Cowden Disease

Differential Diagnosis

Juvenile Polyposis	Cowden Disease
No associated mucocutaneous lesions	Most have facial mucocutaneous lesions
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%
Ganglion cells not seen in GI polyps	Ganglion cells may be present in GI polyps

The gastrointestinal polyps are otherwise largely indistinguishable

Cowden Disease	Peutz-Jeghers Syndrome
Most have facial and oral papillomas, fibromas and skin tumors	Perioral mucocutaneous hyperpigmentation
Smooth muscle not a part of polyps	Prominent arborizing smooth muscle bundles in GI polyps
Lacks pseudoinvasion	May have displaced mucosa with pseudoinvasion of underlying muscularis propria
PTEN mutations in 80%	STK11 mutations in 30-70%

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

Cowden Disease	Hereditary Mixed Polyposis Syndrome
Most cases present in childhood	Mean age at presentation 41 years
Usually 50-200 polyps	Usually 1-15 polyps, rarely >50
Adenomas infrequent	Adenomas common
Most have facial mucocutaneous lesions, see description	No associated mucocutaneous lesions
Frequent breast hamartomas and carcinomas	No association with breast hamartomas or carcinomas
Frequent thyroid carcinomas	No association with thyroid carcinomas

The polyps in some cases are indistinguishable

Gastric Hyperplastic Polyp	Cowden Disease
No association with similar polyps in the colorectum	Many cases involve the colorectum
No associated mucocutaneous lesions	Most have facial and oral papillomas, fibromas and skin tumors
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)

Gastric hyperplastic polyps are indistinguishable from the polyps of Cowden disease

Mucosal Prolapse / Cloacogenic Polyp	Cowden Disease, Colorectal Polyp
Surface erosions with granulation tissue frequent	Surface erosions infrequent
Irregular glands with scattered dilation	Prominent, regularly dilated glands
Smooth muscle extension into lamina propria of polyps	No smooth muscle in lamina propria of polyps
Restricted to rectum (rarely in sigmoid)	May involve any part of colorectum
No associated lesions	Most have facial and oral papillomas, fibromas and skin tumors, see description LINK
No genetic abnormality	PTEN mutations in 80%