Cronkhite-Canada syndrome: An elusive gastrointestinal disorder with multisystem involvement-pathogenesis, diagnosis, and therapeutic strategies

Table 1 Differences between Cronkhite-Canada syndrome and other syndromes causing gastrointestinal polyps

	Cronkhite-Canada syndrome	Peutz-Jeghers syndrome	Juvenile Polyposis syndrome	Familial adenomatous polyposis
Etiology	Idiopathic	Genetic (STK11 mutation)[57]	Genetic (SMAD4 or BMPR1A mutation)[58]	Genetic (APC gene)[59]
Inheritance	Sporadic (non-familial)	Autosomal dominant[60]	Autosomal dominant[61]	Autosomal dominant[62]
Age	Middle-age	Adolescents[63]	Teenage (16-18 years)[61]	About 16 years[64]
Polyp type	Inflammatory and hamartomatous	Hamartomatous[65]	Hamartomatous polyps[61]	Adenomatous polyps[66]
Polyp distribution	Diffuse throughout the stomach and small intestine. The esophagus is commonly spared	Predominantly the small intestine; also the colon and the stomach[65]	Mainly the colon and rectum[67]	Initially, mostly in the distal colon (rectosigmoid), but later spread throughout the colon[68]
GI symptoms	Chronic diarrhea, abdominal pain, anorexia, protein-losing enteropathy	Intestinal obstruction, bleeding, stomach pain, intussusception[69]	Rectal bleeding, anemia[70]	Abdominal pain, change in bowel habits, constipation, diarrhea, abdominal pain, or palpable abdominal masses[71]
Ectodermal manifestations	Alopecia, nail dystrophy, hyperpigmentation, xerostomia, hypogeusia	Mucocutaneous pigmentation (lips, buccal mucosa)[69]	None	Anemia, osteomas, dental abnormalities, Congenital Hypertrophy of the Retinal Pigment Epithelium, desmoid tumors, or extracolonic cancers (thyroid, liver, bile ducts, central nervous system)[72]
Histo-pathology	Edematous lamina propria, cystic gland dilation, inflammatory infiltrate	Arborizing smooth muscle core in polyps[73]	Cystically dilated glands with inflammatory stroma[74]	Ranges from tubular, tubulo-villous, and villous[68]
Malignancy risk	Moderate (adenomatous transformation possible)	High (GI and pancreatic cancers)[75]	Moderate (colorectal cancer risk)[76]	Low (GI, pancreatic, mucinous adenomas, brain tumors, hepatoblastoma)[77]

GI: Gastrointestinal.