Original contributionFibro-osseous pseudotumor of digits and myositis ossificans show consistent COL1A1-USP6 rearrangement: a clinicopathological and genetic study of 27 cases☆,☆☆
Introduction
Myositis ossificans (MO) and fibro-osseous pseudotumor of digits (FOPD) are localized, self-limiting bone-producing lesions affecting mainly younger adults, although broad age distribution was reported [1], [2], [3], [4], [5], [6], [7]. Both lesions are typified by hypercellular nodular fasciitis (NF)–like fibroblastic proliferation and osteoid and immature woven bone production, which may eventually develop into more mature lamellar bone. From the early descriptions to the present days, zonal maturation was emphasized as the most important feature in differentiating MO from sarcomas [1], [2], whereas FOPD was reported to show less well-organized structure without the typical zoning pattern of MO [5]. However, later studies showed that MO and FOPD share both clinical and histological features [4], [6], [7] and that the subtle differences between MO and FOPD may be related only to the site of occurrence, for example, the musculature in MO and more superficial subcutaneous tissues in FOPD [4], [6]. In the current World Health Organization classifications of tumors of soft tissue, MO and FOPD are classified together [8].
Because of the rapid and painful growth, hypercellularity, and high mitotic activity of the myofibroblastic proliferation and because of the presence of osteoid, immature bone and in some cases mildly atypical and hypercellular hyaline cartilage, MO and FOPD often raise clinical and/or histological suspicion of malignancy. Some of these lesions regress spontaneously, and their recurrence is exceedingly rare; nevertheless, many MO/FOPD cases are sent for a second opinion with a diagnosis of sarcoma, most commonly being overdiagnosed as extraskeletal or parosteal osteosarcoma [4], [5], [6], [7]. This makes MO/FOPD one of the most eminent examples of pseudosarcoma [9].
Traditionally, MO and FOPD were thought to be of non-neoplastic/reactive origin, with a history of trauma or repetitive minor injury documented in 60%-75% of cases [8]. Recently, however, USP6 rearrangement was reported as a consistent genetic finding in MO and FOPD, thus expanding the spectrum of clonal “transient” neoplasms harboring USP6 translocation, which currently also includes aneurysmal bone cyst (ABC) and NF [10], [11].
COL1A1 was described as a fusion partner of USP6 in a subset of MO cases [12], but the fusion partners of USP6 in the USP6-rearranged FOPDs have not been reported to date. We therefore analyzed a series of MO and FOPD cases using next-generation sequencing (NGS) and the Archer FusionPlex Sarcoma kit “(ArcherDX Inc, Boulder, CO)” to find out whether FOPD cases will show the same genetic change as MO.
Section snippets
Materials and methods
Fifteen cases of MO and 12 cases of FOPD were retrieved from Tumor Registry at Bioptical Laboratory Plzen, Czech Republic. Some cases of FOPD have been reported previously [7]. Hematoxylin-eosin slides were reviewed to confirm the diagnosis of MO and FOPD, respectively, and to evaluate the histologic features.
For NGS analysis, 2-3 formalin-fixed, paraffin-embedded sections (10 μm thick) were macrodissected to isolate tumor-rich regions. Total nucleic acid was extracted from tumor samples using
Clinicopathological findings
The clinical and molecular features of all cases are summarized in the Table.
The study group consisted of 15 MO and 12 FOPD cases. Of these cases, 15 were men and 12 were women, and their median age was 35 years (range 5-64 years). For MO cases, the median age was 35 years (range 6-62 years), and the median age of FOPTD cases was 32 years (range 5-64 years).
Sixteen cases were seen in consultation, and the tentative diagnosis or differential diagnosis was provided by the submitting pathologist
Discussion
Initially identified in ABC [13], [14], [15] and later in NF [16], USP6 gene rearrangement is a common finding in a group of so-called USP6-induced neoplasms [17]. Extraosseal soft tissue ABC [18], [19], giant cell reparative granuloma of the hands and feet (best regarded as a solid variant of ABC of small bones) [20], and cellular fibroma of tendon sheath (best viewed as tenosynovial variant of NF) [21] are other USP6-induced tumor family members. The nature of these lesions was long
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Competing interests: The authors have no conflict of interest to disclose.