Solid-variant aneurysmal bone cysts in the craniofacial skeleton: the role of genomic analysis

Solid variant aneurysmal bone cysts (SVABCs) are a rare but well-described subtype of ABCs. While classic ABCs are readily identified radiographically, SVABCs lack these characteristic radiographic features and thus have a wide differential diagnosis on presentation (including Ewing sarcoma, Langerhans cell histiocytosis, osteosarcoma, metastasis, and giant cell tumor). Genomic/molecular analyses are often necessary for the diagnosis of SVABCs, with USP6 rearrangements being a characteristic finding. We present two cases in which genomic analysis was critical in the diagnosis of SVABCs and revealed unique gene fusions that may provide insight into SVABC pathogenesis.

Two 13-year old male children presented to our institution with new mass lesions involving the craniofacial skeleton. Magnetic resonance imaging (MRI) in both cases revealed predominantly solid, avidly enhancing masses, one of the squamous portion of the temporal bone, and the other arising from the sphenopalatine foramen with extension into the ipsilateral maxillary and ethmoid sinuses. Histopathology displayed predominantly solid morphology, and next generation sequencing (NGS) revealed a FAT1-USP6 gene fusion in the temporal lesion, and a MIR22HG-USP6 gene fusion in the maxillofacial lesion, the latter of which was not identified on fluorescence in situ hybridization (FISH). These findings were most consistent with a diagnosis of SVABC in each case.

These two cases highlight novel gene fusions in atypically located SVABCs and emphasize the ability of NGS to more accurately and consistently identify USP6 gene fusions, particularly in SVABCs that may otherwise be indistinguishable from alternative pathologies.