Angiomatoid fibrous histiocytoma with CDK4 and MDM2 expression misdiagnosed as dedifferentiated liposarcoma: The first case report and literature review.

Abstract

Angiomatoid fibrous histiocytoma is a rare intermediate soft tissue tumor with uncertain differentiation and prone to misdiagnosis because of atypical morphology and aberrant biomarker expression. Herein, we report a unique case of occipital scalp angiomatoid fibrous histiocytoma in a 33-year-old female, which presented with rapid tumor growth, marked nuclear pleomorphism, elevated mitotic activity, and atypical positive expression of CDK4 and MDM2 immunohistochemically, leading to an initial misdiagnosis of dedifferentiated liposarcoma. Preoperative routine blood tests, biochemical examinations, and inflammatory biomarker detection, including C-reactive protein, erythrocyte sedimentation rate, and interleukin-6, were performed, and all hematological indicators were within normal reference ranges without systemic inflammatory or hematological abnormalities. The patient underwent complete marginal resection of the tumor, and no adjuvant radiotherapy or chemotherapy was administered postoperatively because of the absence of high-risk malignant features, residual lesions, and distant metastasis. Molecular testing confirmed EWSR1 gene rearrangement without CDK4 or MDM2 gene amplification, which confirmed the final diagnosis of angiomatoid fibrous histiocytoma. The patient achieved a favorable prognosis with no recurrence or metastasis during 20 months of postoperative follow-up. Distinct from previously reported conventional angiomatoid fibrous histiocytoma cases with low proliferative activity and negative liposarcoma-related markers, the present case is characterized by atypical dual positive expression of CDK4/MDM2 and a markedly elevated Ki-67 proliferation index, which fills the clinical data gap of atypical angiomatoid fibrous histiocytoma with liposarcoma-mimicking immunophenotype. This study further clarifies the differential diagnostic criteria between angiomatoid fibrous histiocytoma and dedifferentiated liposarcoma, verifies that isolated CDK4/MDM2 immunohistochemical positivity cannot independently support the diagnosis of liposarcoma, and highlights the irreplaceable value of molecular testing in the definitive diagnosis of atypical angiomatoid fibrous histiocytoma, providing a reliable reference for pathologists to avoid diagnostic errors in similar rare soft tissue tumors.