Epithelioid Fibrous Histiocytoma: Morphology and Clinical Course

Epithelioid fibrous histiocytoma (EFH) is a rare, benign skin tumor arising from fibroblastic and histiocytic cells. While typically indolent, its distinct cellular features can pose diagnostic challenges. Recognizing its presentation and behavior is essential for accurate identification and clinical management.

Morphological Features

EFH exhibits a distinct histological profile, primarily characterized by epithelioid cells with abundant eosinophilic cytoplasm and vesicular nuclei. These cells form cohesive nests or sheets within a collagenous stroma, sometimes mimicking more aggressive neoplasms. Unlike conventional fibrous histiocytomas, which predominantly feature spindle-shaped fibroblastic cells, EFH’s epithelioid morphology sets it apart.

The tumor is typically well-circumscribed, with a pushing border rather than true infiltration. Mitotic activity is low, and necrosis is absent, reinforcing its benign nature. A dense inflammatory infiltrate, often comprising lymphocytes and scattered eosinophils, can obscure tumor cells and create diagnostic confusion with melanocytic lesions and epithelioid sarcoma.

A notable feature is EFH’s perivascular arrangement, with tumor cells clustering around small blood vessels, sometimes resembling vascular tumors. Additionally, stromal hyalinization is often present, further distinguishing EFH from other fibrohistiocytic proliferations.

Typical Sites of Presentation

EFH most commonly arises in the dermis of the extremities, particularly the lower limbs, with the thighs and calves being frequent sites. This distribution aligns with fibrous histiocytomas, which tend to develop in areas exposed to minor trauma or chronic irritation. The upper extremities, including the forearms and hands, are also affected, though less frequently.

Beyond the extremities, EFH can appear on the trunk, particularly the upper back and shoulders. While less common, these locations highlight the tumor’s presence in areas of increased dermal thickness. The face and neck are rare sites of involvement but have been documented, particularly in middle-aged adults. In these regions, EFH may be mistaken for adnexal tumors or basal cell carcinoma due to its nodular growth pattern.

In pediatric and young adult populations, EFH has been observed on the buttocks and periscapular region, suggesting possible age-related variation. Typically presenting as a painless, slow-growing nodule measuring 0.5 to 2 cm in diameter, the lesion’s well-circumscribed nature and lack of ulceration contribute to its benign course, though occasional tenderness or pruritus has been reported.

ALK Protein Involvement

Anaplastic lymphoma kinase (ALK) protein expression is a defining molecular feature of EFH, distinguishing it from other fibrohistiocytic tumors. Immunohistochemical analysis frequently reveals strong cytoplasmic ALK positivity. Unlike ALK-positive malignancies, EFH exhibits a unique ALK gene fusion, most commonly with DCTN1, leading to constitutive ALK expression without aggressive behavior.

Molecular studies confirm the DCTN1-ALK fusion in most cases, with fluorescence in situ hybridization (FISH) and next-generation sequencing supporting its presence. While ALK overexpression plays a role in EFH’s development, the tumor does not exhibit uncontrolled proliferation or invasive growth. The absence of high mitotic activity or cytologic atypia suggests that ALK involvement serves as a diagnostic rather than prognostic marker.

Diagnostic Techniques

Diagnosing EFH requires histopathological evaluation and immunohistochemical profiling to differentiate it from other cutaneous neoplasms. Biopsy specimens typically show a well-circumscribed dermal proliferation of epithelioid cells within a collagenous stroma, often with a perivascular arrangement.

Immunohistochemistry is essential for confirmation, with consistent ALK protein expression distinguishing EFH from conventional fibrous histiocytomas. Additionally, EFH typically expresses CD68 and Factor XIIIa, markers of fibrohistiocytic lineage, while lacking melanocytic markers like S-100 and HMB-45, as well as epithelial markers such as cytokeratin. The absence of INI1 loss further differentiates EFH from epithelioid sarcoma.

Clinical Course

EFH generally follows a benign course, presenting as a slow-growing, painless dermal nodule. Its well-circumscribed nature and low mitotic activity contribute to its indolent behavior, making local excision the preferred treatment. Recurrence is rare, typically occurring in cases of incomplete excision, but regrowth remains localized without aggressive progression. Unlike malignant soft tissue tumors, EFH does not metastasize, reinforcing its favorable prognosis.

Occasionally, EFH may exhibit atypical features such as rapid enlargement or mild tenderness, raising initial concerns for malignancy. These cases often prompt additional histopathological and molecular evaluation. Long-term follow-up is generally unnecessary after complete excision, though patients with unusual presentations may benefit from periodic monitoring. The absence of systemic involvement or distant spread further distinguishes EFH from other ALK-positive neoplasms.