title: Insulinoma in childhood: clinical, radiological, molecular and histological aspects of nine patients.
abstract: BACKGROUND
  Insulinomas are a rare cause of hyperinsulinaemic hypoglycaemia (HH) in children. The clinical features, investigations, management and histology of these rare pancreatic tumours in children have not been described in a large cohort of patients.
  
  
  METHODS
  We conducted a retrospective review of cases diagnosed between 2000 and 2012, presenting to two referral centres in the United Kingdom. Clinical, biochemical, imaging (magnetic resonance imaging (MRI) and 6-L-¹⁸F-fluorodihydroxyphenylalanine (¹⁸F-DOPA) PET/CT scanning) and histological data were collected.
  
  
  RESULTS
  Nine children (age range 2-14.5 years) were diagnosed during the study period at Great Ormond Street Hospital (n=5) and Royal Manchester Children's Hospital (n=4). The combination of abdominal MRI scan (7/8) and ¹⁸F-DOPA PET/CT scan (2/4) correctly localised the anatomical location of all insulinomas. Before surgery, diazoxide therapy was used to treat hypoglycaemia, but only four patients responded. After surgical resection of the insulinoma, hypoglycaemia resolved in all patients. The anatomical localisation of the insulinoma in each patient was head (n=4), uncinate process (n=4) and tail (n=2, one second lesion) of the pancreas. Histology confirmed the diagnosis of insulinoma with the presence of sheets and trabeculae of epithelioid and spindle cells staining strongly for insulin and proinsulin, but not for glucagon or somatostatin. Two children were positive for MEN1, one of whom had two separate insulinoma lesions within the pancreas.
  
  
  CONCLUSIONS
  We describe a cohort of paediatric insulinoma patients. Although rare, insulinomas should be included in the differential diagnosis of HH, even in very young children. In the absence of a single imaging modality in the preoperative period, localisation of the tumour is achieved by combining imaging techniques, both conventional and functional.
authors.affiliation: Pediatric Endocrinology, Royal Manchester Children's Hospital, Manchester M13 9WL, UK.
authors.forename: Raja
authors.initials: R
authors.lastname: Padidela
authors.forename: Miriam
authors.initials: M
authors.lastname: Fiest
authors.forename: Ved
authors.initials: V
authors.lastname: Arya
authors.forename: Virpi V
authors.initials: VV
authors.lastname: Smith
authors.forename: Michael
authors.initials: M
authors.lastname: Ashworth
authors.forename: Dyanne
authors.initials: D
authors.lastname: Rampling
authors.forename: Melanie
authors.initials: M
authors.lastname: Newbould
authors.forename: Gauri
authors.initials: G
authors.lastname: Batra
authors.forename: Jacqueline
authors.initials: J
authors.lastname: James
authors.forename: Neville B
authors.initials: NB
authors.lastname: Wright
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Dunne
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clayton
authors.forename: Indraneel
authors.initials: I
authors.lastname: Banerjee
authors.forename: Khalid
authors.initials: K
authors.lastname: Hussain
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D057286:Electronic Health Records; D004739:England; D005260:Female; D006776:Hospitals, Pediatric; D006786:Hospitals, Urban; D006801:Humans; D006946:Hyperinsulinism / Q000209:etiology / Q000517:prevention & control; D007003:Hypoglycemia / Q000209:etiology / Q000517:prevention & control; D007340:Insulinoma / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D010179:Pancreas / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011877:Radionuclide Imaging; D012017:Referral and Consultation; D012074:Remission Induction; D012189:Retrospective Studies; D014463:Ultrasonography
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins