Normal Serum Chromogranin A level in a patient with Vasoactive Intestinal Polypeptide Tumour (VIPoma)

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 306-326-Neoplasia of Endocrine Tissues: Case Reports
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-315
Huiling Liew*1, Hong Tar Khor1, Daniel Ek Kwang Chew1, Stanley Lam1, Melvin Khee Shing Leow2 and Rinkoo Dalan1
1Tan Tock Seng Hospital, Singapore, Singapore, 2Singapore Institute for Clinical, Singapore, Singapore

VIPoma is a rare neuroendocrine tumor with the usual clinical presentation with WDHA syndrome (watery diarrhea, hypokalaemia and achlorhydria). Clinical suspicion leading to the diagnosis depends on an elevated serum Chromogranin A (CgA), 5-HIAA and serum VIP concentrations. We describe a  case of VIPoma who presented with WDHA syndrome. Interestingly, a normal serum CgA concentration was seen. We discuss possible reasons for the discrepancy.

Case Study

A 37 years old  man presented with chronic diarrhea for 1 year requiring multiple hospitalizations. Physical examination revealed cachexia, dehydration and hyperactive bowel sounds. Investigations showed metabolic acidosis, dehydration and severe hypokalemia. CT showed a 3.4 x 5.8 pancreatic tail mass with a small liver segment lesion, suggestive of liver metastasis.Plasma CEA, CA19-9 and 24-hour 5HIAA were normal. CgA was 22.4 ug/L (0.0-100.0), 5HIAA was 12.9 umol/day (3.6 – 42.6). A FNA cytology

 of the tumor under EUS was suggestive of a neuroendocrine tumor. A trial of octreotide showed good response. He underwent a distal pancreatectomy, splenectomy and wedge resection of hepatic lesions. VIP was elevated at 530 pg/ml (reference interval <75 pg/ml). Histology described a 7.5cm infiltrative neuroendocrine tumor with acinar and trabecular pattern of growth, speckled chromatin pattern, mild to moderate nuclear pleomorphism and granular eosinophilic cytoplasm. Positive staining with synaptophysin, chromogranin and cytokeratin AE1/3 present. The elevated serum VIP level and pancreatic neuroendocrine lesion is congruent with the diagnosis of VIPoma. His symptoms resolved completed and the VIP concentration normalised.


CgA can be used as a  robust screening and prognostic marker for neuroendocrine tumour. CgA had been found to be elevated in all VIPoma patients especially in patients with liver metastases in one study (1).In this case the CgA and 5 H-IAA were normal although the VIP levels were very high and the patient had a relatively large tumor with liver metastases. CgA production depend on tumor type and differentiation with a low sensitivity in moderately or poorly differentiated neuroendocrine tumor. Another possible reason may be limitations of the assay which can only detect intact CgA so post translational cleavage may lead to decreased levels.

(1)Ramage JK et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut 2005;54:1-16.(2) Nakayama S et al. VIPoma with expression of both VIP and VPAC1 receptors in a patient with WDHA syndrome. Endocrine 2009;35:143-146.(3)Nikou GC et al. VIPomas: An update in diagnosis and management in a series of 11 patients. Hepatogastroenterology. 2005;52:1259-1265.(4)Deftos LJ. Chromogranin A: its role in endocrine function and as an endocrine and neuroendocrine tumor marker. Endocrine review 1991;12:181-188. (5)Perrachi M et al. Plasma chromogranin A in patients with sporadic gastro-entero-pancreatic neuroendocrine tumors or multiple endocrine neoplasia type 1. EJE 2003;148:39-43. (6) Seregni E et al. Clinical significance of blood chromogranin A measurement in neuroendocrine tumours. Ann Onco 2001;12 (suppl 2):s69-72 . (7) Zatelli MC et al. Chromogranin A as a maker of neuroendocrine neoplasia: an Italian multicenter study. Endocrine-related cancer 2007;14:473-482.(8)Modlin IM et al. Chromogranin A-Biological Function and clinical utility in neuroendocrine tumor disease. Ann Surg Oncol 2010;17:2427-2443.(9)Kjell Oberg. Circulating biomarkers in gastroenteropancreatic neuroendocrine tumours [ supplement paper] . Endocrine-Related Cancer 2011;18: S17-S25

Nothing to Disclose: HL, HTK, DEKC, SL, MKSL, RD

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