title: Thoracic Myoepithelial Tumors: A Pathologic and Molecular Study of 8 Cases With Review of the Literature.
abstract: Thoracic myoepithelial tumors (MTs) are a rare group of tumors showing predominant or exclusive myoepithelial differentiation. They are poorly characterized from both a morphologic and genetic standpoint, in particular features that separate benign from malignant behavior. We examined the histologic and immunohistochemical features of 8 primary thoracic MTs and performed fluorescence in situ hybridization for EWSR1, FUS, PLAG1, and HMGA2, as well as several partner genes. Half (4/8) of the MTs occurred in large airways, and 3 had infiltrative borders. All cases showed immunoreactivity for epithelial markers, in conjunction with S100 protein or myogenic markers. MTs showed morphologic characteristics analogous to MTs at other sites, with no tumors having ductal differentiation. Necrosis and/or lymphovascular invasion was present in 5 cases, with mitotic activity ranging from 0 to 6 mitoses/2 mm² (mean 1). Metastases occurred in 2 cases, and no patients died of disease. Gene rearrangements were identified in half of the cases, with EWSR1-PBX1, EWSR1-ZNF444, and FUS-KLF17 fusions identified in 1 case each and 1 case having EWSR1 rearrangement with no partner identified. No cases were found to have HMGA2 or PLAG1 abnormalities. Compared with fusion-negative tumors, fusion-positive tumors tended to occur in patients who were younger (50 vs. 58 y), female (1:3 vs. 3:1 male:female ratio), and demonstrated predominantly spindle and clear cell morphology. Using a combined data set of our case series with 16 cases from the literature, poor prognosis was significantly correlated with metastases (P=0.003), necrosis (P=0.027), and ≥5 mitoses/2 mm²/10 high-power field (P=0.005). In summary, we identify a subset of thoracic MTs harboring rearrangements in EWSR1 or FUS, and our data suggest that necrosis and increased mitotic activity correlate with aggressive clinical behavior.
authors.affiliation: *Department of Pathology, Memorial Sloan Kettering Cancer Center‡Department of Pathology, New York Hospital Queens -Weill Cornell Medical College, New York, NY†Department of Pathology, Istanbul University, Cerrahpasa School of Medicine, Istanbul, Turkey§Department of Pathology, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Charles
authors.initials: C
authors.lastname: Leduc
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Buge
authors.initials: B
authors.lastname: Öz
authors.forename: Jean
authors.initials: J
authors.lastname: Luo
authors.forename: Junya
authors.initials: J
authors.lastname: Fukuoka
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001706:Biopsy; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D005260:Female; D050939:Gene Fusion; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D025202:Molecular Diagnostic Techniques; D009208:Myoepithelioma / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000556:secondary / Q000628:therapy; D009361:Neoplasm Invasiveness; D010641:Phenotype; D011237:Predictive Value of Tests; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D012307:Risk Factors; D013899:Thoracic Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D014057:Tomography, X-Ray Computed
chemical_list: D014408:Biomarkers, Tumor; D002148:Calmodulin-Binding Proteins; C500986:EWSR1 protein, human; C000599550:FUS protein, human; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins