Nodular fasciitis: A novel model of transient neoplasia induced by MYH9-USP6 gene fusion

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Laboratory Investigation (Impact Factor: 3.68). 08/2011; 91(10):1427-33. DOI: 10.1038/labinvest.2011.118
Source: PubMed


Nodular fasciitis (NF) is a relatively common mass-forming and self-limited subcutaneous pseudosarcomatous myofibroblastic proliferation of unknown pathogenesis. Due to its rapid growth and high mitotic activity, NF is often misdiagnosed as a sarcoma. 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. This finding led us to further examine the mechanisms underlying USP6 overexpression in these lesions. Upon subsequent investigation, genomic rearrangements of the USP6 locus were found in 92% (44 of 48) of NF. Rapid amplification of 5'-cDNA ends identified MYH9 as the translocation partner. RT-PCR and direct sequencing revealed the fusion of the MYH9 promoter region to the entire coding region of USP6. Control tumors and tissues were negative for this fusion. Xenografts of cells overexpressing USP6 in nude mice exhibited clinical and histological features similar to human NF. The identification of a sensitive and specific abnormality in NF holds the potential to be used diagnostically. Considering the self-limited nature of the lesion, NF may represent a model of 'transient neoplasia', as it is, to our knowledge, the first example of a self-limited human disease characterized by a recurrent somatic gene fusion event.

  • Source
    • "This lesion was often misdiagnosed as a sarcoma because of its rapid growth, rich cellularity, and mitotic activity [1,2]. Recently USP6 rearrangement and MYH9-USP6 gene fusions have been identified in a high percentage of NF suggestive that this is the driving translocation [3]. Histologically, NF is mainly made up of plump myofibroblasts which resemble the fibroblasts in tissue culture or granulation tissue, and the background is variably myxoid or fibrous [4]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Nodular fasciitis is the most common pseudosarcomatous lesion of soft tissue. Ki67 was considered as a useful marker for distinguishing some benign and malignant lesions. To study the usefulness of Ki67 in diagnosis of nodular fasciitis, the expression of Ki67 was examined by using immunostaining in 65 nodular fasciitis specimens, 15 desmoid fibromatosis specimens and 20 fibrosarcoma specimens. The results showed that there was a variable Ki67 index in all 65 cases of nodular fasciitis, and the mean labeling index was 23.71±15.01%. In majority (70.77%) of all cases,the index was ranged from 10% to 50%, in 6.15% (4/65) of cases the higher Ki67 index (over 50%) could be seen. The Ki67 proliferative index was closely related to duration of lesion, but not to age distribution, lesion size, sites of lesions and gender. Moreover, the mean proliferative index in desmoid fibromatosis and fibrosarcoma was 3.20±1.26% and 26.15±3.30% respectively. The mean Ki67 index of nodular fasciitis was not significantly lower than fibrosarcoma, but higher than desmoid fibromatosis. The variable and high Ki67 index in nodular fasciitis may pose a diagnostic challenge. We should not misdiagnose nodular fasciitis as a sarcoma because of its high Ki67 index. The recurrence of nodular fasciitis is rare; and the utility of Ki67 immunostaining may be not suitable for recurrence assessment in nodular fasciitis. Virtual slides The virtual slide(s) for this article can be found here:
    Full-text · Article · Mar 2013 · Diagnostic Pathology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bone tumors are considered by most pathologists difficult to diagnose as they are rare, have overlapping morphology, need radiological correlation, and the usefulness of immunohistochemistry is limited, making conventional morphology the cornerstone of the diagnosis. Over the past decade, more and more has become known of the molecular background of bone tumors. Three groups of bone tumors are recognized, namely, tumors with specific translocations combined with a relatively simple karyotype involving chromosomal translocations (Ewing sarcoma, aneurysmal bone cyst), tumors with specific gene mutations or amplifications (chondrosarcoma, fibrous dysplasia, chordoma), and sarcomas with genetic instability and as a consequence complex karyotypes (osteosarcoma). Technical advancements will rapidly reveal new alterations in the more rare sarcoma subtypes for which the molecular background has remained enigmatic. Opening the archives and using new technologies, as well as refinement of existing technologies for decalcified paraffin-embedded tissue, may bring to light more specific genetic aberrations in bone tumors that can be applied in molecular diagnostics in the near future.
    Full-text · Article · May 2012 · Cancer Genetics
  • [Show abstract] [Hide abstract]
    ABSTRACT: The skeletal system may be affected by a variety of nonneoplastic lesions, which may potentially be confused with primary bone tumors on clinical, radiologic, and pathologic grounds. These conditions include fractures, infections, and reactive and degenerative processes, as well as an array of quasineoplastic entities, such as intramedullary cystic lesions like unicameral and aneurysmal bone cysts; fibro-osseous lesions, such as fibrous dysplasia; and exophytic entities, like osteochondromas. To review clinical, radiographic, and histologic features of nonneoplastic lesions of bone, discussing the difficulties in diagnosis and the differential diagnosis with primary neoplasms of bone. The sources include the more relevant medical literature on the different subjects and case-derived material. Because many nonneoplastic bone lesions may require biopsy or resection, the general surgical pathologist must be familiar with these lesions and be aware that review of hematoxylin-eosin slides is only one of the many steps in the diagnostic process, which also includes review of imaging studies and all available clinical information. Morphologic analysis disconnected from the clinical and radiographic context may lead to misinterpretation.
    No preview · Article · Jul 2012 · Archives of pathology & laboratory medicine
Show more