G. Burg

Human Leukocyte Antigen G Up-Regulation in Lung Cancer Associates with High-Grade Histology, Human Leukocyte Antigen Class I Loss and Interleukin-10 Production

Immune evasion in lung cancer results from both structural and functional alterations of human leukocyte antigen (HLA) class I molecules and the local release of immunosuppressive cytokines. Recent data suggest that HLA-G, a nonclassical class Ib molecule, is involved in immune evasion by tumor cells. We sought to determine whether HLA-G could contribute to immunescape in lung cancer. All of 19 tumor specimens examined demonstrated detectable membrane-bound (HLA-G1), as well as soluble (HLA-G5) isoform transcription. Nine of 34 (26%) tumors were positive by immunohistochemistry using monoclonal antibody (mAb) 4H84, recognizing all denatured HLA-G isoforms, of which six were positive using mAb 16G1, recognizing soluble HLA-G. HLA-G immunoreactivity correlated with high-grade histology, with HLA-G being preferentially expressed on large-cell carcinomas. In these patients, loss of classical HLA class I molecules was observed to associate with HLA-G protein up-regulation. Moreover, we found interleukin-10 expressed in 15 of 34 (44%) tumors, and in most of the HLA-G-positive cases (7 of 9), suggesting up-modulation of HLA-G by interleukin-10. It is conceivable that HLA-G expression in lung cancer might be one of the ways how the tumor down-regulates host immune response, in addition to interleukin-10 production and HLA class I loss.

Successful treatment of three cases of nephrogenic fibrosing dermopathy with extracorporeal photopheresis

Background  Nephrogenic fibrosing dermopathy (NFD) is a recently described cutaneous fibrosing disorder associated with renal dysfunction. Patients present with thickened skin or oedematous skin with indurated papules and plaques involving extremities and trunk, and often associated with disabling contracture of the adjacent joints. The aetiology and pathogenesis remain largely unknown. As a consequence, therapeutic measures with proven efficacy are nonexistent to date.

Dermatofibroma: An Abortive Immunoreactive Process Mediated by Dermal Dendritic Cells?

Dermatofibromas are very common tumors of the skin, but little is known about their etiology and pathogenesis. Current concepts of disease pathogenesis are discussed, with special emphasis on an immunoreactive origin. There is recent evidence, that high numbers of cells with dendritic morphology and positive staining for factor XIIIa are concentrated at the periphery of the lesions. Furthermore, they express MHC class II molecules and costimulatory molecules such as B7-1 and B7-2 on their surface. Thus, there are similarities to professional antigen-presenting cells of the dendritic cell family, so-called dermal dendritic cells (DDCs), which have recently been identified in the human dermis. A concept is developed which explains DF as an abortive immunoreactive process, featuring DDCs as initiators of the disease.

Ca2+-binding proteins S100A6 and S100B in primary cutaneous melanoma*

Purpose: Commercially available polyclonal antibodies against a mixture of bovine brain S100 proteins have become an established marker for immunohistochemical characterization of malignant melanoma. However, the commercially available antibodies used are undefined and to date, 13 different human S100 proteins are known. The purpose of this study was to examine the expression of 4 newly available polyclonal antibodies against the human recombinant Ca2+‐binding S100 proteins, S100A1, S100A2, S100A4 and S100A6, in cutaneous melanoma and to correlate these findings with the standard S100 staining as well as with the metastatic potential of the primary.

Acute Generalized Exanthematous Pustulosis due to Doxycycline

Sterile epidermal neutrophilic pustulation can be observed in a variety of diseases. Though drug hypersensitivity is an uncommon cause, it is yet a known entity to be considered in the differential diagnosis of generalized pustulosis. In a 40-year-old woman, who developed a generalized pustular eruption after starting on doxycycline therapy of bronchitis, the rash was concluded to be drug induced after exclusion of other pustular dermatoses. Sensitization to doxycycline was demonstrated by in vitro lymphocyte testing and correlated with clinical drug hypersensitivity after recurrence of the pustular eruption on nonintentional rechallenge with doxycycline.

Generalized Eczematous Skin Rash Possibly due to HMG-CoA Reductase Inhibitors

We report on 3 patients who developed a generalized eczematous skin rash under treatment with simvastatin and pravastatin for hypercholesterolemia. These drugs are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and suppress cholesterol synthesis in the liver. Based on experimental data from the literature that showed eczematous changes in mice treated topically with the HMG-CoA reductase inhibitor lovastatin, we suspect that the rash observed in our patients may be a consequence of skin barrier dysfunction following inhibition of cholesterol biosynthesis.

No detection of HTLV-I proviral DNA in lesional skin biopsies from Swiss and German patients with cutaneous T-cell lymphoma

Summary The search for an infective agent linked to cutaneous T‐cell lymphoma (CTCL) has also included the human T‐cell lymphotropic virus type I (HTLV‐I). Using sensitive techniques such as Southern blotting under low stringency conditions of hybridization and polymerase chain reaction (PCR) with primer sets designed to match pol, env and pX sequences of HTLV‐I, we have screened lesional skin biopsies of 50 Swiss and German patients suffering from CTCL. No evidence of proviral integration of HTLV‐I could be demonstrated in any of our patients. Our results, as well as a review of the literature, indicate that at least for European patients, HTLV‐I does not seem to play a role in the aetiology of CTCL.

The interleukin-2 receptor in lesions and serum of bullous pemphigoid

SummaryThe interleukin-2 receptor (IL-2R) is mainly expressed on activated T cells. Depending on its rate of synthesis, a portion is released from the cell surface as soluble IL-2R (sIL-2R). Since the role of mononuclear cells in the pathology of bullous pemphigoid (BP) is not well understood, we determined the sIL-2R in both blister fluid and serum of 15 BP patients with generalized disease before initiating systemic treatment. In addition, we obtained both lesional and perilesional skin biopsies and examined the mononuclear infiltrate with a panel of monoclonal antibodies. In BP blisters, sIL-2R levels were significantly increased (2070±350 U/ml), (±SEM) compared with serum samples taken at the time of blister puncture (1340±290 U/ml). In six patients with blisters due to second-degree burns or friction and in five suction blister volunteers, sIL-2R levels were normal in both blisters and serum. In BP, elevated serum levels decreased to normal during therapy, correlating with disease activity. The immunohistology showed that 30% of mononuclear cells in the dermal infiltrate of lesional skin expressed the IL-2R, whereas only 15% were positive in perilesional skin. IL-2R-positive cells are the most likely source of the shed receptor in BP blisters. Our results indicate the presence of activated T cells in lesions and peripheral blood of BP and thus underline the importance of cell-mediated immune mechanisms in the pathology of this disease.

Lymphomatoid papulosis and human herpesviruses – A PCR-based evaluation for the presence of human herpesvirus 6, 7 and 8 and related herpesviruses

Lymphomatoid papulosis (LyP) is a chronic, recurrent lymphoproliferative disorder of the skin that belongs to the group of primary cutaneous CD30‐positive T‐cell lymphomas. Ultrastructural and clinical features of LyP suggest that it has a viral etiology. Human herpesviruses have been proposed as causative cofactors for LyP because of their oncogenic potential and their association with other lymphomas.

Eruptive vellus hair cyst and steatocystoma multiplex: hybrid cysts.

Steatocystoma multiplex (SM) and eruptive vellus hair cyst (EVHC) are known as clinically similar but histologically distinct entities, first described by Jamieson in 1873 and Esterly et al. in 1977, respectively. Herein we describe a 24-year-old female patient with both lesions on the anterior chest wall. The biopsy showed portions of two cysts close together with features of SM in one part and features of EVHC in the other part. Our case gives further evidence that these two conditions are closely related. To the best of our knowledge this is the first case where such an anatomically close relationship between these two types of cysts has been described.