title: Malignant pheochromocytoma secreting vasoactive intestinal peptide and response to sunitinib: a case report and literature review.
abstract: OBJECTIVE
  Malignant pheochromocytoma is rare and may be sporadic or have a genetic basis. Vasoactive intestinal peptide (VIP)-secreting pheochromocytoma has rarely been described in the literature, and treatment remains challenging in the absence of well-controlled randomized trials. The hypoxia-inducible factor-vascular endothelial growth factor axis has been implicated in pheochromocytoma when associated with germline Von-Hippel-Lindau (VHL) or succinate dehydrogenase (SDH) mutations, suggesting potential clinical activity of sunitinib in this setting.
  
  
  METHODS
  We present a case report of a patient with a VIP-secreting malignant pheochromocytoma manifested as severe watery diarrhea, with an exquisite clinical response to sunitinib. We review this rare clinical entity and the potential role of sunitinib in this context.
  
  
  RESULTS
  A 51-year-old male initially presented with a pheochromocytoma causing symptoms related to norepinephrine excess. He underwent adrenalectomy, which resulted in complete resolution of his symptoms. Three years later, he developed multifocal metastatic disease from his primary tumor, showing immunohistochemical evidence of VIP production accompanied by severe watery diarrhea and hypokalemia. The patient had a rapid, complete, and durable clinical response to sunitinib, but with only a minor radiological response and without significant toxicity. Genetic testing was negative for germline mutations in VHL, SDHB, SDHC, SDHD, transmembrane protein 127 (TMEM127) and for neurofibromatosis type 1 (NF-1).
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first report of a case of malignant VIP-producing pheochromocytoma that was responsive to sunitinib.
authors.forename: Raya
authors.initials: R
authors.lastname: Leibowitz-Amit
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Raya
authors.initials: R
authors.lastname: Lebowitz-Amit
authors.affiliation: Department of Pathology, University Health Network, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada.
authors.forename: Ozgur
authors.initials: O
authors.lastname: Mete
authors.affiliation: Department of Pathology, University Health Network, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada.
authors.forename: Sylvia L
authors.initials: SL
authors.lastname: Asa
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Shereen
authors.initials: S
authors.lastname: Ezzat
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Joshua