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Diagnosis

Aneurysmal Bone Cyst

Discussion

• A spectrum of USP6-rearranged lesions includes:
  • Aneurysmal bone cyst (ABC)
  • Nodular fasciitis (NF)
  • Myositis ossificans (MO)
  • Fibro-osseous pseudotumor of digits (FOPD)
  • Fibroma of tendon sheath.
• The molecular-genetic hallmark of these lesions is the presence of USP6 (Ubiquitin Specific Peptidase 6, also known as TRE2, located at 17p13) fusion
  • With one of the various partner genes.
• ABC
  • A benign bone tumor with multiloculated cysts often containing bloody fluid
  • Histology:
    • A well-circumscribed cystic mass separated by fibrous septae with myofibroblastic proliferation admixed with osteoclast-like multinucleated giant cells.
  • USP6-CDH11 is the most common gene fusions reported in approximately 30% of USP6 fusion-positive ABC.
    • Other known USP6 fusion partners include TRAP150, ZNF9, OMD, COL1A1, SEC31A, EIF1, FOSL2, RUNX2, STAT3, PAFAH1B1, CTNNB1, USP9X, ANGPTL2, ASAP1, FAT1, SAR1A, and TNC.
• NF
  • A rapidly growing, benign myofibroblastic proliferation that can be self-limiting.
  • Often occurs in the subcutis of the upper extremities, trunk, and head and neck, and rarely in the deep sites, such as intramuscular, intraarticular, and periosteal regions.
  • USP6-MYH9 is the most commonly detected gene fusion.
  • CDH11 and COL1A, which are frequent gene partners in ABC, are rarely seen in NF.
  • A growing number of novel fusion partners have been detected, including RRBP1, CALU, CTNNB1, MIR22HG, SPARC, THBS2, COL6A2, SERPINH1, COL3A1, and EIF5A.
  • An aggressive NF with a PPP6R3-USP6 fusion and amplification was also described.
• MO and FOPD are now thought to be the same entity. They also present with a rapidly growing, benign myofibroblastic proliferation in the subcutis and skeletal muscle, which can be self-limiting. Woven-bone formation rimmed by bland osteoblasts is the feature that distinguishes MO/FP from NF. USP6 rearrangement, often with COL1A1-USP6 fusion, has been detected in these tumors.

References

1. Hiemcke-Jiwa, L.S., et al., USP6-Associated Neoplasms: A Rapidly Expanding Family of Lesions. Int J Surg Pathol, 2020. 28(8): p. 816-825.
2. Svajdler, M., et al., Fibro-osseous pseudotumor of digits and myositis ossificans show consistent COL1A1-USP6 rearrangement: a clinicopathological and genetic study of 27 cases. Hum Pathol, 2019. 88: p. 39-47.
3. Oliveira, A.M., et al., USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts. Am J Pathol, 2004. 165(5): p. 1773-80.
4. Amary, M.F., et al., Detection of USP6 gene rearrangement in nodular fasciitis: an important diagnostic tool. Virchows Arch, 2013. 463(1): p. 97-8.

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