This pathology case study (Case 3) details the diagnosis of Cutaneous Sensational Myoepithelioma (CSM) in a 30-year-old male presenting with a verrucous papule on the trunk. Initial histological examination suggested a nevus, but an unusual sheet-like growth pattern prompted further investigation. Immunohistochemistry (IHC) results were complex, showing positivity for S100, EMA, and—unexpectedly—ALK-1, creating an overlap with Epithelioid Fibrous Histiocytoma. To resolve this diagnostic dilemma, Fluorescence in situ hybridization (FISH) was employed. FISH confirmed the rearrangement of the EWSR1 gene (typical of CSM) but was negative for ALK rearrangement, establishing the final diagnosis as benign Cutaneous Sensational Myoepithelioma. The video highlights that ALK protein expression can occur in the absence of an ALK gene fusion.
Cutaneous Sensational Myoepithelioma: Resolving a Staining Overlap
0:09 Case Presentation: A 30-year-old male presented with a papule on the trunk. Prior topical wart medication treatment resulted in verrucous, wart-like changes on the surface.
0:49 Histology and Differential Diagnosis: The low-power view suggested a nevus, but the lesion displayed an atypical, superficial sheet-like growth of bland, histiocytoid cells pushed against the epidermis. Mitoses were occasionally observed.
1:57 Pathology Pearl: The characteristic "collarette" feature often seen around these lesions is clarified as being formed by adnexal eccrine duct structures, not solely the epidermis.
2:57 Immunohistochemistry (IHC): The lesion was negative for Sox 10 and Keratin. Crucially, it was positive for S100 and EMA (Epithelial Membrane Antigen).
3:11 Diagnostic Twist: The lesion also exhibited unexpected positivity for ALK-1 IHC.
4:00 CSM Diagnosis: The co-expression of EMA and S100, with negative keratin, is characteristic of Cutaneous Sensational Myoepithelioma (CSM), a unique superficial variant of myoepithelioma.
5:06 Key Molecular Marker (CSM): Like other myoepitheliomas, CSM often involves rearrangement of the EWSR1 (Ewing’s Gene), typically fused with the PBX3 partner gene.
6:18 The Dilemma: The ALK-1 IHC positivity suggested Epithelioid Fibrous Histiocytoma (which is ALK-positive but S100/Sox 10 negative), creating an overlap with the CSM markers.
7:04 Molecular Resolution (FISH): To determine the underlying genetic event, FISH testing was performed for both EWSR1 and ALK.
7:15 Takeaway: FISH confirmed EWSR1 rearrangement (positive) but was ALK rearrangement negative.
7:20 Final Diagnosis: The definitive diagnosis is Cutaneous Sensational Myoepithelioma (Benign). The ALK protein expression was deemed aberrant (over-activation or mutation) and not indicative of a true ALK fusion, thus ruling out Epithelioid Fibrous Histiocytoma.
8:49 Conclusion on Surface Changes: The verrucous changes were attributed to reactive trauma from the prior topical wart treatment, although an induction phenomenon cannot be entirely excluded.