Site and Clinical Presentation of Gastroenteropancreatic and Bronchopulmonary NENs

SiteClinical presentation
 GastricType I: atrophic gastritis, gastrin-dependent
Type II (MEN1): menin-dependent, gastrin-related (Zollinger-Ellison syndrome)
Type III: gastrin-independent, clinically aggressive
 DuodenalVarious 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
 ColonicCarcinoid symptoms are rare, and presentation is similar to adenocarcinoma
 RectalLocal 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
 Gastrinoma (Zollinger-Ellison syndrome)Peptic ulceration and secretory diarrhea; 60%–90% malignant behavior
 InsulinomaHypoglycemia, generally small and SSR-negative; 5%–15% malignant and generally SSR-positive
 GlucagonomaSkin rash (migrating necrolytic erythema), weight loss, diabetes; 60% malignant
 VIPomaSecretory diarrhea (Verner–Morrison syndrome); 80% malignant
 SomatostatinomaDiabetes, gallstones, often component of genetic syndrome; 60% malignant
 GRFomaAcromegaly; 30% malignant
 ACTHomaCushing syndrome; aggressive behavior; >90% malignant
 P-NEN causing carcinoid syndromeDiarrhea, flushing; 68%–88% malignant
 P-NEN causing hypercalcemiaHypercalcemia; 80%–90% malignant
 NonfunctioningLocal mass effects; 60%–90% malignant
 Typical carcinoidFrequently 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 carcinoidFrequently peripheral and asymptomatic, may present with coughing and wheezing or functional syndrome; from indolent to aggressive; may be part of MEN1
 Large cell neuroendocrine carcinomaAggressively metastatic and rapidly progressing
 Small cell lung cancerAggressively metastatic and rapidly progressing
 Thymic neuroendocrine tumorsFrequently large, 50% functional, usually adrenocorticotropic hormone–induced Cushing syndrome; frequently metastatic; may be part of MEN1
 Pheochromocytoma/paraganglioma80%–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.