Solid basal cell epithelioma (BCE) possibly originates from the outer root sheath of the hair follicle.

The presence and distribution of several cytokeratins (CKs) in 20 solid basal cell epitheliomas (BCEs) were investigated and compared with the pattern of CKs in normal epidermis, perilesional skin and in the outer root sheath (ORS) of the human hair follicle. Tissue samples were stained with monoclonal antibodies (MoAbs) against human CKs, using the APAAP technique. Additionally, CK profiles were assessed by gel electrophoresis and immunoblot technique. Cells of BCE and ORS were positively stained with the MoAb KL1, whereas the basal layer of normal epidermis remained negative. Six out of 20 BCEs were partially stained with the MoAb RPN1165, which also stained the lower ORS, but not the epidermal basal layer. Using SDS-PAGE and immunoblot, the CK profiles of BCE and ORS were almost identical, showing the presence of CKs 5, 6, 14, 16 and 17; the CK pattern of normal epidermis, however, showed the presence of CKs 1, 5, 10 and 14. Perilesional skin (< 5 mm) showed keratin changes similar to the BCE pattern; the basal layer was stained with the MoAb KL1 and the suprabasal layer was negative to MoAb CK1, in contrast to normal epidermis. Keratin analysis revealed a CK pattern of perilesional skin different from that of normal epidermis (CKs 1, 5, 6, 10, 14, 16 and 17). Our immunohistochemical and biochemical investigations underline the possible role of the lower ORS as a cellular pool for the generation of BCE.

Culture of hair matrix and follicular keratinocytes.

In recent years, a variety of in vitro models for the cultivation of hair follicles and their constituents have been developed. Outer root sheath (ORS) keratinocytes (KC) have been mainly studied in explant cultures, planted on bovine eye lens capsules, collagen substrata, 3T3 cell feeder layers, or dermal equivalents, yielding outgrowth of a multilayered stratified epithelium with some biochemical and ultrastructural characteristics of keratinocytic differentiation. More recently, ORS KC cultures have also been initiated from single cell suspensions, and organotypic cultures have been obtained by recombination with dermal cells, inducing a higher degree of epidermal differentiation. Presumptive human hair matrix cells have been isolated from plucked anagen hair follicles and have been successfully propagated on 3T3 cell or normal human fibroblast feeder layers, giving rise to multilayered stratified KC cultures. In contrast, only preliminary data exist concerning the cultivation of bulge cells that have been suggested to represent follicular stem cells. In conclusion we dispose of several in vitro models today to cultivate ORS KC and hair matrix cells that have increased our knowledge on the regulation of the human hair cycle by soluble factors and dermal-epidermal interactions. Further comparative studies on ORS KC, bulge cells and matrix cells have to be carried out to confirm the distinct character of these hair KC subsets.

[Disappearance of the ozone layer and skin cancer: attempt at risk assessment]. / Ozonabnahme und Hautkrebs: Versuch einer Risikoabschätzung.

The increased incidence of skin cancer recorded worldwide is alarming. The incidence of malignant melanoma has doubled in Germany every 10-15 years during recent decades, for example, as documented in the population-based cancer registry of the Saarland. In 1989, the incidence was 8.3 cases/100,000 inhabitants a year equally for both sexes. Non-melanoma skin cancer (basal cell and squamous cell carcinomas) showed a similar dramatic increase like melanoma and ranged in second place in the Saarland Cancer Registry in 1989, exceeded in men only by lung cancers and in women only by breast cancer. Their incidence was 93.4/100,000 in men and 55.8/100,000 in women. Epidemiological studies worldwide revealed a correlation between the increase of skin cancer incidence and UV exposure in white populations, and Caucasians living in regions near the equator are predominantly affected by this increase. Recently, incidence values for non-melanoma skin cancer in the USA were reported to be 232/100,000, whereas, for Queensland/Australia even numbers as high as 2398/100,000 (males) and 1908/100,000 (females) have been published. So far, the increase in skin cancer incidence has been related to changes in leisure time habits with increasing UV exposure. In this paper, an attempt is made to estimate any additional future risks for the development of skin cancer as a result of increasing UV radiation caused by stratospheric ozone depletion. Its reduction has been reported to be 3% over large areas of the globe (65 degrees North to 65 degrees South) according to the latest study of the United Nations Environment Programme.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth characteristics and differentiation of basal cell carcinoma in vitro--immunohistochemical, gel electrophoretic, and ultrastructural analysis.

Cell cultures were established from 48 solid basal cell carcinomas (BCC) and from the normal epidermis of the same patients. The growth characteristics and differentiation of BCC cells in vitro were compared with normal keratinocytes (nKC) by using immunohistochemistry, two-dimensional gel electrophoresis including immunoblots, transmission electron microscopy, and soft agar suspension culture. After isolation of the tumor tissue under a stereodissection microscope, explants were cultured on feeder layers of mitomycin-treated 3T3 cells. After 3-5 d, 73% of all explants of BCC could be successfully cultured showing spindle-shaped outgrowing cells. Compared to nKC, cultured BCC cells had a lower growth rate and showed a wider intercellular polymorphism regarding size and shape. Their labeling pattern with a wide panel of monoclonal antibodies showed significant differences from that of nKC. In particular, only weak reactions for various cytokeratins, filaggrin and vimentin depending on the BCC cell type (small, middle, large) were found. Two-dimensional gel electrophoresis revealed expression of keratins 5, 6, 14, 16, and 17 in BCC cells and of K 5, 6, 13, 14, 16, 17, and 19 in nKC. These findings were confirmed by immunoblot. On the ultrastructural level, only a few desmosomes and a lower degree of keratinization markers were detected in BCC cells; finally, when cultured in soft agar BCC cells formed colonies whereas nKC did not. Our findings indicate that cultured BCC cells may preserve in vitro some in vivo characteristics and maintain a growth and differentiation pattern that differs from cultured nKC. The culture model presented here provides further insights into the cytogenetic and histogenetic characteristics of BCC.

Long-term therapy of HIV-associated Kaposi's sarcoma with recombinant interferon alpha-2a.

Five young male patients with HIV-associated Kaposi's sarcoma (KS) were treated with recombinant interferon alpha 2a (rIFN-alpha-2a) over a period of 2-2.5 years. An IFN dose of 18 x 10(6) IU was given subcutaneously every day during the first 3 months of treatment and then on alternate days. Additional treatment with radiotherapy and laser therapy was given and, in some cases, isolated skin nodules were excised. Within 7 months of initiation of therapy one patient had a complete remission of his tumours, however, tumour progression recurred after the patient discontinued treatment. In another patient the tumour cleared within 9 months of rIFN therapy, and after 52 months he is still free of KS. The condition of a third patient tended to become stabilized during the first 6 months of therapy, but after 60 months there has been a slow progression. The fourth and fifth patients died 25 and 28 months, respectively, after the histological diagnosis of KS and the initiation of treatment. While on therapy with rIFN-alpha-2a, no life-threatening opportunistic infections occurred. The side-effects were mostly well tolerated, and no severe changes in haematological parameters were caused by the therapy.

Long-term combined rIFN-alpha-2a and zidovudine therapy for HIV-associated Kaposi's sarcoma: clinical consequences and side effects.

Interferon alpha (IFN-alpha) has been shown to be effective in treating HIV-associated KS in at least 30% of patients, and Zidovudine has proved beneficial for AIDS patients. Moreover, both drugs have demonstrated an inhibitory effect on HIV replication. Based on the above, we combined IFN-alpha and zidovudine for treatment of HIV-associated KS in order to evaluate tolerance and clinical efficacy. Twenty-one homosexual men with histologically proved HIV-associated KS were treated in an open trial with rIFN-alpha-2a 18 X 10(6) IU every second day and zidovudine 800-1200 mg/d. Treatment was discontinued within the first month in six patients: three of them developed subjective intolerance, and three others contracted severe opportunistic infections or HIV-cachexia. Fifteen evaluable patients received combination treatment over a period of 2-20 months (average 10 months). The dosage was reduced as required based on drug-induced cytotoxicity. Complete remission was observed in four patients, partial remission in three, stable disease in two, and progression in six, resulting in an overall response rate of 46%. Negative p24 expression prior to treatment was a positive predictor. Although extracutaneous involvement had a negative influence on tumor remission, even patients with a mean initial T-helper cell count below 100 mm3 responded positively. In conclusion, combination therapy of rIFN-alpha-2a with AZT may effectively control HIV-related Kaposi's sarcoma in more than 40% of patients. In contrast to monotherapy with IFN-alpha, patients with severely reduced immune systems will also benefit from combined treatment.

[Borrelia burgdorferi-induced pseudolymphoma with pathogen cultivation in an HIV-1 positive patient]. / Borrelia-burgdorferi-induziertes Pseudolymphom mit Erregeranzüchtung bei einem HIV-1-positiven Kranken.

Cutaneous symptoms and skin diseases are common findings in almost all HIV-1-positive patients. In many cases the clinical presentation and course of the skin diseases are atypical, and occasionally the development of the appropriate circulating antibodies is lacking or impaired. In this report we present a patient seen in our multidisciplinary outpatient clinic for HIV patients. This patient had a Borrelia burgdorferi infection with an unusual course. The acute inflammatory phase of the arthropod reaction was maintained over a period of 9 months with development into pseudolymphoma showing unusual cytological characteristics. Immunohistological evaluation revealed an almost complete lack of T-helper and Langerhans cells, but an increased number of activated cytotoxic cells with class II antigen expression. A marked serological response was observed on IgG-ELISA and in the IgG-immunofluorescence test. Borrelia burgdorferi was cultured in vitro from a skin biopsy of the involved area. To our knowledge this is the first reported case of skin borreliosis in an HIV-1-positive patient.