IllnessPolyposis syndrome, serrated; differential diagnosis

NGS +

[Sanger]

In the prevention of colorectal cancer (CRC), hyperplastic polyps were long considered innocent bystanders, only adenomas were considered CRC precursors. However, serrated polyps can also develop into cancer via the serrated neoplasia route. Patients with multiple serrated polyps, now classified as serrated polyposis cancer syndrome, showed an increased risk of developing CRC, and small carcinomas were detected within the serrated lesions. Serrated polyps, identified in approximately 20% of colonoscopies in average-risk individuals, range in morphology from polyps with only superficial serrations to those with exaggerated serrated architecture and overt dysplasia. A recently proposed terminology for noninvasive serrated lesions (SL) is not yet universally used: Hyperplastic polyp, sessile serrated lesion (SSL), SSL with dysplasia, traditional serrated adenoma, mixed polyp. These polyps are also molecularly heterogeneous and can lead to carcinoma in 15-30% with different clinical course. Mutations in multiple genes can cause SSL. However, <3% of cases of serrated polyposis cancer syndrome are explained by germline mutations, with mutations in RNF43 being the only more frequent cause. Most familial cases are inherited in an autosomal dominant manner. The sensitivity of NGS testing of the relevant genes is unknown. Therefore, clinical diagnosis can by no means be excluded by a negative molecular genetic result.

Reference: https://www.well.ox.ac.uk/publications/692045

https://www.ncbi.nlm.nih.gov/books/NBK107219/

• Alias: Hyperplastic polyposis syndrome
• Alias: Juvenile polyposis syndrome, infantile form (BMPR1A)
• Alias: Sessile serrated polyposis cancer syndrome
• Allelic: Gastric cancer, somatic (MUTYH)
• Allelic: Glioma susceptibility 2 (PTEN)
• Allelic: Lhermitte-Duclos syndrome (PTAN)
• Allelic: Macrocephaly/autism syndrome (PTEN)
• Allelic: Meningioma (PTEN)
• Allelic: Myhre syndrome (SMAD4)
• Allelic: Oligosyndactyly of the hands, Cenani-Linz-like (GREM1)
• Allelic: Pancreatic cancer, somatic (SMAD4)
• Allelic: Prostate cancer, somatic (PTEN)
• Adenomas, multiple colorectal (MUTYH)
• Colorectal cancer, increased risk, association with (GREM1)
• Cowden syndrome 1 (PTEN)
• Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (SMAD4)
• Mixed polyposis syndrome (GREM1)
• Polyposis Syndrome, hereditary mixed (GREM1)
• Polyposis syndrome, hereditary mixed, 2 (BMPR1A)
• Polyposis, juvenile intestinal (BMPR1A)
• Polyposis, juvenile intestinal (SMAD4)
• Sessile serrated polyposis cancer syndrome (RNF43)