Primary Pulmonary Myxoid Sarcoma With EWSR1-CREB1 Fusion

• DOI: 10.1097/pas.0b013e318227e4d2
• Publication Date: 2011-10-13T09:24:12Z
• Authors: Khin Thway; Andrew G. Nicholson; Kay Lawson; David Gonzalez; Alexandra Rice; Bonnie Balzer; John Swansbury; Toon Min; Lisa Thompson; Kwame Adu-Poku; Anne Campbell; Cyril Fisher
• Keywords: Adult; Male; Time Factors; Lung Neoplasms; Genotype; Biopsy; 610; Fluorescence; Disease-Free Survival; 03 medical and health sciences; 0302 clinical medicine; Biomarkers, Tumor; Humans; Cyclic AMP Response Element-Binding Protein; In Situ Hybridization; In Situ Hybridization, Fluorescence; Retrospective Studies; Aged; Gene Rearrangement; Tumor; Reverse Transcriptase Polymerase Chain Reaction; Brain Neoplasms; RNA-Binding Proteins; Sarcoma; DNA; Middle Aged; Prognosis; Immunohistochemistry; 3. Good health; Phenotype; Calmodulin-Binding Proteins; Female; Gene Fusion; Sequence Analysis; Biomarkers

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.