Human papillomavirus type 7 identified in digitated warts on facial seborrhoeic eczema of a non-butcher immunocompetent individual.

Human papillomavirus type 7 (HPV7) is frequently found in butchers' warts and has been demonstrated in several warts of immunocompromised hosts. HPV7 is rarely identified in non-butchers' warts, especially in individuals with normal immune status. We describe the first case of multiple HPV7-induced digitated warts which were developed on the face of a 68-year-old Japanese man, whose immune status was normal and who had no history of meat handling. Interestingly, the warts were developed exclusively on the skin affected with seborrhoeic eczema in the face, suggesting that some biologically active factors associated with seborrhoeic eczema and anatomical factors of sun-exposed facial skin might contribute to the development of HPV7-induced warts.

Familial occurrence of follicular keratosis of the chin.

Follicular keratosis of the chin is a rare and poorly understood pediatric disorder with a characteristic presentation of multiple follicular papules on the chin. Although prolonged friction or pressure over the chin is considered an etiology, such history is not present in most cases. It sometimes occurs within families without any evidence of physical trauma, suggesting a genetic predisposition of the patients to develop the disease. In the present study, we report two brothers with the disease, in whom no definite physical trauma was identified but comedo formation was evident. The clinical presentation of follicular keratosis of the chin is unique, particularly owing to its specific location on the chin with an age predilection from late childhood to puberty. We assume that the hormone status is an etiology of the disease since the chin is an area where androgenic hormones target at puberty and comedogenesis is a well-known biological function of the hormone. We also assumed that the susceptibility to the hormone may involve in the development of the familial follicular keratosis of the chin.

Erythroplasia of Queyrat treated with imiquimod 5% cream: The necessity of regimen guidelines.

Development of noninvasive treatments for erythroplasia of Queyrat, a carcinoma in situ, is expected. This case suggests topical imiquimod might be a candidate with regimens consisting of much longer duration of the treatment than for genital warts and the maintenance phase of the treatment course to prevent the relapse.

Human papillomavirus type 6/11 identified in an epidermoid cyst of the scrotum.

To date, epidermoid cysts associated with human papillomavirus (HPV) infection have been described mainly in palmoplantar locations, and have involved HPV types 60 and 57. In contrast, HPV-6/11 is a major cause of condyloma acuminatum. Here, we report the case of a healthy 31-year-old man who presented to our clinic with a 1-month history of a 1-cm, reddish-brown, cystic scrotal tumor with a punctum. The lesion was studied histologically, immunohistochemically and by DNA-DNAin situ hybridization. Histology revealed an epidermoid cyst with vacuolated keratinocytes with shrunken nuclei (koilocytes) in the cyst wall. Immunostaining was positive for HPV antigens and in situ hybridization revealed HPV-6/11 DNA in the koilocytes. This is the first report of an HPV-6/11-associated epidermoid cyst in the anogenital skin of an immunocompetent individual.

Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia.

Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted.

Molecular cloning and characterization of a novel human papillomavirus, HPV 126, isolated from a flat wart-like lesion with intracytoplasmic inclusion bodies and a peculiar distribution of Ki-67 and p53.

Infection with certain human papillomavirus types induces warts with specific macroscopic and microscopic features. We observed multiple flat wart-like lesions on the chest, neck and extremities of an adult T-cell leukemia patient. Histologically, atypical intracytoplasmic inclusion bodies currently known to be pathognomonic for genus gamma or mu papillomaviruses were disclosed in some cells of the epidermis showing histological features compatible with flat warts. In the present study, a novel human papillomavirus was identified and its whole genome, 7326 bp in length, was cloned and characterized. Phylogenetic analysis showed the virus designated as HPV126 to be a novel type of genus gamma papillomavirus. Strikingly, Ki-67 and p53 expression was found to be increased in all layers of the epidermis except for horny layer, contrasting to expression restricted to the basal and lower spinous layers in ordinary flat warts.

Cutaneous hyalohyphomycosis by Scedosporium apiospermum in an immunocompromised patient.

Scedosporium apiospermum is a ubiquitous filamentous fungus that may infect immunocompetent patients after trauma and may cause severe and often fatal infections in immunocompromised hosts. Here, we present the case of a 28-year-old female with S. apiospermum infection on the left forearm that had developed while she was on long-term immunosuppressant therapy. Analysis of a skin biopsy specimen showed a mixed cell granuloma with hyaline septate hyphae. Culture of the abscess revealed S. apiospermum which was identified as S. apiospermum sensu stricto by sequencing of the internal transcribed spacer-1 region of ribosomal DNA genes. Resection of the eruption and oral itraconazole (100 mg day(-1)) therapy for 4 months was effective in curing the infection.

The expression of SnoN in normal human skin and cutaneous keratinous neoplasms.

BACKGROUND: SnoN is a member of the ski family of proto-oncogenes. It has been revealed that SnoN plays a role in the regulation of cell growth, vertebrate development, and tumorigenesis. This study investigated the expression and significance of SnoN protein in normal human skin and in the development of seborrheic keratosis (SK), basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) of the skin. METHODS: Six frozen sections of normal human skin, three of SK (acanthotic type), six of BCC, six of intraepidermal SCC (actinic keratosis, AK), and six each of poorly and well-differentiated SCC were immunohistochemically stained with a polyclonal antibody against SnoN. RESULTS: In normal epidermis, strong positive staining was observed in the suprabasal layers, whereas the basal cell layer was entirely unstained. Expression was observed in tumor cells with a squamoid phenotype in SK, but not in BCC. In intraepidermal SCC, although a strong signal was seen in the well-differentiated keratinocytes of the superficial epidermal cell layers, no signal was seen in the poorly differentiated atypical cells situated in the lower epidermis. In invasive SCC, a few scattered cells were positive for SnoN in the well-differentiated sample, but much larger numbers of positive cells were observed in the poorly differentiated sample. CONCLUSIONS: On the basis of our results, it is suggested that SnoN is involved in differentiation in normal skin and benign and nonmetastatic skin tumors, but plays a proto-oncogenic role in undifferentiated SCC.

Non-radioisotope method for diagnosing photosensitive genodermatoses and a new marker for xeroderma pigmentosum variant.

Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by photo-induced deterioration of the skin, which often leads to the early development of skin cancers. To diagnose patients with XP and the related disorder Cockayne syndrome (CS), our laboratory has established a simple autoradiographic method that examines three cellular markers of DNA repair: unscheduled DNA synthesis (UDS), recovery of RNA synthesis (RRS) and recovery of replicative DNA synthesis (RDS). However, it is very laborious to measure the three markers using tritiated thymidine or uridine; therefore, we developed a non-isotope method for diagnosing XP and CS. Fibroblasts from the patient were labeled with bromodeoxyuridine (BrdU) instead of tritiated thymidine to measure UDS and RDS, or were labeled with bromouridine (BrU) instead of tritiated uridine to measure RRS. Incorporated BrdU or BrU could be detected using the immunofluorescence method. Moreover, we discovered a new useful marker for XP variant based on checkpoint activity. The non-radioisotope method and the new marker described here comprise an easy way to diagnose XP and CS.

Two cases of anti-epiligrin cicatricial pemphigoid with and without associated malignancy.

Anti-epiligrin cicatricial pemphigoid (AECP) is a chronic, mucous membrane-dominated, subepithelial blistering disease characterized by circulating anti-basement membrane zone auto-antibodies to laminin 5. Recent studies have shown that people with AECP have an increased relative risk for malignant tumours. In this report we describe two patients with AECP. In both cases, indirect immunofluorescence demonstrated circulating IgG anti-basement membrane auto-antibodies that bound to the dermal side of 1M NaCl split normal skin. Immunoblotting using laminin 5 purified from keratinocyte extract as a substrate showed that the IgG antibodies of patient 1 reacted with the 140-kDa beta3 subunit of laminin 5 and IgG antibodies of patient 2 reacted with the 165-kDa and 145-kDa alpha3 subunits. Patient 1 had prostate carcinoma and his blistering was resistant to therapy. Patient 2 had no detectable malignancy and treatment with doxycycline was successful.

A new disorder in UV-induced skin cancer with defective DNA repair distinct from xeroderma pigmentosum or Cockayne syndrome.

We report the characterization of a Japanese woman who exhibited many freckles and skin cancers in sun-exposed areas, but displayed no photosensitivity. Fibroblasts (KPSX7) derived from this patient showed similar UV sensitivity to that of normal human fibroblasts. The KPSX7 cells showed normal levels of unscheduled DNA synthesis, recovery of RNA synthesis, recovery of replicative DNA synthesis, protein-binding ability to UV-damaged DNA, and post-translational modification of xeroderma pigmentosum (XP) C. These results indicate that the patient had neither XP nor Cockayne syndrome. Although these results suggest that the KPSX7 cells were proficient in nucleotide excision repair activity, host-cell reactivation (HCR) activity of KPSX7 cells was reduced. Furthermore, introduction of UV damage endonuclease into the cells restored repair activity in the HCR assay to almost normal levels. These results indicate that KPSX7 cells are defective for some types of repair activity in UV-damaged DNA. In summary, the patient had a previously unknown disorder related to UV-induced carcinogenesis, with defective DNA repair.

Activation of the extracellular signal-regulated kinases signaling pathway in squamous cell carcinoma of the skin.

Activation of the extracellular signal-regulated kinase (ERK) pathway is involved in many human tumors. Little is known about the role of activated ERK1/2 in squamous cell carcinoma (SCC) of the skin. In this study, the expression and distribution of phosphorylated ERK (p-ERK) in normal human skin and SCC with different degrees of differentiation was examined by immunohistochemical analysis using formalin-fixed paraffin embedded sections. PD98059, a specific ERK pathway inhibitor, was used to evaluate the effect a blockade of ERK activation has on the proliferation of a cutaneous SCC cell line (DJM-1) in culture. In this study, p-ERK 1/2 positive staining was observed in all cases of SCC examined but rarely in the control specimens of normal skin. Moreover, the expression of p-ERK1/2 was significantly higher in poorly differentiated SCC in comparison to well-differentiated ones. Expression levels were positively associated with the degree of malignancy and proliferative activity of SCC. In contrast, inhibition of ERK pathway signaling markedly suppressed tumor cell proliferation. These results suggest that ERK1/2 signal pathways play an important role in the proliferation of SCC and that the inhibition of this signal pathway may be effective in the treatment of cutaneous SCC.

Sarcoidal granuloma developing not only at the entry site of industrial lubricating oil, but also at a regional lymph node and entry points of venepuncture.

We describe a 40-year-old male who presented with sarcoidal granulomas not only at the entry site of an industrial lubricating oil containing silicone in the right thumb, but also in a regional lymph node and at the entry points of venepuncture in both forearms. Laboratory tests and chest X-ray showed no evidence of sarcoidosis.

Histochemical analysis of cutaneous HPV-associated lesions.

Hematoxylin and eosin (H&E) staining of cutaneous warts is presented to illustrate the practical methods utilized for histochemical analysis of cutaneous human papillomavirus-associated lesions. Every step of the staining procedure, from sampling of the specimens to microscopic examination of the stained sections, is detailed with reference to the recent achievements in this field.

Simultaneous human papillomavirus 6 (HPV 6) -positive condyloma acuminatum, HPV 31-positive Bowen's disease, and non HPV-associated extramammary Paget's disease coexisting within an area presenting clinically as condyloma acuminatum.

An 83-year-old Japanese man presented with multiple verrucous papules clustering on a plaque located on the frontal aspect of the scrotum. Histologically, there were three distinct epithelial changes compatible with condyloma acuminatum, Bowen's disease, and extramammary Paget's disease (EMPD). By in situ hybridization, the zone of condyloma acuminatum was positive for HPV 6 and well demarcated from HPV 31-positive Bowen's disease. EMPD was negative for targeted HPV 6/11/16/18/31/33 probes. Immunohistochemically, Paget's cells expressing cytokeratin 7 were distributed as scattered single cells or clusters mainly in the lower part of the HPV 6/31-positive epithelium. To the best of our knowledge, this is the first reported case of the occurrence of condyloma acuminatum, Bowen's disease, and EMPD within the same lesion.