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.

The Conundrum of an Accumulating Acuminatum.

BACKGROUND A 70-year-old African American man presented with fatigue, dizziness, generalized weakness, and considerable weight loss of over 20 pounds in 3 weeks. History-taking revealed he was positive for HIV, hepatitis C, and severe chronic condyloma acuminatum, which had been progressing for 16 years. Treatment and surgical intervention had been continuously postponed due to the patient's long-standing history of heroin abuse. CASE REPORT Physical exam and diagnostics showed evidence of sepsis. He was hypotensive, with lactic acidosis and significant leucocytosis, and had acute-on-chronic kidney disease. Urinalysis was positive for nitrites and leukocyte esterase; therefore, broad-spectrum antibiotics were initiated. Additional sources of sepsis were considered due to persistent leucocytosis despite appropriate antibiotic coverage. An MRI of the pelvis was done to evaluate for necrosis of fistulization from potential internal warts as a source of sepsis. The lesions extended from the inguinal areas bilaterally, covering the medial thighs, lower scrotal wall, and wall junction. It had infiltrated the perineum and the entire rectal area, including the gluteal cleft and anus. The patient was consulted by colorectal surgery, urology, and infectious disease services. CONCLUSIONS Surgical biopsies found that he had both low- and high-grade squamous intraepithelial neoplasia. There was no evidence of invasive carcinoma, which was a concern given his weight loss. Surgery devised a plan that included a diverting colostomy (allowing the infected anal area to heal), followed by resection of his giant condyloma, and re-anastomosing of the bowels to return him to a normal baseline anatomy. A favorable prognosis was expected.

Human Papillomavirus-Associated Invasive Condylomas in a Man with Immunosuppressive Comorbidities.

Human papilloma virus (HPV) infections are one of the most common sexually transmitted diseases. We present the case of a 77-year-old Caucasian male with enormous genital warts of the penis, scrotum, groins and anus. Lesions were excised by electrosurgery. The histological examination revealed Condylomata gigantea as well as an invasive perianal squamous cell carcinoma. Mucosal "low-risk" HPV type 6 was detected. The patient had a history of an immunosuppressing disease. During the 4-year follow-up, multiple relapses occurred. Thus, particularly in immunosuppressed patients, early prophylactic HPV vaccination seems to be indicated for use in the prevention of HPV-associated mutilating and life-threatening disease. Vaccination should also protect from "low-risk" HPV.

Successful treatment of giant condyloma in a pediatric heart transplant recipient with topical cidofovir.

We report a case of giant condyloma that developed in a pediatric heart transplant recipient. This infection progressed for several months despite reduction in immunosuppression, topical treatment, and oral cimetidine therapy. Complete resolution was observed following 7 months of topical cidofovir, without evidence of systemic toxicity or rejection.

Anal verrucous carcinoma is not related to infection with human papillomaviruses and should be distinguished from giant condyloma (Buschke-Löwenstein tumour).

AIMS: Verrucous carcinoma (VC) is a variant of well-differentiated squamous cell carcinoma and in the anal region is regarded as synonymous with giant condyloma (Buschke-Löwenstein tumour) (BLT). Aetiology, diagnostic criteria and clinical behaviour of both lesions are controversial. Recent studies suggest that VC at other sites is not associated with human papillomaviruses (HPV). We hypothesized that anal VC is also not related to HPV, while BLT is a HPV-induced lesion. METHODS AND RESULTS: Ten cases of VC and four cases of BLT were included. Several techniques were used for HPV detection: in-situ hybridization for HPV6, 11, 16 and 18, six different polymerase chain reaction (PCR) protocols for detection of at least 89 HPV types from alpha-, beta-, gamma- and mu-PV genera and in-situ hybridization for high-risk HPV E6/E7 mRNA; p16 immunohistochemistry and morphometric analysis were also performed. Alpha-, gamma- and mu-PVs were not found in any case of VC, while HPV6 was detected in all cases of BLT. p16 overexpression was not present in any of the lesions. Among microscopic features, only the absence of koilocytosis and enlarged spinous cells seem to be useful to distinguish VC from BLT. CONCLUSIONS: Our results suggest that anal VC, similarly to VC at other sites, is not associated with HPV infection, and must be distinguished from BLT, which is associated with low-risk HPV. Only with well-set diagnostic criteria will it be possible to ascertain clinical behaviour and optimal treatment for both lesions.

Perianal giant condyloma acuminatum (Buschke-Löwenstein tumor).

A 50-year-old heterosexual, HIV-negative man presented with a giant anal condyloma (Figure). He had iron deficiency anemia, a slow-growing anal wart for many years, and intermittent bleeding and pruritus. Esophagogastroduodenoscopy and colonoscopy findings were normal. Endoscopic ultrasound of the anorectum showed no anal sphincter involvement, and computed tomography did not reveal any pelvic inguinal lymph nodes. Wide-staged excision was performed and the patient recovered well with resolution of symptoms and no local recurrence at 1-year follow-up. Final pathology confirmed human papillomavirus (HPV) 6 strain and a giant condyloma acuminatum with mild atypia and no malignancy. Further examination of his oropharynx showed additional small HPV lesions, which were removed locally.

[Clinical usefulness of diagnostic methods for human papilloma virus dependent lesions]. / Przydatnosc kliniczna metod wykorzystywanych w diagnostyce zmian wywolanych zakazeniem wirusem brodawczaka ludzkiego.

Persistent infection of Human Papilloma Virus (HPV) is confirmed necessary factor for development of cervical cancer and anogenital neoplasia. DNA HPV is detected in 96% of cervical cancer, 40% of vulvar and vaginal cancer, 90% of anal cancer and 26% of oral cavity cancer cases in general population. The most common high-risk HPV types observed in anogenital intraepithelial neoplasia or anogenital cancer are HPV 16, 18 and 45. Numerous diagnostic methods of detection of HPV infection and lesions causes by persistent HPV infection are widely used. Epidemiological data reveals correlation of incidence and mortality reduction due to cervical cancer and consequent prosecution and improvement of screening programmes based on morphological assessment of exfoliative smears. In last decade some limitations of conventional smear method were pointed out and a new diagnostic techniques were introduced: liquid-based cytology and HPV DNA testing. Combination of cytological examination and HPV DNA testing seems to be optimal solution to be introduced in large population because of combining high sensitivity of molecular test with high specificity of cytological smear.

Giant condyloma of the cervix: an uncommon entity associated with low-risk human papilloma virus infection.

"Giant Condylomas" of the cervix are very uncommon, and have not been fully characterized in the English literature. We report 4 cases of cervical giant condyloma seen in our practice. Patients were predominantly young and presented with a cervical lesion producing bleeding or a mass effect. Biopsy/excision revealed a uniformly bland, exophytic squamous epithelial proliferation with viral cytopathic changes and absence of stromal invasion. Human papilloma virus types 6 and 11 were detected in all cases. Follow-up was uneventful without recurrence or spread. Giant condylomas of the cervix as defined in this report signify a benign albeit extensive variant of low-risk human papilloma virus infection. This term is proposed as a specific descriptor for such lesions and should be considered in the setting of any large well-differentiated exophytic cervical squamous lesion in young or immunosuppressed women. The term "giant condyloma of Buschke and Loewenstein" should be discontinued given the lack of specificity.

[Human papillomavirus prophylactic vaccine].

Human papillomavirus causes viral-dependent cancers, including cervical, anal, vulvar, penile, vaginal, and oropharyngeal, and condyloma acuminata. In the last decade, HPV prophylactic vaccine has been developed and spread worldwide after many large-scale clinical studies. These studies demonstrate significant clinical efficacy for prevention of HPV16/18/6/11-related diseases. In particular, prevention of cervical cancer should be the most important role in the world. In Japan, incidence of cervical cancer does not increase, but the peak of age of the patients at 2005 is 25-45 years old and became 20 years younger than that at 1985. The current two HPV vaccines can prevent the infection of HPV16/18 among high-risk HPVs and will provide a significant impact especially on young-age onset cervical cancer. Furthermore, quadrivalent HPV vaccine, Gardasil, has shown population impact that is decrease of patients with condyloma acuminate in several countries. The clinical efficacy seems to be convincing. Here HPV vaccine will be reviewed based on the literatures.

Successful treatment of giant condyloma acuminatum with combination retinoid and interferon-γ therapy.

Giant condyloma acuminatum, or Buschke-Löwenstein tumour, is a unique variant of anogenital warts. It is characterized by locally aggressive behaviour but rarely metastasizes. Many treatment strategies such as radical surgery, radiation and chemotherapy have been used to treat it but their efficacy is often poor and the recurrence rates are high. We report a case of 16-year-old girl who was treated with oral retinoid combined with intramuscular interferon-γ. All lesions cleared within three months. During a follow-up period of more than two years, no recurrence has developed. This relatively painless, non-scarring treatment may represent a novel therapeutic option.

Comprehensive analysis of human papillomavirus prevalence and the potential role of low-risk types in verrucous carcinoma.

The role of human papillomavirus (HPV) infections in the development of verrucous carcinoma, a well-differentiated variant of squamous cell carcinoma with difficult differential diagnosis, is controversial in the literature. In this study, we analysed verrucous carcinoma from different origins for the presence and activity of a broad spectrum of HPV types, and carefully reviewed the histopathological features. A random series of 27 formalin-fixed, paraffin-embedded specimens of verrucous carcinoma was taken, representing the head and neck region (n=6), anogenital area (n=16) and extragenital skin region (n=5). After review of the histological slides, all samples were subjected to different polymerase chain reaction-based HPV detection techniques, together detecting a total of 83 HPV types, including both mucosal and cutaneous types. Histological revision was carefully performed. Lesions with keratinised papillae, blunt stromal invaginations and minimal cytological atypia were considered verrucous carcinoma. Condylomatous lesions with viral changes were defined as giant condyloma. Verrucous lesions that did not meet those criteria were classified as verrucous hyperplasia. Tumours with stromal infiltration were considered as invasive squamous cell carcinoma. Histological revision revealed that 13 out of 27 cases were verrucous carcinoma (one showing a double infection with HPV 35 and 45), 5 invasive squamous cell carcinomas, 5 verrucous hyperplasia (one with a double infection with HPV 4 and 8), 1 pseudoepitheliomatous hyperplasia and 3 giant condylomas. All three giant condylomas were low-risk HPV positive (HPV 6 and 11) and showed active mRNA transcription. None of the HPV-positive samples tested positive for diffuse p16(INK4A) staining. In conclusion, our results do not support a causal role of HPV in the development of verrucous carcinoma. Testing for LR-HPV, particularly HPV 6 and 11, may help in the differential diagnosis of lesions suspicious of verrucous carcinoma as those testing positive for LR-HPV most likely represent giant condylomas.