Acyclovir-Resistant Anogenital Herpes Simplex Virus in an HIV Patient With Pseudoepitheliomatous Hyperplasia Resembling Squamous Cell Carcinoma.

Background: Herpes simplex virus (HSV) is a common infection. However, it may present atypically when patients are immunocompromised, such as with slowly expanding, long-lasting ulcerative or hypertrophic lesions. The histopathologic finding of pseudoepitheliomatous hyperplasia (PEH) can occur in a variety of situations where there is chronic inflammation and can be seen in patients with chronic HSV. Atypical presentations of HSV, particularly hypertrophic lesions with histopathologic findings of PEH, can be misinterpreted as squamous cell carcinoma, create difficulty in diagnosis and hinder appropriate treatment. Case Description: We report a case of a 59-year-old female with a past medical history of human immunodeficiency virus (HIV), who presented at a dermatology clinic with multiple exophytic ulcerations of varying sizes in the perianal region. The patient was diagnosed with HSV and was started on valacyclovir. Over a several-year period, the patient had multiple recurrences of her HSV lesions with persistent vulvodynia despite prophylactic treatment with valacyclovir. Specimens were collected for culture and sensitivities, which revealed acyclovir resistance. The patient's lesions were biopsied due to concern for possible malignancy. Biopsies revealed prominent PEH. The patient had improvement of her HSV with saucerization, topical imiquimod, and increased doses of prophylactic valacyclovir. Conclusion: Atypical, chronic presentations of HSV are common in immunocompromised patients. Hypertrophic HSV is the least common clinical presentation and can be mistaken for squamous cell carcinoma, creating difficulty in diagnosis. Due to concerns for malignancy, our patient's lesions were biopsied, which revealed prominent PEH. While PEH is benign, it can be misdiagnosed as squamous cell carcinoma on histopathology, particularly when there is clinical suspicion for malignancy. In these cases, the clinician needs to alert the pathologist to the immunosuppressed status of the patient. Detailed evaluation for infectious causes, such as HSV, can avoid misinterpretation and potential surgical and oncological overtreatment.