Clinical and Molecular Heterogeneity of Head and Neck Spindle Cell and Sclerosing Rhabdomyosarcoma

摘要

Spindle cell/sclerosing rhabdomyosarcoma (sRMS/scRMS), previously classified as a histologic variant of embryonal RMS (ERMS), has been recently defined as a distinct pathologic subtype of RMS. Despite a uniform histologic appearance, sRMS/scRMS is a heterogeneous group with different outcomes between children and adults and distinct genetic abnormalities with either NCOA2 or VGLL2 related fusions or MYOD1 mutations. As sRMS/scRMS show a predilection for the head and neck, we sought to investigate the clinicopathologic and molecular features of this patient population treated at our Institution in the past 2 decades. There were 13 patients (8 males and 5 females) with head and neck sRMS/scRMS with a mean age at diagnosis of 29 years, including 5 children and 8 adults. The common anatomic sites were buccal/masticator space, tongue and mandibular soft tissue. Three patients presented with distant metastases. Eight cases had spindle cell and five sclerosing morphology. All tumors tested showed diffuse reactivity for myoD1. None of the 7 cases tested showed PAX3/7-FOXO1 fusion. Three of the nine cases tested harbored MYOD1 with or without PIK3CA mutations, all having sclerosing histology and succumbing of disease with recurrences. All except one patient with sclerosing RMS died of disease, in contrast to only one of eight with spindle cell morphology. The only patient with infantile sRMS/scRMS showed an SRF-NCOA2 fusion. All patients except one were treated with multimodality chemotherapy, radiotherapy and/or surgery. Our results show that fatal outcome in head and neck sRMS/scRMS was associated with adult age, sclerosing morphology, and MYOD1 and PIK3CA mutations.