Ⅰ. INTRODUCTION

Oral verruciform xanthoma (OVX) is a rare benign lesion with unknown etiology, characterized by the presence of xanthoma cells within the connective tissue papilla with epithelial hyperplasia.¹⁾ OVX clinically presents as an asymptomatic, well-defined lesion with a verrucous or granular surface. Due to its clinical appearance, OVX needs to be distinguished from other lesions with papillary or verrucous surfaces, such as squamous papilloma, condyloma acuminatum, verrucous leukoplakia, verrucous carcinoma, and squamous cell carcinoma. The etiology of OVX is still unknown. Local trauma, inflammation, an altered immunologic response of the mucosa, or candida infection have been proposed as possible etiologic factors.²⁾ In this study, we retrospectively reviewed twenty-one patients diagnosed with OVX. This study aimed to define the clinicopathological characteristics of OVX and to review the relevant literature.

Ⅱ. MATERIAL and METHODS

A total of 21 patients diagnosed with OVX were retrieved from the archives of the Department of Oral and Maxillofacial Pathology, Dajeon Dental Hospital, College of Dentistry, Wonkwang University, from 2015 to 2023. In all cases, the diagnosis of OVX was established by examining H&E-stained slides. Clinical data, including patients’ age, sex, medical history, location of the lesion, treatment, and duration of follow-up, were retrospectively collected. Periodic acid-Schiff (PAS) staining and immunohistochemistry (IHC) were performed using archived formalin-fixed paraffin-embedded blocks. Antibodies against CD1a (1:1000, Cell signaling, US), CD68 (1:1000, Cell signaling), and S-100 (1:1000, Cell signaling) were used for IHC. Clinicopathological and immunohistochemical findings were analyzed descriptively.

Ⅲ. RESULTS

This study included 13 males and 8 females (M: F=1.6:1) with a mean age of 52 years (Table 1). Three patients had a medical history of hyperlipidemia, pituitary tumor, and lymphoma, respectively, while the other patients had no significant medical history. All patients reported the lesions as asymptomatic. The most affected site was the gingiva (Figure 1a), followed by the hard palate, tongue, and mandibular vestibule. Most lesions presented as a solitary lesion, while only one exhibited multiple papules on the hard palate (Figure 1b). All solitary lesions were surgically excised, and no recurrences were observed during an average follow- up period of 68.7 months (range 30 to 81 months). In the case of multiple lesions, some papules were excised for biopsy, and the remaining lesions were left untreated. During the 34-month follow-up period, there was no recurrence or change in the untreated lesions. Microscopically, the characteristic features of OVX were observed in all specimens. Verrucous epithelial hyperplasia with parakeratin plug were observed, and the rete ridges elongated to a relatively uniform depth (Figure 2a). Connective tissue papillae contained the foamy macrophages (xanthoma cells) (Figure 2a). PAS-positive granules were detected in the cytoplasm of xanthoma cells in 14 specimens (66%) (Figure 2c), and there was no evidence of Candida infection in PAS staining. Immunohistochemistry revealed the positivity of xanthoma cells for CD68 (Figure 2d), while they were negative for CD1a and S-100 (not shown here) in all specimens.

Ⅳ. DISCUSSION

OVX mainly affects the masticatory mucosa including the gingiva and palate. It is more common in middle-aged male patients, but it can develop at any age. Similar gender predilection, average age, and the distribution of the lesions are found in this study.^3,4)

Clinically, the majority of OVX are misdiagnosed as squamous papilloma, verrucous leukoplakia, verrucous carcinoma, or squamous cell carcinoma.⁵⁾ Therefore, OVX should be diagnosed based on microscopic examination. The collection of xanthoma cells in the connective tissue papilla with verrucous epithelial hyperplasia is a pathognomonic feature of OVX. The presence of xanthoma cells is highlighted by CD68 positivity in immunohistochemistry. Xanthoma cells in OVX are known to contain PAS-positive granules.^6,7) Fourteen of 21 (66%) specimens have shown PAS-positive granules in this study. Xanthoma cells also stain positively with PAS-diastase⁷⁾, suggesting that the PAS-positive material in the xanthoma cells is not glycogen.

Most OVXs are solitary, but multiple lesions have rarely been described. According to the systematic search using PubMed/MEDLINE and Google Scholar, five cases of multiple OVX were identified (Table 2).^8-12) Multiple OVX affected four males and one female with a mean age of 34.2 years. Three patients had graft-versus-host disease (GVHD), implying that GVHD may contribute to the development of multiple OVX. Regardless of whether it is solitary or multiple OVX, it has occasionally been reported to occur in association with lupus erythematosus, pemphigus vulgaris, and lichen planus as well as GHVD.¹³⁾ It can be inferred that epithelial damage induced by immune-mediated diseases of oral cavity may result in the breakdown of the phospholipid of cell membranes. As a result, lipid materials are released and phagocytized by subepithelial macrophages.

Most cases of multiple OVX were treated with surgical excision. In one patient with more than 50 papules¹⁰⁾, some lesions were treated with cryotherapy while others were left untreated according to the patient’s request. The treatment and prognosis of multiple OVX are similar to those of solitary OVX.