Introduction: Peutz Jeghers Syndrome (PJS) is a rare, autosomal dominant hereditary polyposis syndrome characterised by hamartomatous polyps, mucocutaneous pigmentation and confirmatory testing of a genetic mutation of serine/threonine kinase 11 or liver kinase B1 (STK11/LKB1). PJS is recognised as a cancer predisposition syndrome with a very high relative risk of gastrointestinal cancers. Some studies, including meta-analysis have suggest a relative risk of up to 13% of small bowel cancers in PJS patients compared to less than 1% of the general population.  However, the European Hereditary Tumour Group Guideline caution that the described risks are likely to be an overestimation due to retrospective review and selection bias. The malignant potential of hamartomatous polyps in PJS has been debated in the literature, controversy exists but presently PJS hamartomatous polyps are not considered precancerous lesions. 

Aim: To evaluate the presence of dysplasia or malignancy in resected PJS polyp specimens in our tertiary referral centre. 

We performed a retrospective review of our histological specimens from patients with a clinical or histological diagnosis of PJS between 2008 to 2025. The histological database was screened for keywords such as “Peutz-Jeghers” “PJS” “Peutz-Jegher’s Syndrome” and “hamartomatous polyps”. Baseline demographic data and histological findings were extracted from electronic patient record and pathology reports.

Seventeen patients with confirmed PJS were identified, with a male predominance (70%). The median patient age was 31years (range 12-72). The median follow-up time was 64 months (range 1-135), accounting to 90.6 patient years. There were 65 polyp specimens of which 47 (72%) were consistent with hamartomatous PJS polyps. The table below characterises the location of the polyps.

PJS polyps: The median patient age for PJS-type polyps was 26 (12-72). The median polyp size for PJS polyps was 20mm (range 4-100mm). 56% of procedures (n=34) for PJS polyps were via device assisted enteroscopy (n=22), ADBE (n=17), RDBE (n=5) remainder were obtained via OGD(n=9), Colonoscopy (n-3). Indications for procedures included polypectomy based on size criteria, symptomatic polyps for intussusception, anaemia and surveillance. The majority (62%) of these procedures were performed for polypectomy of a polyp ≥15mm (n=21), two cases were performed for anaemia; the remainder of the cases were part of routine surveillance procedures. Following MDT consensus review, no polyps demonstrated dysplasia or malignancy, resulting in an estimated incidence of 0 per patient year (95% CI: 0–0.033). 

Non PJS polyps: Of the non PJS polyps; the histological morphology was predominately hyperplastic (50%, n=9). Other morphology included; Tubular adenoma with LGD (n=2), Serrated adenoma (n=1), Pseudopolyp (n=1), epithelial atypia favoured reactive (n=1) normal small bowel mucosa (n=4). The median age in the non-PJS polyps’ group was 59 (19-66), for those who had adenomas the median age was 62 (range 59-66).  Adenomatous polyps were present in 16.7% (95% CI: 4.6%–38.9%).

Our study found that our cohort of PJS patients had no evidence of dysplasia or malignancy in any of their polyp specimens over 91 patient years in our tertiary referral centre.  This study supports previously published studies from PJS registries and supports the argument from the European Hereditary Tumour Group who suggest that previous studies may overestimate risk of cancer due to selection bias and retrospective analysis.