HIV-associated Hypertrophic Herpes Simplex Genitalis With Concomitant Early Invasive Squamous Cell Carcinoma Mimicking Advanced Genital Cancer

Abstract

Hypertrophic herpes simplex genitalis (HHSG) is an uncommon anogenital manifestation of herpes simplex virus (HSV) infection in immunocompromised patients. To date, 24 cases of HHSG have been reported; 23 of them were affected human immune deficiency virus (HIV) type 1-positive patients. We describe the case of a 44-year-old African HIV-1-positive woman who presented with painful ulcerated nodular lesions of the vulva and perianal area measuring up to 7 cm in diameter. Macroscopically, the lesions were highly suspicious of widely invasive cancer. The histologic workup of the resection specimen revealed patchy high-grade vulvar intraepithelial neoplasia Grade 3 (VIN 3) and 2 microscopic foci of superficially invasive squamous cell carcinoma. The nodular lesions were caused by massive tumefactive plasma cell-rich inflammatory infiltrates extending into the subcutis. Multinucleated herpes simplex virus 1 and herpes simplex virus 2-positive epithelial cells with glassy intranuclear inclusions were detected at the borders of the ulcerations, consistent with HHSG. Despite repeated surgery and medical treatment, the patient had 3 recurrences of HHSG within 18 months. The presence of intraepithelial neoplasia in HHSG lesions is relatively rare and has been described in 6 of 18 resected HHSG lesions in the literature so far. With regard to invasive malignancy, the present case is the first report of a superficially invasive squamous cell carcinoma associated with HHSG. Awareness of this condition is necessary to avoid misinterpretation of HHSG as widely invasive squamous cell carcinoma with the hazard of surgical and oncological overtreatment.

Successful treatment of hypertrophic herpes simplex genitalis in HIV‐infected patient with topical imiquimod

“…2 This atypical presentation could be a diagnostic challenge and different disorders causing verrucous anogenital lesions in immunocompromised patients such as giant condyloma acuminatum (Buschke-L€ owenstein tumor), secondary syphilis, mycobacterial infections or even tumoral lesions (squamous cell carcinoma, lymphoma) should be ruled out.…”

Manifestações Clínicas Atípicas de Infeção Genital pelos Vírus Herpes Simplex e sua Abordagem Terapêutica

“…9 O exame histopatológico de biópsias cutâneas é importante para o diagnóstico diferencial e identifica hiperplasia pseudo-epiteliomatosa, células gigantes multinucleadas e um denso infiltrado de linfócitos e plasmóci-tos. 10 Contudo, a sua interpretação é por vezes complexa, dado que as alterações citopáticas herpéticas podem estar obscurecidas por um denso infiltrado inflamatório.…”

“…11 Por vezes, os dois diagnósticos co-existem, sendo identificados focos de tecido neoplásico num substrato de lesão herpética hipertrófica. 10 Outros diagnósticos diferenciais a considerar incluem condilomas acuminados gigantes (tumor de Buschke Lowenstein), lesões de sífilis secundária (condylomata lata), co-infeção pelos vírus herpes zoster ou citomegalovírus (CMV) e molusco contagioso. 6 A terapêutica nos indivíduos com apresentações atí-picas de infeção herpética é complexa, particularmente na presença de seropositividade para VIH, requerendo maior tempo de tratamento e estando associada a uma importante taxa de resistência aos fármacos anti-virais comumente utilizados.…”

“…17,18 Outras opções terapêuticas reportadas como eficazes em lesões herpéticas hipertróficas refratárias incluem a talidomida, o interferão gamma (IFN-γ) e a excisão cirúrgi-ca, particularmente se tiverem grandes dimensões. 10,19 A taxa de recorrência nos doentes com apresentação atípica de infeção pelo VHS é elevada, pelo que após a resolução das lesões é recomendável a administração profilática de terapêutica anti-viral, nas seguintes posologias: aciclovir 400 mg per os, bid-tid, ou valaciclovir 500 mg per os, bid. 13,20 A utilização destes fármacos mantém-se pertinente na presença de infeção prévia por estirpe de VHS resistente aos mesmos, na medida em que alguns trabalhos referem reversão da resistência após terapêutica com cidofovir.…”

Clinico-Epidemiological Profile of Viral Sexually Transmitted Infections in Seropositive Patients Attending a Tertiary Care Hospital in North India

“…[25][26][27][28] The hypertrophic form may in fact mimic early squamous cell carcinoma and may be mistreated. 29 The herpetic ulcers in seropositive patients were significantly less responsive to treatment and had more frequent recurrences than seronegative patients. Increased risk of acyclovir resistance in seropositive patients has also been well reported in the literature.…”