• Case report
• Collision tumor
• Grade 1 well-differentiated neuroendocrine tumor
• Molecular profile
• Pancreatic adenocarcinoma
• Pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms

• Chemotherapy
• MiNEN
• Mixed neuroendocrine non-neuroendocrine carcinoma
• NEN

• Humans
• Male
• Female
• Middle Aged
• Italy/epidemiology
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/mortality
• Aged
• Retrospective Studies
• Neuroendocrine Tumors/drug therapy
• Neuroendocrine Tumors/pathology
• Adult
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/pathology
• Stomach Neoplasms/mortality
• Prognosis
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Intestinal Neoplasms/drug therapy
• Intestinal Neoplasms/pathology
• Intestinal Neoplasms/mortality
• Aged, 80 and over
• Follow-Up Studies
• Survival Rate

• adenocarcinoma
• aspergilloma
• diagnosis
• etiopathogenesis
• prognosis
• typical carcinoid

• Humans
• Lung Neoplasms/complications
• Lung Neoplasms/diagnosis
• Pulmonary Aspergillosis/complications
• Pulmonary Aspergillosis/diagnosis
• Carcinoid Tumor/complications
• Adenocarcinoma/complications
• Male
• Adenocarcinoma of Lung/complications
• Middle Aged
• Aged

• Gastric cancer
• Molecular profiling
• Neuroendocrine carcinoma
• Pure NEC

• Humans
• Carcinoma, Neuroendocrine/genetics
• Carcinoma, Neuroendocrine/pathology
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology
• Adenocarcinoma/pathology
• Mutation
• Carcinogenesis

• Adjuvant chemotherapy
• Gastric cancer
• Gastric mixed neuroendocrine non-neuroendocrine neoplasm
• Microsatellite instability
• Mismatch repair protein

The ampulla of Vater is an anatomically and histologically complex region giving rise to a heterogenous group of tumors. This is, to the best of our knowledge, the first case of intra-ampullary papillary-tubular neoplasm combined with ampullary neuroendocrine carcinoma reported in the literature.

A 61-year-old woman presented to the emergency department for evaluation of painless jaundice. Contrast-enhanced computed tomography (CT) of the abdomen and chest showed a periampullary tumor mass measuring 15 mm × 12 mm × 14 mm, with no evidence of locoregional and distant metastases, for which she underwent pancreatoduodenectomy. Histopathologic examination of a resected specimen revealed an intra-ampullary papillary tubular neoplasm with high-grade dysplasia in combination with poorly differentiated grade 3 neuroendocrine carcinoma with a mitotic count of more than 20 mitoses per 10 high power fields and Ki-67 index of 100%. No positive lymph nodes were identified. Her postoperative course was uneventful. Postoperatively, she remained under close surveillance. Multiple liver metastases were observed on follow-up CT 8 mo after the surgery, so systemic therapy with cisplatin and etoposide was initiated.

The simultaneous occurrence of neuroendocrine and non-neuroendocrine tumors in the ampulla of Vater is rare and the pathogenesis of such tumors is largely unknown. Due to unpredictable clinical behavior and lack of solid evidence on optimal treatment strategy, close patient surveillance is advised after radical resection of the primary tumor.

• Ampulla of Vater
• Neuroendocrine carcinoma
• Mixed tumour
• Pancreaticoduodenectomy
• Prognosis
• Case report

Neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) are extremely rare subtypes of gastric cancer. MiNEN is a mix of carcinomatous components and neuroendocrine neoplasm in the same lesion. NEC and MiNEN have a poor prognosis, are difficult to diagnose, and have no established treatment. Herein, we assessed the clinicopathological characteristics and long-term surgical outcomes of gastric NEC and MiNEN patients in our hospital.

We retrospectively assessed 1538 patients pathologically diagnosed with gastric cancer and who underwent curative surgical resection at our institution between January 1999 and October 2021. Of these patients, 25 (1.6%) were pathologically diagnosed with neuroendocrine neoplasms. From these 25 patients, we retrospectively analyzed the clinicopathological characteristics and surgical outcomes of 13 (0.8%) patients pathologically diagnosed with NEC or MiNEN.

The NEC and MiNEN patients consisted of 11 men and 2 women [mean age, 74 (62–84) years]. The preoperative histological diagnoses were NEC (n = 4) and adenocarcinoma (n = 9). The final pathological diagnoses were large cell neuroendocrine carcinoma (LCNEC; n = 7) and MiNEN (n = 6). Total gastrectomy was the most common surgical procedure (9/13, 69.2%), followed by distal gastrectomy (3/13, 23.1%) and proximal gastrectomy (1/13, 7.7%). Immunohistochemical staining showed 8 CD56-positive patients. All 13 patients were positive for chromogranin A and synaptophysin. The mean Ki-67 value was 64.8 (0–95)%, and the mean mitotic score was 107.9 (0–400). Nine patients survived without recurrence postresection. The median postresection overall survival time was 68.7 (8.0–129) months. The 5-year survival rate was 0.75 ([95% CI] 0.408–0.912).

The surgical treatment outcomes of NEC and MiNEN patients were relatively favorable. Although evidence concerning the effectiveness of surgery alone is meager, radical resection as part of multidisciplinary treatment including chemotherapy can potentially improve prognosis.

• Gastric cancer
• Mixed neuroendocrine-non-neuroendocrine neoplasms
• Neuroendocrine carcinoma

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare mixed tumors containing both neuroendocrine (NE) and non-NE components. Each component must occupy at least 30% of the tumor volume by definition. Recent molecular evidence suggests MiNENs are clonal neoplasms and potentially harbor targetable mutations similar to conventional carcinomas. There have been multiple changes in the nomenclature and classification of MiNENs which has created some confusion among pathologists on how to integrate the contributions of each component in a MiNEN, an issue which in turn has resulted in confusion in communication with front-line treating oncologists. This mini review summarizes our current understanding of MiNENs and outline diagnosis, prognosis, and management of these neoplasms. The authors emphasize the importance of treating the most aggressive component of the tumor regardless of its percentage volume.

• Mixed neuroendocrine non-neuroendocrine neoplasms
• Mixed adenoneuorendocrine carcinoma
• Mixed neuroendocrine neoplasms
• Neuroendocrine
• Non-neuroendocrine

• Carcinoma
• Digestive System/pathology
• Humans
• Mutation
• Neuroendocrine Tumors/genetics
• Neuroendocrine Tumors/therapy
• Prognosis

Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) of the digestive tract are a rare heterogeneous group of tumors that present many challenges in terms of diagnosis and treatment. Over the years, the diagnostic criteria, classification, and clinical behavior of these tumors have been the subjects of ongoing debate, and the various changes in their nomenclature have strengthened the challenges associated with MiNENs. This review is performed to provide an understanding of the key factors involved in the evolution of the designation of these tumors as MiNEN, highlight the current diagnostic criteria, summarize the latest data on pathogenesis and provide information on available treatments. Moreover, this work seeks to increase the awareness about these rare neoplasms by presenting the clinicopathological features and prognostic factors that play important roles in their behavior and discussing their different regions of origin in the gastrointestinal system (GIS). Currently, the MiNEN category also includes tumors in the GIS with a nonneuroendocrine component and epithelial tumors other than adenocarcinoma, depending on the organ of origin. Diagnosis is based on the presence of both morphological components in more than 30% of the tumor. However, this value needs to be reconfirmed with further studies and may be a limiting factor in the diagnosis of MiNEN by biopsy. Furthermore, available clinicopathological data suggest that the inclusion of amphicrine tumors in the definition of MiNEN is not supportive and warrants further investigation. The diagnosis of these tumors is not solely based on immunohistochemical findings. They are not hybrid tumors and both components can act independently; thus, careful grading of each component separately is required. In addition to parameters such as the metastatic state of the tumor at the time of diagnosis and the feasibility of surgical resection, the aggressive potential of both components has paramount importance in the choice of treatment. Regardless of the organ of origin within the GIS, almost MiNENs are tumors with poor prognosis and are frequently encountered in the elderly and men. They are most frequently reported in the colorectum, where data from molecular studies indicate a monoclonal origin; however, further studies are required to provide additional support for this origin.

• Mixed neuroendocrine–nonneuroendocrine neoplasms
• Mixed adeno neuroendocrine carcinoma
• Gastrointestinal system
• Liver
• Pancreas
• Gallbladder

• Adenocarcinoma
• Aged
• Biopsy
• Gastrointestinal Tract/pathology
• Humans
• Male
• Neuroendocrine Tumors/diagnosis

Pulmonary carcinoid tumors rarely coexist with non-small cell lung carcinoma, and only nine cases have been reported previously. The pathogenesis and origin of these combined tumors remain unclear because of its rarity.

We examined two cases of adenocarcinoma coexisting with a typical or atypical carcinoid tumor: Case 1 was a 77-year-old woman and Case 2 was an 83-year-old woman. Both of these cases had no respiratory symptoms, and underwent pulmonary lobectomies due to incidentally detected lung nodules. Recurrence and metastases were not detected after the surgery. Histologically, carcinoid and adenocarcinoma components were present in both cases. The two components coexisted without mixing with each other. Next-generation sequencing was performed on the two components in these cases. In each case, no common genetic variants were detected.

We considered that our cases could histologically and genetically represent collision tumors that did not share common progenitor cells. Comprehensive analyses such as whole genome sequencing could provide important information for elucidating the pathogenesis of adenocarcinoma and carcinoid components.

• Adenocarcinoma
• Carcinoid tumor
• Case report
• Collision tumor
• Composite tumor
• Lung cancer

• MINEN
• STC1
• cell line
• gastric cancer
• neuroendocrine

A 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.

We 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.

The 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.

We 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.

• ATRX
• gastrointestinal
• molecular
• neoplasms
• neuroendocrine
• pathology
• sequence

Neuroendocrine carcinomas and mixed neuroendocrine non-neuroendocrine neoplasms of the gallbladder (NE GBC) are rare and highly aggressive entities. The cell of origin of NE GBC has been a matter of controversy. Here, we performed a comparative histopathologic and molecular analysis of NE GBC cases and, if present, associated precancerous lesions.

We selected cases diagnosed between 2000 and 2019 in the Netherlands. Precursors and carcinomas were immunohistochemically compared and analyzed for mutations, gene amplifications, microsatellite instability, and tumor mutational burden using an next-generation sequencing panel containing 523 cancer-related genes. In addition, presence of fusion genes was analyzed using a panel of 55 genes.

Sixty percent of neuroendocrine cases (6/10) presented with a precursor lesion, either intracholecystic papillary neoplasm (n = 3) or biliary intraepithelial neoplasia (n = 3). Immunohistochemically, neuroendocrine components were different from the epithelial precursor lesions. Molecular profiling, however, revealed TP53 mutations shared between different components in five of six cases, indicating a clonal relation. Furthermore, 40% of cases (4/10) harbored at least one potentially actionable alteration. This included (likely) pathogenic mutations in RAD54L, ATM, and BRCA2; amplifications of ERBB2 and MDM2; and a gene fusion involving FGFR3-TACC3. All cases were microsatellite-stable and had a tumor mutational burden of < 10 mutations/Mb.

Our data provide insight into the development of NE GBC and suggest a common origin of precancerous epithelial lesions and invasive neuroendocrine components, favoring the hypothesis of lineage transformation. Moreover, nearly half of the NE GBCs carried at least one potentially actionable molecular alteration, highlighting the importance of molecular testing in this highly lethal cancer.

• Genetics
• Genomics
• Grade 3 neuroendocrine tumor
• High-grade neuroendocrine neoplasms
• Molecular analysis
• Neuroendocrine carcinoma

• Carcinoma, Neuroendocrine/genetics
• Carcinoma, Neuroendocrine/pathology
• Genomics
• Humans
• Neoplasm Grading
• Neuroendocrine Tumors/genetics
• Neuroendocrine Tumors/pathology
• Pathology, Molecular

• Capecitabine–temozolomide
• Cisplatin–etoposide
• MANET
• MiNEN
• Neuroendocrine neoplasms

• gastric cancer
• genetics
• neuroendocrine carcinoma
• targeted sequencing

• MANEC
• MiNEN
• classification
• mixed neuroendocrine and non-neuroendocrine neoplasm
• prognosis

• Gastric adenocarcinoma
• Neuroendocrine carcinoma
• Overall survival

• Adenocarcinoma/diagnosis
• Adenocarcinoma/mortality
• Adenocarcinoma/pathology
• Adenocarcinoma/therapy
• Adult
• Age Factors
• Aged
• Carcinoma, Neuroendocrine/diagnosis
• Carcinoma, Neuroendocrine/mortality
• Carcinoma, Neuroendocrine/pathology
• Carcinoma, Neuroendocrine/therapy
• Chemotherapy, Adjuvant
• Female
• Follow-Up Studies
• Gastrectomy
• Gastric Mucosa/diagnostic imaging
• Gastric Mucosa/pathology
• Gastric Mucosa/surgery
• Humans
• Male
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Staging
• Prognosis
• Propensity Score
• Retrospective Studies
• Risk Factors
• Sex Factors
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/mortality
• Stomach Neoplasms/pathology
• Stomach Neoplasms/therapy

• 81802735 National Science Foundation for Young Scientists of China
• QML20191101 Beijing Youth Talent Plan
• 2020-11 Science Foundation of Peking University Cancer Hospital

• adenocarcinoma
• liver tumor
• mixed adenoneuroendocrine carcinoma
• neuroendocrine carcinoma

Gastric adenocarcinoma patients with a neuroendocrine (NE) component are frequently observed in routine practice. Several previous studies have investigated the influence of a NE component on the survival of these patients; however, the results were inconsistent.

We retrospectively investigated a consecutive series of 95 gastric adenocarcinoma patients with a NE component and 190 gastric adenocarcinoma patients without a NE component. We adopted 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90% as the cut-off proportions of the NE component, respectively, and analyzed the patients' overall survival according to the proportion of the NE component.

The 1-, 3-, and 5-year actual survival rates of the patients with a NE component were 90.1%, 72.3%, and 67.2%, respectively, and for those without a NE component 94.2%, 79.3%, and 75.7%, respectively. The multivariate analysis showed that the patients with NE components >70% (HR: 2.156; 95% CI: 1.011, 4.597; p=0.047) and >90% (HR: 2.476; 95% CI: 1.088, 5.634; p=0.031) had significantly worse survival than those without a NE component. Only the diameter of tumors (>4.64 cm) (HR: 2.585; 95% CI: 1.112, 6.006; p=0.027) and pN3 (HR: 2.953; 95% CI: 1.051, 8.293; p=0.040) were independently associated with worse overall survival for gastric adenocarcinoma patients with a NE component (all p<0.05).

Gastric adenocarcinoma patients with a NE component >70% and >90% have significantly worse survival than those without a NE component. Only the diameter of tumors and the number of metastatic lymph nodes are independent prognostic factors for gastric adenocarcinoma patients with a NE component.

• Mixed adenoneuroendocrine carcinoma
• Prognosis
• Recurrence
• Risk factors
• Stomach neoplasms

• endoscopic treatment
• gastric MANEC
• gastric triple carcinoma

• Adenocarcinoma/diagnostic imaging
• Adenocarcinoma/pathology
• Adenocarcinoma/surgery
• Aged
• Aged, 80 and over
• Endoscopic Mucosal Resection/methods
• Female
• Gastric Mucosa/diagnostic imaging
• Gastric Mucosa/pathology
• Gastric Mucosa/surgery
• Humans
• Male
• Neuroendocrine Tumors/diagnostic imaging
• Neuroendocrine Tumors/pathology
• Neuroendocrine Tumors/surgery
• Stomach Neoplasms/diagnostic imaging
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery
• Treatment Outcome

• Mixed adenoneuroendocrine carcinoma (MANEC)

Mixed adenoneuroendocrine carcinoma (MANEC) is a tumor of the gastrointestinal tract that contains both exocrine and endocrine components, with each component exceeding 30% of the total tumor area. Because MANECs are exceedingly rare, no therapeutic strategies have been established yet.

An 81-year-old man was referred to our hospital with a 5-month history of dysphagia. Esophagogastroduodenoscopy revealed an ulcerated mass in the lower thoracic esophagus, extending up to the esophagogastric junction (33 to 40 cm from the incisors). The initial biopsy diagnosis was adenocarcinoma. Computed tomography revealed no evidence of lymph node or distant metastasis. The patient was treated by thoracoscopic esophagectomy with three-field lymph node dissection and gastric tube reconstruction via a posterior mediastinal approach, under the diagnosis of esophagogastric junctional cancer (T3N0M0, stage IIA). Histopathological examination revealed two distinct components, namely, a neuroendocrine carcinoma component and an adenocarcinoma component, and the patient was diagnosed as having mixed adenoneuroendocrine carcinoma (MANEC). He presented with liver metastasis 6 months after the surgery. Thereafter, the tumor became even more aggressive, and the patient died 8 months after the surgery.

We report a patient with MANEC of the esophagogastric junction. Close attention should be paid to such patients, as MANEC can be a highly aggressive tumor, showing rapid progression. In the treatment of MANEC, it is necessary to carefully consider the pathological features in each individual case.

• Esophagogastric junction
• Mixed adenoneuroendocrine carcinoma

Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) are a group of rare tumors previously known as mixed adenoneuroendocrine carcinomas (MANECs). The neuroendocrine component is high-grade and may consist of small-cell carcinoma or large-cell neuroendocrine carcinoma. The nonneuroendocrine component may consist of adenocarcinoma or squamous cell carcinoma. We report a unique case of a MiNEN with trilineage differentiation: large-cell neuroendocrine carcinoma, squamous cell carcinoma, and adenocarcinoma. The reported patient presented with symptoms of an upper gastrointestinal bleed and was ultimately diagnosed with a MiNEN with trilineage differentiation. This is the first report of this exceedingly rare tumor type to include next-generation sequencing of the 3 separate tumor entities. In addition, we review the current literature and discuss the role of next-generation sequencing in classifying and treating MiNEN tumors.

• Gastric cancer
• Neuroendocrine neoplasm
• Precision medicine

• Ki67
• MANEC
• NEC
• prognosis

• Carcinoma, Neuroendocrine/genetics
• Carcinoma, Neuroendocrine/pathology
• Cell Proliferation
• Female
• Humans
• Ki-67 Antigen/genetics
• Male
• Prognosis

Our previous study revealed that neuroendocrine differentiation in colorectal cancer is one of the important factors leading to worse prognosis. In this study, we apply immunohistochemical staining, Western-blot, RT-PCR and ELISA to investigate the underlying mechanism that how the neuroendocrine differentiation to affect the prognosis of colorectal cancer. The interaction of colorectal cancer cells, neuroendocrine-like cells and tumor-associated macrophages in colorectal cancer progress is also investigated. By analyzing 82 cases of colorectal cancer patients treated in our institution, we found that colorectal adenocarcinoma with neuroendocrine differentiation had increasing number of tumor-associated macrophages and worse prognosis. Further evaluation of cytology showed that neuroendocrine cells have the ability to recruit tumor-associated macrophages to infiltrate the tumor tissue, and the tumor-associated macrophages enhance the proliferation and invasion abilities of the colon cancer cells. Moreover, we confirmed that CXCL10 and CXCL11 are the key chemokines in neuroendocrine-like cells and they promote the chemotaxis activity of tumor-associated macrophages. The secretion of CXCL10 and CXCL11 by neuroendocrine-like cells can recruit tumor-associated macrophages to infiltrate in tumor tissues. The latter enhances the proliferation and invasion of colorectal cancer cell and lead to poor prognosis.

• colorectal cancer
• neuroendocrine differentiation
• prognosis
• tumor-associated macrophages

The Roux-en-Y gastric bypass is one of the most common procedures currently performed for surgical treatment of patients with severe obesity. Gastric cancer after bariatric surgery is not common, with most of them arising in the excluded stomach. Gastric mixed adenoneuroendocrine carcinomas are a rare type of stomach malignancy, composed of both adenocarcinoma and neuroendocrine tumor-cell components, with the latter comprising at least 30% of the whole neoplasm. In this article, we report a unique case of a mixed adenoneuroendocrine carcinoma with a mixed adenocarcinoma (tubular and poorly cohesive) component arising in the gastric pouch of a patient who underwent previous Roux-en-Y gastric bypass for glycemic control. Since stomach cancer is not usual in patients who have formerly undergone bariatric surgery and symptoms tend to be nonspecific, such diagnosis is often rendered at an advanced stage. Full assessment of these patients when presenting such vague symptoms is critical for an early cancer diagnosis.

• MANEC
• gastric bypass
• gastric cancer
• mixed adenoneuroendocrine carcinomas
• mixed tumor
• neuroendocrine tumors

• Amphicrine carcinoma
• Copy number aberrations
• Mixed adenoneuroendocrine carcinoma
• Neuroendocrine carcinoma
• Prostaglandin E2 receptors

Pancreatic cancer is classified as ductal, acinar, neuroendocrine carcinoma or pancreatoblastoma. Ductal and acinar cells derive from exocrine glands and neuroendocrine cells from endocrine glands; however, mixed acinar-neuroendocrine-ductal carcinoma has different histological carcinomas coexisting within a nodule. The mixed pancreatic carcinoma forms from different developmental origins and therefore requires investigation. The current case report presents a 50-year-old male who had a tumor within the body of the pancreas. Pathological examination clarified the tumor as a mixed acinar-neuroendocrine-ductal carcinoma. The ductal and acinar/neuroendocrine tumor components were isolated using laser-capture microdissection, and next-generation sequencing analysis was performed. Consequently, TP53 frameshift (p.N210fs) and KRAS missense (p.G12R) mutations were identified in both ductal and acinar/neuroendocrine tumors. These results suggested a pancreatic mixed acinar-neuroendocrine-ductal carcinoma was derived from a founder tumor clone, and supports the notion that a founder tumor clone may differentiate and transform into a diverse histological type and form a pancreatic mixed carcinoma.

• acinar
• ductal
• mixed carcinoma
• neuroendocrine
• next generation sequencing
• pancreatic carcinoma

• ampullary MANEC
• pancreaticoduodenectomy

• Classification
• Combined tumor
• Composite tumor
• Mixed adenoneuroendocrine carcinoma
• Mixed neoplasm
• Neuroendocrine

• Female
• Humans
• Immunohistochemistry
• Male
• Neoplasms, Complex and Mixed/classification
• Neuroendocrine Tumors/classification

We report a case of mixed adenoneuroendocrine carcinoma (MANEC) of stomach with tubular adenoma and well-differentiated neuroendocrine tumor (WD-NET) in the primary tumor in the stomach giving rise to biphenotypic regional nodal metastases. A 35-year-old woman with abdominal pain was found to have a 1.8-cm gastric lesion, diagnosed as WD-NET (intermediate grade) on the biopsy. The resection specimen contained residual WD-NET; there was also a gastric adenoma adjacent to the NET and nodal metastasis with both adeno- and neuroendocrine components. The tumor was classified as MANEC. Of note, the entire gastric tissue was submitted and multiple deeper levels of the adenomatous lesion were examined; no adenocarcinoma was present in the primary lesion. While association of gastric adenoma with neuroendocrine neoplasm is rare, presence of biphenotypic metastasis originating from such a lesion is highly unusual and to the best of our knowledge has not been reported.

• Classification
• Mixed adenoneuroendocrine carcinoma
• Prognosis
• Stomach

• Endoderm
• Mixed medullary-follicular carcinoma
• Neural crest
• Neuroendocrine tumours
• Thyroid C cells
• Ultimobranchial body

• GASTRIC PATHOLOGY
• NEUROENDOCRINE TUMOURS
• SURGICAL PATHOLOGY

Mixed glandular-endocrine carcinomas are rare tumours of gastrointestinal tract (MANEC). They are more frequent in stomach and hardly one hundred cases have been described in colon. According to Lewis, they are classified into collision (side by side pattern), composite (intermingled) or amphicrine (neuroendocrine and glandular features inside a same cell). Collision tumours are related to biclonal theory: two simultaneous cancerogenic events. Conversely, multidirectional differentiation from a stem cell is accepted as origin of composite tumours.

The aim of this paper is to analyse the behaviour of these tumours, with an especial concern about how these tumours metastasise, and the different theories about carcinogenesis.

We report a rare case of collision adenocarcinoma-large cell neuroendocrine tumour of colon that after a three-year period of follow-up has presented a retroperitoneal recurrence that features adenocarcinoma and large cell neuroendocrine components.

After an exhaustive review of the English literature, we found that only two cases of collision tumour of colon with metastases showing glandular and endocrine components have been described up to date, so we report the third case, and the first happening in transverse colon.

We conclude that not all collision tumours follow the biclonal theory and more studies are needed to clarify the origin of these neoplasms, and consequently, to reach an adequate treatment.

•

MANEC are defined as mixed adenoneuroendocrine carcinoma.

• Collision
• Colon
• Composite
• MANEC
• Mixed
• Tumour

Collision tumors are rare neoplasms displaying two distinct cell populations developing in juxtaposition to one another without areas of intermingling. They are rare entities with only 63 cases described in English literature. Tumors encountered are gastric adenocarcinomas colliding with lymphomas, gastrointestinal stromal tumors, squamous cell carcinomas, and neuroendocrine tumors. Their cell origin is obsolete by the time of diagnosis. Different tumorigenesis theories have been suggested to explain their behavior, yet none has managed to provide satisfactory explanation for all cases. Clinically they are indistinguishable from the dominant tumor. Lack of data does not allow detailed assessment of their behavior yet they seem aggressive neoplasms with dismal prognosis. The majority of cases have been diagnosed postoperatively during histologic examination of specimens. There are no guidelines or concrete evidence to support best way of adjuvant or other types of treatment. However, these rare neoplasms might help in unlocking secrets of cancer behavior including tumorigenesis, differentiation, and adhesion and thus clinicians should be aware of their existence.

• Aged
• Aged, 80 and over
• Carcinoma/genetics
• Carcinoma/metabolism
• Carcinoma/pathology
• Carcinoma, Neuroendocrine/genetics
• Carcinoma, Neuroendocrine/metabolism
• Carcinoma, Neuroendocrine/pathology
• DNA Repair/genetics
• Female
• Follow-Up Studies
• Gastrointestinal Neoplasms/genetics
• Gastrointestinal Neoplasms/metabolism
• Gastrointestinal Neoplasms/pathology
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Middle Aged
• Multivariate Analysis
• Survival Analysis
• Urogenital Neoplasms/genetics
• Urogenital Neoplasms/metabolism
• Urogenital Neoplasms/pathology

• Adenocarcinoma/pathology
• Adenocarcinoma/surgery
• Aged
• Carcinoma, Neuroendocrine/pathology
• Carcinoma, Neuroendocrine/surgery
• Dissection
• Gastric Mucosa/pathology
• Gastroscopy/methods
• Humans
• Male
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery

• Collision tumour
• Histologically
• Ovary