Surgical Oncology 12 (2003) 153–172 Review Carcinoid tumors of the stomach Irvin M. Modlin a,b, *, Kevin D. Lye a,b , Mark Kidd a a Gastrointestinal Surgical Pathobiology Research Group, Yale University School of Medicine, New Haven, CT 06520-8062, USA b Department of Surgery, Yale University School of Medicine, 333 Cedar Street, PO Box 208062, New Haven, CT 06520-8062, USA Abstract Interest in gastric carcinoid tumors has in recent time amplified considerably as the understanding of both their biological background and clinical significance has developed. The increase in identification associated with the widespread availability of upper gastrointestinal endoscopy has facilitated diagnosis. In addition concern related to the consequences of long-standing hypergastrinemia generated by the use of potent acid-suppressive medications has augmented both clinical and scientific focus on gastric neuro endocrine issues. The elucidation of the regulatory mechanisms of the progenitor cell (ECL cell) of the gastric carcinoid tumor, the refinement of a pathological grading system for ECL cell proliferation, and the availability of specific immunohistologic identification techniques have further amplified the characterization of this lesion. Although the putative malignant potential of gastric carcinoids may ultimately be of only modest concern in a background of hypergastrinemia its relationship to gastric adenocarcinoma is still enigmatic and worthy of further consideration. This review will describe the molecular interrelationship between low-acid states, gastrin, and ECL cell proliferation and will discuss the pathological classification of the distinct types of gastric carcinoid tumors. In addition, the clinical rationale of current diagnostic and therapeutic strategies will be examined, providing a logical basis for the formulation of appropriate management strategies for patient care. r 2003 Elsevier Ltd. All rights reserved. Keywords: Carcinoid; ECL cell; Epidemiology; Gastrin; Metastases; Proliferation; Stomach ARTICLE IN PRESS Contents 1. Introduction ................................................ 154 2. Clinical manifestations ........................................... 155 3. Incidence .................................................. 156 4. Biological basis ............................................... 158 4.1. ECL cells ............................................... 158 4.2. Secretory function .......................................... 159 4.3. Proliferative role ........................................... 159 4.4. Carcinoid and gastric adenocarcinoma ................................ 160 5. Clinical pathology ............................................. 161 6. Gastric carcinoid classification ....................................... 162 6.1. Type i: carcinoids associated with type a chronic atrophic gastritis ................. 162 6.2. Type ii : carcinoids associated with ZES-MEN-1 ........................... 163 6.3. Type iii: sporadic argyrophil carcinoids ............................... 163 7. Diagnosis and management ........................................ 164 7.1. Biochemical diagnosis ........................................ 164 7.2. Histology ............................................... 164 *Corresponding author. Department of Surgery, Yale University School of Medicine, 333 Cedar Street, PO Box 208062, New Haven, CT 06520- 8062, USA. Tel.: +1-203-937-4781; fax: +1-203-937-4783. E-mail address: irvin.modlin@yale.edu (I.M. Modlin). 0960-7404/03/$-see front matter r 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S0960-7404(03)00034-3