Rhabdomyosarcomes du nourrisson : analyse intégrative des cohortes françaises MMT 89-95, RMS 2005 et du Registre National des Tumeurs Solides de l’Enfant

Abstract : Background: RMS in infants, ~4-10% of RMS, is a particular entity with specific clinical presentation and outcome. Recently, molecular rearrangements involving NCOA2 or VGLL2 genes have been described in congenital spindle cell RMS (scRMS). To better understand the clinical heterogeneity of RMS in infants and determine optimal therapy, an integrative clinical, histological and molecular analysis was performed. Methods: all patients with a diagnosis of RMS under 6 months of age and treated in France from 1989 were reviewed with central pathological review and molecular analysis. Results: 37 infants under 6 months of age were identified with a median age at diagnosis of 2.8 months [0-5.8]. Seven patients had congenital malformations and/or predisposition hereditary disorder. Tumor sites were predominantly bladder/prostate (n=11) and head and neck non-parameningeal (n=10). Six patients (16%) had metastatic disease. Five-year eventfree and overall survival (OS) were 62% (95%CI, 47-82) and 49% (95%CI, 35-70). Seventeen infants (48%) had treatment failures: 11 relapsed (31%), mostly loco-regional, 5(14%) had refractory disease, and one died by toxic death. After pathological review, 10 patients (27%) were scRMS (3 VGLL2 fusion and 2 PTCH1 deletion) and 2 poorly differentiated RMS (myogenin positive on immunochemistry) were retrospectively diagnosed as rhabdoid tumors with loss of INI1 expression. The main prognosis factor was histology, scRMS having an excellent prognosis (OS 90%). Eleven fusions among the 28 patients analyzed (39%) were reported. Cluster expression analysis showed 3 main clusters: alveolar RMS, embryonal RMS and the VGLL2-fused cluster, with embryonal RMS spread in both embryonal RMS cluster and VGLL2-fused cluster. Conclusion: this preliminary work help to better understand the phenotypic heterogeneity of the RMS in infants. The RMSsc looks like “intermediate” tumors and have an excellent prognosis while the others RMS have a worse prognosis.
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Master Thesis
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Thibault Butel. Rhabdomyosarcomes du nourrisson : analyse intégrative des cohortes françaises MMT 89-95, RMS 2005 et du Registre National des Tumeurs Solides de l’Enfant. Médecine humaine et pathologie. 2018. ⟨dumas-02124422⟩

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