Upper gastrointestinal neuroendocrine tumors (NETs) are rare tumors which are increasingly recognised by practising endoscopists. After confirmation by endoscopic biopsies of these focal lesions, many questions may arise. As NETs are less frequently encountered compared to other malignancies or gastrointestinal pathology, many endoscopists may not fully understand the natural history, diagnosis and management of these tumors. In this review, we aim to update the practising endoscopist on the key clinical features and management of patients with upper gastrointestinal NET.
Biopsy ; Diagnosis* ; Humans ; Natural History ; Neuroendocrine Tumors* ; Pathology

Pulmonary neuroendocrine tumors are common in pathological practice and its pathological classification and histological grading are not exactly the same as that of those in the digestive tract and pancreas. In 2015 edition of World Health Organization classification, pulmonary neuroendocrine tumors are classified as carcinoid tumors (including typical carcinoid and atypical carcinoid), small cell lung carcinoma, large cell neuroendocrine carcinoma, and precursor lesion diffuse idiopathic neuroendocrine cell hyperplasia; each category has distinctive morphological and immunohistochemical features. The morphologic features including growth patterns and cytological appearances are keys for the diagnosis of neuroendocrine tumor, and immunohistochemical findings are also critical for its diagnosis. Furthermore, the diagnostic criteria vary for different types of specimen. In this article, we present a concise review and summary of the update of clinicopathological characterizations of pulmonary neuroendocrine tumor, with an emphasis on its diagnostic criteria and differential diagnosis.
Carcinoid Tumor ; diagnosis ; pathology ; Diagnosis, Differential ; Humans ; Hyperplasia ; Lung Neoplasms ; diagnosis ; pathology ; Neuroendocrine Tumors ; classification ; diagnosis ; pathology

OBJECTIVETo investigate the clinicopathologic characteristics, diagnosis, differential diagnosis and treatment of primary neuroendocrine tumor (NET) of the testis.

METHODSUsing light microscopy and immunohistochemistry, we studied 7 cases of primary NET of the testis, reviewed relevant literature, and analyzed the clinical manifestations, histomorphologic and immunohistochemical characteristics, treatment and prognosis of the tumor.

RESULTSThe 7 male patients, at the mean age of 40.6 years, all presented with testicular painless masses, none accompanied with carcinoid syndrome. Histologically, the uniform tumor cells were arranged in trabecular, island, solid and/or flake structures and locally in a tubulo glandular pattern, round and polygonal in shape, with a small amount of lipid vacuoles in the eosinophilic cytoplasm. The cells had round nuclei with fine chromatin and rarely identified mitosis. Immunohistochemical staining showed that the tumor cells were positive for Syn, CgA, NSE and CK, with a Ki-67 positive rate of < 2%.

CONCLUSIONPrimary NET of the testis is a rare and low-grade malignancy. Early diagnosis and surgical resection are essential for good prognosis. Immunohistochemistry helps its diagnosis and differential diagnosis from other metastatic neuroendocrine carcinoma, teratomas with carcinoid, seminoma, and Sertoli cell tumor.

Adult ; Carcinoid Tumor ; diagnosis ; pathology ; Diagnosis, Differential ; Humans ; Male ; Middle Aged ; Neuroendocrine Tumors ; diagnosis ; pathology ; Prognosis ; Testicular Neoplasms ; diagnosis ; pathology

The incidence of neuroendocrine neoplasms (NENs) has been gradually increasing and most of NENs are located in gastroenteropancreatic system. With the application of target therapeutic drugs in recent years, the precise pathological diagnosis is required critically for effective clinical treatment: target therapy needs targeted pathological diagnosis. In this article, the definition of NENs, and the century-long evolution of diagnostic terms and grades are reviewed. The eight steps of pathological diagnosis of NENs for clinical needs are described. Four inconsistent concepts in NENs diagnosis are also discussed, that is immunohistochemical biomarkers of pathological diagnosis, subpopulation of neuroendocrine neoplasms with high proliferative activity, general adenocarcinomas with neuroendocrine differentiation and molecular genetics characteristics. To correctly understand these issues would be of great value for diagnosis and treatment of NENs.
Biomarkers, Tumor ; analysis ; Humans ; Immunohistochemistry ; Neoplasm Grading ; Neuroendocrine Tumors ; diagnosis ; pathology ; therapy ; Treatment Outcome

OBJECTIVETo investigate risk factors associated with lymph node metastasis and prognosis of rectal neuroendocrine tumor (NET).

METHODSClinicopathological data of 69 patients with rectal NET in our department from April 2003 to October 2011 were retrospectively analyzed. Associations of clinicopathological factors with lymph node metastasis and prognosis were examined using univariate and multivariate analysis.

RESULTSOf the 69 patients, 9 cases had lymph node metastasis. The lymph node metastasis was significantly associated with tumor size, T stage and G grade by univariate analysis. Multivariate analysis showed that T stage was the only risk factor associated with lymph node metastasis. The overall 5-year survival rate was 90.3%. Prognosis of rectal NET was significantly associated with tumor size, T stage, N stage, M stage, TNM stage and G grade by univariate analysis. Multivariate analysis showed that M stage was significantly associated with long-term survival in rectal NET patients (P=0.000, HR=2.285, 95%CI:1.484~3.518). There was no significant difference in patients with stage I between local and radical resection, while there were significant differences in those with stage II or higher between the two operations (P=0.046).

CONCLUSIONT stage is associated with lymph node metastasis and both TNM stage and M stage can affect the prognosis of patients with NET, which may be used as potential predictive factors for rectal NET. Local resection should be recommended for patients with stage I and radical resection should be recommended for patients with stage II or higher.

Adult ; Aged ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; diagnosis ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Neuroendocrine Tumors ; diagnosis ; pathology ; Prognosis ; Rectal Neoplasms ; diagnosis ; pathology

Neuroendocrine tumor (NET) is a cancer-like tumor that occurs mostly in the gastrointestinal system. Within the gastrointestinal tract, NET most commonly occurs in the rectum whereas appendix is very rarely involved. In most cases of appendiceal NET, it is found at a relatively early stage compared to other NETs because appendiceal NET frequently presents with acute appendicitis because appendiceal NET frequently presents with acute appendicitis even when the size is smaller than 1 cm. Therefore, it is very rare for lymph node metastasis to occur in a young adult. Herein, we report a rare case of grade 1 appendiceal NET with lymph node metastasis which developed in a teenage male.
Adolescent ; Appendiceal Neoplasms/*diagnosis/pathology/surgery ; Carcinoid Tumor/diagnosis/pathology ; Colectomy ; Colonoscopy ; Humans ; Lymphatic Metastasis ; Male ; Neuroendocrine Tumors/*diagnosis/pathology ; Tomography, X-Ray Computed

Neuroendocrine tumors of the extrahepatic biliary tree are extremely rare malignancies accounting for 0.2-2.0% of all gastrointestinal carcinoid tumors. Neuroendocrine tumors obstructing the biliary tree are extremely difficult to diagnose preoperatively and nearly impossible to differentiate from cholangiocarcinoma. Statistically, the most common anatomic location in the biliary tree is the common bile duct, followed by the perihilar region. Herein, we present a case of a small cell neuroendocrine carcinoma of the hilum in a 79-year-old man following laparotomy. To our knowledge, this is the first case of small cell type neuroendocrine carcinoma of hilar bile duct reported in Korea.
Aged ; Bile Duct Neoplasms/*diagnosis/pathology/surgery ; Cholangiopancreatography, Endoscopic Retrograde ; Diagnosis, Differential ; Hepatic Duct, Common/pathology ; Humans ; Male ; Neuroendocrine Tumors/*diagnosis/pathology/surgery ; Tomography, X-Ray Computed

Pancreatic endocrine tumours (PETs) are uncommon tumours with typical morphology characterised by relatively uniform cuboidal cells arranged in nests and festoons, with distinctive nuclear salt-and-pepper chromatin. A lipid-rich variant poses diagnostic difficulties in the midst of other pancreatic tumours and metastatic goblet cell carcinoid. A 22-year-old man presented with symptoms of abdominal pain and jaundice. His liver function test and blood glucose level were normal, but computed tomography of the abdomen suggested the presence of a tumour in the head of the pancreas. Specimen obtained by pancreaticoduodenectomy revealed an infiltrating yellow-tan tumour composed of nests and a cribriform arrangement of polygonal vacuolated cells with pyknotic nuclei, along with focal classical areas of PET. Two foci of early serous microcystic adenoma were seen. Immunohistochemistry contributed to the arrival of a conclusive diagnosis. Von Hippel-Lindau disease was excluded in our patient, as other supportive classical features of the syndrome were absent.
Adenoma ; Blood Glucose ; metabolism ; Carcinoid Tumor ; diagnosis ; pathology ; Humans ; Immunohistochemistry ; Lipids ; chemistry ; Male ; Neoplasm Metastasis ; Neuroendocrine Tumors ; diagnosis ; pathology ; Pancreatic Neoplasms ; diagnosis ; pathology ; Pancreaticoduodenectomy ; Young Adult

OBJECTIVETo investigate the clinicopathologic features and prognostic factors of gastric neuroendocrine neoplasms(gNENs).

METHODSClinicopathologic data of 104 patients with gastric neuroendocrine neoplasms admitted in Chinese PLA General Hospital between January 2000 and December 2014 were analyzed retrospectively. Tumor proliferation activity classification (G1, G2 and G3) and TNM staging were observed. The clinicopathologic features of the whole group were collected and the univariate and multivariate analysis were determined by Log-rank and Cox proportional hazard model to detect the prognosis-determining features.

RESULTSOf all the patients, 66 cases(63.5%) were neuroendocrine carcinoma, 25 cases(24.0%) were mixed adenoendocrine carcinoma and 12 cases (11.5%) were neuroendocrine tumor. For G grades, 92 cases (88.5%) were G3 grade, 8 cases(7.7%) were G2 grade and 4 cases (3.8%) were G1 grade. TNM staging results showed that stageI( was found in 6 cases (5.8%), stageII(A in 6 cases (5.8%), stageII(B in 9 cases (8.7%), stage III(A in 8 cases (7.7%), stage III(B in 55 cases (52.9%) and stageIIII( in 20 cases (19.2%). For T stage, 7 cases (6.7%) were T1, 12 cases (11.5%) were T2, 24 cases (23.1%) were T3, and 61 cases (58.7%) were T4. Lymph node metastasis occurred in 73 cases (70.2%) and distant metastasis occurred in 20 cases(19.2%). Eighty-six patients were followed up for 6 to 186 months. The median survival was 33.0 months(95% CI: 28.3 to 36.6), and 1-, 3-, and 5-year survival rates were 80%, 49% and 31%. Clinicopathologic features which were considered statistically significant on univariate analysis were selected to Cox proportional hazard model. Univariate analysis showed that risk factors of reducing survival rate included tumor size, pathological type, proliferation activity grades, and depth of invasion (all P<0.05), as well as chromogranin A expression, tumor staging, lymph node metastasis and distant metastasis(all P<0.01). The multivariate analysis showed that the stage of gNEN was the independent risk factor of the prognosis (RR=14.213, 95% CI: 1.316 to 153.524, P=0.029).

CONCLUSIONLate staging is the main clinical feature and a prognostic factor for gNENs.

Carcinoma ; diagnosis ; pathology ; Humans ; Lymphatic Metastasis ; Multivariate Analysis ; Neoplasm Staging ; Neuroendocrine Tumors ; diagnosis ; pathology ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms ; diagnosis ; pathology ; Survival Rate

BACKGROUNDPancreatic neuroendocrine tumors (pNETs) are a type of tumors with the characteristics of easy metastasis and recurrence. Till date, the risk factors affecting the prognosis are still in the debate. In this study, several risk factors will be discussed combined with our cases and experience.

METHODSThirty-three patients diagnosed as pNETs were enrolled and the clinical features, blood tests, pathological features, surgical treatment, and follow-up data of these patients were collected and analyzed.

RESULTSIn this study, operation time of G3 cases was longer than G1/G2 cases (P = 0.017). The elevated level of tumor markers such as AFP, CEA, Ca125, and Ca19-9 may predict easier metastasis, earlier recurrence, and poor prognosis (P = 0.007). The presence of cancer embolus and nerve invasion increases along with the TNM stage (P = 0.037 and P = 0.040), and the incidence of positive surgical margin increased (P = 0.007). When the presence of nerve invasion occurs, the chance of cancer embolus and lymph node metastasis also increases (P = 0.016 and P = 0.026).

CONCLUSIONSpNETs were tumors with the features of easy recurrence and metastasis and many risk factors could affect its prognosis such as the elevated levels of tumor markers and the presence of nerve invasion, except some recognized risk factors. If one or more of these factors existed, postoperative treatments may be needed to improve prognosis.

Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; diagnosis ; pathology ; Neoplasm Staging ; Neuroendocrine Tumors ; diagnosis ; pathology ; Pancreatic Neoplasms ; diagnosis ; pathology ; Risk Factors ; Young Adult