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
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
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]
