A pregnant woman with condyloma acuminatum on the vaginal orifice, areola, groin, and umbilicus.

Condyloma acuminatum (CA) is a benign tumor primarily caused by infection with human papillomavirus (HPV) type-6 or type-11, lesions of which are most frequently found on the genital, perianal squamous mucosa, and skin. CA outside the anogenital region is not common. Here, we report a case showing simultaneous presence of CA on the vaginal orifice, areola, groin, and umbilicus in a 32-year-old pregnant woman. Histopathological examination and HPV detection are essential in making a definitive diagnosis of CA on multiple sites. The patient was treated with microwave and liquid nitrogen cryotherapy, but repeated relapse of the lesions were observed. Patients with CA during pregnancy represent a special risk group. These cases are usually characterized by fast-growing warts, multi-site or special site warts, a reduced tolerance, and poor response to treatment. Hence, we should pay more attention to CA in pregnant women in the process of diagnosis and treatment, especially cases outside the anogenital region.

Mixed Nipple Infections Caused by Variant of BPV3 and a Putative New Subtype of BPV in Cattle.

Bovine papilloma is a chronic and proliferative skin and mucosal wart caused by Bovine papillomavirus (BPV). In June, 2013, a leaf-and flat-shaped wart disease was observed on the nipple skins in a cattle farm in Xinjiang. To diagnose the disease, we collected the diseased skins for pathological biopsy and DNA analysis by PCR amplification using a pair of degenerate primers FAP59 and FAP64. Sequencing and phylogenetic analysis showed that the infection was caused by a variant of BPV3 and putatively a new subtype of BPV (BPV/CHI-SW1, belonging to the Xi papillomavirus genus). This is the first report of mixed infection caused by variant of BPV3 and BPV (putatively new subtype) in China, and would be of importance for the molecular epidemiological study of the disease.

Molluscum contagiosum of the areola and nipple: case report and literature review.

Molluscum contagiosum is a common cutaneous infection caused by a double-stranded DNA poxvirus. Skin lesions classically present as small, flesh-colored papules with central umbilication. Lesions are frequently seen on the face, trunk, and extremities of children, or on the genitals of young adults as a sexually transmitted infection. Molluscum contagiosum on the nipple or areola has only been previously described in 4 women. We describe a woman with molluscum contagiosum on the left areola and review the clinical characteristics and histological findings of patients who developed molluscum contagiosum of the nipple or areola.

High-risk human papillomavirus in mammary gland carcinomas and non-neoplastic tissues of Mexican women: no evidence supporting a cause and effect relationship.

Human papillomavirus (HPV) has been implicated in breast carcinogenesis. Consecutive and non-selected mastectomy specimens from Mexican patients harboring breast carcinomas were sampled in order to look for the presence of HPV DNA. HPV-16 was detected in 6 (10%) of 60 breast carcinomas. Two of these also had HPV genome in adjacent non-neoplastic mammary-tissues. Seven cases had HPV DNA only in non-neoplastic tissue specimens. HPV DNA was also detected in 4 (25%) of 10 tumor-bed specimens without residual neoplastic lesions that were obtained from patients who underwent neoadjuvant chemotherapy or neoadjuvant chemotherapy/radiotherapy. HPV-positive tumors tended to be smaller in size, than HPV-negative tumors (p=0.047). Histological distributions of HPV-positive and -negative cases showed no significant difference. Although all the HPV-16 DNA were found integrated, its low viral load rendered it difficult to incriminate this virus in breast carcinogenesis. However, the possibility that HPV infection occurred during carcinoma development cannot be ruled out.

Herpes zoster of the nipple: rapid DNA-based diagnosis by the loop-mediated isothermal amplification method.

A 28-year-old Japanese man presented with grouped erosions and vesicles on an erythematous base affecting the right areola and the surrounding skin. A Tzanck smear from the vesicle revealed giant cells. An initial clinical diagnosis of mammary herpes simplex was considered but to explore the differential diagnosis, viral DNA was amplified by the loop-mediated isothermal amplification (LAMP) method. DNA replication was observed only in varicella zoster virus LAMP mixture, and this confirmed a diagnosis of herpes zoster. The patient was treated with 3000 mg of daily oral valacyclovir for seven days. After antiviral treatment, the lesion had healed and the pain had resolved completely.

Detection of human papillomavirus DNA by DNA chip in breast carcinomas of Korean women.

It remains unclear whether there is an association between human papillomavirus (HPV) infection and human breast cancer. The aim of this study was to investigate the presence of HPV DNA in breast carcinomas of Korean women and to examine the possible association between HPV and breast cancer development. For this purpose, HPV DNAs from 154 patients, including 123 patients with breast carcinoma and 31 with intraductal papilloma, and nipple tissue from 27 cancer patients were examined using the DNA chip method. HPV DNA was detected in 8 breast carcinomas (6.5%) but in no intraductal papilloma. All detected HPV genotypes were of high-risk groups. There was a slightly increased incidence in papillary carcinomas (11.5%) and invasive ductal carcinomas with adjacent intraductal papillomas (11.8%) compared to the other histological subtypes (3.2-4.3%), although the difference was not statistically significant (p = 0.126). The presence of HPV DNA was not correlated with specific prognostic predictors of disease. High-risk HPV DNA sequences were present in 6.5% of Korean patients with breast tumors. However, this study could not demonstrate whether or not such HPVs directly contribute to the development of breast cancer.

Presence of papillomavirus sequences in condylomatous lesions of the mamillae and in invasive carcinoma of the breast.

BACKGROUND: Viruses including Epstein-Barr virus (EBV), a human equivalent of murine mammary tumour virus (MMTV) and human papillomavirus (HPV) have been implicated in the aetiology of human breast cancer. We report the presence of HPV DNA sequences in areolar tissue and tumour tissue samples from female patients with breast carcinoma. The presence of virus in the areolar-nipple complex suggests to us a potential pathogenic mechanism. METHODS: Polymerase chain reaction (PCR) was undertaken to amplify HPV types in areolar and tumour tissue from breast cancer cases. In situ hybridisation supported the PCR findings and localised the virus in nipple, areolar and tumour tissue. RESULTS: Papillomavirus DNA was present in 25 of 29 samples of breast carcinoma and in 20 of 29 samples from the corresponding mamilla. The most prevalent type in both carcinomas and nipples was HPV 11, followed by HPV 6. Other types detected were HPV 16, 23, 27 and 57 (nipples and carcinomas), HPV 20, 21, 32, 37, 38, 66 and GA3-1 (nipples only) and HPV 3, 15, 24, 87 and DL473 (carcinomas only). Multiple types were demonstrated in seven carcinomas and ten nipple samples. CONCLUSIONS: The data demonstrate the occurrence of HPV in nipple and areolar tissues in patients with breast carcinoma. The authors postulate a retrograde ductular pattern of viral spread that may have pathogenic significance.

Characteristics of clear cells and Toker cells in the epidermis of underlying nipple duct adenoma.

Clinically, it is difficult to differentiate between nipple duct adenomas (NDAs) and Paget's disease of the nipple. These lesions share similar morphological and histological characteristics. Clear cell types present in NDA, epidermal clear cells (ECC) and Toker cells (TC), share immunoreactive similarities to Paget cells which can lead to confusion in classification. The aim of this study was to obtain information on the characteristics and histogenesis of ECC and TC, to distinguish these cells from Paget cells. Ten nipple epidermal with NDA were compared to 25 histologically normal nipples. Samples were analyzed for cytokeratins (CKs) 7, 8 and 18, carcinoembryonic antigen (CEA), c-erbB-2/HER2 expression and human papillomavirus (HPV-) DNA. In 13 out of 25 normal nipples the staining sequence demonstrated that ECC and TC cell types are immunoreactive with CKs 7, 8 and 18 in the basal region of the epidermis. In contrast, aggregated CKs 7, 8 and 18-immunoreactive ECC and TC were identified in the epidermal of 8 of the 10 NDA cases. In 2 cases, TC were continuous with the underlying NDA, suggesting that TC might be of ductal origin and migrate through the galactophorous ostia. In NDAs and 25 histologically normal nipples, ECC and TC were negative for CEA, c-erbB-2/HER2 and HPV-DNA. ECC and TC, normally present in the nipple epidermis, may proliferate and form aggregates in the presence of an underlying NDA. These cells show immunoreactivity for CKs 7, 8 and 18 but are negative for c-erbB-2/HER2, CEA and HPV-DNA and should not lead to the mistaken diagnosis of Paget's disease.

Papilloma virus and c-erbB-2 expression in diseases of the mammary nipple.

PURPOSE: The detection of low/intermediate/high risk genital groups of human papillomavirus (HPV) in correlation with a growth-factor receptor c-erbB-2 in benign tumors of the mammary nipple. MATERIALS AND METHODS: Ten nipple duct adenomas (NDAs) and twenty papillomas, all embedded in paraffin and taken from the breast, were analyzed for HPV DNA of the low- and high/intermediate-risk groups. Polymerase chain reaction (PCR) with HPV consensus primers (types 6/11/16/18/33) and dot-blot hybridization with type-specific primers were used for the detection of these HPV-DNA sequences. Indirect in situ PCR (ISPCR) was also used in one case of an HPV-DNA-positive papilloma. In addition, we examined c-erbB-2 oncogene expression in NDAs and central carcinomas of the mamma from an immunohistochemical perspective. RESULTS: Using PCR and dot-blot hybridization we could not detect the gene sequences that are specific for the low- and high/intermediate-risk groups in any of the ten NDAs. Regarding the 20 cases of papilloma, a positive result for HPV types 6/11 was detected by indirect ISPCR; in one case in combination with a condyloma of the skin around the mammary nipple. The oncogene expression of c-erbB-2 displayed a strong signal in the papilloma cells and in the NDAs of the breast. CONCLUSION: Our results showed that the HPV-DNA types of the low- and high/intermediate-risk groups are without relevance for the pathogenesis of benign diseases of the nipple. It was, therefore, not possible to establish a correlation between the oncogene expression of c-erbB-2 and the HPV-DNA types.