Novel EWSR1-SMAD3 Gene Fusions in a Group of Acral Fibroblastic Spindle Cell Neoplasms

Yu-Chien Kao, Uta Flucke, Astrid Eijkelenboom, Lei Zhang, Yun Shao Sung, Albert J.H. Suurmeijer, Cristina R. Antonescu

Research output: Contribution to journalArticle

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Abstract

Benign/low-grade fibroblastic tumors encompass a broad spectrum of tumors with different morphologies and molecular genetic abnormalities. However, despite significant progress in recent genomic characterization, there are still tumors in this histologic spectrum that are difficult to classify, lacking known molecular characteristics. Triggered by a challenging congenital spindle cell neoplasm arising in the heel of a 1-year-old boy, we applied RNA sequencing for genetic discovery and identified a novel EWSR1-SMAD3 gene fusion. On the basis of the index case superficial acral location and fibroblastic appearance with a nonspecific immunophenotype, we searched our files for similar cases and screened them by fluorescence in situ hybridization for these abnormalities. Thus an identical EWSR1-SMAD3 fusion was identified in 2 additional spindle cell tumors with similar clinicopathologic features. Both cases occurred in the feet of adult women (58 and 61 y old) and were characterized by distinctive nodular growth with zonation pattern of peripheral hypercellular areas arranged in short fascicles, transitioning to hypocellular central areas of hyalinization and infarction. Focal stippled calcification in the collagenous area was present in 1 case. All 3 tumors had similar immunoprofiles, being negative for SMA, CD34, CD31, and S100, but showing consistent ERG positivity of uncertain significance. Follow-up information was available in 2 patients who developed local recurrences after incomplete initial excisions, at 5 and 14 months, respectively. None developed metastatic disease. In summary, we report a group of locally recurrent superficial acral tumors, characterized by bland spindle cell fascicular growth, occasional zonation pattern, ERG positivity, and recurrent EWSR1-SMAD3 gene fusions.

Original languageEnglish
Pages (from-to)522-528
Number of pages7
JournalAmerican Journal of Surgical Pathology
Volume42
Issue number4
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

Gene Fusion
Extremities
Neoplasms
RNA Sequence Analysis
Heel
Growth
Fluorescence In Situ Hybridization
Infarction
Foot
Molecular Biology
Recurrence

Keywords

  • acral
  • ERG
  • EWSR1
  • fibroblastic tumor
  • SMAD3
  • spindle cell tumor

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

Kao, Y-C., Flucke, U., Eijkelenboom, A., Zhang, L., Sung, Y. S., Suurmeijer, A. J. H., & Antonescu, C. R. (2018). Novel EWSR1-SMAD3 Gene Fusions in a Group of Acral Fibroblastic Spindle Cell Neoplasms. American Journal of Surgical Pathology, 42(4), 522-528. https://doi.org/10.1097/PAS.0000000000001002

Novel EWSR1-SMAD3 Gene Fusions in a Group of Acral Fibroblastic Spindle Cell Neoplasms. / Kao, Yu-Chien; Flucke, Uta; Eijkelenboom, Astrid; Zhang, Lei; Sung, Yun Shao; Suurmeijer, Albert J.H.; Antonescu, Cristina R.

In: American Journal of Surgical Pathology, Vol. 42, No. 4, 01.01.2018, p. 522-528.

Research output: Contribution to journalArticle

Kao, Y-C, Flucke, U, Eijkelenboom, A, Zhang, L, Sung, YS, Suurmeijer, AJH & Antonescu, CR 2018, 'Novel EWSR1-SMAD3 Gene Fusions in a Group of Acral Fibroblastic Spindle Cell Neoplasms', American Journal of Surgical Pathology, vol. 42, no. 4, pp. 522-528. https://doi.org/10.1097/PAS.0000000000001002
Kao, Yu-Chien ; Flucke, Uta ; Eijkelenboom, Astrid ; Zhang, Lei ; Sung, Yun Shao ; Suurmeijer, Albert J.H. ; Antonescu, Cristina R. / Novel EWSR1-SMAD3 Gene Fusions in a Group of Acral Fibroblastic Spindle Cell Neoplasms. In: American Journal of Surgical Pathology. 2018 ; Vol. 42, No. 4. pp. 522-528.
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