DICER1-Associated Central Nervous System Sarcoma with Neural Lineage Differentiation: A Case Report

Abstract

Background: DICER1-associated central nervous system sarcoma (DCS) without evidence of other cancer-related syndromes is rare. Though the morphology of DCS was highly variable, the immunophenotype was predominant myogenic phenotype. Other lineage markers were consistently negative. Herein, our objective was to identify the clinical, pathogenesis, treatment and driver mutation of DCS with neurogenic differentiation through whole-exome sequencing (WES) and RNA sequencing (RNA-seq) of both leukocytes and tumor tissues.Case presentation: We describe here the case of a 8-year-old female patient presented with a 8-day history of headache, nausea and vomiting. Magnetic resonance imaging (MRI) revealed a heterogeneous mass in left parietal lobe. The patient underwent the craniotomy via left parietal approach. Histologically, the tumor predominately showed fibrosarcoma-like spindle cells with obvious cytoplasmic eosinophilic globules. Immunohistochemically, the tumor stained positively for NF, Syn, MAP-2, Desmin and DICER1. WES of tumor tissues detected the DICER1 somatic mutation. This case harbored tumor-driving mutations mainly including AR, AXL and ETV5 mutations, proved sarcoma-associated genes in other kind of sarcomas growth, in addition to TP53 and RAF1 mutations which were common found in DCS. All theses findings indicated the diagnosis of DCS with neurogenic differentiation. This neural lineage differentiation was further confirmed by the result of Gene Ontology (GO) analysis. The patient subsequently received high dose radiotherapy (60Gy) and chemotherapy. The MRI showed no evidence of tumor recurrence at the 12 months’ follow-up.Conclusions: This unusual case of DCS with neuronal differentiation is an important addition to the immuno-phenotypic spectrum of DCS. The prognosis is poor for DCS, and total tumor resection and high dose radiotherapy may assist in prolonging survival. Further research is needed to better understand the behavior and treatment of this rare DCS with neuronal differentiation.