This pathology case presentation focuses on the diagnosis and key characteristics of Epithelioid Fibrous Histiocytoma (EFH), differentiating it from common Dermatofibroma (DF). The lesion is initially characterized by a prominent epidermal collarette and sharply circumscribed borders—features uncommon in typical DF. EFH is distinguished by its plump epithelioid cells, dense sclerotic collagen background, and dilated vessels. Crucially, the video highlights the molecular basis of EFH: its strong association (approximately 88%) with ALK (Anaplastic Lymphoma Kinase) gene fusions, which sets it apart from DF and aids in differentiating it from other ALK-positive skin neoplasms (like Spitzoid lesions). The discussion also explores the wide morphological spectrum of EFH, including variants with spindled cells, vacuolated/granular cytoplasm, and even chondroblastoma-like or osseous elements.
Epithelioid Fibrous Histiocytoma (EFH): Distinguishing Features and ALK Fusions
0:06 Initial Presentation: The lesion presents as a shave biopsy, initially suggesting a Dermatofibroma (DF).
0:16 Defining Feature - The Collarette: A key observation is the epidermal collarette (the epidermis wrapping down around the periphery of the pushed-up lesion). This feature is noted as atypical for a common DF.
1:25 Diagnosis Refinement: The lesion is diagnosed as Epithelioid Fibrous Histiocytoma (EFH), formerly described as Epithelioid Cell Histiocytoma. EFH is a benign, indolent lesion.
2:49 Differentiation from DF: Unlike DF, which typically infiltrates by trickling into the dermis, EFH is often sharply circumscribed and well-demarcated from the surrounding tissue.
3:17 Atypical Marker Expression: EFH can express EMA (Epithelial Membrane Antigen) in nearly 50% of cases, a finding that is unusual for DF.
3:45 Molecular Hallmark: EFH is highly characterized by ALK-1 (Anaplastic Lymphoma Kinase) positivity (approximately 88% of cases) due to various ALK gene fusions.
4:25 Differential for ALK in Skin: Other ALK-positive entities in the skin include certain Spitzoid neoplasms (nevi and melanomas) and, rarely, systemic Anaplastic Large Cell Lymphoma (ALCL) or Inflammatory Myofibroblastic Tumors (IMFTs). Melanocytic markers (S100/SOX10) are used to exclude Spitzoid lesions.
6:44 Classic Cytology: EFH cells are typically plump and epithelioid, embedded in a background of dense, sclerotic, hyalinized collagen.
7:09 Vascular Component: The presence of dilated, ectatic vessels is a common and helpful morphological feature of EFH.
8:22 Variation in Presentation: Examples show that EFH maintains its sharp demarcation even without a prominent collarette, reinforcing the distinctness of the tumor margin.
10:37 Spindled Variants: The morphology can be variable; some EFH examples may be quite spindled and storyform, mimicking regular DF, necessitating the use of the ALK marker for definitive diagnosis.
11:17 Atypical Cytoplasmic Features: Rare variants include lesions with marked vacuolization, foamy, or granular cytoplasm (sometimes simulating granular cell tumor).
12:47 Rare Differentiation: EFH has also been reported to exhibit areas resembling Chondroblastoma (with bean-shaped cells and lace-like matrix) or even well-formed bone and cartilage, expanding the known morphological spectrum.