Verruciform Xanthoma

Updated: Nov 07, 2019
  • Author: W Clark Lambert, MD, PhD; Chief Editor: William D James, MD  more...
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Verruciform xanthoma is an uncommon lesion with a predilection for the oral mucosa of middle-aged persons or on the scrotum of middle‒aged-to-elderly Japanese men. The most common site for verruciform xanthoma is the oral mucosa. Extraoral verruciform xanthoma is extremely uncommon; it has been reported on the anogenital skin such as the vulva, scrotum, penis, and extremities. [1, 2] Lesions on the perineum or on the skin often have some predisposing factor, such as lymphedema [3] or an epidermal nevus. [4, 5] Verruciform xanthoma can also occur in association with CHILD (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) syndrome. [6]

Most commonly, the lesion has a verruciform appearance, but it may appear polypoid, papillomatous, or sessile. Rarely, verruciform xanthomas have been found to occur in cysts. The primary distinguishing feature of verruciform xanthoma is the presence of large numbers of lipid-laden foamy histiocytes in, and essentially limited to, the connective-tissue papillae in the lesion.

Note the image below.

Xanthelasma. Courtesy of Duke University Medical C Xanthelasma. Courtesy of Duke University Medical Center.


The pathophysiology of verruciform xanthoma remains unknown.



The etiopathogenesis of verruciform xanthoma remains largely unknown. Many authors consider it a reactive process rather than a true neoplasm. In this respect, it may be analogous to malakoplakia occurring in the urinary bladder and elsewhere. Damage to the squamous cells with increased epithelial cell turnover, leading to the deposition of epithelial cell debris that is engulfed by macrophages in the corium, may lead to the development of this lesion. Rawal et al reported that the histologic changes in verruciform xanthomas resemble those of a chronic reactive process. [7]

An immunologic etiology has also been proposed. Khaskhely et al reported a case of verruciform xanthoma associated with human papillomavirus (HPV). [8] Studies using DNA sequencing technology, however, have been negative for viral signal. It has been proposed that several etiopathogenic mechanisms may produce this disorder. [8, 9]

Ide et al report on the development of verruciform xanthoma related to oxidized low-density lipoprotein, suggesting that macrophage-dependent debris disposal may perpetuate verruciform xanthoma. [10]

Zegarelli et al [11] and Mohsin et al [2] have suggested that an unknown inciting agent, potentially trauma, leads to keratinocyte damage and the release of chemotactic chemokines, which attract neutrophils to the site, facilitating keratinocyte degradation. The necrotic neutrophils and keratinocyte debris are phagocytized by macrophages, leading to the eventual formation of foam cells. Further study is needed. [1]

Ide et al and others have suggested possible oral agents such as a wet microenvironment, periodontal pathogens, mechanical stimuli, tobacco, alcohol, drugs, sensitizing or allergic substances or foodstuffs, and dental materials may play a role. [12, 10] Shahrabi Farahani et al has suggested that the histopathological process might be associated with immunosuppression related to chronic oral inflammatory lesions. [13] Poor oral hygiene may be a risk factor. [14]

There have been at least six cutaneous cases reported of verruciform xanthoma in immunocompromised patients, with a proportion greater than expected considering the low prevalence of cutaneous lesions. A suggested explanation is that immunocompromised patients may have a lower number of epidermal Langerhans cells, which results in decreased removal of degenerated keratinocytes and increased dermal macrophage phagocytosis. [15, 16]




Verruciform xanthoma is uncommon, with a frequency of 0.025-0.095%. [17, 18, 19] To date, at least 300 cases have been reported in the oral cavity, [19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29] seven on the lip, [30, 31, 32] 24 on the penis, [1, 2, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54] 20 on the vulva, [40, 55, 56, 57, 58, 59, 60, 61, 62, 63] one in the anal region, [64] three on the nose or nasal vestibule, [65, 66] two on the ear, [67] four on the distal extremities (including three on the feet), [68] and individual cases elsewhere on the skin. At least 23 cases have been reported on the scrotum, almost all of them in Japanese men. [69, 70, 71] Three cases of esophageal verruciform xanthoma have been reported. [40, 72, 73, 74] A single case of multiple verruciform xanthoma lesions has been reported in internal organs; the lesions were in the upper aerodigestive tract of a child with a systemic lipid storage disease. [75]


Most cases of verruciform xanthoma are reported in whites, but blacks are also affected. [76] Most scrotal cases of verruciform xanthoma occur in middle‒aged-to-elderly Japanese men. This may be caused by chronic pressure associated with the Japanese tradition of sitting on the floor. [70]


Verruciform xanthoma has a slight male predominance, [17, 12] and it also has a tendency to occur on the scrotum of middle‒aged-to-elderly Japanese men.


Most oral cases of verruciform xanthoma occur in middle-aged persons (mean age, 40-60 y), and most scrotal cases occur in middle‒aged-to-elderly Japanese men (mean age, 65 y). However, the age at occurrence varies widely; verruciform xanthoma can occur in persons aged 2.5-89 years. [62]

Verruciform xanthoma is exceedingly rare in children aged 10 years or younger, except in epidermal nevi or in the context of CHILD syndrome.



The prognosis for verruciform xanthoma is excellent after local surgical excision, and verruciform xanthoma typically does not require medical, chemical, or radiological treatment after surgery. [77] Recurrence is rare.


Patient Education

Patients should be reassured after adequate excision and accurate diagnosis that verruciform xanthoma is cured.