December 2020 — Bone and Soft Tissue

13-year old male presented with a superficial dermal nodular lesion of the left thigh. The lesion was not painful and on examination, no skin changes were seen on the surface. The excision biopsy of the nodule was sent for consultation. The H&E images (Figure1,2,3), EMA (Figure 4) and S-100 immunostains (Figure 5) are attached for review. The neoplastic cells are negative for HMB45, SOX10, MelanA, ALK1, keratin AE1/AE3, CD68 and desmin.

Figure 1: H&E x2
Figure 2: H&E x10
Figure 3: H&E x40
Figure 4: EMA Immunostain x20
Figure 5: S100 Immunostain x20

What is your diagnosis?

  • Epithelioid sarcoma
  • Cutaneous syncytial myoepithelioma
  • Spitz nevus
  • Epithelioid fibrous histiocytoma

The correct answer is...

The correct answer is Cutaneous syncytial myoepithelioma.

The correct diagnosis is Cutaneous syncytial myoepithelioma, characterized by recurrent EWSR1-PBX3 fusions. Histological sections show relatively well circumscribed mesenchymal neoplasm centered in the dermis (Figure 1). The neoplasm is composed of solid, sheet like syncytial growth pattern of ovoid, spindled to epithelioid cells with moderate to abundant pale eosinophilic cytoplasm (Figure 3). There is a sparse perivascular lymphocytic infiltrate (Figure 2). There is focal cytologic atypia of the reactive type and only rare mitotic figures identified. By immunohistochemistry, the tumor shows positivity for S100 (Figure 4), EMA (Figure 5) and smooth muscle actin. The neoplastic cells are negative for HMB45, SOX10, MelanA, ALK1, keratin AE1/AE3, CD68 and desmin. Based on the overall morphologic and immunophenotypical features, this lesion represents a cutaneous syncytial myoepithelioma. Next generation sequencing study identified EWSR1-PBX3 fusion in this neoplasm.

Cutaneous syncytial myoepithelioma is a distinctive morphological subtype of myoepithelioma, characterized by syncytial solid growth of myoepithelial cells with perivascular lymphocytic infiltrates, absence of chondromyxoid stroma, EMA and S100 immunoreactivity, infrequent keratin staining, recurrent EWSR1-PBX3 fusion and benign behavior. This EWSR1-PBX3 fusion is also reported in intra-osseous syncytial myoepithelioma.

Epitheliod fibrous histiocytoma also presents as a dermal nodule, composed of epitheliod cells surrounded by epithelial collarette. Eventhough EMA is expressed in 60% of cases, they lack S100 and show ALK positivity. Epitheloid sarcoma commonly affects young adults in distal extremities and show infiltrative nodular growth pattern. Although EMA positivity is shared, they can be differentiated by INI-1 loss and negativity for S100. Spitz nevi show junctional component, nested growth pattern, kamino body and downward maturation. Although S100 positivity is shared, they can be differentiaed by theexpression of melanocytic markers.

1. Jo VY, Antonescu CR, Dickson BC, Swanson D, Zhang L, Fletcher CDM, Demicco EG. Cutaneous Syncytial Myoepithelioma Is Characterized by Recurrent EWSR1-PBX3 Fusions. Am J Surg Pathol. 2019 2. Jo VY, Antonescu CR, Zhang L, Dal Cin P, Hornick JL, Fletcher CD. Cutaneous syncytial myoepithelioma: clinicopathologic characterization in a series of 38 cases. Am J Surg Pathol. 2013 3. Choi JH, Ro JY. Epithelioid Cutaneous Mesenchymal Neoplasms: A Practical Diagnostic Approach. Diagnostics (Basel). 2020 4. Boland JM, Folpe AL. Cutaneous neoplasms showing EWSR1 rearrangement. Adv Anat Pathol. 2013

Photo of Judith Jebastin Thangaiah, M.B.B.S. Judith Jebastin Thangaiah, M.B.B.S.
Resident, Bone and Soft Tissue Pathology
Mayo Clinic
Photo of Jorge Torres-Mora, M.D. Jorge Torres-Mora, M.D.
Consultant, Anatomic Pathology
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

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