Clinical and Histologic Overlap and Distinction Among Various Hamartomatous Polyposis Syndromes

Clin Transl Gastroenterol. 2019 May 22;10(5):1-9. doi: 10.14309/ctg.0000000000000035.


Introduction: Hamartomatous polyposis syndromes (HPS) are rare autosomal-dominant inherited disorders associated with gastrointestinal (GI) tract and other cancers. HPS include Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome (JPS), and phosphatase and tensin homolog hamartomatous tumor syndromes (PHTS). Diagnosis, management, and outcome prediction of HPS pose a clinical challenge. To characterize genotype, phenotype, histology and outcomes of individuals with HPS.

Methods: A retrospective cohort study (2004-2017) of consecutive patients that were clinically diagnosed with HPS that visited a specialized GI oncology clinic. Demographic, clinicopathological, and genetic data were obtained from medical records.

Results: Fifty-two individuals from 34 families were included. Common clinical manifestations were GI bleeding (40% JPS, 23% PJS, and 25% PHTS) and bowel obstruction (46.15% PJS and 11.4% JPS). Twenty patients (38.4%) underwent surgery, 5 of whom required multiple procedures. Higher polyp burden was associated with the need for surgery (P = 0.007). Polyp histology varied widely with 69.2% of patients exhibiting histology different from the syndrome hallmark. GI cancer history was positive in 65%, 40%, and 50% of JPS, PJS, and PHTS families, respectively. Five (9.6%) patients developed cancers (one patient each had small bowel-1, colon-1, and thyroid-1, one patient had both small bowel adenocarcinoma and breast cancer, and one had both breast cancer and liposarcoma). Twenty (38.4%) patients tested positive for STK11, PTEN, SMAD4, BMPR1A, or AKT1 mutations: Sanger sequencing and multi-gene next generation sequencing panels detected mutations in 40.9% and 100% of tested cases, respectively.

Discussion: HPS patients present versatile phenotypes with overlapping clinical and histological characteristics. Polyp burden is associated with the need for surgery. Next-generation sequencing increases mutation detection.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Biopsy
  • Child
  • Clinical Decision-Making / methods
  • DNA Mutational Analysis
  • Endoscopy, Gastrointestinal
  • Female
  • Follow-Up Studies
  • Genetic Testing*
  • Hamartoma Syndrome, Multiple / diagnosis*
  • Hamartoma Syndrome, Multiple / genetics
  • Hamartoma Syndrome, Multiple / pathology
  • Hamartoma Syndrome, Multiple / surgery
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Intestinal Polyposis / congenital*
  • Intestinal Polyposis / diagnosis
  • Intestinal Polyposis / genetics
  • Intestinal Polyposis / pathology
  • Intestinal Polyposis / surgery
  • Intestines / diagnostic imaging
  • Intestines / pathology
  • Intestines / surgery
  • Male
  • Medical History Taking
  • Middle Aged
  • Mutation
  • Neoplastic Syndromes, Hereditary / diagnosis*
  • Neoplastic Syndromes, Hereditary / genetics
  • Neoplastic Syndromes, Hereditary / pathology
  • Neoplastic Syndromes, Hereditary / surgery
  • Peutz-Jeghers Syndrome / diagnosis*
  • Peutz-Jeghers Syndrome / genetics
  • Peutz-Jeghers Syndrome / pathology
  • Peutz-Jeghers Syndrome / surgery
  • Retrospective Studies
  • Tumor Burden
  • Young Adult


  • Biomarkers, Tumor

Supplementary concepts

  • Juvenile polyposis syndrome