title: Angiomatoid fibrous histiocytoma: clinicopathological and molecular characterisation with emphasis on variant histomorphology.
abstract: OBJECTIVE
  Angiomatoid fibrous histiocytoma (AFH) is histologically typified by nodules of histiocytoid spindle cells with pseudoangiomatoid spaces, fibrous pseudocapsules and lymphocytic cuffs. The principal goal was to expand the spectrum of AFHs through clinicopathological and molecular characterisation.
  
  
  METHODS
  Thirteen AFHs, including 11 with confirmed hallmark translocation, were reappraised for classic features, reactive osteoclasts, mitoses and stromal, architectural and cytomorphological variations, with CD99, desmin and EMA stained in available cases.
  
  
  RESULTS
  Seven male and six female patients ranged in age from 4 to 63 years (median, 13), including 4 older than 20 years. Tumours were located on the extremities (n=6), trunk (n=4) and scalp (n=3). Although fibrous pseudocapsules were observed in all cases, four showed solid histology without pseudoangiomatoid spaces and another one lacked peripheral lymphoid infiltrates. Nuclear pleomorphism was striking in two cases, moderate in seven and absent in four, with osteoclasts seen in two cases. In three AFHs with sclerotic matrix, one exhibited perivascular hyalinisation and nuclear palisading, reminiscent of a schwannoma. In three varyingly myxoid tumours, one closely resembled a myoepithelioma with prominent reticular arrangement of spindle cells in an abundant myxoid stroma. Besides EWSR1 gene rearrangement detected in four cases by fluorescence in situ hybridisation (FISH), EWSR1-CREB1 fusion was confirmed in nine cases, including a schwannoma-like AFH, and EWSR1-ATF1 fusion detected in a myoepithelioma-like AFH. Immunohistochemically, 56% of AFHs were positive for EMA, 78% for desmin and 100% for CD99.
  
  
  CONCLUSIONS
  Molecular testing is diagnostic of variant AFHs displaying diverse histomorphological alterations in the architectural patterns, cytomorphology and extracellular matrix.
authors.affiliation: Department of Pathology, Shuang Ho Hospital, Taipei Medical University, , Taipei, Taiwan.
authors.forename: Yu-Chien
authors.initials: YC
authors.lastname: Kao
authors.forename: Jui
authors.initials: J
authors.lastname: Lan
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Tai
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.forename: Kai-Wen
authors.initials: KW
authors.lastname: Liu
authors.forename: Jen-Wei
authors.initials: JW
authors.lastname: Tsai
authors.forename: Fu-Min
authors.initials: FM
authors.lastname: Fang
authors.forename: Shih-Chen
authors.initials: SC
authors.lastname: Yu
authors.forename: Hsuan-Ying
authors.initials: HY
authors.lastname: Huang
mesh_terms: D000071443:12E7 Antigen; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001706:Biopsy; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000032:analysis; D002467:Cell Nucleus / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003893:Desmin / Q000032:analysis; D005260:Female; D015321:Gene Rearrangement; D051677:Histiocytoma, Malignant Fibrous / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D018396:Mucin-1 / Q000032:analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010010:Osteoclasts / Q000473:pathology; D011237:Predictive Value of Tests; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000473:pathology; D055815:Young Adult
chemical_list: D000071443:12E7 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C061828:CD99 protein, human; D002148:Calmodulin-Binding Proteins; D015815:Cell Adhesion Molecules; D003893:Desmin; C500986:EWSR1 protein, human; C560860:EWSR1-ATF1 fusion protein, human; C574775:EWSR1-CREB1 fusion protein, human; C060192:MUC1 protein, human; D018396:Mucin-1; D015514:Oncogene Proteins, Fusion; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins
keywords: DIAGNOSTICS; FISH; MOLECULAR PATHOLOGY; SOFT TISSUE TUMOURS