Verruciform Xanthoma: Disease Entity or Histopathologic Reaction Pattern?

Dear Editor, Minor tissue reaction patterns like cornoid lamellation, acantholytic dyskeratosis, and flame figures were initially thought to be specifically related to a distinct disorder or particular disease group, but later were seen in many diverse diseases. Similarly, verruciform xanthoma (VX) has been traditionally described as a distinct benign lesion of the mucocutaneous surfaces. However, accumulating clinicopathological observations suggest that it may be better interpreted as a histopathologic reaction pattern rather than a discrete disease entity. Similar xanthomatous changes with accumulation of lipid-laden macrophages within the connective tissue papillae have been described in association with a variety of disorders, including lichen planus, pemphigus vulgaris, graft-versus-host disease, epithelial nevi, dystrophic epidermolysis bullosa, and mycosis fungoides, to name a few.[1,2] These observations support the hypothesis that epithelial damage and degeneration may lead to the release of lipid material that is subsequently scavenged by macrophages in the papillary dermis or lamina propria, producing the characteristic foam cell aggregates as seen in VX. A 36-year-old male presented with an asymptomatic whitish lesion on the mucosal aspect of the lower lip on the right side for the past 6 months. There was no history of cigarette smoking, tobacco chewing, or any oral–genital sexual activity by the patient. On examination, there was a solitary raised verrucous plaque of approximately 2 cm on the lower mucosal aspect of the lower lip on the right side. The lesion appeared firm and nontender on palpation [Figure 1]. No lymph node enlargement or any other significant examination findings were detected.Figure 1: Solitary white verrucous plaque over the mucosal aspect of the lower lipBiopsy revealed a moderate psoriasiform hyperplasia of epithelium with parakeratosis on the surface. There was a widening of connective tissue papillae, which were stuffed with several foamy macrophages. Occasional mitotic figures were seen in the basal layer. A moderately dense superficial perivascular and patchy lichenoid infiltrate of lymphocytes, few neutrophils, and foamy macrophages in the subepithelial connective tissue was noted [Figure 2A and B]. Based on a clinicopathological correlation, a final diagnosis of VX was rendered.Figure 2: (A) Epithelial hyperplasia with accumulation of foamy macrophages in subepithelial connective tissue along with chronic inflammation (hematoxylin and eosin [H&E], ×100). (B) High power view showing foamy macrophages (black arrows; H&E, ×400)Etiopathogenesis of VX is still controversial. Initially, human papillomavirus (HPV) was implicated as a causative factor; however, many studies do not show HPV presence in VX.[1] One reported case was associated with HPV type 6.[3] Other etiologic factors that have been hypothesized include local trauma, Candida infection, autoimmune inflammatory conditions, pre-malignant, and malignant conditions. While the exact pathogenesis of the occurrence of foamy cells in the connective tissue papillae is not known, it is well known that these foamy cells are of monocyte–macrophage lineage due to their positivity for CD68 marker, and they contain keratinocyte-derived lipid, as supported by immunohistochemical and ultrastructural techniques. Local trauma/irritation or inflammation causes epithelial damage followed by the release of debris in subepithelial connective tissue, which attracts dermal dendrocytes, and they engulf this material and transform into foamy macrophages due to the ingestion of lipids from the degenerating epithelial cells.[4] The epithelial hyperplasia seen in VX has been considered an illusion due to upward pushing and proliferation of foamy macrophages in the subepithelial connective tissue, and there is no actual hyperplasia as proposed by Mostafa et al.[5] However, other workers, like Nowparast et al.[6] and Travis et al.,[7] believe that epithelial hyperplasia is directly induced by the proliferation/accumulation of foamy macrophages. Hegde et al.[8] suggest that the epithelial hyperplasia is due to cytokines released by T lymphocytes, which are a part of chronic local inflammation. We reinforce the fact that recognition of this minor tissue reaction pattern is important for dermatopathologists and clinicians alike, as it underscores that the presence of VX-like change does not necessarily represent a distinct primary disease but may instead reflect an epithelial response to chronic mucosal injury or inflammation. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.