R. Dummer

Serum S100 – A Marker for Disease Monitoring in Metastatic Melanoma

BACKGROUND S100 proteins are low-molecular-weight calcium-binding proteins and appear to play an important role in various cellular processes such as cell division and differentiation. In histopathology, S100 is widely accepted as the marker of choice for immunohistochemical identification of malignant melanoma. When S100 was detected in the serum of patients with malignant melanoma, it was suggested that serum S100 may be a useful marker for the stage of disease. OBJECTIVE The aim of this study was to examine serum S100 concentrations of patients with different stages of malignant melanoma and to determine the value of serum S100 in the follow-up of melanoma patients during treatment. METHODS Sera were obtained from 73 melanoma patients in different stages of the disease. The control group consisted of 130 healthy subjects. In 4 patients with metastatic melanoma, serum S100 was measured serially. Serum levels were measured by a commercially available immunoradiometric assay. RESULTS While only 1 out of 25 stage I/II patients and 3 of 14 patients with lymph node metastases (stage III, 21.4%) showed detectable serum S100 levels, 27 of 34 patients with disseminated disease (stage IV, 79.4%) had elevated serum S100. Interestingly, rising levels of serum S100 in the serial measurement indicated progression of the disease, and a complete decline reflected 2 patient remissions. CONCLUSION The data support the value of serum S100 as a clinical marker for progression of metastatic melanoma and serological monitoring during systemic therapies.

A randomized controlled clinical trial of topical photodynamic therapy with methyl aminolaevulinate in the treatment of actinic keratoses in transplant recipients.

Background  Transplant recipients have an increased propensity to develop multiple actinic keratoses, which demonstrate an increased transformation rate into invasive squamous cell carcinoma.

Baseline staging in cutaneous malignant melanoma.

Background  Baseline staging in patients with primary cutaneous malignant melanoma (MM) is routine, but the diagnostic accuracy and the impact on clinical outcome are still unclear.

Updated Swiss Guidelines for the Treatment and Follow-Up of Cutaneous Melanoma

Melanoma is the most common lethal cutaneous neoplasm. In order to harmonize treatment and follow-up of melanoma patients, guidelines for the management of melanoma in Switzerland have been inaugurated in 2001. These have been approved by all Swiss medical societies involved in the care of melanoma patients. New data necessitated changes concerning the safety margins (reduction to maximally 2 cm) and modifications of the recommendations of follow-up.

Imiquimod in basal cell carcinoma: how does it work?

Imiquimod is a topical immune response modifier that binds to Toll‐like receptor‐7 and ‐8, inducing interferon‐α. We treated superficial basal cell carcinomas (BCC) with imiquimod 5% cream daily for 5–8 days. The BCC lesions were biopsied before treatment and following imiquimod treatment, when the lesion showed the signs of erosion. We applied histology, immunohistochemistry and gene array technology (AffymetrixTM) to gain further insight into the mode of action of imiquimod. Our findings demonstrate that imiquimod‐induced BCC regression is associated with a strong activity of the innate immune response, mediated by cells of macrophage–monocyte origin and is associated with the induction of apoptosis.

Therapy of cutaneous lymphoma: Current practice and future developments

Cutaneous lymphomas include various types of clonal lymphoproliferative disorders. The adequate treatment approach depends on the exact diagnosis and should be non-aggressive in most cases. In early stages, local approaches such as UV or radiotherapy are preferred. In advanced stages, systemic drugs such as interferon-α or bexarotene can be administered. Experimental approaches for cutaneous lymphomas include vaccination and gene therapy.

Blastic natural killer-cell lymphoma of the skin associated with myelodysplastic syndrome or myelogenous leukaemia: a coincidence or more?

We report three patients with blastic natural killer (NK)‐cell lymphoma of the skin associated with myelodysplastic syndrome (MDS) (two patients) or subacute myelomonocytic leukaemia (one patient). In two patients MDS was diagnosed before skin lesions; the patient with leukaemia initially presented with skin lesions. Our patients had several clinical features in common, namely multiple skin lesions with a bruise‐like appearance, involvement of the oral mucosa, and good general status at presentation but very rapid deterioration in the course of the disease. All patients died of disease 4–14 months after the diagnosis. Histopathologically, there were cutaneous infiltrates of slightly pleomorphic medium‐sized cells expressing CD4, CD56, terminal deoxynucleotidyl transferase (focally) and being negative for surface CD3, cytotoxic molecules, B‐cell‐associated markers and myelomonocytic markers. Erythrocyte extravasation was seen in all patients. T‐cell receptor genes were in germline configuration. MDS was classified as refractory cytopenia with multilineage dysplasia and ring sideroblasts and refractory anaemia with transition to refractory anaemia with excess of blasts. We reviewed similar cases reported in the literature showing coexistence of blastic NK‐cell lymphoma/leukaemia and MDS or myelogenous leukaemia. We conclude that given an overall limited number of reported cases of blastic NK‐cell lymphoma/leukaemia, its association with various myelodysplastic/myeloproliferative disorders seen in a subset of patients (≈ 15–20%) is more than coincidental and may indicate their common origin.

Efficacy and safety of bexarotene combined with psoralen-ultraviolet A (PUVA) compared with PUVA treatment alone in stage IB-IIA mycosis fungoides: final results from the EORTC Cutaneous Lymphoma Task Force phase III randomized clinical trial (NCT00056056)

Background  Psoralen plus ultraviolet A (PUVA) is the standard treatment for early stages of mycosis fungoides. There have been no adequate randomized controlled trials with sufficient power comparing this modality with other therapies.

Swiss Guidelines for the Treatment and Follow-Up of Cutaneous Melanoma

Melanoma is the most common lethal cutaneous neoplasm. There is major controversy over the best management of this malignancy. In order to harmonize treatment and follow-up of melanoma patients, guidelines for the management of melanoma in Switzerland have been inaugurated. They have been approved by all Swiss medical societies involved in the care of melanoma patients.

Circulating intercellular adhesion molecule-1 in melanoma patients : induction by interleukin-2 therapy

Intercellular adhesion molecule-1 (ICAM-1, CD54), a molecule bound to the cell surface membrane, mediates various cell-cell interactions in inflammation and immunosurveillance. By means of a new specific enzyme-linked immunosorbent assay (ELISA) for soluble ICAM-1, free circulating ICAM-1 was measured in serum from five healthy volunteers, 10 melanoma patients at different stages of their disease, and eight patients receiving high-dose interleukin-2 (IL-2) for metastatic melanoma. No correlation between the concentration of circulating ICAM-1 and the tumor burden could be detected. In melanoma patients receiving high-dose IL-2, we observed an increase of circulating ICAM-1 of up to 200%, compared to the concentration prior to therapy, ranging between 4 and 13 ng/ml. The increase in circulating ICAM-1 was associated with the induction of tumor necrosis factor-alpha and interferon-gamma.