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Σάββατο 14 Απριλίου 2018

Misses and near misses in diagnosing nodular fasciitis and morphologically related reactive myofibroblastic proliferations: experience of a referral center with emphasis on frequency of USP6 gene rearrangements

Abstract

Although harmless, reactive and benign neoplastic myo-/fibroblastic proliferations represent a diagnostic challenge in routine surgical pathology practice as reflected by their frequency among consultation cases. In addition to resembling each other, the prototypical nodular fasciitis (NF) and NF-like lesions can be mistaken for low-grade or aggressive sarcomas. USP6 translocation was reported recently as the molecular driver and potential diagnostic marker of NF. We reviewed 71 lesions with a diagnosis of NF (n = 48) or NF-like myofibroblastic proliferations (n = 23) and screened them for USP6 translocation by fluorescence in situ hybridization (FISH). Only one third of NFs were correctly diagnosed by submitting pathologists while one third was initially judged as malignant. NF was mentioned in the differential diagnosis in only half of the cases. A high Ki67/mitotic index, misleading immunohistochemistry (false-positive h-caldesmon), and unusual sites/circumscription were main causes behind overdiagnosis as malignant. FISH analysis revealed USP6 translocation in 74.4% of NF cases. None of the reactive/reparative myofibroblastic proliferations showed USP6 translocation. NF is still significantly misdiagnosed by general surgical pathologists, with a higher tendency toward overdiagnosis of malignancy. Inclusion of NF in the differential diagnosis of any fibromyxoid soft tissue lesion and awareness of its diverse morphology are mandatory to avoid misdiagnoses with the risk of disastrous overtreatment. In the appropriate clinicopathological context, USP6 gene translocation is a valuable adjunct for diagnosis of NF, particularly in limited biopsies. Absence of the USP6 gene translocation in NF-like reparative pseudosarcomatous myofibroblastic proliferations underlines their reactive nature and distinguishes them from NF which is currently considered a benign neoplasm with a self-limiting "transient" growth phase.



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