Mixed Adenoneuroendocrine Carcinoma Research Articles

Mixed adenoneuroendocrine carcinoma: case report

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%. 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. Mixed adenoneuroendocrine carcinoma can appear in various organs. They are highly malignant tumors, with a high risk of metastasis. These tumors do not present symptoms or specific radiological or laboratory findings; diagnosis depends on postoperative histopathological and immunohistochemical studies.

MANEC TUMOR OF RECTUM. A RARE CASE SERIES OF 3 PATIENTS AND A LITERATURE REVIEW.

The term Mixed Adeno-Neuro-Endocrine Carcinoma (MANEC) was introduced in 2010 by the WHO Classification of Tumors of the Digestive System. It refers to a neoplasm with dual epithelial and neuroendocrine differentiation, each component representing at least 30% of the tumor. It is an uncommon tumor accounting for < 3% of all colon and rectum malignancies. We report three cases of this extremely rare MANEC of the rectum. All three cases presented with hematochezia, variable constipation, and abdominal pain. They were diagnosed and staged appropriately with colonoscopy, biopsy with immunohistochemistry, and imaging. They underwent an anterior resection with circular stapled anastomoses. Because of the low incidence of this histotype, we reviewed the clinical presentation, diagnostic characteristics, and treatment of MANEC of the colon and rectum.

Sarcopenia and Neuroendocrine Neoplasms.

To summarise the current literature regarding the presence of sarcopenia in patients with neuroendocrine neoplasms (NENs). These are uncommon cancers separated into well-differentiated neuroendocrine tumours (NETs) and poorly differentiated neuroendocrine carcinoma (NECs). For the diagnosis of sarcopenia, there needs to be low muscle strength and low muscle quantity/quality. Five studies exist describing either low muscle strength or low muscle quantity in patients with NETs. The studies used different techniques to analyse muscle strength and muscle quantity, included heterogeneous populations, and performed the analysis at different time points following the diagnosis of the NET. Only 2 studies regarding patients with NECs could be found, both included mainly patients with a mixed adenoneuroendocrine carcinoma (MiNEN) and are, therefore, difficult to interpret for patients with a NEC. The main findings of this review are to describe the presence of sarcopenia in patients with NENs. However, results should be interpreted with caution, and future research should focus on the correct technique, homogenous population and same time point.

Characterization and natural evolution of mixed adeno-neuroendocrine carcinoma of the pancreas

Characterization and natural evolution of mixed adeno-neuroendocrine carcinoma of the pancreas

Smíšený adenoneuroendokrinní karcinom žaludku – kazuistika

Neuroendocrine tumours represent a heterogeneous group of neoplasia arising from different anatomical locations, with approximately 50% of gastrointestinal origin. Main parameters in the evaluation of each case include tumour morphology, mitotic cell count, and Ki-67 index. Mixed adeno-neuroendocrine carcinomas (MANECs) are rare aggressive neoplasms consisting of both adenocarcinomatous and neuroendocrine cells, each component constituting at least 30% of the lesion. Our case represents 77-year-old polymorbid patient who, due to signs of acute bleeding in the upper gastrointestinal tract with anaemic syndrome, underwent a gastroscopic examination for melena with the finding of an ulcer lesion on the front wall of the stomach at the junction of the body and the antrum. The control gastroscopic examinations with biopsies, at first only signs of chronic gastritis with Helicobacter pylori positivity were histologically proven, then fragments of high-grade tubular to tubulovillous adenoma and structures of moderately differentiated tubular adenocarcinoma were found. Histological analysis of the gastric resection showed mixed adeno-neuroendocrine carcinoma with lymphangioinvasion.

S4227 Metastatic Mixed Adenoneuroendocrine Carcinoma Presenting as a Poorly Differentiated Sarcomatoid Neoplasm

S4227 Metastatic Mixed Adenoneuroendocrine Carcinoma Presenting as a Poorly Differentiated Sarcomatoid Neoplasm

Comparison of survival outcomes and survival prediction in patients with primarycolorectal MANEC and primary colorectal SRCC: a population-based propensity-score matching study.

Primary mixed adeno-neuroendocrine carcinoma (MANEC) and primary signet-ring cell cancer (SRCC) are two rare but highly malignant tumors in colorectal cancer. Therefore, we attempted to compare the tumors' survival outcomes, identify risk factors, and ultimately evaluate the prognosis by developing a nomogram. We identified 755 MANEC and 5836 SRCC patients of colorectal cancer. PSM was used to balance the influence of baseline clinical and pathological differences. Kaplan-Meier method was used to compare the prognosis of different pathological grades and AJCC stages. Cox proportional hazards model was used to identify potential prognostic factors for the two groups. Finally, we developed a nomogram and evaluated the feasibility of the model. After PSM, the median OS and CSS of MANEC patients were significantly better than those of SRCC patients in stage III-IV (P < 0.001) but similar in stage I-II. The median OS and CSS of MANEC patients in each pathological grade were also greater than those of SRCC patients. Patients with MANEC and SRCC who underwent lymph node dissection in more than four areas had longer survival time. MANEC patients benefited from postoperative chemotherapy and radiotherapy; among SRCC patients, those who received preoperative and postoperative comprehensive chemotherapy and radiotherapy had benefits in OS and CSS. Both MANEC and SRCC are often diagnosed in advanced stages, highlighting the importance of early screening. Despite the better prognosis of MANEC compared to SRCC, both types of patients require the formulation of personalized treatment strategies based on different risk factors combined with column charts.

Survival Trends and Profiling of Gastric Mixed Adenoneuroendocrine Carcinoma (gMANEC) in the Current Era

Background: Gastric mixed adenoneuroendocrine carcinoma (gMANEC) is a histopathologic diagnosis with at least 30% each of exocrine and endocrine components. Although prognosis is thought to be driven by the relative exocrine or endocrine dominance, gMANEC has been clinically treated as gastric adenocarcinoma (gAC). The overall survival of gMANEC as compared to gastric neuroendocrine carcinoma (gNEC) or gAC remains undefined. Methods: Using the National Cancer Database, patients with gastric tumors were queried from 2004 to 2016 for gMANEC, gNEC, and gAC histologies. Demographic and clinicopathologic features were recorded. Univariate and multivariate Cox proportional hazards analyses were performed to delineate factors associated with overall survival (OS). Results: Overall, 404 patients diagnosed with gMANEC were identified. Patients had a median age 68 years, were majority male, and predominantly Caucasian. Gastric MANEC was more frequently poorly differentiated (73%vs 52% (gAC) vs 20% (gNEC), P &lt; .001) with lymphovascular invasion (57%vs 38%vs 27%, P &lt; .001) and lymph node involvement (59%vs 49%vs 36%, P &lt; .001); these factors were associated with worse OS on univariable analysis. Finally, tumors &gt;5 cm and lymph node involvement were independent predictors of worse survival. The median OS of patients with gMANEC was 41.5 months. Conclusion: Gastric MANEC and gAC have a similarly dismal prognosis and thus should be continued to treat like gAC. Pathologic nodal metastasis, tumor size and grade are useful prognostic factors.

Precise microdissection of gastric mixed adeno-neuroendocrine carcinoma dissects its genomic landscape and evolutionary clonal origins

Gastric mixed adenoneuroendocrine carcinoma (MANEC) is a clinically aggressive and heterogeneous tumor composed of adenocarcinoma (ACA) and neuroendocrine carcinoma (NEC). The genomic properties and evolutionary clonal origins of MANEC remain unclear. We conduct whole-exome and multiregional sequencing on 101 samples from 33 patients to elucidate their evolutionary paths. We identify four significantly mutated genes, TP53, RB1, APC, and CTNNB1. MANEC resembles chromosomal instability stomach adenocarcinoma in that whole-genome doubling in MANEC is predominant and occurs earlier than most copy-number losses. All tumors are of monoclonal origin, and NEC components show more aggressive genomic properties than their ACA counterparts. The phylogenetic trees show two tumor divergence patterns, including sequential and parallel divergence. Furthermore, ACA-to-NEC rather than NEC-to-ACA transition is confirmed by immunohistochemistry on 6 biomarkers in ACA- and NEC-dominant regions. These results provide insights into the clonal origin and tumor differentiation of MANEC.

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

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. 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. 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 gradeIII, tumor size > 2cm, T3-T4 stage, lymph node metastasis, and distant metastasis were independent prognostic factors for patients with MANEC. 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.

Clinicopathological characteristics of mixed neuroendocrine-non-neuroendocrine neoplasms in gastrointestinal tract.

In 2019, the World Health Organization (WHO) classification system updated the definition of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), previously known as mixed adenoneuroendocrine carcinomas (MANECs). The clinicopathological characteristics of this new definition remains to be clarified. We analyzed the clinical data of 43 patients diagnosed with MiNENs in Wuhan Union Hospital from 2011 to 2020 according to the definition of MiNENs proposed in 2019. Among the 43 patients with MiNENs, the top two most common sites were stomach and colon, and 69.8% were males. Nearly half (21/43) of the patients were diagnosed at TNM stage III, and about 53.5% (23/43) of patients were the neuroendocrine neoplasm dominant type. Among the non-neuroendocrine tumor components of 43 MiNENs patients, adenocarcinoma accounted for 95.3% (41/43) and squamous cell carcinoma accounted for 4.7% (2/43)；95.3% (41/43) of the neuroendocrine neoplasm components were neuroendocrine carcinoma (NEC) and 4.7% (2/43) were neuroendocrine tumor (NET). Approximately 60.5% (26/43) neuroendocrine components had a Ki-67 index ≥55%. In addition, we further compared the prognosis of different subtypes of the MiNENs based on the neuroendocrine neoplasm component and non-neuroendocrine neoplasm component, and the results showed that there was no significant difference in survival between different subtypes of MiNENs (P>0.05). MiNENs can exhibit diverse clinicopathological characteristics, and there is no significant difference in prognosis among MiNENs subtypes, indicating that the definition of MiNENs can well summarize the prognosis of this type of tumor.

The other colon cancer: a population-based cohort study of appendix tumour trends and prognosis.

Appendiceal neoplasms are rare subtypes of colorectal tumours that mainly affect younger patients some 20 years earlier than other colon tumours. The aim of this study was to gain more insight into the histological subtypes of this rare disease and include cases previously excluded, such as mucinous neoplasia. The cohort study included 1097 patients from the Munich Cancer Registry (MCR) diagnosed between 1998 and 2020. Joinpoint analysis was used to determine trend in incidence. Baseline demographic comparisons and survival analyses using competing risk and univariate/multivariate methods were conducted according to tumour histology: adenocarcinoma (ADENO), neuroendocrine neoplasia (NEN), mixed adeno-neuroendocrine carcinoma (MANEC), and low- (LAMN) and high-grade mucinous neoplasia (HAMN). Up to 2016 the number of cases increased significantly [annual per cent change (APC)=6.86, p< 0.001] followed by a decline in the following years (APC=-14.82, p= 0.014; average APC=2.5, p= 0.046). Comparison of all patients showed that NEN (48.4%) and mucinous neoplasms (11.6%) had a considerably better prognosis than ADENO (36.0%) and MANEC (3.0%, p< 0.0001). A multivariate analysis within the NEN and ADENO subgroups revealed that further histological classification was not prognostically relevant, while older age and regional tumour spread at diagnosis were associated with a poor prognosis. ADENO histology with high tumour grade and appendectomy only was also associated with poorer survival. Appendiceal neoplasms are histologically heterogeneous; however, this diversity becomes less relevant compared with the marked difference from cancers of the remaining colon. The previously observed increase in cases appears to be abating; fewer cases of appendicitis and/or appendectomies or changes in histopathological assessment may be behind this trend.

Molecular profiling of gastric neuroendocrine carcinomas.

451 Background: Reports of comprehensive genetic analysis of gastric neuroendocrine carcinoma (G-NEC) are limited, and few have described the tumorigenesis of G-NEC. G-NEC usually has NEC and adenocarcinoma components and is considered to have a common origin in gastric adenocarcinoma because these two tumors share common pathogenic mutations and loss of heterozygosity. However, G-NEC without adenocarcinoma also exists, and it may have a different mechanism of tumorigenesis than that of G-NEC with adenocarcinoma. This study aimed to elucidate the tumorigenesis of G-NEC by focusing on the percentage of NEC component, using comprehensive genetic analysis. Methods: Of the 698 patients who had undergone gastrectomy for gastric cancer between January 2014 and March 2019, this study included 13 patients with G-NEC. Comprehensive genetic analysis using whole-exome sequencing, deep sequencing using a target gene panel, and microarray analysis were performed. NEC was classified according to the 2010 WHO classification. G-NEC without an adenocarcinoma component was defined as pure NEC. Results: There were six patients with mixed adeno-neuroendocrine carcinoma (MANEC), four patients with NEC, and three patients with pure NEC. TP53 was detected as the most frequent gene mutation, independent of classification (85%). RB1, ANKRD17, KMT2C, LTBP1, MAATS1, and RYR2 mutations were identified in two of three pure NEC patients but were not detected in other G-NEC patients. Gene expression analysis showed that six key transcripts of importance in NEC tumorigenesis were upregulated in two patients with pure NEC, while they were downregulated in all six MANEC patients. Conclusions: NEC and MANEC with adenocarcinoma components tend to share common pathogenic mutations, but Pure NEC has different genomic and transcriptomic characteristics than other NECs. This suggests that pure NEC has a different mechanism of tumorigenesis than other G-NECs with adenocarcinoma. This is the first study to present a comprehensive genetic analysis of G-NEC, classified by the percentage of NEC components.

Relationships of tumor differentiation and immune infiltration in gastric cancers revealed by single-cell RNA-seq analyses

Gastric cancers are highly heterogeneous malignant tumors. To reveal the relationship between differentiation status of cancer cells and tumor immune microenvironments in gastric cancer, single-cell RNA-sequencing was performed on normal mucosa tissue, differentiated gastric cancer (DGC) tissue, poorly differentiated gastric cancer (PDGC) tissue and neuroendocrine carcinoma (NEC) tissue sampled from surgically resected gastric cancer specimens. We identified the signature genes for both DGC and PDGC, and found that signature genes of PDGC strongly enriched in the epithelial–mesenchymal transition (EMT) program. Furthermore, we found that DGC tends to be immune-rich type whereas PDGC tends to be immune-poor type defined according to the density of tumor-infiltrating CD8+ T cells. Additionally, interferon alpha and gamma responding genes were specifically expressed in the immune-rich malignant cells compared with immune-poor malignant cells. Through analyzing the mixed adenoneuroendocrine carcinoma, we identified intermediate state malignant cells during the trans-differentiation process from DGC to NEC, which showed double-negative expressions of both DGC marker genes and NEC marker genes. Interferon-related pathways were gradually downregulated along the DGC to NEC trans-differentiation path, which was accompanied by reduced CD8+ cytotoxic T-cell infiltration. In summary, molecular features of both malignant cells and immune microenvironment cells of DGC, PDGC and NEC were systematically revealed, which may partially explain the strong tumor heterogeneities of gastric cancer. Especially along the DGC to NEC trans-differentiation path, immune-evasion was gradually enhanced with the decreasing activities of interferon pathway responses in malignant cells.

Mixed neuroendocrine and non-neuroendocrine neoplasia (MiNEN) of the stomach

From the latest WHO classification of neuroendocrine neoplasms (NENs), the term MiNENs refers to mixed neuroendocrinenon-neuroendocrine tumors. A neuroendocrine component coexists with a non-neuroendocrine one in them. They are morphologically and/or immunohistochemically validated. The non-neuroendocrine component implicates adenocarcinoma, apart from other histological subtypes of carcinomas, such as squamous cell carcinoma. The neuroendocrine component can be represented by a high-grade tumour (HGNEC) in addition to neuroendocrine cancer. Gastric NENs also have subgroups of MiNENs such as mixed adenoneuroendocrine carcinoma (Mixed-adenocarcinoma-NEC), which includes both, small or large cell type, neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine tumor (Mixed-adenocarcinoma-NET). Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) is a rare disease. Based on the available data, neuroendocrine component has a highly aggressive biological behaviour represented by a low-differentiated neuroendocrine tumor in the majority of MiNENs cases. The treatment is based on the principles of neuroendocrine tumour therapy. The foregoing shows that it is not possible to provide precise epidemiological data, prognosis and approve treatment strategies.

Peritoneal metastatic mixed adenoneuroendocrine carcinoma treated with cytoreduction surgery and hyperthermic intraperitoneal chemotherapy: a case report.

A 61-year-old man presented with abdominal distension without any symptoms. On colonoscopy and computed tomography findings, it was clinically diagnosed as peritoneal metastasis of sigmoid colon cancer, and diagnostic laparoscopy was performed. Only the peritoneum was partially resected, and the pathology was signet ring cell carcinoma with predominantly local mucinous carcinoma component. However, the patient complained of persistent symptoms and, despite the progress of chemotherapy, the peritoneal dissemination worsened, and additional cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) was performed. Mixed adenoneuroendocrine carcinomas (MANECs) were reported in the appendix with perforated visceral peritoneum. After additional chemotherapy, the patient was discharged. Patients with advanced MANEC with peritoneal spreading may benefit from aggressive treatment by cytoreduction surgery with HIPEC, followed by intravenous chemotherapy.

S2075 Mixed Adeno-Neuroendocrine Carcinoma (MANEC) of Colon: Rare Differential Diagnosis for Iron Deficiency Anemia

Introduction: Colonic Mixed adenoneuroendocrine carcinoma (MANEC) is a rare but highly aggressive tumor. In English Literature only 10 cases or less have been reported of this neoplasm, with the prognosis still unfavorable. Mixed adenoneuroendocrine carcinomas, by definition, are comprised of at least 30% of both a neuroendocrine and an adenocarcinomatous component. Cases are typically diagnosed at advanced stages, and the age of presentation is younger than the average age of colorectal adenocarcinoma (∼60 years old). Metastasis can occur anywhere but usually seen in the liver, regional lymph nodes and rarely peritoneum. The tumor neuroendocrine markers and immunophenotype are essential for the diagnosis, for example chromogranin, synaptophysin, CDX-2, and CD56. Case Description/Methods: A 53-year-old women with a history of abdominal pain was diagnosed with NET via histopathology of the cecum. The patient was referred to us by her hematologist which he ordered CT/pelvis due to her new onset of iron deficiency anemia and CT scan showed irregular bowel wall thickening of proximal ascending colon with infiltration and nodularity of surrounding fat suspicious of colon neoplasm. The patient has diabetes mellitus and hypertension other than that she had no significant history of past illness. A colonoscopy and biopsy were performed that showed poorly differentiated carcinoma with ulceration in large bowel mucosa, morphologically, high grade poorly differentiated malignant neoplasm was noted with ulceration. Histopathology and Immunohistochemical studies show the tumor cells are positive for AE1/3, CK7, synptophysin, CDX-2, while negative for CK20, chromogranin, CD56. Ki-67 shows a high labeling index (−95%). The negative stain of tumor cells for MLH-1 and PMS2 can be associated with microsatellite instability related germ line mutation. The differential diagnosis includes poorly differentiated adenocarcinoma, mixed adenoneuroendocrine carcinoma and large cell endocrine carcinoma. A definitive classification depends on the total resection specimen (Figure 1). Discussion: Mixed adenoneuroendocrine carcinoma of the colon is a neoplasm consisting of 2 components coexisting simultaneously within a tumor. It is a very rare carcinoma that presents at a younger age than colorectal adenocarcinoma. Unfortunately, it is diagnosed usually at late stages when metastasis has occurred. If detected at early stages curative surgery can be the treatment. The prognosis Is poor due to late diagnosis and dual nature of the tumor.Figure 1.: Histology and Immunohistochemical studies.

899P Molecular characterization of gastro-entero-pancreatic advanced mixed adeno-neuroendocrine carcinomas: NIRVANA sub-study

Gastro-entero-pancreatic (GEP) mixed adeno-neuroendocrine carcinomas (MANECs) are rare and aggressive neoplasms with a very poor prognosis and their molecular features are still not properly addressed. Our aim is to evaluate clinical, pathological, and biomolecular data of patients with GEP-MANEC in order to identify prognostic and predictive factors which could potentially correlate with clinical outcomes. This cohort of patients is derived from a larger retrospective - prospective observational dataset of patients with pure or mixed extra-pulmonary (EP) high grade neuroendocrine neoplasms. We reviewed clinical and pathological data of advanced GEP-MANECs managed at our Institute between 2015 and 2021 with available surgical/biopsy specimens. All the tumor tissues were tested for 26 genes by next-generation sequencing (NGS) using a targeted multi-genes NGS panel both in neuroendocrine and non-neuroendocrine component. Descriptive analyses will be performed. Primary and secondary endpoints are descriptive in nature, therefore no formal statistical hypotheses were pre-specified. The study is approved by IEO Ethical Committee. Among 55 high grade neuroendocrine neoplasms, 7 patients with GEP-MANEC resulted eligible. The primary sites were: 2 rectum, 1 appendix, 1 caecum, 1 stomach, 1 gallbladder. Almost all cases showed at least one somatic mutation in > 5% of the tissue. The most frequently mutated genes were KRAS and TP53 (4/7 patients) in both components. Other genes, including PI3K and RB1 were mutated, only in one case and only in the NEC component. All MANECs showed TP53 mutation in NEC and non-NEC component. Five out of seven (71%) received at least one line of chemotherapy, mostly represented by cis/carbo-platinum-based regimens. Among them, 4 patients (80%) received a second-line therapy, mainly irinotecan-containing, and then a 3-line therapy (2 capecitabine/temozolomide). Although low numbers, these preliminary data seem to suggest that the carcinogenesis of the MANECs of the GEP tract relies on its biomolecular features and site of origin. Specific targetable alterations indicate a high potential for personalized treatments. The study is ongoing.

Clinicopathological Features and Postoperative Survival Analysis of Gastric Carcinoma with Neuroendocrine Differentiation

Objectives This study aims at investigating the differences of clinicopathological features and postoperative prognosis in three different types of neuroendocrine differentiation-related gastric cancers. Methods From January 1, 2015 to September 30, 2016, 47 patients diagnosed with neuroendocrine differentiation-related gastric cancers were collected from 1095 patients with gastric cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery, Jiangsu Cancer Hospital. Patients were followed up regularly, and the last follow-up time was October 25, 2021. A total of 38 cases met the inclusion criteria and completed follow-up. The clinicopathological characters and immunohistochemical results of these three special pathological types of gastric cancer (adenocarcinoma with neuroendocrine differentiation, mixed adenoneuroendocrine carcinoma, and neuroendocrine carcinoma of the stomach) patients were compared. Tissues from these patients were tested with immunohistochemical markers synaptophysin (Syn), chromogranin A (CgA), and Ki-67. The Kaplan–Meier method and log-rank test were used to analyze the effect of different histological types of gastric cancer on overall survival (OS). The differences in positive rates of chromogranin A (CgA) and Ki-67 were analyzed by univariate Cox regression analysis as independent risk factors that may affect the survival of gastric cancer patients. Results Ki-67 and N staging were significantly correlated with OS in gastric cancer patients and were independent prognostic factors affecting the survival of gastric cancer patients. There was no statistical difference in OS between the two histopathological types (adenocarcinoma with neuroendocrine differentiation and mixed adenoneuroendocrine carcinoma) of gastric cancer patients. There were no significant differences in the positive rates of immunohistochemical markers Syn, CgA, and Ki-67 in gastric cancer patients with different histological types. Conclusion The combined detection of Syn and CgA is of great value for the diagnosis of neuroendocrine differentiation-related gastric cancers, Ki-67 is of significance for the prognosis prediction of neuroendocrine differentiation-related gastric cancers, regional lymph node metastasis has a great impact on tumor prognosis, and the N staging determines the necessity of postoperative adjuvant chemotherapy for patients with neuroendocrine differentiation-related gastric cancer.

Metastasis of Mixed Adenoneuroendocrine Carcinoma of the Uterine Cervix to Thyroid Gland.

The thyroid metastasis from cervical cancer is extremely rare compared to other organs. It is sometimes difficult to distinguish primary tumors from metastases, as most metastatic thyroid nodules are asymptomatic. In this case, a 54-year-old woman had undergone radical hysterectomy due to cervical tumor of stage IB1 mixed adenoneuroendocrine carcinoma (MANEC) 5 years ago. After 3 years, ultrasound examination revealed a suspicious malignant nodule in the left lobe of thyroid gland at regular postoperative follow-up. This patient had no obvious clinical symptoms. The ultrasonography (US)-guided core needle biopsy (CNB) of the thyroid nodule was performed on the patient. The immunohistochemistry analyses revealed that it was poorly differentiated small-cell neuroendocrine carcinoma (SCNEC). Subsequently, the patient underwent left hemithyroidectomy plus isthmusectomy. The postoperative pathology and immunohistochemistry, combining with clinical history, confirmed that the thyroid nodule was a metastasis from cervical MANEC. Conventional chemotherapy and regular follow-up were carried out after the operation. The patient was readmitted 1 year later for pancreatic metastatic lesions and died 1 month after surgery. Early detection of metastatic cancer is potentially helpful, and when necessary, ultrasound-guided puncture biopsy can be utilized to further diagnose metastatic thyroid cancer.