a, VX presenting as a red plaque with a granular surface on the gingiva mesio-palatal to a maxillary molar. (Courtesy of Dr. Benoît Lalonde). b, High-power view of a VX demonstrating the collections of foamy macrophages in the connective tissue papillae, papillomatosis and orange hyperparakeratosis (original magnification × 200, Hematoxylin & eosin) (Courtesy of Dr. Adel Kauzman) (from Non-HPV Papillary Lesions of the Oral Mucosa: Clinical and Histopathologic Features of Reactive and Neoplastic Conditions)
VX is an uncommon benign mucocutaneous lesion of unknown etiology, characterized by the presence of numerous lipid-laden histiocytes below the epithelium. The oral cavity is the site of predilection, but genital lesions have also been reported. Case series with more than ten patients have shown a slight male predilection and an average age at diagnosis between 45 and 53 years. Several etiologic factors have been proposed, including trauma, inflammation, an altered immunological response, epithelial degeneration and lipid accumulation. Contrary to other dermal xanthomas (such as xanthelasma palpebrarum) that can signalize dyslipidemia, atherothrombotic disease or type II diabetes, there is no such association with VX. Interestingly, VX is part of CHILD syndrome, a trait caused by mutations in the NSDHL gene involved in the cholesterol biosynthetic pathway. Although VX is a papillary lesion, HPV has only been detected in a few instances and no definitive viral cause has been recognized.
VX appears as a well-demarcated, painless, slow-growing, plaque or nodule with a verrucous or granular surface. The color can range from yellow, pink, white or red. The size of the lesion rarely exceeds 2 cm in diameter. The majority of cases occur on the masticatory mucosa (attached gingiva and hard palate). Other oral mucosal sites are less commonly affected. Clinically, VX is often mistaken for a squamous papilloma, verruca vulgaris, condyloma, leukoplakia and occasionally for early verrucous carcinoma or OSCC. Most lesions are excised and diagnosed microscopically.
The histological features of VX are similar for all lesions. They include a papillary proliferation of stratified squamous epithelium associated with hyperparakeratosis. The thick parakeratin layer tends to have a noticeable salmon or orange color when stained with hematoxylin and eosin and extends into the epithelial crypts to form parakeratin plugs. The rete ridges are uniformly elongated. The outstanding characteristic feature of VX is the presence of numerous foamy lipid-laden histiocytes (xanthoma-like cells) within the connective tissue papillae. These foamy cells do not extend below the tips of the rete ridges. They show cytoplasmic immunopositivity for CD69, CD63 and CD163. A moderate chronic inflammatory infiltrate is dispersed in the underlying connective tissue.
VX is treated by conservative surgical excision. The prognosis is excellent. There are no reports of VX undergoing malignant transformation.