Hepatocellular adenoma in glycogen storage disorder type I: a clinicopathological and molecular study Stratigoula Sakellariou, 1,2 Hussa Al-Hussaini, 1 Astrid Scalori, 1 Marianne Samyn, 1 Nigel Heaton, 1 Bernard Portmann, 1 Khalid Tobal 3 & Alberto Quaglia 1 1 Institute of Liver Studies, King’s College Hospital, London, UK, 2 Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece, and 3 Molecular Oncology Diagnostics Unit, GSTS Pathology, Guy’s Hospital, London, UK Date of submission 17 July 2011 Accepted for publication 21 September 2011 Sakellariou S, Al-Hussaini H, Scalori A, Samyn M, Heaton N, Portmann B, Tobal K & Quaglia A (2012) Histopathology Hepatocellular adenoma in glycogen storage disorder type I: a clinicopathological and molecular study Aims: Glycogen storage disease type I is a metabolic disorder resulting from deficiency of the glucose-6- phosphate complex. Long-term complications include the development of hepatocellular adenoma (HCA). In this retrospective study, our aim was to reclassify according to geno-phenotypic characteristics nodular lesions identified in hepatectomy specimens of such patients transplanted between 1998 and 2008 at our institution. Methods and results: Clinicopathological data of seven consecutive transplanted patients with glycogen storage disease type I were reviewed. Liver nodules were re-examined histologically and by immunohisto- chemistry. Molecular analysis was performed addition- ally in a case with specific features. Four patients had multiple tumours. We concluded that 26 of 38 nodules available for study had features of inflammatory hepatocellular adenomas, seven comprised adenomas not otherwise specified and five were found to be focal nodular hyperplasia. Conclusions: Further studies are needed to clarify the pathogenesis of hepatocellular adenomas in glycogen storage disease; in particular to determine whether they share abnormal metabolic pathways with inflammatory adenomas in the general popula- tion. Testing for acute phase proteins may be a helpful tool in the early detection of HCA in such patients. Finally, there is a need to further define their risk of malignant transformation, in relation to age and possible cofactors. Keywords: glycogen storage disease type I, hepatocellular adenoma, immunohistochemistry, mutational screening, qRT–PCR, transplantation Abbreviations: CK7, cytokeratin 7; FNH, focal nodular hyperplasia; GS, glutamine synthetase; GSDI, glycogen storage disease type I; HCA, hepatocellular adenoma; HCC, hepatocellular carcinoma; HNF1-a, hepatocyte nuclear factor 1 alpha; L-FABP, liver type fatty acid binding protein; NOS, not otherwise specified; qRT–PCR, quantitative reverse transcription–polymerase chain reaction; SAA, serum amyloid A Introduction Glycogen storage disease type I (GSDI) is a metabolic disorder with an autosomal recessive type of inheri- tance resulting from deficiency of the glucose-6-phos- phate complex, an enzyme catalysing the conversion of glucose-6-phosphate to glucose. Severe fasting hypo- glycaemia due to decreased hepatic glucose production and excessive accumulation of glycogen in the liver, kidney and intestine are the main short-term compli- cations of the disease. Long-term complications include progressive renal disease and the development of hepatocellular adenoma (HCA). 1,2 In a recent collab- orative European Study on GSDI, the prevalence of Address for correspondence: S Sakellariou, Mikras Asias 75, Goudi, Athens 11527, Greece. e-mail: stratigoula.sakellariou@nhs.net Ó 2012 Blackwell Publishing Limited. Histopathology 2012 DOI: 10.1111/j.1365-2559.2011.04153.x