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Case Reports

Abstract

Li-Fraumeni syndrome (LFS) is a rare hereditary cancer predisposition syndrome associated with germline TP53 mutations and a wide spectrum of malignancies. Cutaneous manifestations in LFS are uncommon and poorly characterized. We report two cases of atypical smooth muscle neoplasms presenting in patients with confirmed LFS. The first patient is a 36-year-old woman with a history of high-grade serous ovarian carcinoma and papillary thyroid carcinoma, and the second is a 35-year-old man with a history of colon adenocarcinoma. Both presented with slow-growing, firm, skin-colored plaques on the lower extremities. Histopathologic examination revealed dermal proliferation of spindle cells arranged in fascicles and nodular aggregates. The cells exhibited elongated, cigar-shaped nuclei and peri-nuclear halos, without significant pleomorphism or necrosis. Some of the lesional cells demonstrated cytologic atypia. Immunohistochemical stains showed diffuse strong positivity for smooth muscle actin and desmin, confirming smooth muscle differentiation. Increased cellular proliferation was further supported by PHH3 staining in the first case and Ki-67 staining in the second. Both lesions were re-excised to ensure complete removal. The occurrence of atypical smooth muscle neoplasms in LFS patients may support a role for TP53 loss in the etiology of these lesions. Given the uncertain potential for malignant transformation and rare reports of cutaneous leiomyosarcomas in patients with LFS, recognition of these lesions in the context of LFS is critical for appropriate clinical management and surveillance. To our knowledge, these represent rare and underreported presentations of smooth muscle neoplasms in LFS, warranting further investigation into their biologic behavior and molecular profile.