Site and Clinical Presentation of Gastroenteropancreatic and Bronchopulmonary NENs
| Site | Clinical presentation |
| Gastrointestinal | |
| Gastric | Type I: atrophic gastritis, gastrin-dependent |
| Type II (MEN1): menin-dependent, gastrin-related (Zollinger-Ellison syndrome) | |
| Type III: gastrin-independent, clinically aggressive | |
| Duodenal | Various phenotypes: gastrinoma, so-called carcinoid, somatostatinoma |
| Jejunal | “Carcinoid”: classic symptoms (flushing, diarrhea), clinically aggressive |
| Ileal | “Carcinoid”: classic symptoms (flushing, diarrhea), clinically aggressive; typical CT appearance of contrast-enhancing spiculated mass, sometimes containing calcifications, surrounded by lines of desmoplastic reactions |
| Appendiceal | “Carcinoid”: usually present as appendicitis or incidental finding at laparotomy/laparoscopy and generally radically cured after surgical excision |
| Goblet cell “carcinoid” (mucinous carcinoid): clinically aggressive | |
| Colonic | Carcinoid symptoms are rare, and presentation is similar to adenocarcinoma |
| Rectal | Local manifestations: pain, bleeding |
| Hepatic | >95% are metastases from gastroenteropancreatic NEN primary; typical CT appearance of hypodense masses, with rich enhancement during arterial phase, reverting to hypodense during portal phase; on MRI (most sensitive technique), lesions enhance after gadolinium, and best sequences are arterial phase and fast spin-echo T2-weighted |
| Pancreatic | |
| Gastrinoma (Zollinger-Ellison syndrome) | Peptic ulceration and secretory diarrhea; 60%–90% malignant behavior |
| Insulinoma | Hypoglycemia, generally small and SSR-negative; 5%–15% malignant and generally SSR-positive |
| Glucagonoma | Skin rash (migrating necrolytic erythema), weight loss, diabetes; 60% malignant |
| VIPoma | Secretory diarrhea (Verner–Morrison syndrome); 80% malignant |
| Somatostatinoma | Diabetes, gallstones, often component of genetic syndrome; 60% malignant |
| GRFoma | Acromegaly; 30% malignant |
| ACTHoma | Cushing syndrome; aggressive behavior; >90% malignant |
| P-NEN causing carcinoid syndrome | Diarrhea, flushing; 68%–88% malignant |
| P-NEN causing hypercalcemia | Hypercalcemia; 80%–90% malignant |
| Nonfunctioning | Local mass effects; 60%–90% malignant |
| Bronchopulmonary | |
| Typical carcinoid | Frequently central, with cough, wheezing, hemoptysis, and signs of bronchial obstruction; functional when metastatic (carcinoid, Cushing, acromegaly, or syndrome of inappropriate antidiuretic hormone secretion); relatively indolent biologic behavior; may be part of MEN1 |
| Atypical carcinoid | Frequently peripheral and asymptomatic, may present with coughing and wheezing or functional syndrome; from indolent to aggressive; may be part of MEN1 |
| Large cell neuroendocrine carcinoma | Aggressively metastatic and rapidly progressing |
| Small cell lung cancer | Aggressively metastatic and rapidly progressing |
| Thymic neuroendocrine tumors | Frequently large, 50% functional, usually adrenocorticotropic hormone–induced Cushing syndrome; frequently metastatic; may be part of MEN1 |
| Chromaffin | |
| Pheochromocytoma/paraganglioma | 80%–85% arise from adrenal medulla, 15%–20% extraadrenal; majority associated with catecholamine hypersecretion (most frequently, hypertension, tachycardia, headache, pallor, sweating, and anxiety), with frequent paroxysmal component |
VIP = vasoactive intestinal peptide; GRF = growth hormone–releasing factor; ACTH = adrenocorticotropic hormone; P-NEN = pancreatic neuroendocrine neoplasm.