Recurrent fungating tumor and a chronic rash in an immunosuppressed transgender patient: a case of Buschke-Lowenstein condyloma and epidermodysplasia verruciformis.

A transgender female in her 40s with history of HIV and testicular cancer status post-genital X-irradiation presented with a perianal mass and pruritic rash across her chest. Physical examination revealed a bulky, verrucous tumor protruding outward from the anus involving the medial buttocks. Examination of the chest and arms showed numerous guttate, pink, flat-topped papules coalescing into plaques. Clinically and histologically the lesions were consistent with Buschke-Löwenstein condyloma (BLC) and acquired epidermodysplasia verruciformis (AEDV). Buschke-Löwenstein condyloma incisional biopsy tested negative for common low- and high-risk human papillomavirus (HPV) subtypes, including 6, 11, 16, and 18, possibly implicating beta HPV subtype or a less common pathogenic subtype. The patient underwent abdominoperineal resection of the BLC, which tested positive for low-risk HPV subtypes, suggesting the possibility of multiple implicated HPV subtypes in the same tumor. This case demonstrates a possible role of beta HPV or rarer HPV subtypes in the pathogenesis of verrucous carcinoma, particularly in the setting of immunosuppression.

Epidermodisplasia verruciforme / Epidermodysplasia verruciformis

La epidermodisplasia verruciforme (EV) es una genodermatosis rara, caracterizada por el desarrollo de verrugas planas y lesiones similares a pitiriasis versicolor, asociada a infección crónica por Virus Papiloma Humano. Se reporta el caso de EV. Mujer de 49 años con múltiples lesiones verrucosas de larga evolución distribuidas en las cuatro extremidades y antecedente familiar de cuadro similar. Biopsia a los 19 años evidenció verrugas sin atipia. Nuevo estudio histológico informó carcinoma escamoso, decidiéndose extirpación de lesiones. La clínica inicia en edades tempranas, con elevado riesgo de transformación maligna. No existe tratamiento específico. Es esencial la fotoprotección estricta y manejo precoz de lesiones para prevención de progresión a carcinoma.

Epidermodysplasia verruciformis (EV) is a rare genodermatosis, characterized by the development of plane warts and pityriasis versicolor-like lesions, associated with chronic infection caused by the Human Papilloma virus. An EV case is reported. 49 year-old woman with multiple long standing warty lesions distributed on the four limbs and family background of similar cases. Biopsy at 19 years old evidenced warts without atypia. New histological study reported squamous cell carcinoma, deciding the removal of the lesions. The clinic begins at early age, with high risk of malignant transformation. There is no specific treatment. Strict photoprotection and early management of the lesions is essential to prevent the progression to carcinoma.

Clinical presentation of tuberculoid leprosy in an epidermodysplasia verruciformis patient.

Epidermodysplasia verruciformis (EV) is triggered by a variety of mechanisms that at least partly include genetic background. We present a Brazilian man with a 30-year history of flat, wart-like lesions with clinical, histopathological, and evolutive aspects consistent with papillomavirus (HPV)-associated EV. Histological analysis of the wart lesions showed epidermis with hyperkeratosis, regular acanthosis, hypergranulosis, and cells with abundant basophilic cytoplasm. Moreover, a perivascular lymphocytic infiltrate was found in the superficial dermis, consistent with a viral wart. Type-2-HPV DNA was detected in various fragments of skin-wart lesions using the polymerase chain reaction (PCR). Two years after the EV diagnosis, the patient presented with an anesthetic well-demarcated, erythematous and mildly scaly plaque on his right forearm. A histopathological analysis of this lesion demonstrated the presence of a compact tuberculoid granuloma. Ziehl-Neelsen staining demonstrated the presence of rare acid-fast bacilli and confirmed the tuberculoid leprosy diagnosis. The patient's Mitsuda Intradermal Reaction was positive. To elucidate the possible mechanism involved in this case of EV, we genotyped the HLA genes of this patient. DQB genotyping showed the polymorphic HLA alleles DQB1*0301 and 0501. The patient was treated with a paucibacillary multi-drug therapy scheme, and the disease was cured in six months. This report describes an EV patient with an M. leprae infection, confirming that tuberculoid leprosy patients possess a relatively specific and efficient cell-mediated immunity against the bacillus and, therefore, localized forms of the disease. Moreover, we show the possible involvement of the polymorphic HLA alleles DQB1*0301 and 0501 in EV induction mechanisms.

Epidermodysplasia verruciformis: clinical presentation with varied forms of lesions.

Epidermodysplasia verruciformis is a rare inherited skin disorder spread by HPV, with cases linked to chromosome X. It is characterized by hypo- or hyper-pigmented macular lesions, pityriasis versicolor-like lesions and an early tendency to develop skin malignancies. We present a case of epidermodysplasia verruciformis with a variety of lesions such as multiple plane warts, pityriasis versicolor-like lesions and aggressive squamous cell carcinoma on the face.

Epidermodisplasia verruciforme: apresentação clínica com variadas formas de lesões / Epidermodysplasia verruciformis: clinical presentation with varied forms of lesions

Epidermodisplasia verruciforme é uma genodermatose rara caracterizada por infecção disseminada por HPV, de caráter recessivo, com casos ligados ao cromossoma X. É caracterizada clinicamente por lesões maculares hipo ou hiperpigmentadas, lesões pitiríase versicolor like, verrugas planas e desenvolvimento precoce de carcinomas cutâneos. Descreve-se um caso de paciente com quadro clínico exuberante, apresentando todas as formas de lesões desta doença, inclusive presença de carcinoma espinocelular agressivo na face.

Epidermodysplasia verruciformis is a rare inherited skin disorder spread by HPV, with cases linked to chromosome X. It is characterized by hypo- or hyper-pigmented macular lesions, pityriasis versicolor-like lesions and an early tendency to develop skin malignancies. We present a case of epidermodysplasia verruciformis with a variety of lesions such as multiple plane warts, pityriasis versicolor-like lesions and aggressive squamous cell carcinoma on the face.

Strong inverse correlation between microRNA-125b and human papillomavirus DNA in productive infection.

Infection by the human papillomavirus (HPV) is a cause of cervical intraepithelial neoplasia (CIN) and cancer. microRNA (miRNA) in situ analysis of the transformation zone epithelia, the site of initial cervical HPV infection, showed that miRNAs let-7c, -99a, 26a, and 125b were the most abundantly expressed. In situ testing of CIN 1 showed a dramatic reduction in miR-125b expression in the koilocytes, the cytologic marker of productive HPV infection. A marked reduction in miR-125b was likewise observed in the HPV-infected cells of the condyloma acuminatum, verruca vulgaris, and epidermodysplasia verruciformis. Reverse transcriptase in situ polymerase chain reaction (PCR) showed that the pre-miRNA 125b was present in the koilocyte, suggesting direct inactivation of the mature miRNA. HEK cells transfected with only the antimiR-125b showed perinuclear halos equivalent to HPV-infected koilocytes. NIH 3T3 cells transfected with the HPV 16 full-length genome and mimetic miR-125b showed a marked reduction in viral DNA and protein synthesis by quantitative PCR and in situ-based analyses, respectively (P=0.002). Alternatively, cotransfection with anti-miR-125b and HPV 16 markedly increased HPV DNA (P=0.002). Sequence analyses showed strong homology between L2 of different HPV genotypes and miR-125b. Transfection with HPV 16 L2 resulted in a marked reduction in miR-125b levels in the NIH 3T3 cells. HPV L2-induced inactivation of miR-125b is associated with the classic cytologic changes of the koilocyte, and the exogenous application of mimetic miR-125b markedly inhibits HPV DNA synthesis.

Post-ART epidermodysplasia verruciformis in a patient with AIDS.

Epidermodysplasia verruciformis (EV) is a rare disorder characterized by persistent human papillomavirus (HPV) infection. Here, we describe a 48-year-old, black, married male with AIDS, presenting a 1-year history of asymptomatic hypopigmented lesions that appeared 3 years after antiretroviral therapy (ART) initiation. Pre-ART, the initial CD4 count was 32 cells/mm(3) and the skin lesions appeared when the CD4 count reached 122 cells/mm(3). Dermatological examination demonstrated thin, scaly, slightly verrucous hypopigmented macules and papules, isolated or presenting with a linear aspect (Köbner phenomenon) in some areas, distributed on the neck, trunk, and superior and inferior members. Skin biopsy of a macular lesion revealed epidermal acanthosis with vacuolated keratinocytes presenting blue-gray pallor, arranged in clusters at the granular and upper spinous layer. Immunohistochemistry revealed expression of p16( INK4a) with diffuse positivity in the upper third of the epithelium, corresponding to the vacuolated keratinocytes. Polymerase chain reaction (PCR) was positive for type 12 HPV, and a diagnosis of EV-like associated to AIDS was made. EV-like is a rare disease and in this patent might be a manifestation of immune reconstitution inflammatory syndrome.

Comparative analysis of the expression of cytokeratins (1, 10, 14, 16, 4), involucrin, filaggrin and e-cadherin in plane warts and epidermodysplasia verruciformis plane wart-type lesions.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genodermatosis with susceptibility to human papillomavirus (HPV) infection, and high risk of skin cancer considered a model of viral oncogenesis. METHODS: Fifteen cases of EV plane wart (PW)-type lesions (EV) and 14 cases of PW in healthy individuals were subjected to immunohistochemical technique for cytokeratins (K) 1, 10, 14, 16, 4, involucrin, filaggrin and e-cadherin. RESULTS: K1/10 showed retarded or negative expression in EV, being substituted by K14. Expression of K14 occurred in the basal and suprabasal layers in both groups, but in EV, its expression was observed up to the more superficial layers. Both groups showed positivity for K16 and K4, involucrin expression in lower levels of the spinous layer and unaltered filaggrin expression. E-cadherin expression was diminished at the koilocytotic foci of both lesions, more superficially in EV. CONCLUSION: Infection by HPV may alter the differentiation status of the epidermis, leading to a major expression of K14, delayed or absent expression of K1/10 and earlier involucrin expression, especially in EV. It also stimulates the expression of K16 and K4. Filaggrin expression is not altered, and e-cadherin is diminished in superficial koilocytotic cells' foci in EV.

An unusual presentation of human papillomavirus (HPV) infection in a black epidermodysplasia verruciformis (EV) patient.

A 25-year-old black man had a 20-year history of disseminated plaques on his body. Two years before consultation he noticed several tumors on the genitalia. Physical examination revealed generalized, coalescing, hypopigmented plaques with a very defined and keratotic border that resembled actinic porokeratosis. (Fig. 1). Multiple verrucous and moist tumors were observed on the scrotum (Fig. 2). His past medical history was unremarkable, and no family member had the disease. Histology of the body lesions revealed hyperkeratosis with a horny-layer, basket-weave appearance, large and clear blue-gray keratinocytes with finely granular cytoplasm and vacuolized nuclei, and abundant keratohyaline granules located in the upper epidermal layer (Fig. 3). Scrotum biopsy showed hyperkeratosis, irregular acanthosis with papillomatosis, and koilocytic figures. The genital lesions were treated with monthly cryotherapy plus surgical excision with complete disappearance of the lesions. A decrease in ultraviolet exposure and daily sun-block were encouraged for epidermodysplasia verruciformis lesions. After genital wart clearance, follow-ups are being scheduled every 4 months, with no new lesions to date.

HPV typing in Brazilian patients with epidermodysplasia verruciformis: high prevalence of EV-HPV 25.

BACKGROUND: Epidermodysplasia verruciformis is a rare genetic disorder characterized by development of lesions associated with HPV#5 or HPV#8 in early childhood; malignant transformation occurs in approximately half of individuals during adulthood. OBJECTIVE: Our goal was to study the presence and spectrum of EV-HPV types in Brazilian EV patients, a population that had never been studied in this regard. PATIENTS AND METHODS: Forty-one biopsies from different lesions (benign and skin tumors) and one biopsy from clinically normal skin from each of 20 Brazilian patients with EV were studied for HPV typing using nested PCR. RESULTS: EV-HPV DNA was detected in all 41 skin lesions of the patients and was also identified in specimens considered as normal skin from 8 patients (40%). In this study HPV-EV 25 was the most prevalent (70%), and HPV 14d (67%) was highly associated with malignant lesions. CONCLUSION: EV-HPV 25 was the most prevalent in our study. The noteworthy association of EV-HPV type 14d with skin cancers suggests its possible oncogenic role in malignant transformation in this population.

Clinical aspects of epidermodysplasia verruciformis.

Thirteen patients with epidermodysplasia verruciformis (EV) were studied over a period of 7 years. EV is a rare genodermatosis characterized by a generalized infection with a specific group of human papilloma virus (HPV) and a propensity for developing skin malignant tumours in 30%-50% of patients. The diagnosis of EV was confirmed by histopathological and immunohistochemical findings. Three of our patients had the benign form of EV, which is characterized by monomorphous lesions and no malignant changes, whereas 10 had the malignant form, which is characterized by polymorphic lesions and development of cutaneous malignant tumours. All EV patients with the malignant form developed multiple skin tumours (77%). They started to appear at age 20, predominantly on the forehead (50%). Most were squamous cell carcinoma, extremely aggressive and invasive, which provoked metastasis and death in two patients.

A novel human papillomavirus identified in epidermodysplasia verruciformis

Epidermodysplasia verruciformis (EV) is a rare inherited condition in which there is widespread infection with human papillomavirus (HPV). Patients have a high risk of developing squamous cell carcinoma and Bowen's disease on sun-exposed sites. We describe a Jamaican man with the typical clinical and histopathological features of EV.HPV 8, 24 and a subtype of HPV 38, along with a novel HPV sequence most closely related to HPV 9 have been detected in his skin lesions. Although skin tumours are rare in black patients with EV and he has lived in a temperate climate most of his life, several of the lesions showed bowenoid atypia and he is at risk of developing invasive cutaneous malignancies.(AU)