Primary pulmonary myxoid sarcoma with an unusual gene fusion between exon 7 of EWSR1 and exon 5 of CREB1
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Primary pulmonary mesenchymal tumors are rare, yet they compromise a variety of entities. A novel low-grade malignant neoplasm coined primary pulmonary myxoid sarcoma (PPMS) has been introduced in the WHO classification of lung tumors. Molecular analysis in PPMS revealed recurrent gene fusions between EWSR1 and CREB1, a member of the cAMP response element binding protein (CREB) family. However, only 23 PPMS have been reported in the literature reflecting their exceedingly low incidence. Here, we describe the case of a 41-year-old female patient with a lung tumor obstructing the right main bronchus. Histologically, the tumor was composed of spindle-shaped and epithelioid cells exhibiting a reticular growth pattern within a prominent myxoid matrix. Solid areas were also observed. Molecular analysis by next-generation sequencing identified a fusion transcript with an unusual gene fusion involving exon 7 of EWSR1 and exon 5 of CREB1. Together, the diagnosis PPMS was established.
KeywordsEWSR1 CREB1 Primary pulmonary myxoid sarcoma NGS
G.M. conceived the project. C.K. wrote the manuscript. L.T. coordinated data generation. A.S. and O.N. analyzed molecular data. C.P.H., R.E. and H.W. provided tumor samples and metadata. All authors read and approved the final manuscript.
Compliance with ethical standards
Written informed consent for publication is obtained from the patient.
Conflict of interest
The authors declare that they have no conflict of interest.
- 3.Jeon YK, Moon KC, Park SH, Chung DH (2014) Primary pulmonary myxoid sarcomas with EWSR1-CREB1 translocation might originate from primitive peribronchial mesenchymal cells undergoing (myo)fibroblastic differentiation. Virchows Arch 465:453–461. https://doi.org/10.1007/s00428-014-1645-z CrossRefPubMedGoogle Scholar
- 4.Kao YC, Sung YS, Zhang L, Chen CL, Vaiyapuri S, Rosenblum MK, Antonescu CR (2017) EWSR1 fusions with CREB family transcription factors define a novel myxoid mesenchymal tumor with predilection for intracranial location. Am J Surg Pathol 41:482–490. https://doi.org/10.1097/PAS.0000000000000788 CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Kirchner M, Neumann O, Volckmar AL, Stogbauer F, Allgauer M, Kazdal D, Budczies J, Rempel E, Brandt R, Talla SB, von Winterfeld M, Leichsenring J, Bochtler T, Kramer A, Springfeld C, Schirmacher P, Penzel R, Endris V, Stenzinger A (2019) RNA-based detection of gene fusions in formalin-fixed and paraffin-embedded solid cancer samples. Cancers (Basel):11. https://doi.org/10.3390/cancers11091309 CrossRefGoogle Scholar
- 7.Matsukuma S, Hisaoka M, Obara K, Kono T, Takeo H, Sato K, Hata Y (2012) Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion, resembling extraskeletal myxoid chondrosarcoma: case report with a review of literature. Pathol Int 62:817–822. https://doi.org/10.1111/pin.12014 CrossRefPubMedGoogle Scholar
- 9.Opitz I, Lauk O, Schneiter D, Ulrich S, Maisano F, Weder W, Bode-Lesniewska B (2019) Intraluminal EWSR1-CREB1 gene rearranged, low-grade myxoid sarcoma of the pulmonary artery resembling extraskeletal myxoid chondrosarcoma (EMC). Histopathology 74:526–530. https://doi.org/10.1111/his.13773 CrossRefPubMedGoogle Scholar
- 10.Smith SC, Palanisamy N, Betz BL, Tomlins SA, Mehra R, Schmidt LA, Lucas DR, Myers JL (2014) At the intersection of primary pulmonary myxoid sarcoma and pulmonary angiomatoid fibrous histiocytoma: observations from three new cases. Histopathology 65:144–146. https://doi.org/10.1111/his.12354 CrossRefPubMedGoogle Scholar
- 11.Thway K, Nicholson AG, Lawson K, Gonzalez D, Rice A, Balzer B, Swansbury J, Min T, Thompson L, Adu-Poku K, Campbell A, Fisher C (2011) Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: a new tumor entity. Am J Surg Pathol 35:1722–1732. https://doi.org/10.1097/PAS.0b013e318227e4d2 CrossRefPubMedGoogle Scholar
- 13.Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG (2015) WHO classification of tumours of the lung. Pleura, Thymus and Heart IARC Press, LyonGoogle Scholar