Juvenile polyposis syndrome

Abstract

Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34. Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes. Clinically, juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum, juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis. In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found. Both genes play a role in the BMP/TGF-beta signalling pathway. It has been suggested that cancer in juvenile polyposis may develop through the so-called "landscaper mechanism" where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma. Recognition of this rare disorder is important for patients and their families with regard to treatment, follow-up and screening of at risk individuals. Each clinician confronted with the diagnosis of a juvenile polyp should therefore consider the possibility of juvenile polyposis syndrome. In addition, juvenile polyposis syndrome provides a unique model to study colorectal cancer pathogenesis in general and gives insight in the molecular genetic basis of cancer. This review discusses clinical manifestations, genetics, pathogenesis and management of juvenile polyposis syndrome.

Keywords: BMPR1A; Colorectal cancer; Hamartoma; Juvenile polyposis syndrome; SMAD4.

Figure 1

Macroscopic appearance of juvenile polyposis. A: Bowel resection of a patient with juvenile polyposis syndrome showing multiple spherical pedunculated polyps with a smooth surfaces; B: Gross appearance of a juvenile polyp from a patient with juvenile polyposis syndrome. Note the smooth surface, in contrast with a Peutz-Jeghers polyp.

Figure 2

Histological appearance of juvenile polyposis. A: Histological section of a juvenile polyp from a juvenile polyposis patient with a germline mutation of BMPR1A. Typically, juvenile polyps are characterized by prominent lamina propria with edema and inflammatory cells, and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes; B: Histological section of a juvenile polyp from a juvenile polyposis patient with a germline mutation of SMAD4. This polyp shows relatively fewer stroma, fewer dilated glands and more proliferative smaller glands; C: SMAD4 immunohistochemistry on a juvenile polyp showing absent SMAD4 expression in the epithelium, indicating that this patient carries a germline SMAD4 mutation.