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Cronkhite-Canada Syndrome

Definition

  • Gastrointestinal hamartomatous polyps with associated ectodermal changes

Diagnostic Criteria

  • Adult onset non-inherited disorder
    • Mean age at onset 60, range 31-86
  • Multiple polyps throughout the GI tract
    • Esophagus excepted – very rare
    • Usually large numbers
      • Reported range 5 to innumerable
  • Polyps show hamartomatous features
    • Essentially indistinguishable from the polyps of Juvenile Polyposis
      • Edematous inflamed stroma
        • Eosinophils may be prominent
      • Irregular, tortuous glands
      • Mucus retention cysts in most cases
      • Largely intact surface
      • Small amounts of smooth muscle may be present in lamina propria
    • Most polyps sessile at all sites
    • No dysplasia
  • Mucosa between polyps typically also shows lamina propria edema and inflammation and mild crypt dilation
  • Diagnostic ectodermal findings
    • Alopecia
    • Onychodystrophy
    • Cutaneous hyperpigmented macules
      • Most frequent on extremities and face
      • Biopsies show increased basal layer pigmentation
  • May have increased IgG4 plasma cells

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting: 12/27/09, 11/13/11

Differential Diagnosis

Cronkhite-Canada Syndrome Juvenile Polyposis
Most colorectal polyps sessile Most colorectal polyps polypoid
Hair, nail, skin changes present No associated ectodermal changes
No dysplasia Infrequent cases may have focal dysplasia
Not familial Autosomal dominant, 75% are new mutations without family history
The gastrointestinal polyps are largely indistinguishable

 

Cronkhite-Canada Syndrome Cowden Disease
Hair, nail, skin pigmentation changes present Most have facial mucocutaneous lesions, see description
No association with breast hamartomas or carcinomas Frequent breast hamartomas and carcinomas
No association with thyroid carcinomas Frequent thyroid carcinomas
PTEN mutations not seen PTEN mutations in 80%
Not familial Autosomal dominant (half are new mutations without family history)
The gastrointestinal polyps are largely indistinguishable

 

Cronkhite-Canada Syndrome Peutz-Jeghers Syndrome
May have facial pigmented macules but no mucosal involvement described Mucocutaneous hyperpigmentation
Hair, nail, skin pigmentation changes present Internal neoplasms and non-GI polyps may occur
Smooth muscle absent or only small amounts in lamina propria Prominent arborizing smooth muscle bundles in GI polyps
Frequent mucous retention cysts Lacks retention cysts
Lacks pseudoinvasion May have displaced mucosa with pseudoinvasion of underlying muscularis propria
Not familial Autosomal dominant

 

Cronkhite-Canada Syndrome Hereditary Mixed Polyposis Syndrome
Usually >50 polyps Usually 1-15 polyps, rarely >50
Adenomas infrequent (sporadic adenomas may occur) Adenomas common
Hair, nail, skin pigmentation changes present No associated extra-GI lesions
Not familial Autosomal dominant
The polyps in some cases are indistinguishable

 

Cronkhite-Canada Syndrome, Gastric Involvement Hyperplastic Polyps of the Stomach
Usually >50 polyps Usually solitary
Hair, nail, skin pigmentation changes present No associated extra-GI lesions
Colorectal polyps very common Not associated with colorectal polyps
The polyps in some cases are indistinguishable

 

Cronkhite-Canada Syndrome, Gastric Involvement Menetrier Disease
Hair, nail, skin pigmentation changes present No associated extra-GI lesions
Colorectal polyps very common Not associated with colorectal polyps
On biopsy, the polyps and polypoid mucosa in some cases are indistinguishable and both are associated with protein losing enteropathy

Clinical

  • Presents with diarrhea, weight loss, abdominal pain
    • Frequent protein losing enteropathy
  • Association with carcinoma controversial
    • 9% incidence of colorectal carcinoma has been reported
    • 5% incidence of gastric carcinoma has been reported
  • Variable course
    • Spontaneous remissions and relapses may occur
    • Death may occur due to malnutrition, GI bleeding or intussusception
  • Response to steroids and azathioprine and increased IgG4 plasma cells have led to the proposal that this is an autoimmune disorder (Sweetser 2011)

Bibliography

  • Ward EM, Wolfsen HC. Review article: the non-inherited gastrointestinal polyposis syndromes. Aliment Pharmacol Ther. 2002 Mar;16(3):333-42.
  • Oberhuber G, Stolte M. Gastric polyps: an update of their pathology and biological significance. Virchows Arch. 2000 Dec;437(6):581-90.
  • 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.
  • 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.
  • Calva D, Howe JR. Hamartomatous polyposis syndromes. Surg Clin North Am. 2008 Aug;88(4):779-817.
  • Chen HM, Fang JY. Genetics of the hamartomatous polyposis syndromes: a molecular review. Int J Colorectal Dis. 2009 Aug;24(8):865-74
  • Sweetser S, Ahlquist DA, Osborn NK, Sanderson SO, Smyrk TC, Chari ST, Boardman LA. Clinicopathologic Features and Treatment Outcomes in Cronkhite-Canada Syndrome: Support for Autoimmunity. Dig Dis Sci. 2011 Sep 1. [Epub ahead of print]
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