Bowen's disease of the feet. Presence of human papillomavirus 16 DNA in tumor tissue

A 36-year-old black man with bilateral squamous cell carcinoma in situ of the feet is described. The DNA hybridization analysis performed on the tumor tissue demonstrated the presence of human papillomavirus 16 DNA. Human papillomavirus 16 has been detected repeatedly in genital carcinomas, and evidence is mounting that it may play an important role in the development of malignancy.     

Bowen's disease on the sole: p16INK4a overexpression associated with human papillomavirus type 16

We report a case of Bowen's disease on the sole presenting clinically as an exophytic, blackish-grey, verrucous tumour, and showing human papillomavirus (HPV) type 16 on analysis with polymerase chain reaction. Positive stains for HPV particles by immunohistochemical analysis were limited to several cell nuclei at the upper stratum Malpighii. However, all the tumour cells in the epidermis exhibited strong and diffuse nuclear and cytoplasmic stains for the tumour suppressor protein p16INK4a. We speculate that dysregulation of the retinoblastoma/p16INK4a pathway may be involved in the pathogenesis of the lesion, and p16INK4a overexpression might serve as a useful surrogate marker for identifying Bowen's disease harbouring high-risk types of HPV infection.     

Detection of human papillomavirus type 16 in Bowen's carcinoma of the toe

Background Human papillomavirus (HPV) is known to cause cervical cancer. Because it has been detected in lesions of Bowenoid papulosis, Bowen’s disease, and Bowen’s carcinoma, HPV infection has been implicated in the pathogenesis of these diseases. Methods A 44‐year‐old man was diagnosed clinicopathologically with Bowen’s carcinoma of the right great toe. He developed multiple organ metastases and died. We examined HPV DNA in skin biopsy specimens from the primary and skin metastatic lesions by polymerase chain reaction (PCR) and in situ hybridization (ISH). The PCR assay was carried out using primer sets specifically designed for detecting the E6 and E7 genes of the HPV types associated with malignancy. Purified and cloned PCR products were subjected to DNA sequence analysis. The ISH studies used INFORM^® HPV III probes. Results We found HPV DNA in specimens from both the primary and the skin metastatic lesions. DNA sequencing detected HPV type 16. We compared the base sequences of viral DNA from the primary and metastatic lesions. Point mutations of the base sequences of the E6 and E7 genes were observed in viral DNA from metastases but not in that from primary lesions. The E6 gene had mutated from G to A in the 383rd base sequence, causing a Glu‐to‐Lys amino acid change. Results of ISH showed punctuate signals in the nuclei of tumor cells. Conclusions We suspect an association between HPV 16 infection and the development of this malignant occurrence.     

Detection of human papillomavirus DNA on the fingers of patients with genital warts

OBJECTIVE: To determine whether patients with genital warts carry human papillomavirus (HPV) DNA on their fingers. METHODS: 14 men and eight women with genital warts had cytobrush samples taken from genital lesions, finger tips, and tips of finger nails. Samples were examined for the presence of HPV DNA by the polymerase chain reaction. RESULTS: HPV DNA was detected in all female genital samples and in 13/14 male genital samples. HPV DNA was detected in the finger brush samples of three women and nine men. The same HPV type was identified in genital and hand samples in one woman and five men. CONCLUSION: This study has identified hand carriage of genital HPV types in patients with genital warts. Although sexual intercourse is considered the usual mode of transmitting genital HPV infection, our findings raise the possibility of transmission by finger-genital contact.     

Epidermodysplasia verruciformis. A case associated with primary lymphatic dysplasia, depressed cell-mediated immunity, and Bowen's disease containing human papillomavirus 16 DNA

Epidermodysplasia verruciformis is a rare, often hereditary disease characterized by a generalized cutaneous infection with human papillomavirus (HPV), depressed cell-mediated immunity, and a propensity for transformation of the warty lesions to squamous cell carcinoma on primarily sun-exposed areas of the skin. A 37-year-old man with congenital lymphatic dysplasia and a history of squamous cell carcinoma of the groin and foot was observed by us to have edema of all four extremities, numerous flat warts, and pityriasis versicolor-like papules over the trunk and arms. Condylomatous lesions were noted in the groin and a periungual verrucous nodule on the thumb. Biopsies showed the trunk and arm lesions to be verrucae and the thumb lesion to be Bowen's disease. Results of molecular hybridization studies from four lesions of the arms showed the presence of only HPV 3 DNA; HPV 16-related DNA was detected in the intraepidermal carcinoma on the thumb. Immunologic evaluation revealed anergy to routine skin testing, depressed mitogen-stimulated lymphocyte transformation, decreased B-lymphocyte count, and a severe reversal of the T-lymphocyte helper:suppressor ratio.     

Identification of a human papillomavirus type 58 lineage in multiple Bowen's disease on the fingers: Case report and published work review

Human papillomavirus (HPV) has been detected in some cases of Bowen's disease, particularly on the fingers and genitalia. HPV‐58 is classified as a high‐risk mucosal type and accounts for a high percentage of cervical cancer in Asia. Moreover, several HPV‐58 lineages, including sublineage A1, have a high prevalence in Asia. However, the nature of HPV‐58‐associated skin cancer is still unknown. Here, we report a case of a Japanese patient with multiple Bowen's disease on the fingers. A 33‐year‐old man presented with multiple reddish‐brown scaly plaques on his left middle finger and right ring finger. All lesions were surgically excised, and the diagnosis of Bowen's disease was made. We performed Sanger sequencing using DNA extracted from paraffin‐embedded samples and identified HPV‐58 sublineage A1. Additionally, we review previous reports on HPV‐58‐associated skin cancers, including our case, showing a high regional prevalence in Asia. Further studies would be needed to reveal the relationship between HPV‐58 lineages and carcinogenesis in the skin.     

Nestin expression in Bowen's disease and Bowen's carcinoma associated with human papillomavirus

Human papillomaviruses (HPVs) have been detected in lesions of Bowen's disease (BD) and Bowen's carcinoma (BC); the invasive tumor retains the cytological characteristics of BD. Previous reports suggest that nestin-expressing hair follicle stem cells are undifferentiated and pluripotent, and nestin expression in some tumors indicates poor differentiation and high grade of malignancy. We identified HPV-DNA in BD (n=25) and BC (n=23) by in situ hybridization (ISH) analysis with INFORM(?) HPV III (Ventana Medical Systems. AZ, USA) and determined nestin expression by indirect immunohistochemical staining with anti-nestin polyclonal antibody (IBL, Gunma, Japan). We detected HPV-DNA in 68% of BD and in 87% of BC. In BD, 13 cases demonstrated the punctuate pattern, and four showed nestin expression. In BC, 19 cases showed the punctuate pattern and 16 showed nestin expression. HPV-DNA integrates into the host genome, and this is observed as the punctuate pattern on ISH. The nestin expression was statistically high in group of BC than BD (P<0.01). These results therefore suggest that HPV-DNA integrated in the genome of tumor cells of these diseases and contributed to malignant alteration. From the standpoint of tumorigenesis, BC might represent one type of poorly differentiated, high-grade squamous cell carcinoma.     

Detection of human papillomavirus in nongenital Bowen's disease by in situ DNA hybridization

Genital Bowen's disease has been strongly linked in recent studies to human papillomavirus (HPV). Nongenital Bowen's disease has been less well investigated, although isolated reports, all of which involved detection of HPV after extraction of DNA from fresh-frozen tissue, have been made. We investigated 25 cases of nongenital Bowen's disease in 5 black and 20 white patients for the presence of HPV types 1, 6, 11, 16, and 18 using paraffin-embedded tissues. Human papillomavirus was present in six specimens from 3 of the 5 black patients (one previously reported to be positive on Southern blot) and 3 of the 20 white patients; HPV 16 was detected in all 6 cases on low-stringency testing, but only 4 remained positive on high-stringency testing. This suggests an HPV closely related to but not entirely homologous with HPV 16 in the 2 remaining cases. Five of the 6 positive specimens were lesions from the hands and feet and 1 was from the volar aspect of the arm. Clinical factors associated with the presence of HPV included black race, location on the palmar surface and the feet, young age, and verrucous or hyperkeratotic clinical appearance. Of the 6 positive cases, all 5 of the patients available for examination also had evidence of HPV-associated genital lesions. No specific histopathologic features were found to be indicative of the presence or absence of HPV.     

Detection of human papillomavirus type 56 in Bowen's disease involving the nail matrix

Background As Bowen’s disease of the nail apparatus is quite rare, there have been only a few reports on the prevalence of human papillomavirus (HPV) infection in this condition. Objectives The purpose of this study was to clarify the association of HPV with this disease involving the nail apparatus. Methods Five patients with Bowen’s disease of the nail apparatus were investigated clinically, virologically and histologically. Total DNAs extracted from excised skin lesions were analysed using polymerase chain reaction (PCR) for the presence of HPV DNA and the amplified products were subjected to DNA sequence analyses. Histological localization of HPV DNA was examined by in situ hybridization. Results In three of five patients, HPV was detected by PCR amplification, and subsequent sequence analyses of the PCR products showed the sequences of HPV type 56. A common clinical feature of the three HPV‐positive patients was longitudinal melanonychia. In contrast, the two HPV‐negative patients presented with a convex nail deformity and a periungual ulcerative lesion. In two of three positive cases, there was a silent point mutation in the L1 gene of each HPV. In the remaining one case, the nucleotide sequence was consistent with the consensus sequence of HPV 56. Sequence analyses of the E6 gene revealed the infection of different variants of HPV 56 among the three cases. The viral genomes were located in keratinocyte nuclei upon in situ hybridization. Conclusions HPV 56 may be involved in the carcinogenesis of Bowen’s disease affecting the nail matrix with longitudinal pigmentation.     

巢式PCR方法检测非生殖器部位Bowen病HPV DNA

目的 建立一种巢式ＰＣＲ方法,探讨HPV DNA在非生殖器部位Bowen病中的检出率。方法 巢式PCR方法,用5对不同引物包括CN1FR、CN2FR、CN3FR、CN4FR以及CN5FR进行扩增。结果 通过ClustalX软件,将所设计的每对引物与已知HPV亚型的碱基序列逐一相比较,得知改良设计的引物可以使69种HPV亚型得到扩增,包括黏膜型HPV、皮肤型 HPV以及疣状表皮发育不良相关性 HPV;PCR反应体系的敏感度在10-2～10-3拷贝之间。41例非生殖器部位Bowen病的组织标本中,5例HPV DNA阳性,其中高危黏膜型3例（2例HPV16,1例HPV33）,皮肤型2例（HPV27和HPV76各1例）。结论 改良的巢式PCR方法具有较高的敏感性、特异性,部分非生殖器部位Ｂowen病发病与黏膜高危型ＨＰＶ感染相关。     

Detection of human papillomavirus type 58 in polydactylous Bowen's disease on the fingers and toes of a woman - concurrent occurrence of invasive vulval and cervical carcinomas

The group related to human papillomavirus (HPV) type 16 (HPV-16, -31, -33, -35, -52, -58 and -67) is dominantly identified in cervical intraepithelial neoplasia and cervical carcinomas. HPV-16 has also been frequently detected in Bowen's disease on the hands and feet. We describe herein a case of polydactylous Bowen's disease on the fingers and toes of a woman who had had radical vulvectomy and hysterectomy for concomitant invasive vulval and cervical carcinomas. All the lesions, except for the lesions on the periungual side of her left index, middle and ring fingers, harbored HPV-58 DNA with more than 100 entire viral genome copies per cell detected by Southern blot hybridization. The histological localization of the viral DNA was confirmed in all the lesions by in situ hybridization. We could also retrospectively demonstrate HPV-58 DNA in her invasive vulval and cervical carcinoma tissues.     

原位杂交检测鲍温样丘疹病及Bowen病中HPV16 DNA

采用生物素标记的核酸探针原位杂交技术,检测了30例鲍温样丘疹病、15例Bowen病中16型人乳头瘤病毒(HPV16)感染的组织定位及染色模式。结果显示,30例鲍温样丘疹病中,HPV16阳性13例;15例Bowen病中,HPV16阳性6例。鲍温样丘疹病、Bowen病中HPV16感染累及棘细胞全层;主要为核内团块状着色。Bowen病中,HPV16感染尚累及基底层细胞且存在HPV的点状染色模式。提示鲍温样丘疹病与Bowen病比较,HPV16感染的组织定位及染色模式均有所不同。     

Detection of papillomavirus capsid antigens and human papillomavirus 16-related DNA in Bowenoid papulosis and Bowen disease

In one out of 22 cases of histologically diagnosed bowenoid papulosis, we could detect human papilloma virus (HPV) capsid antigen in paraffin sections fixed with formalin by means of the peroxidase-antiperoxidase (PAP) test; there were no positive findings regarding biopsies taken from Bowen's disease. Southern blot hybridization technique revealed HPV 16 DNA in 8 out of 10 cases of bowenoid papulosis; there was one positive identification out of 5 cases of Bowen's disease.     

Characteristic intracytoplasmic material in a perianal wart that contains human papillomavirus type 56 and 16 DNA

We report the case of a perianal wart in which human papillomavirus type 56 and 16 DNAs were detected, arising in a 29-year-old healthy Japanese female. Clinically, moist erythema and small flat pinkish papules appeared around the anus and worsened over a period of 6 months. Histopathologically, no signs of dysplasia or atypia were apparent. An area of intracytoplasmic material, which was homogeneous and eosinophilic, was contained in each epidermal cell. The wart showed HPV-56 and HPV-16 DNAs by PCR and reverse-phase dot blot hybridization. Additional Southern blot analysis showed the amount of HPV-56 DNA to be more than 10 times that of HPV-16 DNA. This is the first case, to our knowledge, of a perianal wart with intracytoplasmic material, which contains HPV DNAs causing mucous lesions.