Fat-free pleomorphic lipoma of the buccal mucosa: An immunohistochemical study and literature review

•Careful morphological analysis is recommended to avoid misdiagnosis.•Low-fat and fat-free variants of PL have no prognostic relevance.•Conservative surgical excision is the treatment of choice and recurrence is uncommon. Pleomorphic lipomas are extremely rare in the oral cavity. Due to the significant overlap of morphological findings with several benign and malignant soft tissue tumors, especially in the absence of adipocytes, the diagnosis is challenging. We reported the clinicopathological and immunohistochemical features of an uncommon case of a fat‐free variant of pleomorphic lipoma in a 48-year-old female presenting clinically as a painless nodule on the buccal mucosa. Microscopically, the lesion showed atypical spindle cells, numerous floret-like giant multinucleated cells, and abundant ropey collagen fibers bundles. Immunohistochemistry showed strong positivity for vimentin and CD34. Mast cell tryptase highlighted numerous mast cells distributed throughout all tumor stroma. S-100 protein, pan-cytokeratin, desmin, α-SMA, EMA, CD68, STAT6, Bcl-2, MDM2, and CDK4 were negative. Conservative surgical excision was carried out, and no recurrence was observed after 13 months of follow‐up. Careful histopathological and immunohistochemistry analysis of these lesions is recommended to ensure the correct diagnosis and provide adequate management through a conservative surgical approach. To the best of our knowledge, this is the second case of fat‐free pleomorphic lipoma in the oral cavity.