Case ReportIntracranial Angiomatoid Fibrous Histiocytoma with EWSR1-CREB Family Fusions: A Report of 2 Pediatric Cases
Introduction
First described almost 40 years ago,1 angiomatoid fibrous histiocytomas (AFHs) are rare neoplasms with intermediate malignant potential, accounting for approximately 0.3% of soft tissue tumors.2 They contribute to a diverse group of mesenchymal tumors biologically characterized by oncogenic fusions between the Ewing sarcoma breakpoint region1 gene (EWSR1) and members of the cAMP response element binding (CREB) gene family, notably ATF1, CREB1, and CREM.3 The predominant fusion reported in AFHs is EWSR1–CREB1. Histologically, AFHs may demonstrate a morphologic spectrum, but representative features include a fibrous pseudocapsule, ovoid or pleomorphic cells, pseudoangiomatoid, spaces, and lymphoplasmocytic cuffing.4, 5
AFHs usually involve the limb extremities of adolescents and young adults; the median age at presentation is 14 years.2 The brain has represented a very rare primary site, with only 5 “typical” AFH adult patients reported to date (Table 1).4, 9, 11, 12, 13 In the past 2 years, intracranial AFH-like tumors have been reported in both children and adults, characterized by increased vascularity, epithelioid cells, and a prominent myxoid background.6, 7, 8, 10 These myxoid lesions harbor novel EWSR–CREB family fusions (e.g., EWSR1–CREM) not identified in the aforementioned adult intracranial AFH patients, questioning whether they represent either a myxoid AFH variant or a novel tumor entity entirely.
We enhance knowledge of this tumor group further by reporting the first 2 pediatric cases of typical intracerebral AFH, confirmed by biologic analysis, including 1 harboring the novel EWS1–CREM fusion previously associated only with the myxoid tumor variant. We discuss the management and prognostic implications of intracranial AFH and present a literature review of all published cases.
Section snippets
Patient 1
A 13-year-old girl presented with a 3-month history of intermittent frontal headaches. Examination at presentation identified horizontal nystagmus. Magnetic resonance imaging (MRI) of the brain revealed an isolated, predominantly cystic, contrast-enhancing tumor in the right frontal lobe, with a solid tumor nodule along its medial wall. Surrounding edema was detected with mild midline shift (Figure 1A, B). There was no evidence of metastatic disease.
The patient underwent craniotomy and
Discussion
To our knowledge, these 2 patients represent the youngest patients reported with classical nonmyxoid intracranial AFH. Both were confirmed by molecular analysis with 1 patient demonstrating the novel EWS1–CREM1 fusion, hitherto described only in myxoid variant intracranial cases.
The typical histologic appearance of AFH defines a predominantly cystic lesion with a central hemorrhagic/necrotic core.14 Common features include a fibrous pseudocapsule surrounded by a dense lymphoplasmocytic
Conclusion
We present 2 children with histologically classical nonmyxoid intracranial AFH, tumors only previously described in adults. Both were confirmed by molecular analysis. One child's tumor harbored the EWS1–CREM1 fusion, hitherto exclusive to myxoid variant AFHs. Our cases and subsequent literature review suggest that classical and myxoid-variant intracranial AFH may belong to an as yet unnamed lesional entity encompassing a histologic spectrum of tumors that share EWSR1–CREB family fusions. Our
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Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.