Ectomesenchymal Chondromyxoid Tumor: A Neoplasm Characterized by Recurrent RREB1-MKL2 Fusions

Brendan C. Dickson, Cristina R. Antonescu, Prokopios P. Argyris, Elizabeth A. Bilodeau, Martin J. Bullock, Paul D. Freedman, Douglas R. Gnepp, Richard C. Jordan, Ioannis G. Koutlas, Cheng Han Lee, Iona Leong, Mihai Merzianu, Bibianna M. Purgina, Lester D.R. Thompson, Bret Wehrli, John M. Wright, David Swanson, Lei Zhang, Justin A. Bishop

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Ectomesenchymal chondromyxoid tumor is a rare and benign neoplasm with a predilection for the anterior dorsal tongue. Despite morphologic heterogeneity, most cases are characterized by a proliferation of bland spindle cells with a distinctive reticular growth pattern and myxoid stroma. The immunophenotype of these neoplasms is likewise variable; most cases express glial fibrillary acid protein and S100 protein, with inconsistent reports of keratin and myoid marker expression. The molecular pathogenesis is poorly understood; however, a subset of cases has been reported to harbor EWSR1 gene rearrangement. Following identification of an RREB1-MKL2 fusion gene by RNA Sequencing in an index patient, a retrospective review of additional cases of ectomesenchymal chondromyxoid tumors was performed to better characterize the clinical, immunohistochemical, and molecular attributes of this neoplasm. A total of 21 cases were included in this series. A marked predisposition for the dorsal tongue was confirmed. Most cases conformed to prior morphologic descriptions; however, hypercellularity, hyalinized stroma, and necrosis were rare attributes not previously emphasized. The neoplastic cells frequently coexpressed glial fibrillary acid protein, S100 protein, keratin, smooth muscle actin, and/or desmin; a single case was found to contain significant myogenin expression. An RREB1-MKL2 fusion product was identified in 19 tumors (90%), a single tumor (5%) had an EWSR1-CREM fusion product, and the remaining case lacked any known fusion gene by RNA Sequencing. The latter 2 cases subtly differed morphologically from many in the cohort. This series illustrates that recurrent RREB1-MKL2 fusions occur in most, perhaps all, cases of ectomesenchymal chondromyxoid tumor.

Original languageEnglish (US)
JournalAmerican Journal of Surgical Pathology
DOIs
StateAccepted/In press - Jun 15 2018

Fingerprint

Neoplasms
RNA Sequence Analysis
S100 Proteins
Gene Fusion
Glial Fibrillary Acidic Protein
Keratins
Tongue
Myogenin
Desmin
Gene Rearrangement
Smooth Muscle
Actins
Necrosis
Growth

Keywords

  • CREM
  • ectomesenchymal chondromyxoid tumor
  • EWSR1
  • gene rearrangement
  • MKL2
  • RREB1
  • tongue

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

Ectomesenchymal Chondromyxoid Tumor : A Neoplasm Characterized by Recurrent RREB1-MKL2 Fusions. / Dickson, Brendan C.; Antonescu, Cristina R.; Argyris, Prokopios P.; Bilodeau, Elizabeth A.; Bullock, Martin J.; Freedman, Paul D.; Gnepp, Douglas R.; Jordan, Richard C.; Koutlas, Ioannis G.; Lee, Cheng Han; Leong, Iona; Merzianu, Mihai; Purgina, Bibianna M.; Thompson, Lester D.R.; Wehrli, Bret; Wright, John M.; Swanson, David; Zhang, Lei; Bishop, Justin A.

In: American Journal of Surgical Pathology, 15.06.2018.

Research output: Contribution to journalArticle

Dickson, BC, Antonescu, CR, Argyris, PP, Bilodeau, EA, Bullock, MJ, Freedman, PD, Gnepp, DR, Jordan, RC, Koutlas, IG, Lee, CH, Leong, I, Merzianu, M, Purgina, BM, Thompson, LDR, Wehrli, B, Wright, JM, Swanson, D, Zhang, L & Bishop, JA 2018, 'Ectomesenchymal Chondromyxoid Tumor: A Neoplasm Characterized by Recurrent RREB1-MKL2 Fusions', American Journal of Surgical Pathology. https://doi.org/10.1097/PAS.0000000000001096
Dickson, Brendan C. ; Antonescu, Cristina R. ; Argyris, Prokopios P. ; Bilodeau, Elizabeth A. ; Bullock, Martin J. ; Freedman, Paul D. ; Gnepp, Douglas R. ; Jordan, Richard C. ; Koutlas, Ioannis G. ; Lee, Cheng Han ; Leong, Iona ; Merzianu, Mihai ; Purgina, Bibianna M. ; Thompson, Lester D.R. ; Wehrli, Bret ; Wright, John M. ; Swanson, David ; Zhang, Lei ; Bishop, Justin A. / Ectomesenchymal Chondromyxoid Tumor : A Neoplasm Characterized by Recurrent RREB1-MKL2 Fusions. In: American Journal of Surgical Pathology. 2018.
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abstract = "Ectomesenchymal chondromyxoid tumor is a rare and benign neoplasm with a predilection for the anterior dorsal tongue. Despite morphologic heterogeneity, most cases are characterized by a proliferation of bland spindle cells with a distinctive reticular growth pattern and myxoid stroma. The immunophenotype of these neoplasms is likewise variable; most cases express glial fibrillary acid protein and S100 protein, with inconsistent reports of keratin and myoid marker expression. The molecular pathogenesis is poorly understood; however, a subset of cases has been reported to harbor EWSR1 gene rearrangement. Following identification of an RREB1-MKL2 fusion gene by RNA Sequencing in an index patient, a retrospective review of additional cases of ectomesenchymal chondromyxoid tumors was performed to better characterize the clinical, immunohistochemical, and molecular attributes of this neoplasm. A total of 21 cases were included in this series. A marked predisposition for the dorsal tongue was confirmed. Most cases conformed to prior morphologic descriptions; however, hypercellularity, hyalinized stroma, and necrosis were rare attributes not previously emphasized. The neoplastic cells frequently coexpressed glial fibrillary acid protein, S100 protein, keratin, smooth muscle actin, and/or desmin; a single case was found to contain significant myogenin expression. An RREB1-MKL2 fusion product was identified in 19 tumors (90{\%}), a single tumor (5{\%}) had an EWSR1-CREM fusion product, and the remaining case lacked any known fusion gene by RNA Sequencing. The latter 2 cases subtly differed morphologically from many in the cohort. This series illustrates that recurrent RREB1-MKL2 fusions occur in most, perhaps all, cases of ectomesenchymal chondromyxoid tumor.",
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