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VIPoma in a 37-year-old man
Case Report
VIPoma in a 37-year-old man Stanley Lam, Huiling Liew, Hong Tar Khor, Rinkoo Dalan, Yin Chian Kon, Michelle Jong, Daniel E K Chew, Melvin Khee-Shing Leow Lancet 2013; 382: 832 Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore (S Lam MB ChB, H Liew MRCP, H T Khor FAMS, R Dalan FRCP, Y C Kon FRCP, M Jong FRCP, D E K Chew FAMS, M K-S Leow FRCP) Corresponding author: Dr Stanley Lam, Department of Endocrinology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433 [email protected]
A
In September, 2011, a 37-year-old man with a past history of pulmonary tuberculosis came to our hospital with persistent watery diarrhoea, weight loss, and hypokalaemia of 2 years’ duration. The diarrhoea did not stop with fasting, and serum potassium had remained at 2∙5 mmol/L despite multiple cycles of intravenous potassium replacement. Physical examination and routine blood investigations were normal, as were both upper and lower gastrointestinal tract endoscopies. An abdominal CT showed a 5∙9 × 3∙4 cm lesion in the pancreatic tail and a solitary hepatic metastasis, confirmed by MRI (figure). However, in view of the patient’s past history of tuberculosis, the medical team waited for mycobacterial culture results before making a diagnosis of probable stage IV pancreatic adenocarcinoma. Meanwhile, an endocrine referral was made to address the hypokalaemia. The patient’s signs and symptoms made the clinical team consider the extremely rare diagnosis of a vasoactive intestinal peptide endocrine tumour— VIPoma, also known as Verner-Morrison syndrome. We requested serum chromogranin A and 24-h urinary 5-hydoxyindoleacetic acid, which were both negative. The news of Steve Jobs’s death from a neuroendocrine tumour, which occurred around this time, prompted the clinical team to reconsider this diagnosis despite initial negative results. Endoscopic ultrasound-guided pancreatic tail biopsy was therefore done next, and immunohistochemistry of the tumour tissue stained positive for cytokeratin AE1/3, synaptophysin, and chromogranin. Blood samples were taken for vasoactive intestinal peptide ELISA assay, before a trial of octreotide was initiated. His diarrhoea resolved within 3 days, accompanied by the resolution of hypokalaemia. The plasma vasoactive intestinal peptide was 175 pmol/L (normal <25 pmol/L). He underwent an uneventful distal pancreatectomy, splenectomy, and liver lobectomy. His 2-month postoperative vasoactive intestinal peptide level fell to 5 pmol/L, and a 68-Ga DOTA-TATE fusion PET/ CT scan was done to look for residual metastases missed on MRI (figure). A further lesion was identified and shown on laparoscopic resection to be a metastasis B
C
Figure: VIPoma (A) CT scan showing pancreatic mass (arrows). (B) MRI scan showing liver metastasis (arrow). (C) 68-Ga DOTA-TATE fusion PET/CT scan showing a residual liver metatstasis (arrow).
832
5 mm in diameter. At the patient’s last follow-up in January, 2013, he remained well. VIPoma is a rare neuroendocrine tumour first described by Priest and Alexander in 1957.1 The incidence is 1 in 10 million per year.2 Most cases arise within the pancreas, with others reported in the lungs, colon, liver, adrenals, and neuroganglia.3 Symptomatic pancreatic VIPomas are usually solitary, and >3 cm in diameter.3 About 75% occur in the pancreatic tail, and 60–80% are already metastasised at diagnosis.3 Being slow growing, VIPomas are generally compatible with long survival of 5–10 years. Most adult patients are diagnosed between 30–50 years of age.2 High volume secretory diarrhoea (>700 mL/day) that persists with fasting is virtually universal.2 Hypokalaemia occurs in 70–100% of patients.2 Investigations include serum vasoactive intestinal peptide, pancreatic polypeptide, and chromogranin A.2 Functional PET imaging such as 68-Ga DOTA fusion PET/CT scans have sensitivity of about 97%,4 compared with about 80% in CT scans,2 and 85% in MRIs.2 This higher accuracy facilitates much earlier detection of metastases. When used therapeutically, peptide receptor radionuclide therapy was reported in one case report to reduce widespread metastatic disease down to a single liver metastasis at 1-year follow-up.4 A limitation of peptide receptor radionuclide therapy is the potential lack of somatostatin receptor expression by the tumour.4 In such cases, sunitinib and everolimus (both in phase III trials)5 are among the most promising alternatives to traditional hepatic-directed therapies including resection, ablation, hepatic artery embolisation, and liver transplantation. Surgery remains the definitive treatment for VIPoma.2 Octreotide is useful in suppressing VIP secretion, and interferon-alpha and glucocorticoids are sometimes used in refractory cases to improve symptoms of hormonal secretion.2 Contributors All authors looked after the patient and wrote the report. Written consent to publish was obtained. References 1 Priest WM, Alexander MK. Islet cell tumor of the pancreas with peptic ulceration, diarrhoea and hypokalaemia. Lancet 1957; 273: 1145–47. 2 Ghaferi AA, Chojnacki KA, Long WD, et al. Pancreatic VIPomas: subject review and one institutional experience. J Gastrointest Surg 2008; 12: 382–93. 3 Perry RR, Vinik AI. Clinical review 72: diagnosis and management of functioning islet cell tumors. J Clin Endocrinol Metab 1995; 80: 2273–78. 4 Baum RP, Kulkarni HR. Theranostics: from molecular imaging using Ga-68 labeled tracers and PET/CT to personalized radionuclide therapy—the bad berka experience. Theranostics 2012; 2: 437–47. 5 Strosberg JR, Cheema A, Kvols LK. A review of systemic and liver-directed therapies for metastatic neuroendocrine tumors of the gastroenteropancreatic tract. Cancer Control 2011; 18: 127–37.
www.thelancet.com Vol 382 August 31, 2013
VIPoma in a 37-year-old man Stanley Lam, Huiling Liew, Hong Tar Khor, Rinkoo Dalan, Yin Chian Kon, Michelle Jong, Daniel E K Chew, Melvin Khee-Shing Leow Lancet 2013; 382: 832 Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore (S Lam MB ChB, H Liew MRCP, H T Khor FAMS, R Dalan FRCP, Y C Kon FRCP, M Jong FRCP, D E K Chew FAMS, M K-S Leow FRCP) Corresponding author: Dr Stanley Lam, Department of Endocrinology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433 [email protected]
A
In September, 2011, a 37-year-old man with a past history of pulmonary tuberculosis came to our hospital with persistent watery diarrhoea, weight loss, and hypokalaemia of 2 years’ duration. The diarrhoea did not stop with fasting, and serum potassium had remained at 2∙5 mmol/L despite multiple cycles of intravenous potassium replacement. Physical examination and routine blood investigations were normal, as were both upper and lower gastrointestinal tract endoscopies. An abdominal CT showed a 5∙9 × 3∙4 cm lesion in the pancreatic tail and a solitary hepatic metastasis, confirmed by MRI (figure). However, in view of the patient’s past history of tuberculosis, the medical team waited for mycobacterial culture results before making a diagnosis of probable stage IV pancreatic adenocarcinoma. Meanwhile, an endocrine referral was made to address the hypokalaemia. The patient’s signs and symptoms made the clinical team consider the extremely rare diagnosis of a vasoactive intestinal peptide endocrine tumour— VIPoma, also known as Verner-Morrison syndrome. We requested serum chromogranin A and 24-h urinary 5-hydoxyindoleacetic acid, which were both negative. The news of Steve Jobs’s death from a neuroendocrine tumour, which occurred around this time, prompted the clinical team to reconsider this diagnosis despite initial negative results. Endoscopic ultrasound-guided pancreatic tail biopsy was therefore done next, and immunohistochemistry of the tumour tissue stained positive for cytokeratin AE1/3, synaptophysin, and chromogranin. Blood samples were taken for vasoactive intestinal peptide ELISA assay, before a trial of octreotide was initiated. His diarrhoea resolved within 3 days, accompanied by the resolution of hypokalaemia. The plasma vasoactive intestinal peptide was 175 pmol/L (normal <25 pmol/L). He underwent an uneventful distal pancreatectomy, splenectomy, and liver lobectomy. His 2-month postoperative vasoactive intestinal peptide level fell to 5 pmol/L, and a 68-Ga DOTA-TATE fusion PET/ CT scan was done to look for residual metastases missed on MRI (figure). A further lesion was identified and shown on laparoscopic resection to be a metastasis B
C
Figure: VIPoma (A) CT scan showing pancreatic mass (arrows). (B) MRI scan showing liver metastasis (arrow). (C) 68-Ga DOTA-TATE fusion PET/CT scan showing a residual liver metatstasis (arrow).
832
5 mm in diameter. At the patient’s last follow-up in January, 2013, he remained well. VIPoma is a rare neuroendocrine tumour first described by Priest and Alexander in 1957.1 The incidence is 1 in 10 million per year.2 Most cases arise within the pancreas, with others reported in the lungs, colon, liver, adrenals, and neuroganglia.3 Symptomatic pancreatic VIPomas are usually solitary, and >3 cm in diameter.3 About 75% occur in the pancreatic tail, and 60–80% are already metastasised at diagnosis.3 Being slow growing, VIPomas are generally compatible with long survival of 5–10 years. Most adult patients are diagnosed between 30–50 years of age.2 High volume secretory diarrhoea (>700 mL/day) that persists with fasting is virtually universal.2 Hypokalaemia occurs in 70–100% of patients.2 Investigations include serum vasoactive intestinal peptide, pancreatic polypeptide, and chromogranin A.2 Functional PET imaging such as 68-Ga DOTA fusion PET/CT scans have sensitivity of about 97%,4 compared with about 80% in CT scans,2 and 85% in MRIs.2 This higher accuracy facilitates much earlier detection of metastases. When used therapeutically, peptide receptor radionuclide therapy was reported in one case report to reduce widespread metastatic disease down to a single liver metastasis at 1-year follow-up.4 A limitation of peptide receptor radionuclide therapy is the potential lack of somatostatin receptor expression by the tumour.4 In such cases, sunitinib and everolimus (both in phase III trials)5 are among the most promising alternatives to traditional hepatic-directed therapies including resection, ablation, hepatic artery embolisation, and liver transplantation. Surgery remains the definitive treatment for VIPoma.2 Octreotide is useful in suppressing VIP secretion, and interferon-alpha and glucocorticoids are sometimes used in refractory cases to improve symptoms of hormonal secretion.2 Contributors All authors looked after the patient and wrote the report. Written consent to publish was obtained. References 1 Priest WM, Alexander MK. Islet cell tumor of the pancreas with peptic ulceration, diarrhoea and hypokalaemia. Lancet 1957; 273: 1145–47. 2 Ghaferi AA, Chojnacki KA, Long WD, et al. Pancreatic VIPomas: subject review and one institutional experience. J Gastrointest Surg 2008; 12: 382–93. 3 Perry RR, Vinik AI. Clinical review 72: diagnosis and management of functioning islet cell tumors. J Clin Endocrinol Metab 1995; 80: 2273–78. 4 Baum RP, Kulkarni HR. Theranostics: from molecular imaging using Ga-68 labeled tracers and PET/CT to personalized radionuclide therapy—the bad berka experience. Theranostics 2012; 2: 437–47. 5 Strosberg JR, Cheema A, Kvols LK. A review of systemic and liver-directed therapies for metastatic neuroendocrine tumors of the gastroenteropancreatic tract. Cancer Control 2011; 18: 127–37.
www.thelancet.com Vol 382 August 31, 2013