Somatostatinoma syndrome seen only in rare patients
Diabetes mellitus, steatorrhea, cholelithiasis
About half of cases associated with neurofibromatosis type 1
Pheochromocytoma frequently associated in such cases
Same behavior as sporadic cases
Rare cases reported associated with MEN1 syndrome
Invades locally and may metastasize
Duodenal wall, pancreas
Local node metastases (35%)
Metastases to liver (10%) and very rarely beyond
In spite of spread, after debulking, we are not aware of any reported cases of disease progression and/or death
Note that about half of somatostatinomas arise instead in the pancreas with a different biology
Frequently demonstrates somatostatinoma syndrome, metastases and mixed secretory products
Infrequently associated with neurofibromatosis type 1 or psammoma bodies
50% 10 year survival
Rare cases reported elsewhere in and out of GI tract
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting/updates: 7/27/10, 12/24/11, 3/10/12
Supplemental studies
Somatostatin stain diffusely positive
(Scattered somatostatin positive cells may be seen in other neuroendocrine neoplasms)
May also have focal cells positive for calcitonin, pancreatic polypeptide, ACTH, gastrin, serotonin
Synaptophysin usually positive
Chromogranin variable, may be negative
Argyrophil variable, argentaffin negative
PASd stains luminal border and secretions but not cytoplasm
Grading
WHO 2010 recommends the following grading scheme, but it is not clear if it applies to somatostatinomas
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.
Mitotic rate may be moderate to high, may have atypical forms
May have insular or trabecular pattern
Insular and trabecular patterns unusual
Not associated with overlying adenoma
May be associated with overlying adenoma
50% have psammoma bodies
Psammoma bodies not seen
Somatostatin diffusely positive
Somatostatin negative
Synaptophysin usually positive, chromogranin may be positive
Synaptophysin, chromogranin negative
The frequent glandular pattern and invasion seen in somatostatinomas make this a more difficult distinction than for many other well differentiated gi endocrine neoplasms
Lists
Gastrointestinal Endocrine Cell Proliferations and Neoplasms
Well differentiated processes including carcinoids
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
Burke AP, Sobin LH, Shekitka KM, Federspiel BH, Helwig EB. Somatostatin-producing duodenal carcinoids in patients with von Recklinghausen's neurofibromatosis. A predilection for black patients. Cancer. 1990 Apr 1;65(7):1591-5.
Williams GT. Endocrine tumours of the gastrointestinal tract-selected topics. Histopathology. 2007 Jan;50(1):30-41.
Dayal Y, Tallberg KA, Nunnemacher G, DeLellis RA, Wolfe HJ. Duodenal carcinoids in patients with and without neurofibromatosis. A comparative study. Am J Surg Pathol. 1986 May;10(5):348-57.
Green BT, Rockey DC. Duodenal somatostatinoma presenting with complete somatostatinoma syndrome. J Clin Gastroenterol. 2001 Nov-Dec;33(5):415-7.
Mao C, Shah A, Hanson DJ, Howard JM. Von Recklinghausen's disease associated with duodenal somatostatinoma: contrast of duodenal versus pancreatic somatostatinomas. J Surg Oncol. 1995 May;59(1):67-73.
Tanaka S, Yamasaki S, Matsushita H, Ozawa Y, Kurosaki A, Takeuchi K, Hoshihara Y, Doi T, Watanabe G, Kawaminami K. Duodenal somatostatinoma: a case report and review of 31 cases with special reference to the relationship between tumor size and metastasis. Pathol Int. 2000 Feb;50(2):146-52.
Bettini R, Falconi M, Crippa S, Capelli P, Boninsegna L, Pederzoli P. Ampullary somatostatinomas and jejunal gastrointestinal stromal tumor in a patient with Von Recklinghausen's disease. World J Gastroenterol. 2007 May 21;13(19):2761-3.
Patel VG, Henderson VJ, Fairweather DA, Fortson JK, Weaver WL, Martin DM, Lyons R, Hamami A. Malignant duodenal somatostatinoma presenting in association with von Recklinghausen disease. Am Surg. 2003 Dec;69(12):1077-82.
Soga J, Yakuwa Y. Somatostatinoma/inhibitory syndrome: a statistical evaluation of 173 reported cases as compared to other pancreatic endocrinomas. J Exp Clin Cancer Res. 1999 Mar;18(1):13-22.
Garbrecht N, Anlauf M, Schmitt A, Henopp T, Sipos B, Raffel A, Eisenberger CF, Knoefel WT, Pavel M, Fottner C, Musholt TJ, Rinke A, Arnold R, Berndt U, Plöckinger U, Wiedenmann B, Moch H, Heitz PU, Komminoth P, Perren A, Klöppel G. Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: incidence, types, biological behavior, association with inherited syndromes, and functional activity. Endocr Relat Cancer. 2008 Mar;15(1):229-41.
Nesi G, Marcucci T, Rubio CA, Brandi ML, Tonelli F. Somatostatinoma: clinico-pathological features of three cases and literature reviewed. J Gastroenterol Hepatol. 2008 Apr;23(4):521-6.
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.
