Peutz Jeghers syndrome

Patients with Peutz-Jeghers syndrome (PJS) have characteristic GI hamartomatous polyps, mucocutaneous pigmentation and predisposition to GI, breast, and other cancers.

The prevalence of PJS is between 1/8,300 and 1/29,000. A full description with management guidelines is available.

Diagnostic criteria

In a single individual, a clinical diagnosis of PJS may be made when any one of the following is present:

  • Two or more histologically confirmed PJ polyps
  • Any number of PJ polyps detected in one individual who has a family history of PJS in a close relative
  • Characteristic mucocutaneous pigmentation in an individual who has a family history of PJS in a close relative
  • Any number of PJ polyps in an individual who also has characteristic mucocutaneous pigmentation

Pigmentation

The characteristic freckling of the lips and perioral region is seen in 95%, but not all. It develops during childhood, but usually fades from the third decade onwards. Nostrils, hands/fingers/toes, anus and vulva may also show freckling.

Polyps

The histology of PJ polyps is characteristic and diagnostic, consisting of a branched or frond-like pattern in the stroma, termed arborization. They are often confused with juvenile polyps. Small bowel PJ polyps can exhibit ‘pseudoinvasion’ which can be mistaken for invasive cancer. For further information see: Frayling, IM and Arends MJ. ‘How can histopathologists help clinical genetics in the investigation of suspected hereditary gastrointestinal cancer?’ Diagnostic Histopathol 2015.

70–90% of PJS patients have small bowel (usually jejunum), 50% have colorectal, and 25% have gastric polyps. PJ polyps tend to be large and pedunculated and PJS patients commonly present as a surgical emergency in childhood with small bowel obstruction due to intussusception.

Polyps and cancers also occur outside of the GI tract, eg nose, respiratory tract, uterus, urinary tract, and gall bladder/biliary tree.

Genetics

80-94% of PJS patients have autosomal dominantly inherited, generally protein-truncating, mutation in LKB1 (STK11), which encodes a serine/threonine kinase that is part of the mTOR pathway.

No LKB1/STK11 genotype-phenotype correlations have been reported. Rare families  not linked to LKB1/STK11 have been observed, so genetic heterogeneity is possible.

Risks

GI intussusception

Small bowel obstruction in childhood is the commonest presentation, and is usually due to intussusception caused by a polyp.

Cancer

A variety of malignancies are associated with PJS, particularly of the GI tract, but also including pancreas, breast, uterus, and gonadal tumours.

Colorectal cancer risk predominates with a significant rise in risk after the age of 50y. However, female breast and gynaecological cancer risks are also significant. Sex cord tumours (SCTAT) and other, sometimes hormone secreting, gonadal tumours are also seen, often at a young age.

Cumulative cancer risk by site and age in Peutz-Jeghers syndrome patients is described in Hearle et al. and Giardiello et al. – download below.

Management

Management centres around identifying and removing GI tract polyps before they cause symptoms, and surveillance of high-risk cancer sites (although evidence of benefit is lacking).

Content updated 18 Oct 2016