Clinical and Histologic Overlap and Distinction Among Various Hamartomatous Polyposis Syndromes.

Abstract

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.

• Authors: Ophir Gilad, Guy Rosner, Naomi Fliss-Isakov, Sivan Aharon-Kaspi, Hana Strul, Nathan Gluck, Revital Kariv
• Journal: Clinical and translational gastroenterology (Clin Transl Gastroenterol) Vol. 10 Issue 5 Pg. 1-9 (05 22 2019) ISSN: 2155-384X [Electronic] United States
• PMID: 31107726 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor

Topics

• 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, genetics, pathology, surgery)
• High-Throughput Nucleotide Sequencing
• Humans
• Intestinal Polyposis (congenital, diagnosis, genetics, pathology, surgery)
• Intestines (diagnostic imaging, pathology, surgery)
• Male
• Medical History Taking
• Middle Aged
• Mutation
• Neoplastic Syndromes, Hereditary (diagnosis, genetics, pathology, surgery)
• Peutz-Jeghers Syndrome (diagnosis, genetics, pathology, surgery)
• Retrospective Studies
• Tumor Burden
• Young Adult