Hamartomatous polyps: Diagnosis, surveillance, and management

Table 1 Studies investigating the malignancy risk associated with Peutz-Jeghers syndrome

Ref.	N	Location	Outcome
Chen et al[80]	336	China	Patients with PJS possess a 50% cumulative malignancy risk by the age of 60, with the most common malignancy being colorectal cancer at a median age of 41
Hearle et al[81]	419	United Kingdom	The risk of developing a malignancy is 85% at the age of 70 in patients with PJS, most common being gastrointestinal in origin
Ishida et al[82]	583	Japan	Patients with PJS possess a cumulative malignancy risk of 83% by the age of 70, with an increased rate of gynecologic malignancy in comparison to previously reported data
Korsse et al[83]	144	Netherlands	The cumulative risk of pancreatico-biliary malignancy is 32% by the age of 70 in patients with PJS
Mehenni et al[84]	149	Switzerland	Patients with PJS have a cumulate malignancy risk of 67% at age 70, particularly with STK11/LKB1 mutations in exon 6. Malignancies most commonly occur in the GI tract
Resta et al[11]	119	Italy	The STK11/LKB1 mutation is associated with a relative overall cancer risk of 15.1, with pancreatic and cervical malignancies being the most common; median age of diagnosis noted to be 41 yr
Van Lier et al[8]	133	Netherlands	Patients with PJS possess a cumulative malignancy rate of 76% by the age of 70; malignancies most commonly occur in the GI tract and in women

GI: Gastrointestinal; PJS: Peutz-Jeghers syndrome.

Table 2 Malignancy screening for Peutz-Jeghers syndrome[4,8,10,16-18,85,86]

Malignancy	Screening
Breast	Annual self-breast exam beginning at the age of 18. Annual breast exam with MRI or mammography beginning at the age of 25, and as needed
Cervical	Cervical smear annual beginning at the age of 20, and as needed
Colon	Colonoscopy every 1-3 yr beginning at the age of 8, and as needed. Routine surveillance at 18 if baseline endoscopy at age 8 is negative
Pancreas	Annual endoscopic ultrasound or MRCP/ERCP beginning at the age of 30, and as needed
Stomach	EGD every 1-3 yr beginning at the age of 8, and as needed. Routine surveillance at 18 if baseline endoscopy at age 8 is negative
Small bowel	Capsule endoscopy or CT/MRI enterography every 2-3 yr, beginning at the age of 8, and as needed
Testicular	Annual testicular exam and ultrasound beginning at birth
Uterus	Annual pelvic ultrasound and exam beginning at the age of 25, and as needed; consider total hysterectomy once complete with child-bearing

MRI: Magnetic resonance imaging; CT: Computed tomography; MRCP: Magnetic resonance pancreatography; ERCP: Endoscopic retrograde cholangiopancreatography; EGD: Esophagogastroduodenoscopy.

Table 3 Major and minor criteria for the diagnosis of Cowden syndrome[37]

Major criteria	Minor criteria
Breast malignancy	Fibrocystic changes of the breast
Lhermitte-Duclos disease	Fibromas
Macrocephaly	Gastrointestinal hamartomas
Thyroid malignancy	Genitourinary tumors or malformations
	Lipomas
	Mental retardation
	Thyroid lesions, i.e. goiter

Table 4 Studies investigating the malignancy risk associated with phosphatase and tensin homolog mutation

Ref.	N	Location	Outcome
Tan et al[87]	3399	North America, Europe, and Asia	Patient with PTEN mutations possess a lifetime breast cancer risk of 85%, thyroid cancer risk of 35%, renal cell carcinoma of 35%, endometrial cancer risk of 28%, colorectal cancer risk of 9%, and melanoma risk of 6%
Fackenthal et al[88]	2	United States	There is an increased risk of male breast cancer in patient with PTEN mutations and CS
Harach et al[89]	11	Argentina	Patients with CS have increased likelihood of developing benign thyroid lesions, with increased risk of malignant transformation
Ngeow et al[90]	2723	United States	CS and CS-like phenotypes possess standardized incidence rate for thyroid cancer of 72%, particularly follicular thyroid cancer
Heald et al[91]	127	North America and Europe	PTEN mutations are associated with early-onset (age < 50) colorectal malignancy; routine colonoscopy should be encouraged

PTEN: Phosphatase and tensin homolog; CS: Cowden syndrome.

Table 5 Malignancy screening for phosphatase and tensin homolog mutation[92]

Malignancy	Screening
Breast	Annual self-breast exam at the age of 18; annual clinical breast exam at the age of 25; annual MRI at the age of 30
Colon	Colonoscopy every 5 yr at the age of 35, and as needed
Endometrial	Annual exam with biopsy at the age of 35, and as needed. Hysterectomy upon childbearing completion
Kidney	Annual renal ultrasound at the age of 40; CT or MRI as indicated
Skin lesion	Annual dermatologic exams, no consensus on initiation age
Thyroid	Annual thyroid ultrasound at the age of 7

MRI: Magnetic resonance imaging; CT: Computed tomography.

Table 6 Studies investing the malignancy risk associated with juvenile polyposis syndrome

Ref.	N	Location	Outcome
Brosens et al[73]	84	United States	Patients with JPS possess a lifetime cumulative risk of 38.7% for development of colorectal cancer, with the average age of diagnosis being 43.9
Latchford et al[56]	44	United Kingdom	The SMAD4 gene is a poor prognostic indicator for development of gastric malignancy. Colonic polyps have predominance to ascending colon
Howe et al[93]	117	United States	Kindred of patients with JPS possess approximately 50% cumulative risk of developing gastric malignancy

JPS: Juvenile polyposis syndrome.

Table 7 Malignancy screening for juvenile polyposis syndrome[18,77,94-96]

Malignancy	Screening
Colorectal	Colonoscopy every 1-3 yr between the ages of 12-15; screening should be initiated sooner if earlier onset of symptoms
Gastric	Esophagogastroduodenoscopy every 1-3 yr between the age of 12-15; screening should be initiated sooner if earlier onset of symptoms
HHT mutation	Brain MRI, cardiac echocardiogram, testing for lung arterio-venous malformations

HHT: Hereditary hemorrhagic telangiectasia; MRI: Magnetic resonance imaging.