Earlier reports of primary nodal gastrinomas and of diffuse gastrin overproduction in the stomach appear to be due instead to very small (<1 mm) duodenal neoplasms
Functioning G cell neoplasms (gastrinomas) may be solitary or multiple and may be located throughout the duodenum or into proximal jejunum
Local lymph nodes frequently involved (50-80%)
May occur even if primary neoplasm is <1 mm
Liver involved at presentation in about 5%
Most cases of ZE syndrome due to sporadic gastrinomas
Approximately 20% associated with MEN1
Duodenal G cell neoplasms associated with MEN1 are more often multiple
Same behavior as sporadic neoplasms if matched for function and stage
Sporadic G cell neoplasms more often solitary and <1 cm
10 year survival >90%
for duodenal gastrinomas without liver metastases
(Weber 1995, Stabile 1985)
10 year survival if liver metastases found at presentation 30%
Local lymph node involvement not predictive of poor behavior
10 year survival if regional nodes involved also >90%
Same behavior even if incompletely resected
Note that WHO 2008 incorrectly gives 10 year survival of 59% for duodenal gastrinomas without liver metastases, referencing Weber 1995 who actually reported 94% survival
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting/updates : 7/27/10, 11/22/11, 12/28/11
Grading
WHO recommends the following grading scheme, but a number of other factors are predictive of behavior, see Criteria
Proposed grading scale based on proliferation
Grade
Mitotic count per 10 hpf
% of cells Ki67+
G1
<2
≤2
G2
2-20
3-20
G3
>20
>20
Mitotic counts based on 50 hpf
Ki67 % based on 500-2000 cells
If discrepant, use higher grade
Scale proposed by European Neuroendocrine Society (ENETS)
Carcinoids / neuroendocrine tumors may be G1 or G2
G3 is definitional for high grade neuroendocrine carcinoma
Progression from G1/2 to G3 is quite rare
G3 appears to be a separate process
Grading/Staging References
Rindi G, Klöppel G, Couvelard A, Komminoth P, Körner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2007 Oct;451(4):757-62.
Rindi G, Klöppel G, Alhman H, Caplin M, Couvelard A, de Herder WW, Erikssson B, Falchetti A, Falconi M, Komminoth P, Körner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B; and all other Frascati Consensus Conference participants; European Neuroendocrine Tumor Society (ENETS). TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2006 Oct;449(4):395-401.
Staging
Use TNM
Differential Diagnosis
Determination of common sites of origin for metastatic well differentiated endocrine neoplasms
Riddell RH, Petras RE, Williams GT, Sobin LH. Tumors of the Intestines, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 32, 2003.
Bosman FT, Carneiro F, Hruban RH, Thiese ND (Eds). WHO Classifiication of Tumors of the Digestive System, IARC, Lyon 2010
Weber HC, Venzon DJ, Lin JT, Fishbein VA, Orbuch M, Strader DB, Gibril F, Metz DC, Fraker DL, Norton JA, et al. Determinants of metastatic rate and survival in patients with Zollinger-Ellison syndrome: a prospective long-term study. Gastroenterology. 1995 Jun;108(6):1637-49.
Donow C, Pipeleers-Marichal M, Schröder S, Stamm B, Heitz PU, Klöppel G. Surgical pathology of gastrinoma. Site, size, multicentricity, association with multiple endocrine neoplasia type 1, and malignancy. Cancer. 1991 Sep 15;68(6):1329-34.
Delcore R Jr, Cheung LY, Friesen SR. Outcome of lymph node involvement in patients with the Zollinger-Ellison syndrome. Ann Surg. 1988 Sep;208(3):291-8.
Anlauf M, Enosawa T, Henopp T, Schmitt A, Gimm O, Brauckhoff M, Dralle H, Musil A, Hauptmann S, Perren A, Klöppel G. Primary lymph node gastrinoma or occult duodenal microgastrinoma with lymph node metastases in a MEN1 patient: the need for a systematic search for the primary tumor. Am J Surg Pathol. 2008 Jul;32(7):1101-5.
Anlauf M, Garbrecht N, Henopp T, Schmitt A, Schlenger R, Raffel A, Krausch M, Gimm O, Eisenberger CF, Knoefel WT, Dralle H, Komminoth P, Heitz PU, Perren A, Klöppel G. Sporadic versus hereditary gastrinomas of the duodenum and pancreas: distinct clinico-pathological and epidemiological features. World J Gastroenterol. 2006 Sep 14;12(34):5440-6.
Srivastava A, Hornick JL. Immunohistochemical staining for CDX-2, PDX-1, NESP-55, and TTF-1 can help distinguish gastrointestinal carcinoid tumors from pancreatic endocrine and pulmonary carcinoid tumors. Am J Surg Pathol. 2009 Apr;33(4):626-32.
Stabile BE, Passaro E Jr. Benign and malignant gastrinoma. Am J Surg. 1985 Jan;149(1):144-50.
