Letters to the Editor
To the Editor:
We read with interest the authoritative study by Zayour and Lazova1 on pseudoepitheliomatous hyperplasia (PEH) published in the April issue. In their review, the authors describe the diverse conditions associated with PEH under the headings of infections, neoplasia, dermatosis with chronic inflammation and irritation, and miscellaneous processes.
An interesting condition not mentioned by the authors is verrucciform xanthoma (VX). PEH can be exophytic (verrucoid epidermal hyperplasia) or endophytic (invasive acanthosis). Thus, VX can be classified as a kind of verrucoid epidermal hyperplasia. VX is an uncommon, benign, mucocutaneos, nondestructive lesion that can mimic verrucous carcinoma or squamous cell carcinoma both clinically and histopathologically.2,3 Furthermore, the lesion can recur.4
The lesion may be verrucous, papillary, and flat in type5 and has a typical rough and granular surface. This entity is most frequently located in the oral mucosa but has also been described in other mucocutaneous locations including penis, scrotum, anal region, extremities, digits, axilla, neck, nose, lips, larynx, glottis, epiglottis, and esophagus.6 This lesion is commonly solitary but may be multifocal. It is usually sporadic and can be associated with acquired or congenital lesions such as lichen planus, lichen sclerosus, warty dyskeratoma, epidermal nevi, pemphigus vulgaris, recessive epidermolysis bullosa, in situ or invasive squamous cell carcinoma, discoid lupus erithematosus, psoriasis under PUVA therapy, odontogenic keratocyst, arteriovenous hemangioma, lymphedema, graft versus host disease, CHILD (congenital hemidysplasia, ichthyosiform erythroderma, and limb defect) syndrome, nevus syndrome, and systemic lipid storage disease.6
VX etiology is unknown, but several inciting agents, including cutaneous trauma,7 could play a role. Mohsin et al8 proposed that chemotactic factors released from damaged squamous cells attract neutrophils toward the intraepithelial compartment. These cells induce keratinolysis and disintegration of the lipid components of membranes, which leads to the appearance of lipid-laden macrophages in the adjacent dermis.
It is commonly believed that VX is an unusual reaction pattern, rather than a specific lesion, present exclusively in organs lined by stratified squamous epithelium.
We recently observed a case that exemplifies the features of this process. A 65-year-old man consulted for a verrucous scrotum lesion that had gradually increased in size. Physical examination revealed a reddish verrucous pedunculated lesion measuring 1 cm in its larger diameter. The histopathologic features of the lesion included regular acanthosis, in which the rete pegs extended to a uniform level into the dermis. Hyperkeratosis with parakeratosis often extended deep into these rete pegs (Fig. 1). There was an intense neutrophilic infiltrate of the acanthotic epidermis and groups of CD68+ xanthoma cells restricted to the papillary dermis mixed with other chronic inflammatory cells (Fig. 2). The neutrophilic infiltrate was predominant in the upper third of the epidermis. There was no evidence of cytologic atypia.
Two hallmark features of VX present in our case were the intraepithelial neutrophilic infiltrate and the significant groups of xanthoma cells restricted to the papillary dermis. These 2 indicated hallmarks are helpful diagnostic features. However, in a small and superficial biopsy, xanthoma cells may be scant and can be missed.
In conclusion, VX is a chronic reactive process that must be differentiated from diverse epidermal, hyperplastic lesions. The pathological recognition and correct diagnosis is important because VX may occur associated with other cutaneous and systemic lesions and may mimic verrucous carcinoma.
1. Zayour M, Lazova R. Pseudoepitheliomatous hyperplasia: A review. Am J Dermatopathol. 2011;33:112–126.
2. Takiwaki H, Yokota M, Ahsan K, et al.. Squamous cell carcinoma associated with verruciform xanthoma of the penis. Am J Dermatopathol. 1996;18:551–554.
3. Mannes KD, Dekle CL, Requena L, et al.. Verruciform xanthoma associated with squamous cell carcinoma. Am J Dermatopathol. 1999;21:66–69.
4. Reich O, Regauer S. Recurrent verruciform xanthoma of the vulva. Int J Gynecol Pathol. 2003;23:75–77.
5. Yu CH, Tsai TC, Wang JT, et al.. Oral verruciform xanthoma: a clinicopathologic study of 15 cases. J Formos Med Assoc. 2007;106:141–147.
6. Herrera-Goepfert R, Lizano-Soberón M, Garcia-Perales M. Verruciform xanthoma of the esophagus. Hum Pathol. 2003;34:814–815.
7. Cumberland L, Dana A, Resh B, et al.. Verruciform xanthoma in the setting of cutaneous trauma and chronic inflammation: report of a patient and a brief review of the literature. J Cutan Pathol. 2010;37:895–900.
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8. Mohsin SK, Lee MW, Amin MB, et al.. Cutaneous verruciform xanthoma: a report of five cases investigating the etiology and nature of xanthomatous cells. Am J Surg Pathol. 1998;22:479–487.