polyps of the colon and rectum. Estimates of the population prevalence of Juvenile Polyposis syndrome suggest a frequency of around 1:100 000. It accounts for less than 0.1% of all colorectal cancer cases.(JPS) is defined by the presence of multiple hamartomatous
Histological differences and topographical distribution within the gastrointestinal tract serve to distinguish between this disorder and (PJS). Juvenile hamartomatous polyps have an apparently normal epithelium with a dense stroma, an inflammatory infiltrate, and a smooth surface with dilated, mucus-filled cystic glands in the lamina propria with smooth muscle fibres, which distinguishes these from PJS polyps. The glandular proliferative characteristics of adenomas are typically absent.
The term ‘juvenile’ refers to the polyp type rather than to the age of onset, although most individuals with juvenile polyposis have some polyps by 20 years of age. Most individuals with JPS have some polyps by age 20 years; some may have only four or five polyps over their lifetime, whereas others in the same family may have more than a hundred. Juvenile polyposis usually manifests during childhood, but diagnosis of the condition is confounded by the occurrence of isolated juvenile-type polyps in children. These solitary polyps are noteworthy because their identification in childhood does not necessarily indicate a heritable cancer predisposition syndrome, and they do not appear to be associated with excess cancer risk. In contrast, juvenile polyposis is associated with a colorectal cancer risk of around 10-38% and a gastric cancer risk of 21%.
If the polyps are left untreated, they may cause bleeding and anemia. Most juvenile polyps are benign; however, malignant transformation can occur. Risk of GI cancers in families with JPS ranges from 9% to 50%. Most of this increased risk is attributed to colon cancer, but cancers of the stomach, upper GI tract, and pancreas have been reported.
Around 20% of cases are due to mutations in the SMAD4 gene, while a further 20% are due to mutations in another gene in the same TGF-beta molecular signaling pathway, BMPR1A, indicative of genetic heterogeneity. Mutations in BMPR1A have been particularly implicated in European populations and SMAD4 mutations may have a more aggressive clinical phenotype. A combined syndrome of JPS and hereditary hemorrhagic telangiectasia (HHT) (termed JPS/HHT) may be present in 15%-22% of individuals with an SMAD4 mutation.
JPS is clinically diagnosed if any one of the three following findings is present:
- More than five juvenile polyps of the colorectum
- Multiple juvenile polyps throughout the GI tract
- Any number of juvenile polyps and a family history of juvenile polyps
Testing relatives at risk: When the family-specific mutation is known, it is appropriate to perform molecular genetic testing on at-risk family members in the first to second decade of life to identify those who will benefit from early surveillance and intervention.
UK BSG Screening Guidelines
< Large bowel surveillance for at-risk individuals and mutation carriers every 1-2 years is recommended from age 15-18 years, or even earlier if the patient has presented with symptoms. Screening intervals could be extended at age 35 years in at-risk individuals. However, documented gene carriers or affected cases should be kept under surveillance until age 70 years and prophylactic surgery discussed. The intervention should visualise the whole colon and so colonoscopy is the preferred modality. Although isolated juvenile polyps are relatively common, juvenile polyposis is rare and consequently experience is limited. There are few large descriptive studies, and no comparative study to demonstrate potential benefit. Nonetheless, there is a substantial risk of colorectal cancer amounting to 10-38%. Many polyps are located in the right colon, and so the whole colon should be visualised. There is particular risk of malignancy in cases where there is adenomatous change, or where there is a dysplastic element to the polyps.
Upper gastrointestinal surveillance
< Upper gastrointestinal surveillance every 1-2 years is recommended from age 25 years, contemporaneously with lower gastrointestinal surveillance. The risk of gastric and duodenal cancer in juvenile polyposis is round 15-21%.
- Hereditary Colorectal Cancer Syndromes (familyhistorybowelcancer.wordpress.com)
- Peutz-Jeghers Syndrome (PJS) (familyhistorybowelcancer.wordpress.com)
- Polyposis (familyhistorybowelcancer.wordpress.com)
- ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making (familyhistorybowelcancer.wordpress.com)