Cronkhite-Canada Syndrome Workup

Updated: Feb 22, 2019
  • Author: Melba Estrella, MD; Chief Editor: Dirk M Elston, MD  more...
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Workup

Laboratory Studies

Various laboratory studies may include the following:

  • Electrolyte and micronutrient determination - Hypokalemia; hypocalcemia; depressed serum levels of zinc, iron, copper, and magnesium; and vitamin B-12

  • Hematology - Depressed white blood cell count, hemoglobin, red blood cell count, and hematocrit

  • Serum proteins - Hypoproteinemia with hypoalbuminemia; increased in alpha1 globulin level

  • Raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)

  • Elevated serum levels of gastrin, histamine-fast achlorhydria, hypochlorhydria.

  • Biochemical and hematologic tests - Total protein level; albumin level; glucose and lipids concentration; iron, magnesium, zinc, calcium, sodium, potassium, and copper concentrations; ESR; CRP

  • Decreased cholinesterase activity

  • Stool examination - Occult blood and Sudan III staining

  • H pylori infection test

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Imaging Studies

Endoscopic (also wireless capsule endoscopy [52] ) procedures (ie, panendoscopy, [53] gastroscopy, colonoscopy, sigmoidoscopy) reveal polyp lesions of the sessile or semipedunculated type throughout the stomach, duodenum, ileum, and colon, sparing the esophagus. Ikeda et al found pedunculated polyps in patients with Cronkhite-Canada syndrome (CCS). A few reports have described selective sparing of the stomach, small intestine, and/or the colorectum. [54, 55] Lesion size has varied from a few millimeters to 2 cm in diameter. [56] Endoscopic findings in the stomach also include reddish and edematous granular lesions with mucoid exudate and giant folds.

Murata et al applied a prototype of a magnifying single-balloon enteroscope to observe the entire small bowel intestine in a patient with Cronkhite-Canada syndrome. Further analysis should be done to investigate its usefulness as a diagnostic tool. [57]

Abdominal CT scanning may reveal thickened gastric folds.

Regarding radiography, a barium enema and small intestine double-contrast radiology examination show polypoid lesions.

A CT endoscopy using a multidetector-row CT scan with 3-dimensional reconstruction has been shown to be useful for the detection of Cronkhite-Canada syndrome polyps and for the monitoring of effects of therapy. [42]

Magnified chromoendoscopy with crystal violet reveals sparsely distributed crypt openings with widening of the pericryptal space on the surface of the polyps and the intervening colonic mucosa. [58]

Fluoroscopic examination of the stomach may show rough granular changes of the mucosa with edematous giant rugae and polypoid lesions.

Scintigraphy using technetium Tc 99m–labeled human albumin may result in leakage to the gastrointestinal tract.

Consider intraoperative or postoperative examination of p55 immunoreactivity accumulation in the tissue suspected of having a carcinomatous component.

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Other Tests

Other tests may include the following:

  • Presence of antinuclear antibodies, usually with a nucleolar pattern

  • Malignancy markers (carcinoembryonic antigen, alpha-fetoprotein)

  • D-xylose absorption test (impaired)

  • Glucose tolerance test (may be impaired)

  • Fecal fat excretion (increased)

  • Gastrointestinal clearance of alpha-1 antitrypsin (usually elevated)

  • Culture of nail scrapings for fungi (for differential diagnosis)

  • HIV testing (possibly)

  • Stool culture for C difficile, Salmonella, Shigella, Yersinia, and Campylobacter species and for parasites

  • ath tests - Bacterial overgrowth syndrome, small intestinal bacterial overgrowth [7]

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Procedures

Procedures may include the following:

  • Endoscopic procedures (gastroscopic, duodenoscopic, and colonoscopic examinations)

  • X-ray procedures (eg, barium enema examination, small intestine double-contrast radiology after Sellink)

  • Fluoroscopic examination of the gastrointestinal tract

  • Abdominal computed tomographic scan

  • Endoscopic biopsy of the polypoid lesion

  • Histologic examination of polypoid lesions and, if necessary, the scalp lesion

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Histologic Findings

Hyperpigmentation is related to an increase in melanin within the basal layer with or without the melanocyte proliferation, pigment incontinence, hyperkeratosis, and nonspecific perivascular inflammation. [59, 60]

Ong et al reported an increased number of telogen hair follicles, hair follicle miniaturization, presence of pigment casts and peribulbar lymphoid cell infiltrate. These findings point to alopecia areata incognito as the probable cause of hair loss in Cronkhite-Canada syndrome (CCS). This variant of alopecia areata is characterized by acute diffuse hair thinning. [61, 19]

Such results contrast those formerly reported by Watanabe-Okada et al in two patients with Cronkhite-Canada syndrome. They described a diffuse anagen-telogen conversion with increased telogen hair follicles in the absence of miniaturization or hair follicle inflammation, previously suggesting that acute telogen effluvium triggered by malnutrition was the preceding factor inducing hair loss in Cronkhite-Canada syndrome. [62] Given the complex spectrum of the syndrome, further research on scalp biopsies is required.

A case report presented the histologic evaluation of a nail matrix biopsy showing hypergranulosis. Matrix hypergranulosis is a common finding in numerous inflammatory nail diseases, suggesting that nail changes found in Cronkhite-Canada syndrome could be an inflammatory reaction, rather than a consequence of malnutrition as previously believed. [63]

Histologically, polyps in patients with Cronkhite-Canada syndrome are pseudopolypoid-inflammatory changes with cystic dilatation. Ikeda et al found that some of the colon polyps presented a histologic pattern of a tubulovillous adenoma and others exhibited that of a juvenile-type polyp. [56] The latter polyps were characterized by the presence of elongated and/or tortuous crypts with microcystic dilatation and inflamed edematous wide stroma. The areas of focal intestinal metaplasia were present. Even though cellular atypia was present, the adenomatous polyps showed histologic similarity to juvenile polyps with inflamed edematous stroma and occasional cystic glands. Extensive diffuse mucosal thickening has been reported instead of individual polyp growth. Often, this diffuse thickening, possibly an early active stage of disease, is seen in the upper gastrointestinal tract, leading to giant gastric and/or duodenal rugal folds. [26] Although rare, flat or atrophic mucosa has also been described in patients with Cronkhite-Canada syndrome. [55]

According to Burke and Sobin, [64] Cronkhite-Canada syndrome polyps are characterized by their broad sessile base, expanded edematous lamina propria, and cystic glands. The only reliable distinction between Cronkhite-Canada syndrome and colonic juvenile polyposis is the pedunculated growth of the latter with the exception of the gastric polyps. Gastric polyps in Cronkhite-Canada syndrome are sessile and composed of focally dilated irregular foveolar glands within a lamina propria expanded by edema and often an inflammatory infiltrate. Most polyps contain smooth muscle fibers in the lamina propria, and a minority has surface erosions. Gastric Cronkhite-Canada syndrome polyps are quite similar to juvenile or hyperplastic polyps. Prominent mast cells, eosinophils, and IgG4 plasma cell infiltration have all been reported as well. [5, 65]

The most constant features of Cronkhite-Canada syndrome polyps are a sessile base, an expanded edematous lamina propria, and dilated glands. Other features, including inflammation, a small number of smooth muscle fibers, and a complex contour, are variable.

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