title: Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: a new tumor entity.
abstract: We present clinicopathologic data on 10 pulmonary myxoid sarcomas, which are defined by distinctive histomorphologic features and characterized by a recurrent fusion gene, that appear to represent a distinct tumor entity at this site. The patients [7 female, 3 male; aged 27 to 67 y (mean, 45 y)] presented with local or systemic symptoms (n=5), symptoms from cerebral metastasis (1), or incidentally (2). Follow-up of 6 patients showed that 1 with brain metastasis died shortly after primary tumor resection, 1 developed a renal metastasis but is alive and well, and 4 are disease free after 1 to 15 years. All tumors involved pulmonary parenchyma, with a predominant endobronchial component in 8 and ranged from 1.5 to 4 cm. Microscopically, they were lobulated and composed of cords of polygonal, spindle, or stellate cells within myxoid stroma, morphologically reminiscent of extraskeletal myxoid chondrosarcoma. Four cases showed no or minimal atypia, 6 showed focal pleomorphism, and 5 had necrosis. Mitotic indices varied, with most tumors not exceeding 5/10 high-power fields. Tumors were immunoreactive for only vimentin and weakly focal for epithelial membrane antigen. Of 9 tumors, 7 were shown to harbor a specific EWSR1-CREB1 fusion by reverse transcription-polymerase chain reaction and direct sequencing, with 7 of 10 showing EWSR1 rearrangement by fluorescence in situ hybridization. This gene fusion has been described previously in 2 histologically and behaviorally different sarcomas: clear cell sarcoma-like tumors of the gastrointestinal tract and angiomatoid fibrous histiocytomas; however, this is a novel finding in tumors with the morphology we describe and that occur in the pulmonary region.
authors: Department of Histopathology, Royal Marsden Hospital, London, UK. khin.thway@rmh.nhs.uk
authors: Khin
authors: K
authors: Thway
authors: Andrew G
authors: AG
authors: Nicholson
authors: Kay
authors: K
authors: Lawson
authors: David
authors: D
authors: Gonzalez
authors: Alexandra
authors: A
authors: Rice
authors: Bonnie
authors: B
authors: Balzer
authors: John
authors: J
authors: Swansbury
authors: Toon
authors: T
authors: Min
authors: Lisa
authors: L
authors: Thompson
authors: Kwame
authors: K
authors: Adu-Poku
authors: Anne
authors: A
authors: Campbell
authors: Cyril
authors: C
authors: Fisher
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D001932:Brain Neoplasms / Q000235:genetics / Q000556:secondary; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D050939:Gene Fusion; D015321:Gene Rearrangement; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012509:Sarcoma / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D017422:Sequence Analysis, DNA; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; C115163:CREB1 protein, human; D002148:Calmodulin-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein; C500986:EWSR1 protein, human; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins