Volker Mielke

A subset of macrophages located along the basement membrane ("lining cells") is a characteristic histopathological feature of psoriasis.

In this paper, we describe the immunophenotype and ultrastructure of a new macrophage subpopulation present in inflamed but not in normal human skin. In biopsy material from patients with psoriasis (n = 4), atopic dermatitis (n = 4), and positive patch test reactions (n = 4), spindle-shaped macrophages located along the basement membrane were detected staining positive for CDllc (LeuM5high, Ki-Ml low), CD68 (Ki-M6 low), and Ki-M8 (low). This subpopulation was most prominent in psoriasis, where a median of 34 macrophages neighbored 100 basal keratinocytes, thus covering about 80% of the dermoepidermal junction. The numbers of atopic and positive patch test reactions were 11 and 13, respectively, accounting for about 20% of the dermoepidermal junction. Transmission electron microscopy revealed an electron-lucent nucleus with dense deposits of chromatin along the nuclear membrane. Interruptions of the integrity of the basement membrane neighboring these cells were also seen. We repeatedly observed parts of basal keratinocytes merging through these openings and macrophages exhibiting cytoplasmic extentions directed toward the porus. Our observations suggest vigorous interactions between macrophages and basal keratinocytes and support the hypothesis that these interactions are an important regulatory event in the pathogenesis of psoriasis.

Cellular and molecular composition of human skin in long‐term xenografts on SCID mice

Abstract We report on the immunophenotypical characterization of adult human skin transplanted onto severe combined immunodeficienl (SCID) mice. Thirty animals were followed for up to 12 months after receiving split‐thickness xenografts. of which 28 were tolerated for the whole test period. Antigen mapping revealed an almost complete preservation of human cellular and extracellular tissue components in long‐term trans‐plants including skin immune cells (Langerhans‐cells, macrophages. lymphocytes) and also parts of the engrafted endolhelium. Hence, xeno‐grafts on SCID mice offer a versatile experimental tool for the in vivo study of both human skin immune cell function and endothelial cell‐mediated interactions in an environment completely devoid of inter‐ferences by adoptive host immune response.

Retikuläres elastolytisches Riesenzellgranulom Eine Variante des anulären elastolytischen Riesenzellgranuloms

ZusammenfassungDie vorliegende Kasuistik beschreibt eine neue klinische Variante des elastolytischen Riesenzellgranuloms, das sich am häufigsten in Form anulärer randbetonter Herde im Gesicht und am Hals manifestiert. Bei einer 40jährigen Patientin entwickelten sich im Verlauf von 10u2005Jahren retikuläre, bräunliche bis livide, teils atrophische Herde in der Schulterregion und im Decolletée. Subjektive Symptome bestanden nicht. Histologisch dominierte ein herdförmig betontes lymphohistiozytäres Infiltrat im oberen und mittleren Korium mit zahlreichen Fremdkörperriesenzellen. Muzinablagerungen waren nicht nachweisbar. Mit der Elastikafärbung ließ sich eine Rarefizierung der elastischen Fasern darstellen. Zum Teil fanden sich Fragmente dieser elastischen Fasern in Makrophagen und Riesenzellen. Wir schlagen für diese Variante die Bezeichnung „Retikuläres elastolytisches Riesenzellgranulom“ vor.n SummaryThe case report presented describes a new variant of annular elastolytic giant cell granuloma. Over a period of 10u2005years, a 40-year-old woman had developed reticular, brown to livid, partly atrophic skin lesions on the shoulders and decolletée. The patient had no subjective symptoms. Histology revealed a patchy lymphohistiocytic infiltrate in the dermis, with many giant cells. Elastic fibres were less frequently found in these infiltrates; in a few of the giant cells and macrophages fragments of elastic fibres were demonstrated within the cytoplasm. There were no deposits of mucin. For this new variant we propose the term “reticular elastolytic giant cell granuloma.”

Predominant usage of distinct T-cell receptor V beta regions by epidermotropic T cells in psoriasis

Abstract To investigate the role of T cells in psoriasis, we analyzed the T‐cell receptor (TCR) repertoire in peripheral blood lymphocytes (PBLs) and in skin lesions of 9 patients with chronic plaque‐stage psoriasis by means of immunohistochemistry. An extended panel of monoclonal antibodies detecting 11 different V(3 families was employed in this study. In the peripheral blood, no predominant TCR Vβ expression was detected and interindividual differences were small. Skin‐infiltrating T cells showed only marginal differences in the TCR Vβ usage when compared with PBLs. However, in 3 patients the intraepidermal infiltrate comprised up to 40% of T cells expressing a TCR Vβ region which was virtually absent in the peripheral blood and the dermal infiltrate. Thus, although the TCR Vβ usage of skin‐infiltrating T cells showed little difference compared to PBLs, several cases exhibited a significant increase of epider‐motrophie T cells using one particular Vβ region.

Parakeratosis variegata nach Pityriasis lichenoides et varioliformis acuta

ZusammenfassungEs wird über einen 34jährigen Patienten mit dem seltenen Krankheitsbild einer Parakeratosis variegata berichtet, die nach einem Zeitraum von 4 Jahren nach einer Pityriasis lichenoides et varioliformis acuta auftrat. Um einem möglichen pathogenetischen Bezug dieser Erkrankungen aus der Gruppe der Parapsoriasisveränderungen untereinander und bzgl. ihrer Beziehung zum niedrigmalignen Non-Hodgkin-Lymphom des T-Zelltyps zu untersuchen, führten wir histologische, immunhistochemische und molekulargenetische Analysen durch. Während beide Erkrankungen charakteristische histologische Veränderungen sowie ein überwiegendes lymphozytäres epidermotropes T-Zellinfiltrat aufwiesen, konnte ein monoklonales Rearrangement des T-Zell-Rezeptors innerhalb beider Veränderungen nicht gesichert werden. Somit interpretieren wir beide Erkrankungen als eigene Entitäten und in diesem Fall ohne Bezug zum niedrig malignen Non-Hodgkin-Lymphom des T-Zelltyps.SummaryWe report on a 34-year-old male patient who developed generalized parakeratosis variegata lesions 4 years after suffering from pityriasis lichenoides et varioliformis acuta. For further investigation of a possible interrelationship between these two diseases of the parapsoriasis group and their relationship to the T-cell type of cutaneous non-Hodgkin-lymphoma, histological, immunohistological and molecular-biological techniques were applied. We were able to demonstrate typical morphological features common to both diseases, and a polyclonal T-cell infiltrate in both. It is concluded that pityriasis lichenoides et varioliformis acuta and parakeratosis variegata are separate entities without monoclonal rearrangement or signs of malignancy.n

Granulomatous slack skin – cutaneous elastolytic lymphoma. Two case reports

Zusammenfassung. Granulomatous slack skin (GSS) ist eine von Ackermann eingeführte Bezeichnung für ein 1973 von Convit etu2005al. erstmals beschriebenes Krankheitsbild. Es handelt sich um ein sehr seltenes kutanes Lymphom, das mit umschriebenen Cutis-laxa-artigen elastolytischen Herden und einem granulomatösem Infiltrat einhergeht. Wir berichten im deutschen Schrifttum erstmals über 2 männliche Patienten mit dem Vollbild dieser Erkrankung. Beide zeigten unter einer Therapie mit Interferon-α2b eine deutliche Remission, die bei einem der Patienten unter Clofazimin aufrechterhalten werden konnte. Die Gemeinsamkeiten beider Patienten werden dargestellt und eine Übersicht über die bisher veröffentlichten Fälle gegeben.Abstract. The term granulomatous slack skin (GSS) was introduced by Ackermann for a disease first described by Convit etu2005al. in 1973. GSS represents a rare cutaneous lymphoma characterized by localized elastolytic lesions with a granulomatous infiltrate. We recently observed two male patients with the characteristic features of this disease. Both patients responded well to therapy with interferon-α2b. In one patient clinical remission was stable under long-term treatment with clofazimine. We report on common features of these two patients and give a review of the cases published in the literature.

Systemic treatment for cutaneous lymphomas.

Primary malignant T cell lymphomas of the skin form a heterogenous group. Relevant classifications were recently made to separate different entities by various criteria. This is of great importance, because one should only rely on those therapeutical trials in which patients were included according such classifications. In this paper, we will mainly focus on therapeutic modalities for mycosis fungoides, which is the most frequent cutaneous T cell lymphoma and which may serve as a model disease. In principle, local (e.g., psoralens and ultraviolet A, PUVA) and systemic therapies (e.g., interferon-alpha 2a) can be applied. Very recently, we were able to demonstrate that even in initial stages of mycosis fungoides, the T cell clone is not restricted to the skin, but rather is present in low amounts in the peripheral blood. Therefore, systemic therapeutic modalities alone or in combination with local strategies (interferon-alpha 2a and acitretin/PUVA and interferon-alpha 2a) should be more effective, which will be proven by currently running clinical trials.

Adhesion Receptors in Normal Skin and Cutaneous Malignant Lymphomas: Pathophysiological and Clinical Correlations

The molecular mechanisms underlying the phenomenon of epidermotropism are still poorly understood. To determine the importance of adhesion molecules and their ligands in the process of T-cell migration into the epidermis, we analyzed, by immunohistochemistry, the expression pattern of adhesion molecules belonging to the integrin and immunoglobulin superfamilies in inflammatory skin disorders and malignant T-cell lymphomas. Cases with diffuse, focal, or no epidermotropism were distinguished in the lymphomas investigated. LFA-1 and LFA-3 were present on infiltrating cells in all cases of epidermotropic and nonepidermotropic cutaneous T-cell lymphoma (CTCL) as well as in reactive processes. β1-integrins showed differential expression, most prominent in the case of VLA-1 and VLA-6: These molecules were expressed on infiltrating cells in the majority of cases, with epidermotropic MF comparable to inflammatory conditions, and were absent in most other CTCLs. Thus, differential expression and regulation of avidity seem to contribute to the phenomenon of epidermotropism, with VLA-1 being the most influential β1 integrin.