Clinical and Radiographic Gastrointestinal Findings in Patients with Mccune-Albright Syndrome

Presentation Number: MON 339
Date of Presentation: April 3rd, 2017

Cemre Robinson*1, Andrea Estrada2, Atif Zaheer3, Vikesh K. Singh4, Christopher L Wolfgang4, Michael Goggins4, Ralph H Hruban4, Laura D. Wood4, Michaël Noë4, Elizabeth A. Montgomery4, Lori C. Guthrie1, Anne Marie Lennon4, Alison M Boyce1 and Michael T. Collins1
1Section on Skeletal Disorders and Mineral Homeostasis, Bethesda, MD, 2Children’s National Health System, Washington, DC, 3Johns Hopkins Medical Institutions, Baltimore, MD, 4Johns Hopkins University School of Medicine, Baltimore, MD

Abstract

Background: McCune-Albright syndrome (MAS) is rare disorder characterized by fibrous dysplasia of bone, café-au-lait macules, and hyperfunctioning endocrinopathies. It arises from somatic activating mutations in GNAS, which encodes the cAMP-regulating protein Gαs. Gastrointestinal (GI) disease, including reflux, pancreatitis, pancreatic cysts, polyps, and hepatic lesions, have been reported in MAS, but the clinical spectrum and prevalence of MAS-associated GI disease is not yet established. The disease-causing GNAS mutations in MAS have been found in up to 66% of intraductal papillary mucinous neoplasms (IPMNs), which are pancreatic neoplasms that are precursors of pancreatic cancer. IPMNs in the general population typically occur in patients aged 60 and older.

Objective: Define the spectrum and prevalence of MAS-associated GI pathology, and outline the optimal care for patients.

Subjects and Methods: Fifty-four consecutive subjects (28 M, 26 F, age range 7-67) from the National Institutes of Health MAS cohort were screened with abdominal MRI and magnetic resonance cholangiopancreatography (MRCP). Lesions identified as IPMNs were categorized according to the 2012 international consensus guidelines into those with either high risk or worrisome features; including main duct dilatation ≥5 mm, cysts ≥ 3 cm, thickened wall or solid component, mural nodule, jaundice or history of pancreatitis.

Results:Twenty-five subjects (25/54, 46%) had radiographic GI abnormalities. Twenty-one (81%) had IPMNs, all of which exhibited high-risk stigmata. Nine subjects had IPMNs alone, 12 had IPMNs and liver cysts. Four (15%) had liver cysts alone. A 26-year-old man with IPMNs and recurrent pancreatitis underwent pancreatectomy, with pathology showing high grade dysplasia. A 56-year-old man with IPMNs and radiographically worrisome features underwent pancreatectomy, with pathology showing IPMN with low grade dysplasia and an adenomatous lesion at the gastroesophageal junction with high grade dysplasia. Seven subjects had benign lesions (metaplasia, hyperplasia and/or polyps) in the esophagus, stomach and/or small bowel. The group of subjects with MAS-associated GI pathology had a higher prevalence of pancreatitis (p=0.01) and diabetes (p=0.004) in comparison to subjects without GI disease. There was no difference in age between subjects with and without GI pathology (mean, 36.52 ±16.22 & 18.71 ± 5.82, respectively).

Conclusions: There is a broad spectrum of GI pathology associated with MAS. GI neoplasms, particularly IPMNs, are common and occur at a younger age compared to the general population. All MAS patients should undergo clinical screening, with a focused GI history. Regardless of symptomatology, MAS patients should have baseline radiographic screening via abdominal MRCP. Further determination of the natural history and malignant potential of IPMNs in MAS is needed.

 

Nothing to Disclose: CR, AE, AZ, VKS, CLW, MG, RHH, LDW, MN, EAM, LCG, AML, AMB, MTC