EWSR1::SMAD3-rearranged fibroblastic tumor: A case with twice recurrence and literature review

Abstract

EWSR1::SMAD3-rearranged fibroblastic tumor is a recently described entity that mostly occurs in acral locations. Only 15 cases have been reported in the English literature, with a wide age range and marked female predominance. The most common sites are the foot, followed by the hand and the distal lower leg. There are four cases that recurred locally during 5-120 months of follow-up, with no metastases to date. Herein, we presented a case of EWSR1::SMAD3-rearranged fibroblastic tumor that recurred twice in a 20-year-old man. The patient presented with a second recurrent painful nodule in the left plantar of the second toe. Grossly, the lesion was pale solid and well-defined, measuring 9 × 8 × 9 mm in size. Histological examination revealed a monomorphic spindle cell tumor composed of cellular fascicles of bland fibroblasts in a collagenous to myxoid stroma with low mitotic activity, which evoked a wide spectrum of differential diagnoses. Immunohistochemically, the tumor cells were diffusely and strongly positive for ERG while negative for S100, α-SMA, CD34, and other vascular markers. An unbalanced rearrangement of EWSR1 was demonstrated by fluorescence in situ hybridization (FISH), and a gene fusion between EWSR1 exon 7 and SMAD3 exon 6 was confirmed by RT-PCR and Sanger sequencing. This case recurred twice within 6 years with no sign of further relapse and metastasis at another 9-month follow-up since the last surgery, indicating that this tumor was benign but prone to local recurrence. Nevertheless, more cases and further studies are needed to better interpret the biological behavior of this new entity.

Keywords: ERG; EWSR1; SMAD3; case report; fibroblastic tumor.

Figure 1

The timeline showed the clinicopathological process.

Figure 2

Histologic and immunohistochemical features. (A) Histological examination revealed a relatively well-defined, nodular tumor without capsule (H&E, low magnification). (B) Monomorphic spindle cell tumor composed of cellular fascicles of bland fibroblasts with hyalinization and mucoid degeneration (H&E, medium magnification). (C) Spindle cells showed elongated nuclei with finely dispersed chromatin and small inconspicuous nucleoli (H&E, high magnification). (D) Tumor cells showed diffuse nuclear staining for ERG (medium magnification).

Figure 3

Molecular detection. (A) FISH assay showed an unbalanced rearrangement of EWSR1 with loss of the telomeric part (green). (B) FISH assay showed EWSR1 (green) and SMAD3 (red) fusion signal (yellow). (C) RT-PCR identified exon 7 of EWSR1 and exon 6 of SMAD3 gene fusion. FISH, fluorescence in situ hybridization.