Pancreatic cancer has a dismal prognosis. We have studied this cancer through the eyes of Charles Darwin: with the focus on how these tumors arise and evolve. With molecular techniques and analyses from evolution theory, we have definitively shown how cysts in the pancreas can result in pancreatic cancer. We ... read more also describe that when these cystic precursor lesions start to invade into the surrounding tissue, this is associated with mutations in the SMAD4 and TGFBR2. In addition, we studied the three-dimensional morphology of this cancer through tissue clearing techniques. We found that pancreatic cancer has multiple mechanisms of invasion in the surrounding tissue and that the cancerous cells often grow next to veins. This explains why pancreatic cancer has such a bad prognosis and why these tumors metastasize in a very early stage to the liver: because the pancreatic veins drain the blood from the pancreas to the liver and they can take easily take cancer cells with them. show less
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.
