Case 6 -

Cronkhite-Canada syndrome Barbara McKenna

Case History: The patient is a 77 year old man who developed diarrhea following a flu shot, then was diagnosed with ulcerative colitis based on a colonoscopy performed at another institution. He also reports having lost all of his fingernails and much of his hair, and developed some hyperpigmentation. Upper endoscopy was performed at another hospital after the patient had significant weight loss. Enlarged antral folds were biopsied and reported as foveolar hyperplasia. Small bowel biopsies were read as possible common variable immune deficiency based on villous blunting and decreased plasma cells. Repeat upper and lower endoscopies were performed at our institution, and numerous polyps and areas of nodular mucosa were seen. The patient ultimately underwent colectomy, from which these sections are taken. Histology: This slide is from a resection of a case of Cronkhite-Canada syndrome (CCS). The mucosa has several irregular polyps or nodules that are formed by edematous and inflamed expansions of the lamina propria, accompanied by architecturally disordered crypts. Some crypts are trapped in the expanded lamina propria and cystically dilated. The intervening flat mucosa is also diffusely abnormal, with the same lamina propria expansion and distortion, just to a lesser degree. Case 6 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Cronkhite-Canada Syndrome CCS is a rare disorder that was originally described by Leonard Wolsey Cronkhite Jr., an internist, and Wilma Jeanne Canada, a radiologist, in 1955. The syndrome is characterized by abnormalities of the gastrointestinal mucosal surfaces and the skin, together with clinical features of severe protein-losing malnutrition, gastrointestinal blood loss and the secondary effects of these. About 75% of the reported affected patients are Japanese, and the remainder European or North American. There are no know familial occurrences, and the etiology is not known. Gastrointestinal pathology The gastrointestinal mucosal abnormalities may affect any part of the gastrointestinal tract except the esophagus. The stomach and colon are the most commonly involved sites, as well as the duodenum and distal ileum. The mucosal abnormalities are caused by expansions of the lamina propria, primarily be edema, but also inflammatory cells and macrophages. The epithelium is distorted and pits or crypts are cystically dilated. This expanded lamina propria may form polyps or nodular elevations, or may result in diffusely enlarged gastric or intestinal folds. To some, these polyps resemble juvenile polyps, and this disorder has been grouped with the hamartomatous polyposis syndromes, but this categorization is arbitrary. The intervening flat mucosa is also abnormal, with lesser degrees of these changes. Cutaneous features The cutaneous features of the syndrome generally follow the GI symptoms by weeks or months. These include alopecia involving scalp, eyebrows, face and eventually complete hair loss is some patients. Onychodystrophic changes include thinning, splitting, onycholysis (partial separation of nail from bed), and onychomadesis (loss of finger and toenails). Hyperpigmentation in the form of pigmented macules and plaques on the hands and arms and elsewhere is the third cutaneous abnormality that may be seen. These skin changes may be the result of the profound malnutrition that results from the gastrointestinal disease. Abnormally increased melanin deposition, with or without melanocyte proliferations is present in biopsies of hyperpigmented skin. Clinical features Cronkhite-Canada syndrome is a disease of older individuals, with a mean age of onset around 60 years. The most common presenting symptoms are diarrhea, weight loss, nausea, vomiting, anorexia, and hypogeusia (altered taste sensations). Other clinical features, based on malnutrition and electrolyte abnormalities, include neurologic symptoms—paresthesias, seizures, tetany. The mortality of CCS has been said to be 50-60%, with death due to malnutrition, anemia, and their contributions to other medical disorders in elderly patients. Treatment approaches have included nutritional support, including enteral alimentation, antibiotics, and corticosteroids, and surgical resection of the most affected areas. There is some suggestion that patients with CCS have an increased risk of gastrointestinal cancers. Carcinomas of the stomach, colon and rectum have been reported, as have CCS polyps with dysplasia. References Samoha S, Arber N. Cronkhite-Canada Syndrome. Digestion 2005;71:199-200 Ward EM, Wolfsen HC. Review article: the non-inherited gastrointestinal polyposis syndromes. Aliment Pharmacol Ther 2002;16:333-342