title: Angiomatoid fibrous histiocytoma: comparison of fluorescence in situ hybridization and reverse transcription polymerase chain reaction as adjunct diagnostic modalities.
abstract: Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm of intermediate biologic potential and uncertain differentiation, most often arising in the extremities of children and young adults. Although it has characteristic histologic features of a lymphoid cuff surrounding nodules of ovoid cells with blood-filled cystic cavities, diagnosis is often difficult due to its morphologic heterogeneity and lack of specific immunoprofile. Angiomatoid fibrous histiocytoma is associated with recurrent chromosomal translocations, leading to characteristic EWSR1-CREB1, EWSR1-ATF1, and, rarely, FUS-ATF1 gene fusions; fluorescence in situ hybridization (FISH), detecting EWSR1 or FUS rearrangements, and reverse transcription-polymerase chain reaction (RT-PCR) for EWSR1-CREB1 and EWSR1-ATF1 fusion transcripts have become routine ancillary tools. We present a large comparative series of FISH and RT-PCR for AFH. Seventeen neoplasms (from 16 patients) histologically diagnosed as AFH were assessed for EWSR1 rearrangements or EWSR1-CREB1 and EWSR1-ATF1 fusion transcripts. All 17 were positive for either FISH or RT-PCR or both. Of 16, 14 (87.5%) had detectable EWSR1-CREB1 or EWSR1-ATF1 fusion transcripts by RT-PCR, whereas 13 (76.5%) of 17 had positive EWSR1 rearrangement with FISH. All 13 of 13 non-AFH control neoplasms failed to show EWSR1-CREB1 or EWSR1-ATF1 fusion transcripts, whereas EWSR1 rearrangement was present in 2 of these 13 cases (which were histopathologically myoepithelial neoplasms). This study shows that EWSR1-CREB1 or EWSR1-ATF1 fusions predominate in AFH (supporting previous reports that FUS rearrangement is rare in AFH) and that RT-PCR has a comparable detection rate to FISH for AFH. Importantly, cases of AFH can be missed if RT-PCR is not performed in conjunction with FISH, and RT-PCR has the added advantage of specificity, which is crucial, as EWSR1 rearrangements are present in a variety of neoplasms in the histologic differential diagnosis of AFH, that differ in behavior and treatment.
authors: Sarcoma Unit, Royal Marsden Hospital, London, UK. Electronic address: khin.thway@rmh.nhs.uk.
authors: Khin
authors: K
authors: Thway
authors: Molecular Diagnostics, Royal Marsden Hospital, Sutton, Surrey, UK.
authors: David
authors: D
authors: Gonzalez
authors: Molecular Diagnostics, Royal Marsden Hospital, Sutton, Surrey, UK.
authors: Dorte
authors: D
authors: Wren
authors: Clinical Cytogenetics, Royal Marsden Hospital, Sutton, Surrey, UK.
authors: Melissa
authors: M
authors: Dainton
authors: Clinical Cytogenetics, Royal Marsden Hospital, Sutton, Surrey, UK.
authors: John
authors: J
authors: Swansbury
authors: Sarcoma Unit, Royal Marsden Hospital, London, UK.
authors: Cyril
authors: C
authors: Fisher
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D051677:Histiocytoma, Malignant Fibrous / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D034702:RNA-Binding Protein FUS / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: C560860:EWSR1-ATF1 fusion protein, human; C574775:EWSR1-CREB1 fusion protein, human; C000599550:FUS protein, human; D015514:Oncogene Proteins, Fusion; D034702:RNA-Binding Protein FUS
keywords: Angiomatoid fibrous histiocytoma; EWSR1-ATF1; EWSR1-CREB1; FUS-ATF1; genetics; soft tissue tumor; translocation