glycogen and Hamartoma-Syndrome--Multiple

Cowden's disease is a rare autosomal dominant condition characterized by multiple hamartomas of ectodermal, endodermal, and mesodermal origin affecting many organ systems. Gastrointestinal manifestation includes the formation of multiple polyps of various benign histopathological types throughout the alimentary tract. Recent literature suggests that the frequency of gastrointestinal involvement is approximately 70-85%. The diagnosis of Cowden's disease, however, relies mainly on subtle dermatologic findings, which may not be obvious to the gastroenterologist. We describe a patient with Cowden's disease and review the English literature on the topic of gastrointestinal polyposis and Cowden's disease. These studies suggest that gastrointestinal polyposis is commonly found in this disease, and that diffuse esophageal glycogenic acanthosis is a characteristic feature of Cowden's disease. We propose that the finding of extensive glycogenic acanthosis in the presence of other benign gastrointestinal polyposis should be considered pathognomonic for the diagnosis of Cowden's disease.

Topics: Colonic Polyps; Duodenal Neoplasms; Esophageal Diseases; Esophagoscopy; Ganglioneuroma; Glycogen; Hamartoma Syndrome, Multiple; Humans; Hyperplasia; Intestinal Polyps; Jejunal Neoplasms; Lipoma; Male; Middle Aged

Cowden syndrome is characterized by diffuse hamartomas involving the whole digestive tract. The gastrointestinal expression of the disease is inconstant, but hamartomatous polyposes are frequent. In a multicenter study we studied the endoscopic appearance of Cowden syndrome--as defined by fulfillment of international consortium criteria--in 10 patients. In 6 of the 10 patients the connection with Cowden syndrome was made retrospectively on the basis of the gastrointestinal endoscopic findings. All patients had upper and lower gastrointestinal tract involvement. Mean follow-up duration was 9.5 years (range: 2-26 years). Mean age was 37 years (range: 18-56 years). Polyps of the upper gastrointestinal tract were hamartomas, ganglioneuromas, lipomas, and adenomas. Diffuse glycogenic acanthosis was reported in nine patients. Besides the classical hamartomatous polyposis, diffuse macroscopic esophageal acanthosis and microscopic ganglioneuromatosis are other key findings associated with a diagnosis of Cowden syndrome. Physicians should be aware of these characteristics in order to diagnose Cowden syndrome early.

Topics: Adenoma; Adolescent; Adult; Colonic Polyps; Colonoscopy; Endoscopy, Digestive System; Esophageal Diseases; Female; Ganglioneuroma; Glycogen; Hamartoma Syndrome, Multiple; Humans; Intestinal Neoplasms; Male; Middle Aged; Retrospective Studies; Stomach Neoplasms; Young Adult

A 62-yr-old man was referred for management of GI polyposis. Large bowel polyps were initially diagnosed >25 yr ago, and the patient had undergone multiple colonoscopies and polypectomies. Personal and family history were notable for thyroid goiter and hypothyroidism. Physical examination was notable for lingular papillomatosis. No cutaneous lesions were seen. Upper endoscopy revealed esophageal glycogen acanthosis. There were multiple polyps throughout the stomach and the small and large intestines. Histology of these polyps showed multiple cell types including juvenile polyps, inflammatory polyps with fibromuscular proliferation and lamina propria ganglion cells, and focal adenomatous change. A clinical diagnosis of Cowden syndrome was made. Mutation analysis revealed a variant in exon 8 of the PTEN gene. Direct sequencing revealed a germline heterozygous C.892-895InsA, which is predicted to result in a truncated PTEN protein. Cowden syndrome is an underdiagnosed, underrecognized, autosomal dominant, inherited syndrome. For the gastroenterologist, esophageal acanthosis and multiple hamartomatous polyps should suggest the diagnosis. Sensitive molecular diagnostic tests looking for mutations in the appropriate genes are clinically available. Together with genetic counseling, molecular diagnostic testing will allow more accurate risk assessment and surveillance for cancer for both the patient and family members.

Topics: Endoscopy; Esophageal Diseases; Esophagus; Gastrointestinal Neoplasms; Germ-Line Mutation; Glycogen; Hamartoma Syndrome, Multiple; Humans; Hyperplasia; Male; Middle Aged; Mucous Membrane; Pedigree; Phosphoric Monoester Hydrolases; Polyps; PTEN Phosphohydrolase; Skin Diseases; Tumor Suppressor Proteins