PC2151: Pediatric Manifestations of Lynch Syndrome: A Single Center Experience

Introduction: Lynch syndrome (LS) is an autosomal dominant condition caused by a heterozygous pathogenic variant in the DNA mismatch repair (MMR) gene that pre-disposes individuals to early onset colorectal cancers. LS is considered an adult-onset disorder, with malignancy rarely manifesting in childhood. Herein, we describe four cases managed at our center of children with LS with associated early onset colorectal cancers.

Case Description: Case 1: 17-year-old previously healthy male who presented with abdominal pain and was found to have perforated adenocarcinoma of the transverse colon (Stage IIIC). He had a family history of LS and associated cancers. Panel based genetic testing identified that he carried the known familial MSH2 pathogenic variant (c.942+3A>T). He had not undergone screening or genetic testing prior to the cancer diagnosis. He underwent resection, chemotherapy, and immunotherapy, and has no evidence of disease (NED) at one year.

Case 2: 14-year-old previously healthy female presented with obstruction and was diagnosed with rectal adenocarcinoma (Stage IV), with no known family history of LS or associated cancers. The patient underwent panel based genetic testing which identified a heterozygous pathogenic variant in MLH1 (c.2157dup). Neither parent was found to carry the variant. The patient underwent chemotherapy, immunotherapy, and resection, and continues treatment with a follow-up of 16 months.

Case 3: 15-year-old previously healthy male diagnosed with rectal adenocarcinoma (Stage IIIC). He had no established family history of LS but did have several family members with potentially LS associated cancers. Testing identified a variant in MSH2 (c.942+3A>T). Parental testing was not documented. The patient underwent resection and chemoradiation and is NED at three years.

Case 4: 15-year-old previously healthy female who presented with abdominal pain and anemia and was found to have sigmoid adenocarcinoma (Stage IV). Tumor immunohistochemistry (IHC) testing identified loss of PMS2 expression. Genetic testing was unable to be completed for insurance reasons. Family history was significant for colon cancer in her paternal grandfather at age 75. She underwent chemotherapy, resection, and immunotherapy, and continues treatment at two years.

Discussion: Colorectal cancer is rare in children, but LS can be an important cause. This series supports the need for thorough colorectal cancer symptom education in affected families, as well as open discussion with children in order to best facilitate early detection. Given the frequency of LS in pediatric colorectal cancers, it is important that specimens from these cases undergo IHC testing to screen for LS. When LS is suspected, strong consideration should be given to genetic panel-based testing, as even in a family with a known single pathogenic variant there may be other relevant variations.

Conclusion: Further studies are merited to better delineate the frequency with which Lynch syndrome truly does contribute to pediatric colorectal cancers.