Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: a new tumor entity

Am J Surg Pathol. 2011 Nov;35(11):1722-32. doi: 10.1097/PAS.0b013e318227e4d2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Biopsy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / secondary
  • Calmodulin-Binding Proteins / genetics*
  • Cyclic AMP Response Element-Binding Protein / genetics*
  • Disease-Free Survival
  • Female
  • Gene Fusion*
  • Gene Rearrangement
  • Genotype
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Phenotype
  • Prognosis
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins / genetics*
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sarcoma / chemistry
  • Sarcoma / genetics*
  • Sarcoma / mortality
  • Sarcoma / secondary
  • Sarcoma / surgery
  • Sequence Analysis, DNA
  • Time Factors


  • Biomarkers, Tumor
  • CREB1 protein, human
  • Calmodulin-Binding Proteins
  • Cyclic AMP Response Element-Binding Protein
  • EWSR1 protein, human
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins