Lesions of the Lower Intestinal Tract
Moderators: Dr. Henry Appelman and Dr. Joel K. Greenson
Case 6 -
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
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
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.
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.
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.
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.
- 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