DP19 Spindle-cell-predominant epithelioid fibrous histiocytoma: a diagnostic pitfall in spindle cell dermal lesions

Abstract

Epithelioid fibrous histiocytoma (EFH) is a biologically distinct cutaneous neoplasm defined by ALK (anaplastic lymphoma kinase) gene rearrangements. Although it is historically linked to benign fibrous histiocytoma, molecular evidence confirms it is a separate entity. While the classic form is epithelioid, a spindle-­cell-predominant variant expands this morphological spectrum and presents a diagnostic pitfall due to overlap with other dermal spindle cell tumours. The aim of this report is to raise awareness of this rare variant and emphasize its inclusion in the differential diagnosis of spindle cell dermal lesions. We present two new cases of spindle-cell-predominant EFH and review 12 previously documented cases. Both our cases showed exclusive dermal spindle cell proliferation with absence of epithelioid areas and a whorled or storiform architecture. Initial assessment on haematoxylin and eosin sections generated a broad differential diagnosis, including neural and smooth muscle tumours. A negative initial immunohistochemical panel led to the consideration of a spindle cell variant of EFH, prompting an ALK (D5F3) stain, which showed diffuse positivity in both cases. Molecular analysis in one case demonstrated a DCTN1::ALK fusion. Spindle-cell-predominant EFH departs from classic EFH morphology, showing a storiform or whorled proliferation of spindle cells within variably myxoid or sclerotic stroma, often with perivascular accentuation. A review of 12 cases demonstrated absence of epithelioid areas in five cases and limited epithelioid components comprising 20–40% of the lesion in the remaining seven. Characteristic EFH features such as a polypoid configuration with epidermal collarette may be absent, complicating diagnosis and expanding the differential to include perineurioma, melanocytic lesions and cellular dermatofibromas. Spindle-cell-predominant EFH should be considered in the differential diagnosis of spindle cell dermal lesions, particularly those exhibiting whorled or storiform architecture. Routine use of ALK immunohistochemistry is essential to avoid misclassification. Recognition of these cases expands the limited literature, which currently comprises only 12 reported cases.