Send to

Choose Destination
Am J Surg Pathol. 2018 Apr;42(4):522-528. doi: 10.1097/PAS.0000000000001002.

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

Author information

Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
Department of Pathology, Radboud University Medical Center Nijmegen, Nijmegen.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wolters Kluwer Icon for PubMed Central
Loading ...
Support Center