[Adjuvant therapy of primary malignant melanoma with natural human interferon-beta. Significant survival advantage in 96 treated patients in comparison with 288 untreated symptomatic controls]. / Adjuvante Therapie des primären malignen Melanoms mit natürlichem humanen Interferon-beta. Signifikanter Uberlebensvorteil bei 96 behandelten Patienten im Vergleich zu 288 unbehandelten Symptomenzwillingen.

In the dermatological department of Dortmund's Municipal Medical Centre, between May 1986 and April 1991 a total of 105 patients with primary malignant melanoma (stage I) underwent adjuvant treatment with 5 million IU natural interferon beta as a 30-min i.v. infusion three times weekly for 6 months. During follow-up the patients were examined at short intervals and all recurrences and disease-related cases of death were documented up to September 1992. We evaluated the outcome of patients treated with interferon beta (n = 96 with valid notes of tumour thickness) compared with untreated historical controls (n = 288) matched for tumour thickness, localization, and sex, taken from the Central Malignant Melanoma Registry (CMMR) of the German Dermatological Society. Therefore, the main prognostic factors were identical between cases and controls. A computerized randomization was used to fit three control patients to each treated patient. Survival rate and recurrence-free survival were estimated in both groups for a period of 5 years. During the follow-up 3 patients died in the interferon beta group and the 5-year survival rate was 95%, as against 89% in the control group (P < 0.05 for difference between survival curves). Recurrence-free survival curves were also more favourable for interferon-treated patients than for the control group (P = 0.06). A detailed analysis of high-risk patients with tumour thickness of over 1.5 mm also demonstrated obviously better survival (5 years: 95% vs 77%; P = 0.012) and recurrence-free survival rates (5 years: 75% vs 53%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Bicomponent keratohyalin in normal human ridged skin.

Up to now, bicomponent keratohyalin has only been described for rat epithelium and human intraepidermal sweat ducts and fetal nail organ cells. In normal human interductal epidermis, the keratohyalin appears homogeneous, osmiophilic and stellate in shape. Under pathological conditions, bicomponent keratohyalin has been observed in different palmoplantar keratoses and has therefore been thought to be associated with abnormal keratosis. We studied the keratinization process in normal human plantar epidermis, in which keratohyalin was found to exhibit several morphological differences as compared to that seen in non-ridged skin. The most striking feature was seen in upper granular cells, where the keratohyalin granules consisted of two components of differing electron density. The electron-dense component formed the main part of the composite granule and was found in the cytoplasm of lower and upper granular cells. The less-electron-dense component was attached to the main component and appeared in the cytoplasm of upper granular cells, forming the convex contact zone. No intranuclear osmiophilic inclusions were present. The respective electron densities of the two keratohyalin components of ridged skin were obviously different to that of the bicomponent keratohyalin granules seen in the epidermal sweat-duct cells of the same specimen. These findings indicate the presence of at least two different types of keratohyalin proteins in normal human ridged skin. They can be distinguished at the electron-microscope level and differ from the keratohyalin of human non-ridged skin as well as from bicomponent keratohyalin granules derived from human epidermal sweat-duct cells or from rat epithelium.

Hereditary palmoplantar keratosis of the Gamborg Nielsen type. Clinical and ultrastructural characteristics of a new type of autosomal recessive palmoplantar keratosis.

A new kind of diffuse palmoplantar keratoderma with autosomal recessive inheritance and without associated symptoms was described in Norrbotten, Sweden by Gamborg Nielsen in 1985. Clinically, it ranges between the less severe dominant Unna-Thost type and the more severe recessive Meleda type, as it is milder than the latter. Skin biopsies of five patients from three different families with this new palmoplantar keratoderma, as well as five obligatory heterozygotes from one family, were investigated ultrastructurally in order to characterize this new entity and to differentiate it from the Meleda type. Several features are common to both autosomal recessive palmoplantar keratoses. They show a broadened granular layer, a transit region consisting of cells with a marginal envelope, and considerable hyperkeratosis. Morphologically, this transformation delay is less pronounced in the Gamborg Nielsen type than in the classical Meleda type. As is typical for ridged skin, both types of palmoplantar keratoses possess composite keratohyaline granules. In contrast to the normal appearance of keratohyaline granules in the Meleda type, the Gamborg Nielsen type also shows qualitative deviations of keratohyaline granules with different degrees of spongiosity and electron density and sometimes with a granular border. It seems that abnormal keratohyaline proteins are synthesized that behave differently. The sudden transformation of a granular into a horny cell is physiologically regulated by different enzymes. A delay in this process may be caused by a mutation that reduces or alters the enzymes concerned. We assume the palmoplantar keratoderma of the Gamborg Nielsen type to be a variant of the heterogeneous group of the Meleda type of palmoplantar keratoderma with autosomal recessive inheritance.