We review the clinical, imaging, and histopathological findings and differential diagnosis of solid ABC, and highlight the usefulness of identifying the USP6 gene rearrangement on FISH to distinguish this lesion from other lesions with secondary ABC formation.
All assessable cases except one (8/9) showed rearrangement of USP6 providing evidence that myositis ossificans is genetically related to nodular fasciitis and aneurysmal bone cyst.
For paranasal sinus bone or soft tissue tumors containing numerous giant cells, molecular analysis including the USP6 gene may serve as a useful diagnostic tool to distinguish solid ABCs from other giant cell-rich lesions.
Four cases (80%) harbored USP6 rearrangements showing that fibro-osseous pseudotumors of digits belongs to the spectrum of clonal transient neoplasms including aneurysmal bone cyst, nodular fasciitis, myositis ossificans and giant cell lesion of small bones.
Previously, it was observed that USP6 is sufficient to drive formation of tumors mimicking ABC and nodular fasciitis, and that it functions through JAK1/STAT3 signaling.
Including our case, the list of currently known USP6 fusion partners in primary ABC include: CDH11, CNBP, COL1A1, CTNNB1, EIF1, FOSL2, OMD, PAFAH1B1, RUNX2, SEC31A, SPARC, STAT3 and THRAP3.
Our findings not only expanded the repertoire of the partner genes of USP6 in ABC but also can serve as a reference for future studies to better understand the correlation between various gene fusions and the progression of ABC.
Ectopic expression of USP6 is known to drive formation of tumors, which recapitulate key features of ABC and nodular fasciitis; however, the identity of USP6's relevant substrates has been obscure.
The identification of USP6 fusion genes in aneurysmal bone cyst (ABC) and, more recently, in nodular fasciitis led to a better understanding of the pathogenesis of these lesions.
In this review, we discuss the most up-to-date findings on the molecular functions of TRE17, the role of its USP and TBC domains, and potential models for how it contributes to transformation and ABC pathogenesis.
We report a case of solid aneurysmal bone cyst in which fluorescence in situ hybridization (FISH) analysis indicated rearrangements of both USP6 and SS18, but histologic features were consistent with aneurysmal bone cyst throughout the lesion.
While studying the USP6 biology in aneurysmal bone cyst and other mesenchymal tumors, we identified high expression levels of USP6 mRNA in two examples of NF.
In sum, these studies reveal that TRE17 is sufficient to initiate tumorigenesis, identify MMPs as novel TRE17 effectors that likely contribute to ABC pathogenesis and define the underlying signaling mechanism of their induction.
These findings indicate that a subset of cases with apparent classic histologic and imaging features of MO are rather better classified as being soft-tissue ABC with clonal USP6 rearrangements.