Background Rhabdomyosarcoma (RMS) is rare cancer affecting children and adults. Pleomorphic RMS histology is almost exclusive to adult patients and often resistant to chemotherapy.
Objective We report the case of a 19-year-old patient who presented with a metastatic chemoresistant pleomorphic RMS.
Methods Considering the poor prognosis and the few systemic therapeutic options, we decided to carry out a whole exome sequencing (WES) of the tumour and germline DNA.
Results WES identified a germline variation (c.1863_1864insT) in the MLH1 gene corresponding to a pathogenic mutation: (p. Leu622Serfs*10), whereas the family history did not fit with classical criteria for Lynch syndrome. Loss-of-heterozygosity at MLH1 locus was found in the tumour. Immunohistochemistry showed loss of MLH1 and PMS2 nuclear expression in the tumour cells. In view of the mismatch repair defects and a high programmed cell death ligand 1 (PD-L1) expression (60% of tumour cells expressed PD-L1), we administrated an anti-PD-1 antibody to the patient. He achieved a rapid complete response of the lung metastases, which appears sustained after a 1-year follow-up.
Conclusion This observation of an RMS revealing an unexpected Lynch syndrome underlines the overlap between tumorous and germline molecular genetics and emphasises the major impact of cancer genomic medicine in clinical practice for guiding treatment decision.
- lynch syndrome
- cancer predisposition
- genomic medicine
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Contributors CT, KL, A-PG-R, AM-L, JC, HB and PL-P: have made substantial contributions to the conception and design of the work; and the acquisition, analysis and interpretation of data for the work. EP, FL, PB-R, MV and FG: have made substantial contributions to the acquisition, analysis and interpretation of data for the work.
Funding This work was supported by the grant EXORARE from the Cancéropôle Ile de France/INCa, by the Cancer Research for Personalized Medicine program (CARPEM). This work was supported by the Cochin Immunomodulatory Therapies Multidisciplinary Study group (CERTIM).
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.