Cronkhite-Canada Syndrome Workup

  • Author: Kruti Parikh; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Jan 14, 2016
 

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
Next

Imaging Studies

Endoscopic (also wireless capsule endoscopy[31] ) procedures (ie, 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. A few reports have described selective sparing of the stomach, small intestine, and/or the colorectum.[32, 33]  Their size varied from a few millimeters to 2 cm in diameter.[34] Endoscopic findings in the stomach also include reddish and edematous granular lesions with mucoid exudate and giant folds. 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.[35]

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.[36]

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.

Previous
Next

Other Tests

See the list below:

  • 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 Salmonella, Shigella, Yersinia, and Campylobacter species and for parasites.
Previous
Next

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
Previous
Next

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.[37, 38]

Scalp biopsy shows a marked noninflammatory loss of follicular units, miniaturization of the hair shafts, markedly dilated follicles, a heavy deposition of glycosaminoglycans in the reticular dermis, and anagen-telogen conversion.[39]

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.[34] 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.[17] Although rare, flat or atrophic mucosa has also been described in patients with Cronkhite-Canada syndrome.[33]

According to Burke and Sobin,[40] 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, 41]

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.

Previous
 
 
Contributor Information and Disclosures
Author

Kruti Parikh Rutgers Robert Wood Johnson Medical School

Disclosure: Nothing to disclose.

Coauthor(s)

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Franklin Flowers, MD Department of Dermatology, Professor Emeritus Affiliate Associate Professor of Pathology, University of Florida College of Medicine

Franklin Flowers, MD is a member of the following medical societies: American College of Mohs Surgery

Disclosure: Nothing to disclose.

Agnieszka B Serwin, MD, PhD Consulting Staff, Department of Dermatology and Venereology, Medical Academy of Bialystok, Poland

Disclosure: Nothing to disclose.

Acknowledgements

Hanna Mysliwiec, MD Staff Physician, Department of Dermatology and Venereology, Medical Academy of Bialystok, Poland

Disclosure: Nothing to disclose.

References
  1. Cronkhite LW Jr, Canada WJ. Generalized gastrointestinal polyposis; an unusual syndrome of polyposis, pigmentation, alopecia and onychotrophia. N Engl J Med. 1955 Jun 16. 252(24):1011-5. [Medline].

  2. Sweetser S, Ahlquist DA, Osborn NK, Sanderson SO, Smyrk TC, Chari ST, et al. Clinicopathologic Features and Treatment Outcomes in Cronkhite-Canada Syndrome: Support for Autoimmunity. Dig Dis Sci. 2011 Sep 1. [Medline].

  3. Kao KT, Patel JK, Pampati V. Cronkhite-Canada syndrome: a case report and review of literature. Gastroenterol Res Pract. 2009. 2009:619378. [Medline].

  4. Chen HM, Fang JY. Genetics of the hamartomatous polyposis syndromes: a molecular review. Int J Colorectal Dis. 2009 Aug. 24 (8):865-74. [Medline].

  5. Riegert-Johnson DL, Osborn N, Smyrk T, Boardman LA. Cronkhite-Canada syndrome hamartomatous polyps are infiltrated with IgG4 plasma cells. Digestion. 2007. 75 (2-3):96-7. [Medline].

  6. Murata I, Yoshikawa I, Endo M, et al. Cronkhite-Canada syndrome: report of two cases. J Gastroenterol. 2000. 35(9):706-11. [Medline].

  7. Negoro K, Takahashi S, Kinouchi Y, et al. Analysis of the PTEN gene mutation in polyposis syndromes and sporadic gastrointestinal tumors in Japanese patients. Dis Colon Rectum. 2000 Oct. 43(10 Suppl):S29-33. [Medline].

  8. Senesse P, Justrabo E, Boschi F, et al. [Cronkhite-Canada syndrome and arsenic poisoning: fortuitous association or new etiological hypothesis?]. Gastroenterol Clin Biol. 1999 Mar. 23(3):399-402. [Medline].

  9. Ward EM, Wolfsen HC. Review article: the non-inherited gastrointestinal polyposis syndromes. Aliment Pharmacol Ther. 2002 Mar. 16 (3):333-42. [Medline].

  10. de Silva DG, Fernando AD, Law FM, Premarathne M, Liyanarachchi DS. Infantile Cronkhite-Canada syndrome. Indian J Pediatr. 1997 Mar-Apr. 64(2):261-6. [Medline].

  11. Scharf GM, Becker JH, Laage NJ. Juvenile gastrointestinal polyposis or the infantile Cronkhite-Canada syndrome. J Pediatr Surg. 1986 Nov. 21 (11):953-4. [Medline].

  12. Devulder F, Bouche O, Diebold MD, et al. [Cronkhite-Canada syndrome: a new French case]. Gastroenterol Clin Biol. 1999 Mar. 23(3):407-8. [Medline].

  13. Goto A. [Cronkhite-Canada syndrome; observation of 180 cases reported in Japan]. Nihon Rinsho. 1991 Dec. 49 (12):221-6. [Medline].

  14. Blonski WC, Furth EE, Kinosian BP, Compher C, Metz DC. A case of Cronkhite-Canada syndrome with taste disturbance as a leading complaint. Digestion. 2005. 71 (4):201-5. [Medline].

  15. She Q, Jiang JX, Si XM, Tian XY, Shi RH, Zhang GX. A severe course of Cronkhite-Canada syndrome and the review of clinical features and therapy in 49 Chinese patients. Turk J Gastroenterol. 2013. 24 (3):277-85. [Medline].

  16. Yun SH, Cho JW, Kim JW, Kim JK, Park MS, Lee NE, et al. Cronkhite-Canada syndrome associated with serrated adenoma and malignant polyp: a case report and a literature review of 13 cronkhite-Canada syndrome cases in Korea. Clin Endosc. 2013 May. 46 (3):301-5. [Medline].

  17. Daniel ES, Ludwig SL, Lewin KJ, Ruprecht RM, Rajacich GM, Schwabe AD. The Cronkhite-Canada Syndrome. An analysis of clinical and pathologic features and therapy in 55 patients. Medicine (Baltimore). 1982 Sep. 61(5):293-309. [Medline].

  18. Vernia P, Marcheggiano A, Marinaro V, Morabito S, Guzzo I, Pierucci A. Is Cronkhite-Canada Syndrome necessarily a late-onset disease?. Eur J Gastroenterol Hepatol. 2005 Oct. 17(10):1139-41. [Medline].

  19. Kindblom LG, Angervall L, Santesson B, Selander S. Cronkhite-Canada syndrome. Case report. Cancer. 1977 Jun. 39 (6):2651-7. [Medline].

  20. Yasuda T, Ueda T, Matsumoto I, Shirasaka D, Nakajima T, Sawa H, et al. Cronkhite-Canada syndrome presenting as recurrent severe acute pancreatitis. Gastrointest Endosc. 2008 Mar. 67(3):570-2. [Medline].

  21. Naoshima-Ishibashi Y, Murofushi T. A case of Cronkhite-Canada syndrome with vestibular disturbances. Eur Arch Otorhinolaryngol. 2004 Nov. 261(10):558-9. [Medline].

  22. Sweetser S, Alexander GL, Boardman LA. A case of Cronkhite-Canada syndrome presenting with adenomatous and inflammatory colon polyps. Nat Rev Gastroenterol Hepatol. 2010 Aug. 7(8):460-4. [Medline].

  23. Bruce A, Ng CS, Wolfsen HC, Smallridge RC, Lookingbill DP. Cutaneous clues to Cronkhite-Canada syndrome: a case report. Arch Dermatol. 1999 Feb. 135(2):212. [Medline].

  24. Yashiro M, Kobayashi H, Kubo N, Nishiguchi Y, Wakasa K, Hirakawa K. Cronkhite-Canada syndrome containing colon cancer and serrated adenoma lesions. Digestion. 2004. 69(1):57-62. [Medline].

  25. Hutnik CM, Nichols BD. Cataracts in systemic diseases and syndromes. Curr Opin Ophthalmol. 1999 Feb. 10(1):22-8. [Medline].

  26. Peitl A, Vucic Peitl M, Pavlovic E, Ljubicic D. Acute brain syndrome as a consequence of the Cronkhite-Canada syndrome. Psychiatr Danub. 2005 Jun. 17(1-2):90-3. [Medline].

  27. Nakayama M, Muta H, Somada S, et al. Cronkhite-Canada syndrome associated with schizophrenia. Intern Med. 2007. 46(4):175-80. [Medline].

  28. Kim MS, Jung HK, Jung HS, et al. [A Case of Cronkhite-Canada syndrome showing resolution with Helicobacter pylori eradication and omeprazole]. Korean J Gastroenterol. 2006 Jan. 47(1):59-64. [Medline].

  29. Hanzawa M, Yoshikawa N, Tezuka T, et al. Surgical treatment of Cronkhite-Canada syndrome associated with protein-losing enteropathy: report of a case. Dis Colon Rectum. 1998 Jul. 41(7):932-4. [Medline].

  30. Bacher T, Schonekas H, Steurer KT, Wunsch PH. [The Cronkhite-Canada Syndrome. A rare differential diagnosis of generalized gastrointestinal polyposis]. Dtsch Med Wochenschr. 1997 May 23. 122(21):676-81. [Medline].

  31. Cao XC, Wang BM, Han ZC. Wireless capsule endoscopic finding in Cronkhite-Canada syndrome. Gut. 2006 Jun. 55(6):899-900. [Medline].

  32. Misra SP, Misra V, Dwivedi M, Singh PA, Gupta SC. Cronkhite--Canada syndrome without colonic polyps. Endoscopy. 1997 May. 29 (4):333. [Medline].

  33. De Petris G, Chen L, Pasha SF, Ruff KC. Cronkhite-Canada syndrome diagnosis in the absence of gastrointestinal polyps: a case report. Int J Surg Pathol. 2013 Dec. 21 (6):627-31. [Medline].

  34. Ikeda K, Sannohe Y, Murayama H. A case of Cronkhite-Canada syndrome developing after hemi-colectomy. Endoscopy. 1981 Nov. 13(6):251-3. [Medline].

  35. Nagata K, Sato Y, Endo S, Kudo SE, Kushihashi T, Umesato K. CT endoscopy for the follow-up of Cronkhite-Canada syndrome. Int J Colorectal Dis. 2007 Sep. 22(9):1131-2. [Medline].

  36. Okamoto K, Isomoto H, Shikuwa S, Nishiyama H, Ito M, Kohno S. A case of Cronkhite-Canada syndrome: remission after treatment with anti-Helicobacter pylori regimen. Digestion. 2008. 78(2-3):82-7. [Medline].

  37. Herzberg AJ, Kaplan DL. Cronkhite-Canada syndrome. Light and electron microscopy of the cutaneous pigmentary abnormalities. Int J Dermatol. 1990 Mar. 29 (2):121-5. [Medline].

  38. Ortonne JP, Bazex J, Berbis P. [Cronkhite-Canada disease. Discussion apropos of a case and study of the pigmentation]. Ann Dermatol Venereol. 1985. 112 (12):951-8. [Medline].

  39. Watanabe-Okada E, Inazumi T, Matsukawa H, Ohyama M. Histopathological insights into hair loss in Cronkhite-Canada syndrome: diffuse anagen-telogen conversion precedes clinical hair loss progression. Australas J Dermatol. 2014 May. 55 (2):145-8. [Medline].

  40. Burke AP, Sobin LH. The pathology of Cronkhite-Canada polyps. A comparison to juvenile polyposis. Am J Surg Pathol. 1989 Nov. 13(11):940-6. [Medline].

  41. Anderson RD, Patel R, Hamilton JK, Boland CR. Cronkhite-Canada syndrome presenting as eosinophilic gastroenteritis. Proc (Bayl Univ Med Cent). 2006 Jul. 19 (3):209-12. [Medline].

  42. Allbritton J, Simmons-O'Brien E, Hutcheons D, Whitmore SE. Cronkhite-Canada syndrome: report of two cases, biopsy findings in the associated alopecia, and a new treatment option. Cutis. 1998 Apr. 61(4):229-32. [Medline].

  43. Takahura M, Adachi H, Tsuchihashi N. A case of Cronkhite-Canada Syndrome markedly improved with mesalazine therapy. Digest Endos. 2004. 16:74-8.

  44. Sampson JE, Harmon ML, Cushman M, Krawitt EL. Corticosteroid-responsive Cronkhite-Canada syndrome complicated by thrombosis. Dig Dis Sci. 2007 Apr. 52(4):1137-40. [Medline].

  45. Oberhuber G, Stolte M. Gastric polyps: an update of their pathology and biological significance. Virchows Arch. 2000 Dec. 437(6):581-90. [Medline].

 
Previous
Next
 
 
Medscape Consult
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.