Clinical and Radiographic Gastrointestinal Abnormalities in McCune-Albright Syndrome

Abstract

Context: McCune-Albright syndrome (MAS) is a rare disorder characterized by fibrous dysplasia of bone, café-au-lait macules, and hyperfunctioning endocrinopathies. It arises from somatic gain-of-function mutations in GNAS, which encodes the cAMP-regulating protein Gαs. Somatic GNAS mutations have been reported in intraductal papillary mucinous neoplasms (IPMNs) and various gastrointestinal (GI) tumors. The clinical spectrum and prevalence of MAS-associated GI disease is not well established.

Objective: Define the spectrum and prevalence of MAS-associated GI pathology in a large cohort of patients with MAS.

Design: Cross-sectional study.

Setting: National Institutes of Health Clinical Center and The Johns Hopkins Hospital.

Methods: Fifty-four consecutive subjects with MAS (28 males; age range, 7 to 67 years) were screened with magnetic resonance cholangiopancreatography (MRCP).

Results: Thirty of 54 subjects (56%) had radiographic GI abnormalities. Twenty-five (46%) of the screened subjects had IPMNs (mean age of 35.1 years). Fourteen of the 25 had IPMNs alone, and 11 had IPMNs and abnormal hepatobiliary imaging. The 30 patients with MAS-associated GI pathology had a higher prevalence of acute pancreatitis, diabetes mellitus, and skeletal disease burden of fibrous dysplasia than patients without GI disease.

Conclusions: A broad spectrum of GI pathology is associated with MAS. IPMNs are common and occur at a younger age than in the general population. Patients with MAS should be considered for screening with a focused GI history and baseline MRCP. Further determination of the natural history and malignant potential of IPMNs in MAS is needed.

Trial registration: ClinicalTrials.gov NCT00001727.

Figures

Figure 1.

Summary flow diagram describing the radiographic findings and clinical management of patients with MAS-associated pancreatic lesions. MRCP findings in 54 consecutively screened patients with MAS are shown. Thirty subjects were identified as having radiographic GI pathology. A total of 25 subjects had IPMNs; 14 had IPMNs only, and 11 had IPMNs and additional findings, most commonly benign liver lesions. Five of the 30 subjects had various GI abnormalities without IPMNs. Within the cohort who screened positive for GI pathology, seven subjects underwent detailed evaluation including esophagogastroduodenoscopy, EUS, and/or pancreatic cyst fluid analysis. All seven subjects were found to have benign upper GI polyps. Two subjects underwent pancreatic surgery.

Figure 2.

Representative radiographic GI findings in MAS. (A) MRCP imaging from a 55-year-old man shows diffuse dilation of the main pancreatic duct (arrowhead) along with a cystic lesion in the pancreatic head (thin arrow). A biliary cyst is also seen (thick white arrow). (B) Coronal postcontrast image demonstrates heterogeneously enhancing lesions in the spine and left iliac wing (arrows) in the same patient, consistent with fibrous dysplasia of the bone. (C and D) MRCP images in the same patient who underwent distal pancreatectomy and removal of a gastroesophageal junction polyp are shown. (C) Axial and (D) coronal postcontrast T1-weighted images show the gastroesophageal junction polyp (arrows).

Figure 3.

Representative hepatic lesions. (A‒D) MRCP imaging from a 22-year-old woman with MAS shows (A) a heterogeneous hyperintense mass in the dome of the liver on axial T2-weighted image (arrow). (B) The mass is hypointense on T1-precontrast image (arrow), (C) shows arterial enhancement on the T1-postcontrast arterial phase image (arrow), and (D) washout on the venous phase postcontrast image (arrow). The signal and enhancement characteristics are suggestive of an adenoma.

Figure 4.

Representative endoscopic findings. (A) Several gastric polyps (arrows) are shown. (B) A retroflexed view shows the gastric cardia. The endoscope is seen as the black tube in the center of the image and is surrounded by a large mass (arrows), consistent with a gastric adenoma with high-grade dysplasia. (C) Endoscopic view of the distal esophagus shows a polypoid lesion (black arrow) and several flat lesions (white arrows). (D) Endoscopic ultrasonographic image of a large cyst (highlighted by arrows) is consistent with an IPMN in the pancreas.