Metachronous cutaneous squamous cell carcinoma in a young patient as the only presenting symptom to uncover Lynch syndrome with MLH1 Germline mutation

Karam Khaddour, Ryan C. Fields, Michael Ansstas, Ilana S. Rosman, George Ansstas

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3 Scopus citations


Background: Cutaneous malignancies are rare complications of Lynch syndrome and can include Muir-Torre and Turcot syndromes that are associated with sebaceous gland tumors and keratoacanthomas. The incidence and clinical course of cutaneous squamous cell carcinoma have not been well documented in Lynch syndrome due to its rarity. Case presentation: A 49-year male presented with an enlarging groin skin lesion that was biopsed and demonstrated cutaneous squamous cell carcinoma for which he underwent a surgical resection. The patient experienced later a recurrence of cutaneous squamous cell carcinoma around the resected margins. Next generation sequencing of tumor tissue revealed mutations in MSH6 and MLH1, in addition to high microsatellite instability. The patient underwent pembrolizumab treatment with complete resolution of the cutaneous lesion in the groin, but subsequently developed a new mass in the right antecubital fossa shortly after discontinuation of pembrolizumab. Repeat biopsy of the antecubital fossa lesion revealed a recurrence of cutaneous squamous cell carcinoma. Germline mutation testing revealed MLH1 mutation, compatible with Lynch syndrome, and the patient restarted pembrolizumab which was associated with a complete response. The patient was referred for genetic counseling and cancer screening. Conclusions: Cutaneous squamous cell carcinoma, although rare, can be the initial presenting symptom in patients with Lynch syndrome. This association has been described in patients with germline mutations in MLH1. Lynch syndrome should be considered when evaluating young patients presenting with recurrent cutaneous squamous cell carcinoma with positive family history of malignancy and/ or without any identifiable risk factors for skin cancers, including those with a durable and rapid response to immunotherapy.

Original languageEnglish
Article number23
JournalHereditary Cancer in Clinical Practice
Issue number1
StatePublished - Dec 2020


  • Cutaneous squamous cell carcinoma
  • Germline mutation
  • Lynch syndrome
  • MLH1
  • Microsatellite instability
  • Pembrolizumab


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