The First Case of Lynch Syndrome-Associated Penile Cancer Harboring a Heterozygous PMS2 Frameshift Variant.

INTRODUCTION

Penile squamous cell carcinoma (PSCC) is a rare malignancy in men with poor survival in metastatic disease. Lynch syndrome (LS) is a cancer predisposition, autosomal-dominant, inherited disorder that arises from loss of function variants in mismatch repair genes.

CASE PRESENTATION

Here, we reported a PSCC patient who was suspected with LS caused by a heterozygous PMS2 D526Afs69 variant. A 57-year-old male with PSCC underwent pelvic lymph node dissection and bilateral groin lymph node dissection due to metastatic disease. He has a family history of colon cancer and brain cancer. Comprehensive genomic sequencing of his tumor specimen identified 19 somatic mutations with a high tumor mutation burden (14.03 mutations per Mb) and a high frequency of microsatellite instability. Additionally, a germline PMS2 D526Afs69 mutation was identified in the peripheral blood sample. Immunohistochemistry analysis showed complete loss of PMS2 and MLH1 expression in his tumor.

CONCLUSION

These observations provided evidence suggesting that PSCC could be part of the LS spectrum.