Common skin bacteria protect their host from oxidative stress through secreted antioxidant RoxP.

Cutibacterium acnes is an abundant skin commensal with several proposed mutualistic functions. A protein with strong antioxidant activity was recently identified from the C. acnes secretome. This protein, termed RoxP, facilitated aerobic bacterial growth in vitro and ex vivo. As reducing events naturally occurred outside of the bacterial cell, it was further hypothesized that RoxP could also serve to modulate redox status of human skin. The biological function of RoxP was here assessed in vitro and in vivo, through oxidatively stressed cell cultures and through protein quantification from skin affected by oxidative disease (actinic keratosis and basal cell carcinoma), respectively. 16S rDNA amplicon deep sequencing and single locus sequence typing was used to correlate bacterial prevalence to cutaneous RoxP abundances. We show that RoxP positively influence the viability of monocytes and keratinocytes exposed to oxidative stress, and that a congruent concentration decline of RoxP can be observed in skin affected by oxidative disease. Basal cell carcinoma was moreover associated with microbial dysbiosis, characterized by reduced C. acnes prevalence. C. acnes's secretion of RoxP, an exogenous but naturally occurring antioxidant on human skin, is likely to positively influence the human host. Results furthermore attest to its prospective usability as a biopharmaceutical.

Dermatomycosis in Cutaneous Tumors is a Predictor for Non-malignancy: A Cross-sectional Study.

The aim of this study was to evaluate the presence of spores and/or hyphae in benign cutaneous tumors (CT) and compare their presence in malignant cutaneous tumors. In this cross-sectional study we evaluated 328 CTs positive for spores and/or hyphae. The results show that the greatest number of involved CTs which contained spores and/or hyphae were found in compound nevi 181 (55.18%) and seborrheic warts 61 (18.60%). No spores and/or hyphae were observed in the melanoma samples, and a very low prevalence was found in squamous cell carcinomas (SCCs) (2; 0.61%) and basal cell carcinoma (BCC) (1; 0.30%). The presence of spores and/or hyphae could be a good indicator for non-malignancy, allowing differential diagnosis between benign CTs and SCCs or BCCs as well as between melanoma and nevi.

Staphylococcus aureus and squamous cell carcinoma of the skin.

Squamous cell carcinoma (SCC) of the skin is a tumor with greatly increased incidence among immunosuppressed patients; therefore, an infectious cause of SCC has long been sought. We performed a hospital-based case-control study of Staphylococcus aureus and biopsies of SCC (n = 82), basal cell carcinoma (n = 142), actinic keratosis (n = 57), and seborrhoeic keratosis (n = 72) in comparison with biopsies from healthy skin of these 353 immunocompetent patients. In a S. aureus-specific PCR, targeting the nuc gene, presence of S. aureus DNA was strongly associated with SCC (29.3% positive specimens; adjusted odds ratio, 6.23; 95% confidence interval, 3.10-12.53) compared with healthy skin (5.7% positive specimens). There was also a tendency for association of S. aureus with actinic keratosis, but no association was found for basal cell carcinoma or seborrhoeic keratosis. Analysis using cotton swab samples taken on top of the lesions and from healthy skin gave similar results (adjusted odds ratio for SCC compared with healthy skin, 2.67; 95% confidence interval, 1.47-4.83). In conclusion, there is a strong association between SCC and presence of S. aureus. The study design used cannot determine whether the association implies that presence of S. aureus might influence carcinogenesis or whether it may imply that SCC has an increased susceptibility to S. aureus colonization.

Estudio inmunohistoquímico de la calretinina en el folículo piloso normal y neoplasias con diferenciación folicular / Immunohistochemical study of calretinin in normal hair follicles and tumors with follicular differentiation

Introducción. La inmunotinción selectiva con calretinina evidencia la capa más interna de la vaina radicularexterna del folículo piloso normal, difícil de distinguir con la tinción de hematoxilina-eosina. Objetivo. Conocer si calretinina nos permite identificar neoplasias anexiales con diferenciación hacia la vaina radicular externa del folículo piloso. Material y métodos. Hemos analizado el patrón de inmunotinción para calretinina en 49 biopsias de distintas neoplasias anexiales cutáneas con diferenciación folicular. Resultados. Quince de las 49 tinciones correspondían a tricolemomas/queratosis folicular invertida, observándose positividad con calretinina en el epitelio de las áreas más superficiales de la lesión y en los remolinos escamosos; 10 quistes tricolémicos con positividad en su pared, tres carcinomas basocelulares con positividad variable dependiendo del tipo de diferenciación folicular de cada variante, un panfoliculoma con positividad focal, dos hamartomas sebáceos infundíbulo-quísticos con positividad en el conducto excretor de las glándulas sebáceas, dos pilomatricomas y tres tumores tricolemales proliferantes con positividad en las capas celulares cercanas a la luz de las estructuras quísticas, 9 tricoblastomas/tricoepiteliomas, dos quistes infundibulares, un poro dilatado de Winer y dos acantomas de la vaina folicular resultaron negativos. Conclusión. El estudio inmunohistoquímico de la calretinina nos permite identificar neoplasias anexiales del folículo piloso o componentes de éste, con diferenciación hacia la vaina radicular externa del folículo piloso (AU)

Background. Selective immunostaining for calretinin labels the innermost layer of the outer root sheath of normal hair follicles, which is difficult to distinguish with hematoxylin-eosin staining. Objective. The aim of this study was to determine whether immunohistochemistry for calretinin allows identification of cutaneous adnexal tumors with follicular differentiation towards cells of the outer root sheath.Material and methods. We analyzed the staining pattern for calretinin by immunohistochemistry in 49 biopsies of cutaneous adnexal tumors with follicular differentiation. Results. Fifteen biopsies corresponded to trichilemmomas/inverted follicular keratosis and had staining for calretinin in the epithelium of the most superficial areas of the lesions and in squamous eddies. Ten were trichilemmalcysts, which displayed staining of the cyst wall. Three were basal cell carcinomas with variable staining according to the type of follicular differentiation in each variant. One was a panfolliculoma that had focal staining. Two were folliculosebaceous cystic hamartomas with staining of the excretory duct of the sebaceous glands. Two pilomatricomas and 3 proliferative trichilemmal tumors had positive staining in the cellular layers close to the lumen of the cystic structures. Nine trichoblastomas/trichoepitheliomas, 2 infundibular cysts, 1 dilated pore of Winer, and2 acanthomas of the follicular sheath were negative for calretinin. Conclusion. Immunohistochemistry for calretinin allows identification of cutaneous adnexal tumors of the hair follicle or a component of the follicle with differentiation towards cells of the outer root sheath (AU)

[Large condylomatous lesions of the vulva and their malignant transformation]. / Golemi kondilomatozni lezii na vulvata i tiakhnoto maligneno izrazhdane.

For the period of 1987 till 2001 were examined 23 women with big condilomatous lesions of the vulva. There were examined the diagnostic and the therapeutical approach and in the last few years the type of HPV in some of these patients. Our aim was to study and reveal the potential for malignant transformation of the big condimatous lesions of the vulva. Different histological types squamous cell cancer of the vulva were found in 18 women (78.26%): condilomatous cancers--9, verucous--7 and basaloid types--2 vulvar cancer. HPV type 16 was found in 6 cases (4 condilomatous and 2 basaloid cancers). HPV type 6 was revealed in 6 cases with verucous cancer, type 11 in 1 case with verucous and 1 case with condilomatous cancer. In 1 case with condilomatous cancer we found HPV type 18. We used mostly radical vulvectomy with bilateral inguinofemoral lymph dissection a modo Ducuing. This kind of operation was performed in all women with the exception of the benign lesions with negative lymph nodes, where simple vulvectomy was mostly used. Wide local excision was used in 1 woman with verucous cancer and in 1 patient with basaloid cancer hemivulvectomy was performed.

Nanobacteria and calcinosis cutis.

BACKGROUND: The nanobacteria are a recently characterized group of extremely small bacteria capable of precipitating calcium salts implicated in the pathogenesis of urinary calculi and calcific atherosclerosis. The pathogenesis of calcinosis cutis and its significance in conjunction with a variety of unrelated scarring and pre-existing cutaneous entities are incompletely understood. METHODS: A series of cases, including basal cell carcinoma with dystrophic calcification, subepidermal calcified nodule, pilomatricoma, and tumoral calcinosis, were ultrastructurally examined for the presence of Nanobacteria sp. RESULTS: All cases, including three basal cell carcinomas, two subepidermal calcified nodules, three cases of pilomatricoma, and two cases of tumoral calcinosis, were negative for Nanobacteria. CONCLUSIONS: The dystrophic calcification that occurs in conjunction with the above entities does not likely involve a bacterial-induced etiology. The cause of these entities remains unknown.

Corynebacterium diphtheriae threats in cancer patients.

The aim of this study was to determine the bacteriological properties of Corynebacterium diphtheriae strains isolated from bronchiole washing and cancer lesions. Bacteriological characterization included fluorescence/double sugar urease (King/DSU) screening tests, pyrazinamidase (PYZ), CAMP-reactions and radial immunodiffusion toxigenicity assay. Microorganisms produced fluorescence under ultraviolet light and were catalase positive; urea and aesculin hydrolysis negative; fermentation of glucose, maltose and sucrose and no fermentation of mannitol and xylose; PYZ and CAMP reaction negative. The API-Coryne system was used for bacterial preliminary identification at local hospital laboratory and produced numerical profiles 1010325 and 0010325 for sucrose positive C. diphtheriae var. mitis (nitrate positive) and C. diphtheriae var. belfanti (nitrate negative), respectively. The hemagglutination, adherence to glass and polystyrene assays evaluated adhesive characteristics. Strains were toxigenic and able to adhere to glass, polystyrene and human erythrocyte surfaces (titer 4). C. diphtheriae strains isolated from cancer patients expressed adhesive characteristics similar to strains isolated from immunocompetent hosts. Circulation of toxigenic C. diphtheriae continues to present a threat for children and adults including patients with cancer in hospital environment. Laboratories should remain alert to the possibility of isolation of diphtheria bacilli from adults with neoplastic disease.

Corynebacterium diphtheriae threats in cancer patients

The aim of this study was to determine the bacteriological properties of Corynebacterium diphtheriae strains isolated from bronchiole washing and cancer lesions. Bacteriological characterization included fluorescence/double sugar urease (King/DSU) screening tests, pyrazinamidase (PYZ), CAMP-reactions and radial immunodiffusion toxigenicity assay. Microorganisms produced fluorescence under ultraviolet light and were catalase positive; urea and aesculin hydrolysis negative; fermentation of glucose, maltose and sucrose and no fermentation of mannitol and xylose; PYZ and CAMP reaction negative. The API-Coryne system was used for bacterial preliminary identification at local hospital laboratory and produced numerical profiles 1010325 and 0010325 for sucrose positive C. diphtheriae var. mitis (nitrate positive) and C. diphtheriae var. belfanti (nitrate negative), respectively. The hemagglutination, adherence to glass and polystyrene assays evaluated adhesive characteristics. Strains were toxigenic and able to adhere to glass, polystyrene and human erythrocyte surfaces (titer 4). C. diphtheriae strains isolated from cancer patients expressed adhesive characteristics similar to strains isolated from immunocompetent hosts. Circulation of toxigenic C. diphtheriae continues to present a threat for children and adults including patients with cancer in hospital environment. Laboratories should remain alert to the possibility of isolation of diphtheria bacilli from adults with neoplastic disease.(AU)

Extensive destruction of the eyeball by invasion of basal cell carcinoma of the eyelid.

BACKGROUND: Eyeball destruction caused by invasion of basal cell carcinoma of the eyelid. CASE: A 100-year-old woman showed extensive eyeball destruction caused by the invasion of basal cell carcinoma of the eyelid. Complete ophthalmologic examinations, including computed tomographic (CT) scans of the orbit, were performed. The patient underwent incisional biopsy and bacteriological examination of the exudate from the lesion. OBSERVATIONS: Orbital CT scan showed a mass in the extraconal space of the right orbit, with extension to the adjacent sinus cavity without brain involvement. The remnant of the eyeball was posteriorly displaced. Pseudomonas aeruginosa was identified by culture examination of the exudate. Histological study of the biopsy specimen showed basal cell carcinoma of the noduloulcerative type. CONCLUSIONS: Basal cell carcinoma of the eyelid had caused severe periorbital and eyeball destruction.

Cutaneous-malignancy and leprosy. Report of a patient with Mycobacterium leprae and basal cell carcinoma concurrently present in the same lesion.

BACKGROUND: Leprosy is a chronic systemic infection caused by the bacillus Mycobacterium leprae. Cutaneous neoplasms have been observed in patients with leprosy. Also, albeit less commonly, M. leprae have been documented in the lesions of skin cancer. OBJECTIVE: To describe a 62-year-old man with chronic sun exposure and exposure to armadillos who subsequently developed lepromatous leprosy, to discuss the cutaneous malignancies that have occurred in patients with leprosy, and to review the literature concerning the concurrent presence of an infectious pathogen and a cutaneous neoplasm in the same lesion. METHODS: Our patient's basal cell carcinomas were excised, his abdominal plaques were biopsied, and his leprosy infection was treated with dapsone and rifampin. The types of cutaneous malignancies in leprosy patients and infectious pathogens concurrently found in lesions of skin tumors were summarized after evaluating previously published reports. RESULTS: Skin biopsies from our patient demonstrated M. leprae bacilli not only in his abdominal plaques, but also in all of his basal cell carcinoma lesions. Fungal, mycobacterial, and viral pathogens have concurrently been observed in skin lesions of basal cell carcinomas, Kaposi's sarcoma, melanoma, mycosis fungoides, and squamous cell carcinoma. CONCLUSION: Patients with leprosy can develop skin cancers and the histologic interpretation of those skin cancers can show evidence of leprosy. It is uncertain to what degree the decreased cell-mediated immunity in patients with lepromatous leprosy either enhances their susceptibility to and/or influences the course of their cutaneous neoplasms; also, in these patients, the coexistence of M. leprae organisms and cutaneous malignancy in the same lesion is likely to be secondary to the high bacillary load that is present.

Specific types of human papillomavirus found in benign proliferations and carcinomas of the skin in immunosuppressed patients.

A total of 118 biopsies from skin lesions of 46 renal allograft patients was analyzed for human papillomavirus (HPV) DNA by polymerase chain reaction with degenerate primers and also partially by subsequent sequencing of the amplified fragment. Sixty-two % of the benign proliferations (31 of 50) contained DNA of known HPV types as well as HPV sequences related to a number of epidermodysplasia verruciformis-associated HPV types. HPV DNA sequences were found in 14 (56%) of 25 biopsies from squamous cell and basal cell carcinomas. One squamous cell carcinoma contained HPV 41 DNA. A novel 640-base pair fragment sharing homology with HPV 29 (82.7%) was found in 15% (3 of 20) of squamous cell carcinomas, in 9.4% (3 of 32) of dysplastic warts and in 8.5% (4 of 47) common warts. The remaining positive carcinoma biopsies contained HPV-related DNA in such a low copy number that additional analysis is required. The identification of new HPV types in skin cancers of immunosuppressed patients (other than epidermodysplasia verruciformis patients) further expands the spectrum of HPV-linked human malignancies and permits new approaches to study the pathogenesis of skin cancers.

Human papillomavirus DNA in the dermis of condyloma acuminatum.

Condyloma acuminatum (CA) has high recurrence rates after local treatments. Why this lesion is difficult to eradicate is unclear. One possible explanation for recurrence after superficial destructive therapy is the presence of residual human papillomavirus (HPV) in the superficial dermis beneath the treated epidermis. Thirteen samples of CA were excised from 13 patients. Thirteen samples of basal cell carcinoma (BCC) were studied for purposes of control. Epidermis was separated from dermis by treatment with sodium bromide. DNA was extracted from both tissues and used sodium bromide solution and amplified for the presence of HPV DNA using the polymerase chain reaction. HPV DNA was detected in the epidermis of 11 samples of CA. HPV type 6 was seen in 7 specimens; HPV type 11, in 4. HPV DNA was found in the dermis of 3 specimens of CA; type 6 in 2 and type 11 in 1. Two samples were excluded because of contamination of the sodium bromide solution by HPV. HPV DNA was not detected in tissue samples from BCC. The presence of HPV DNA in the dermis of some condylomata may explain recurrence in sporadic cases.

On a possible protective effect of HLA-A11 against skin cancer and keratotic skin lesions in renal transplant recipients.

Renal transplant recipients who have skin cancer potentially related to human papillomavirus were HLA typed with a special focus on HLA-A11, which in nonimmunosuppressed patients is negatively associated with the occurrence of virus-related carcinoma of the cervix. We found also a negative association between HLA-A11 and skin cancer; none of the 66 transplant recipients with skin cancer were positive for HLA-A11. As HLA-A11 seems to have a protective effect against skin cancer, we speculate that antigens induced by squamous cell carcinomas and possibly also by human papillomavirus may be efficiently presented through HLA-A11 to cytotoxic T cells. We also investigated a possible influence of other HLA alleles on the susceptibility of renal transplant recipients to skin cancer. The frequency of HLA-B27 was significantly higher in the transplant recipients with skin cancer, with a relative risk of 3.4 relative to healthy controls. No significant differences were found for other HLA class I or class II antigens.

Occurrence of human papillomavirus type 16 DNA in cutaneous squamous and basal cell neoplasms.

Sixty-eight cutaneous squamous cell neoplasms (in situ and invasive) and 26 basal cell carcinomas from 89 patients were analyzed for DNA sequences homologous to the human papillomavirus (HPV) types found predominantly in the genital tract. Thirty-six (53%) of the squamous cell neoplasms contained HPV DNA as detected by filter or in situ hybridization analysis. The frequency of detection of HPV DNA was dependent on the site of the lesion. Of 40 genital squamous cell neoplasms (penile, vulvar, and perianal), 27 (68%) had detectable HPV DNA. In 25 of these, the HPV type was 16 or HPV-16-related, which was similar to the results for the squamous cell neoplasms of the finger (HPV DNA in 9 of 11 tumors with HPV-16 in seven). None of 16 squamous cell neoplasms from sites other than the genital tract or the finger had detectable HPV DNA. HPV DNA was detected in one of the 26 basal cell carcinomas (4%). We conclude that, for cutaneous epithelial malignancies, HPV-16 is restricted to squamous cell neoplasms of the genital tract and finger. These data are consistent with venereal transmission of HPV-16 to the periungual region and suggests a role for this virus in the evolution of squamous cell carcinoma at this site.

Premalignant lesions and cancers of the skin in the general population: evaluation of the role of human papillomaviruses.

To evaluate the role of human papillomaviruses (HPV) in the development of premalignant lesions and cancers of the skin in the general population, 314 biopsies obtained from 227 patients with benign neoplasms, premalignant lesions, and cancers of the skin and from 25 patients with squamous cell carcinoma of the lip were analyzed by Southern blot hybridization. DNA probes specific for various cutaneous and genital HPV types were used in hybridizations conducted under nonstringent or stringent conditions. HPV DNA sequences were only detected in eight specimens obtained from six patients: HPV 34 in one case of periungual Bowen's disease, HPV 36 and an as yet uncharacterized HPV in two cases of actinic keratosis, HPV 20 in one case of basal cell carcinoma, an as yet unrecognized HPV in one case of squamous cell carcinoma, and HPV 16 in one case of squamous cell carcinoma of the lip. None of the specimens of cutaneous horn and keratoacanthoma contained detectable HPV DNA. In contrast, HPV DNA sequences, mostly HPV 16, were detected in 13 of 23 cases of anogenital Bowen's disease and invasive Bowen's carcinoma. HPV DNA sequences were not detected in 90 cutaneous samples further analyzed by the polymerase chain-reaction technique, using amplification primers that contain conserved sequences among the genomes of HPV. These results strongly suggest that the known HPV types play only a minor role, if any, in skin carcinogenesis in the general population.

Human papillomavirus type 2-associated basal cell carcinoma in two immunosuppressed patients.

Human papillomavirus-2 genomes were detected by molecular hybridization in two cases of basal cell carcinomas that developed in immunosuppressed individuals. This form of human papillomavirus is usually responsible for common warts in the general population. Although it does not appear to have oncogenic potential, it may be, in some cases, associated with cutaneous malignancy.

Aerobiology of irradiation with the carbon dioxide laser.

The ability of a carbon dioxide laser to scatter debris and aerosolize bacteria from human skin was tested by collecting the aerosols liberated with glass impingers together with a slit sampler. Two sets of tests were done--one to detect dispersal of cells from treatment of rodent ulcers or warts, and the other on pieces of skin obtained from autopsy material, which had been injected with spores. With low power levels a few bacterial particles were collected, together with some whole cells, however, at levels greater than 750 W cm-2 all the cultures were sterile.

Oncornavirus-like particles in human skin cancers.

A high-molecular-weight RNA encapsulated with an RNA-instructed DNA polymerase in particles possessing the density characteristic of the RNA tumor viruses has been detected in 13 out of 14 human malignant melanomas. The [3H]DNA synthesized by these particles in an endogenous reaction hybridizes to RNA extracted from the human melanoma particulate structures, but not to RNA from normal skin. Similar particles containing RNA and enzyme have been found in basal cell and squamous cell carcinomas of the skin. The RNA of the melanoma particles is easily distinguishable by hybridization from the RNAs found in the particles of the basal and squamous cell carcinomas.