms.

Purpose: Studies on early recurrence in gastrointestinal neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC) are lacking and risk factors related to early recurrence are not clear. We evaluated risk factors for early recurrence in such patients and developed a predictive scoring model.Methods: Patients undergoing curative surgery for GI-NEC or MANEC between January 2010 and January 2019 were included. Early recurrence was defined as recurrence within 12 months after surgery. Risk factors for early recurrence were identified using logistic regression.Results: Of the 80 included patients, 27 developed early recurrence and 53 had no early recurrence. Independent risk factors associated with early recurrence included tumor location in the midgut/hindgut [odds ratio (OR) = 5.077, 95% confidence interval (CI) 1.058–24.352, p = 0.042], alkaline phosphatase (ALP) >80 (OR = 5.331, 95% CI 1.557–18.258, p = 0.008), and lymph node ratio (LNR) >0.25 (OR = 6.578, 95% CI 1.971–21.951, p = 0.002). Risk scores were assigned to tumor location (foregut, 0; midgut/hindgut, 1), ALP (≤80, 0; >80, 1), and LNR (≤0.25, 0; >0.25, 1). Patients with a high risk (score 2–3) for early recurrence had significantly shorter disease-free survival and overall survival than those with low- (score 0) and intermediate risks (score 1) (both p < 0.001). The novel scoring model had superior predictive efficiency for early recurrence over TNM staging (area under the curve 0.795 vs. 0.614, p = 0.003).Conclusion: Tumor location, preoperative ALP, and LNR were independent factors associated with early recurrence after curative surgery for GI-NEC or MANEC. The risk scoring model developed based on these three factors shows superior predictive efficiency.

Poorly differentiated neuroendocrine carcinomas of the gastrointestinal tract: A single-institute study of 43 cases

ObjectivesTo characterize the clinicopathologic and immunohistochemical features of poorly differentiated neuroendocrine carcinomas (NEC) in the gastrointestinal tract. DesignA total of 43 cases were identified and reassessed based on modern classification. ResultsThe cohort (27M, 16F; median age: 66 years) included 16 (37%) large cell NEC, 12 (28%) small cell NEC, 5 (12%) NEC not otherwise specified, and 10 (23%) mixed adenoneuroendocrine carcinomas. Tumor predominantly involved the colon (n = 14, 33%), rectum (n = 13, 30%), and esophagus (n = 9, 21%). Immunohistochemically, INSM1 was the most sensitive marker for neuroendocrine differentiation (28/28, 100%), followed by synaptophysin (40/43, 93%), CD56 (22/35, 63%), and chromogranin (18/40, 45%). SATB2, CDX2, CK20, CK7, abnormal p53, and PD-L1 was positive in 21/26 (81%), 26/37 (70%), 11/35 (31%), 10/35 (29%), 19/24 (79%), and 12/23 (52%) cases, respectively. Three of 25 (11%) were mismatch repair protein deficient. Of 21 resected tumors, 19 (90%) were ≥ pT3 and 13 (62%) had nodal metastasis. Twenty-eight (65%) had distant metastasis. The 5-year survival rate was 21%. The prognosis was stage dependent (p < 0.05), but not associated with tumor type, location, or specific immunomarkers. ConclusionGastrointestinal NECs are aggressive neoplasms. INSM1, synaptophysin, and SATB2 are sensitive markers, although not site or tumor type specific.

Mixed adenoneuroendocrine carcinomas of stomach and ampulla of vater after curative-intent resection: a single center cases series

BackgroundMixed adenoneuroendocrine carcinoma is a rare clinical manifestation, especially in the gastric and ampullary. The purpose of this study was to investigate the clinicopathological features and prognosis of mixed adenoneuroendocrine carcinoma in the gastric and ampullary and summarize related treatment suggestions.MethodsIn all, 32 cases of mixed adenoneuroendocrine carcinoma in the gastric and ampullary that were diagnosed from resected specimens were analyzed from 2009 to 2015. The corresponding demographic, clinicopathological and survival data were retrospectively reviewed.ResultsThe 1-year, 3-year and 5-year survival rates were 78.1%, 28.1 and 9.4%, respectively, and the median overall survival was 28.0 months. In all, 75.0% (24/32) had lymph node metastasis at the time of initial diagnosis. A multivariate analysis revealed that TNM stage (HR 6.444 95%CI 1.477–28.121 P = 0.013), lymph nodes metastasis (HR10.617 95%CI 1.409–79.997 P = 0.022), vascular invasion (HR 5.855 95%CI 1.719–19.940 P = 0.005), grade of the adenocarcinoma component (HR 3.876 95%CI 1.451–10.357 P = 0.007) and CD56 positivity (HR 0.265 95%CI 0.100–0.705 P = 0.008) were independent predictors of overall survival.ConclusionsMixed adenoneuroendocrine carcinoma is an aggressive clinical entity with a poor prognosis. Taking both the neuroendocrine component and the adenocarcinoma component into consideration of optimal treatment is strongly recommended.

Comparison of Survival and Patterns of Recurrence in Gastric Neuroendocrine Carcinoma, Mixed Adenoneuroendocrine Carcinoma, and Adenocarcinoma

Gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma are rare pathological types of gastric cancer, and there is a lack of multicenter studies comparing the prognosis and recurrence patterns of gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. To compare the differences in long-term survival and patterns of recurrence among gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. This cohort study included patients with resectable gastric neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma at 23 hospitals in China from January 2006 to December 2016. In addition, patients with gastric adenocarcinoma were selected as controls. Propensity score-matched analysis was used to match pathological stage among the different pathological types, and disease-free survival (DFS), postrecurrence survival (PRS), and patterns of recurrence were examined. Data analysis was conducted from July 15, 2020, to October 21, 2020. Curative resection for gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. The main outcomes were DFS and patterns of recurrence. A total of 3689 patients were analyzed (median [interquartile range] age, 62 [55-69] years; 2748 [74.5%] men), including 503 patients (13.6%) with gastric neuroendocrine carcinoma, 401 patients (10.9%) with gastric mixed adenoneuroendocrine carcinoma, and 2785 patients (75.5%) with gastric adenocarcinoma. After propensity score matching, 5-year DFS was 47.6% (95% CI, 42.7%-52.5%) for patients with gastric neuroendocrine carcinoma, compared with 57.6% (95% CI, 55.1%-60.1%) with gastric adenocarcinoma (P < .001) and 51.1% (95% CI, 46.0%-56.2%) for patients with gastric mixed adenoneuroendocrine carcinoma, compared with 57.8% (95% CI, 55.1%-60.5%) patients with gastric adenocarcinoma (P = .02). Multivariable analyses found that, compared with gastric adenocarcinoma, gastric neuroendocrine carcinoma (hazard ratio [HR], 1.64; 95% CI, 1.40-1.93) and gastric mixed adenoneuroendocrine carcinoma (HR, 1.25; 95% CI, 1.05-1.49) were independent risk factors associated with worse DFS. Compared with matched patients with gastric adenocarcinoma, patients with gastric neuroendocrine carcinoma were more likely to have distant recurrence (268 patients [17.2%] vs 101 patients [23.7%]; P = .002), as were patients with gastric mixed adenoneuroendocrine carcinoma (232 patients [17.3%] vs 76 patients [22.8%]; P = .02). In multivariate analysis, gastric neuroendocrine carcinoma (HR, 2.22; 95% CI, 1.66-2.98) and gastric mixed adenoneuroendocrine carcinoma (HR, 1.70; 95% CI, 1.24-2.34) were independent risk factors associated with distant recurrence. Additionally, T3 to T4 stage (odds ratio, 2.84; 95% CI, 1.57-5.14; P = .001) and lymph node metastasis (odds ratio, 2.01; 95% CI, 1.31-3.10; P = .002) were independent risk factors associated with distant recurrence of gastric neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma. This cohort study found that patients with gastric neuroendocrine carcinoma or gastric mixed adenoneuroendocrine carcinoma had worse prognoses and were more prone to distant recurrence than those with gastric adenocarcinoma. Thus, different follow-up and treatment strategies should be developed to improve the long-term survival of patients with gastric neuroendocrine carcinoma or gastric mixed adenoneuroendocrine carcinoma, especially patients with tumors penetrating into the subserosa or deeper layers or with lymph node metastasis.

Neoadjuvant and Adjuvant Chemotherapeutic Strategy of Colorectal Mixed Adeno-Neuroendocrine Carcinomas.

Mixed adeno-neuroendocrine carcinomas (MANEC) is a rare pathological diagnosis characterized by the presence of both adeno-carcinomatous and neuroendocrine differentiation with each component comprising 30% of the tumor. This literature review is aimed at the extraction of all existing clinical studies and reviews on colorectal MANEC so as to ensure that a suitable chemotherapeutic regimen is chosen to improve survival outcomes and prognosis of the disease. Parallel search strategies were employed to extract past 10 years articles from PubMed, PubMed Central and Google Scholar databases. A total of 30 records consisting of one clinical trial, five retrospective cohort studies, one case control study, one case series, 16 case reports and six review papers were shortlisted. Chemotherapeutic regimens that were administered as an adjuvant and a neoadjuvant therapy were analyzed with their survival outcomes. The overall survival rate of those administered with neoadjuvant and adjuvant therapy can be as high as 57.4% and 69%, respectively. Multiple chemotherapeutic regimens were employed in colorectal MANEC and superiority of one regimen over the other can’t be established. Any drug or combination of drugs that is responsive against either of the MANEC components is found to be effective against the tumor. However, excellent responsiveness has been found with 5-fluorouracil regimens as a neoadjuvant therapy and platinum-based combinations as an adjuvant therapy. XELOX, streptozocin and S1 regimens also prove to be drugs of choice in aggressive and metastasized disease conditions. Our analysis allows for improved chemotherapeutic management of individuals with colorectal MANEC and establishes an increased potential for use of streptozocin therapy in the clinical setting. However, newer drugs like amrubicin require further research prior to describing its efficacy in colorectal MANEC.

Upper gastrointestinal bleeding due to mixed adenoneuroendocrine carcinoma and radiation esophagitis treated with cap-mucosectomy combined with radiofrequency ablation.

Upper gastrointestinal bleeding due to mixed adenoneuroendocrine carcinoma and radiation esophagitis treated with cap-mucosectomy combined with radiofrequency ablation.

Clinicopathologic characteristics of extrahepatic biliary neuroendocrine neoplasm: A single center experience of gallbladder, extrahepatic biliary tract and ampulla of Vater

Neuroendocrine neoplasm of extrahepatic bile ducts are very rare. The aim of this study to elucidate the clinicopathological characteristics, therapeutic approach and prognosis of these patients. The subjects were 16 patients who were diagnosed with neuroendocrine neoplasm or mixed adenoneuroendocrine carcinoma (MANEC) after curative resection. There were 8 ampulla of Vater and 8 non ampulla of Vater (6 gallbladder and 2 distal bile duct). The female to male ratio was 1.3/1 with mean age of 57.9 years (ranging from 36 to 74 years). There were 8 cases of incidental diagnosis in health screenings and 2 cases during evaluation for other disease. The most common symptoms were abdominal discomfort (3 pain and 1 dyspepsia) and jaundice (2 cases). According to the 2010 WHO classification, 1 patient had NET G1, 5 NET G2, 6 NET G3 and 5 MANEC. G3 and MANEC were small cell type. Pancreatoduodenectomy was performed in 9 patients (1 combined minor hepatectomy), extended cholecystectomy in 6 cases (1 combined pancreaticoduodenectomy and right hemicolectomy) and radical bile duct resection in 1 case. There were no association between OS and DFS with various clinicopathological factors including TNM stage. Ki-67 (cut-off 20%) was only prognostic factor in OS (5-year survival: 100% vs. 42.3%; p = 0.044) and DFS (5-year survival: 100% vs. 47.6%; p = 0.059). In NET of extrahepatic bile duct, the titer of Ki-67 is more important than TNM according to AJCC, and attention of Ki-67 titer may be needed in treatment of recurrence.

Coronavirus disease 2019 in patients with neuroendocrine neoplasms: Preliminary results of the INTENSIVE study

BackgroundSpecific data regarding coronavirus disease 2019 (COVID-19) in patients with neuroendocrine neoplasms (NENs) are lacking. The aim of this study is to describe the characteristics of patients with NENs who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive. Material and methodsThis is a worldwide study collecting cases of patients with NENs along with a positive nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between June 1, 2020, and March 31, 2021. Centres treating patients with NENs were directly contacted by the principal investigator. Patients with NENs of any primary site, grade and stage were included, excluding small-cell lung carcinoma and mixed adenoneuroendocrine carcinoma. ResultsAmong 81 centres directly contacted, 88.8% responded and 48.6% of them declined due to lack of cases or interest. On March 31st, 2021, eight recruiting centres enrolled 89 patients. The median age was 64 years at the time of COVID-19 diagnosis. Most patients had metastatic, non-functioning, low-/intermediate-grade gastroenteropancreatic NENs on treatment with somatostatin analogues and radioligand therapy. Most of them had comorbidities. Only 8% of patients had high-grade NENs and 12% were receiving chemotherapy. Most patients had symptoms or signs of COVID-19, mainly fever and cough. Only 3 patients underwent sub-intensive treatment, whereas most of them received medical therapies, mostly antibiotics. In two third of cases, no changes occurred for the anti-NEN therapy. More than 80% of patients completely recovered without sequelae, whereas 7.8% patients died due to COVID-19. ConclusionsPatients included in this study reflect the typical NEN population regardless of SARS-CoV-2. In most cases, they overcome COVID-19 without need of intensive care, short-term sequelae and discontinuation of systemic oncological therapy.

Massive Mixed Adenoneuroendocrine Carcinoma: A Case Report

Mixed adenoneuroendocrine carcinoma (MANEC) of the gastrointestinal (GI) tract is a rare subtype of mixed tumors, and it is scarcely described in the literature. MANEC tumors are composed of adenocarcinoma and neuroendocrine carcinoma components, each of which comprises at least 30% of the lesion. Diagnosing MANEC requires specific histological and immunohistochemistry (IHC) analysis. Typically, MANEC tumors carry a poor prognosis due to their very aggressive nature.We report the case of a 70-year-old female patient with no past medical history who presented with a three-week history of abdominal pain and one episode of hematemesis one week prior to presentation. Initial CT of the abdomen showed a large, 8 x 6 x 6-cm mass arising from the stomach and extending to the lesser sac as well as the central crus of the diaphragm with bilateral retroperitoneal lymphadenopathy. Upper endoscopy revealed an excavated, ulcerated, and partially necrotic mass on the lesser curvature of the proximal gastric body. Tissue biopsy of the lesion showed infiltrating mixed poorly differentiated adenocarcinoma and neuroendocrine carcinoma. On IHC, the adenocarcinoma component stained positively for CDX2 and pancytokeratin, and the neuroendocrine component stained positively for synaptophysin and chromogranin. Further workup included CT of the chest, which demonstrated extensive bilateral pulmonary emboli and new liver lesions with moderate ascites not seen on the initial abdominal CT. The latter was repeated and showed remarkable enlargement of the gastric mass (up to 12 cm) with extensive retroperitoneal adenopathy and mesenteric implants. Given the rapid clinical deterioration and progression of tumor burden, comfort measures were offered and the patient passed away soon after. MANEC tumors are highly aggressive subtypes of "collision" tumors, which are not well described in the medical literature due to their rarity. The etiology is poorly understood with various theories proposing different pathophysiological mechanisms. Standard therapy is not well developed at present; however, a few reports have demonstrated successful outcomes with surgery or combined chemotherapy (cisplatin with irinotecan or etoposide) if diagnosed at an early stage.

Clinicopathological characteristics and prognosis of 232 patients with poorly differentiated gastric neuroendocrine neoplasms.

BACKGROUNDPoorly differentiated gastric neuroendocrine neoplasms (PDGNENs) include gastric neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma, which are highly malignant and rare tumors, and their incidence has increased over the past few decades. However, the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated.AIMTo investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs.METHODSThe data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively.RESULTSAmong the 232 patients with PDGNENs, 191 (82.3%) were male, with an average age of 62.83 ± 9.11 years. One hundred and thirteen (49.34%) of 229 patients had a stage III disease and 86 (37.55%) had stage IV disease. Three (1.58%) of 190 patients had no clinical symptoms, while 187 (98.42%) patients presented clinical symptoms. The tumors were mainly (89.17%) solitary and located in the upper third of the stomach (cardia and fundus of stomach: 115/215, 53.49%). Most lesions were ulcers (157/232, 67.67%), with an average diameter of 4.66 ± 2.77 cm. In terms of tumor invasion, the majority of tumors invaded the serosa (116/198, 58.58%). The median survival time of the 232 patients was 13.50 mo (7, 31 mo), and the overall 1-year, 3-year, and 5-year survival rates were 49%, 19%, and 5%, respectively. According to univariate analysis, tumor number, tumor diameter, gastric invasion status, American Joint Committee on Cancer (AJCC) stage, and distant metastasis status were prognostic factors for patients with PDGNENs. Multivariate analysis showed that tumor number, tumor diameter, AJCC stage, and distant metastasis status were independent prognostic factors for patients with PDGNENs.CONCLUSIONThe overall prognosis of patients with PDGNENs is poor. The outcomes of patients with a tumor diameter > 5 cm, multiple tumors, and stage IV tumors are worse than those of other 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.

96 Mixed Adenoneuroendocrine Carcinoma in Crohn's Disease: A Case Report and Literature Review

Abstract Introduction Mixed adenoneuroendocrine carcinoma (MANEC) is a rare neoplasm with dual adenocarcinomatous and neuroendocrine differentiation. Subgroup analysis demonstrates an increased frequency of both adenocarcinomas and neuroendocrine tumours in patients with Crohn’s disease (CD), though the incidence of MANEC is unknown. Method A 58-year-old male with a 31-year history of CD presented with small bowel obstruction. After failed conservative management, the patient underwent right hemicolectomy, with subsequent histology demonstrating MANEC. A literature search was performed to identify further cases of patients with concomitant MANEC and CD. Results 11 cases were identified. The mean duration of CD before presentation was 19.5 years, and 58% of cases involved the terminal ileum. 60% of cases demonstrated nodal spread and metastatic disease was evident in 25%. 42% of patients with MANEC were initially treated for an exacerbation of CD. Conclusions MANEC is a rare tumour of uncertain aetiology. The terminal ileum is commonly affected, with most cases exhibiting a longstanding CD history. Diagnosis is challenging, with symptoms of MANEC mirroring exacerbations of CD. Future research should strive to identify imaging modalities or biochemical markers which aid in distinguishing the two pathologies, preventing futile medical management of MANEC, and reducing the risk of metastatic spread due to delayed diagnosis.

Mixed adenoneuroendocrine tumour with squamous differentiation: a case report

Mixed adenoneuroendocrine carcinoma is a rare neoplasm with both epithelial and neuroendocrine components. To date, only a few cases of this neoplasm have been reported in the literature among which gastric mixed adenoneuroendocrine carcinoma is very rare. We are reporting a case of gastric mixed adenoneuroendocrine carcinoma with squamous cell differentiation. Histopathological features, biological behaviour and the treatment of this rare tumour type have been discussed briefly.

Next-generation sequencing facilitates differentiating between multiple primary lung cancer and intrapulmonary metastasis: a case series

BackgroundIn lung cancer management, differential diagnosis between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IMP) is a critical point that is of direct therapeutic and clinical importance. However, this process often suffers from absence of a gold standard, resulting in equivocal cases. Herein, we present a series of three cases, in which genomic alteration patterns revealed by next-generation sequencing (NGS) facilitated the differential diagnosis between MPLC and IMP.Case presentationCase 1 was a 57-year-old female with two separate lesions in the upper lobe and the lower lobe of left lung, which were both histopathologically determined as T2aN0M0 adenocarcinomas. NGS identified an EGFR L858R in one lesion and an EGFR 20 exon insertion in the other one, suggestive of double primary malignancies. The patient underwent wedge resections and received an adjuvant treatment of icotinib and chemotherapy. She had a disease-free survival (DFS) of 19 months and counting. Case 2 was a 55-year-old female with multiple small lesions in both lungs. Histopathological examinations of resected lesions from right upper lobe revealed three subtypes: atypical adenomatous hyperplasia of alveolar epithelium, adenocarcinomas in situ and minimally invasive adenocarcinoma. NGS identified two different BRAF driver mutations G466E and V600_K601delinsE in two lesions of adenocarcinoma in situ, and a BRAF K601E in a lesion of minimally invasive adenocarcinoma. Case 3, a 68-year-old male, had the right upper lobe lesion histophathologically classified as a stage T3NxM0 mixed adenoneuroendocrine carcinoma and the left upper lobe lesion as a stage T1aN0M0 adenocarcinoma. NGS performed with different loci of surgical tissues revealed a rare sensitizing EGFR mutation G719A shared by the right upper lobe lesion and lymph node, and two EGFR mutations L861Q and G719S in left upper lobe lesion. The patient received icotinib treatment postoperatively and achieved a stable disease with a progression-free survival of 5 months.ConclusionOur cases provide evidence for utility of NGS in facilitating diagnosis and treatment decisions.

A Rare Case of Mixed Ductal Neuroendocrine Tumor of the Pancreas

Collision tumors are tumors that have at least two types of tumors in the same anatomical site with no area of mixing within the transition zone. In 2010 WHO classification of neuroendocrine tumors consists of an adenocarcinoma component and a neuroendocrine carcinoma component in which each of the components accounts for 30% of the tumor. Such tumors are defined as mixed adenoneuroendocrine carcinomas. Occurrence of exocrine and endocrine tumors of the pancreas is extremely rare. The aim of our study was to describe a case in a 60 years old male who was diagnosed with this rare tumor. Gross, microscopic features and immunohistochemistry were used to diagnose this rare condition. Immunohistochemistry markers such as synaptophysin, chromogranin, EMA and Pan CK were used to come to a definitive diagnosis. Synaptophysin and chromogranin were found to be positive in the neuroendocrine component. EMA and Pan CK were found to be positive in the ductal component. Hence a diagnosis of mixed ductal neuroendocrine tumour (collision tumor) was made.

Mixed adenoneuroendocrine carcinoma of the caecum presenting as extensive ileocolonic intussusception.

Mixed adenoneuroendocrine carcinoma of the caecum presenting as extensive ileocolonic intussusception.

Gastric Neuroendocrine Neoplasm : WHO Classification 2019

A B S T R A C TNeuroendocrine neoplasm (NEN) of gastric is a term that includes all tumour types withneuroendocrine differentiation of gastric, well differentiated or poorly differentiatedtumour. NEN is a new term in 2019 World Health Organization (WHO) classification ofdigestive system tumours. In WHO 2019 had many updates, one of them isneuroendocrine tumours (NET) grade 3 have been included in tumour category of welldifferentiated tumour or NET. Previously, NET G3 in WHO 2010 are included as poorlydifferentiated tumour or neuroendocrine carcinoma (NEC). This neoplasm is geneticallywell differentiated and because of that, WHO 2019 classification included them as a welldifferentiated tumour. For NEC, WHO 2019 subdivided them as NEC with small cells(SCNEC) and NEC with large cells (LCNEC). In WHO 2010, mixed type neuroendocrineneoplasms with other components of carcinoma are called mixed adenoneuroendocrinecarcinoma (MANEC). But, not all of non-neuroendocrine components areadenocarcinoma and it is possible that one of the components in not carcinoma. Becauseof that, in WHO 2019 the term has been changed to mixed neuroendocrine-nonneuroendocrine neoplasm (MiNEN).

Mixed adenoneuroendocrine carcinoma (MANEC) as a rare case of the rectum

Introduction: Mixed adenoneuroendocrine carcinoma (MANEC) is a rare tumor consist of two components, adenocarcinoma and neuroendocrine differentiation. Every each have to represents at least 30% of the tumor. Diagnosis is based on cytology, architecture and immunostaining. Specific neuroendocrine markers for MANEC are chromogranin A and synaptophysin. Purpose: In this paper, we aimed to present a case of MANEC arising from rectum. Case presentation: 67-years-old man was admitted to the hospital due to abdominal pain, obstruction and blood in the stool. From the colonoscopy simple, the histopathological examination exposed microfoci of adenocarcinoma. Small pelvis MRI disclosed clinically known circular, solid infiltrate in the middle and upper part of the rectum. Local advancement in MRI was T4b N2 EMVI + CRM +. Patient underwent the neoadjuvant radiochemo-therapy. The control MRI revealed tumor reduction. Local advancement in MRI was yT3d yN0 EMVI + CRM + RG3. The histopathological examination of the surgical material revealed MANEC tissue consisting of Adenocarcinoma G2 (60%) and Large cell neuroendocrinal carcinoma (40%) pT3 pN0 pMx. Immunohistochemical staining revealed a positive expression of chromogranin A, synaptophysin and Ki67 - 80% in the neuro-endocrine component. Lymphonodulitis reactiva 19/19. Seminal vesicles without neoplastic infiltration. The patient was discharged in good general condition, with a recommendation of a follow-up visit at a surgical clinic. Conclusions: MANEC is rare as a rectal neoplasm. Has no specific clinical symptoms. The most important in the diagnostic process is histopatho-logical analysis. Updating the knowledge about MANEC by new reports may optimize the diagnostic process, classification and treatment of this cancer.