Survey among patients with basal cell carcinoma in The Netherlands.

This paper describes the findings of a survey distributed among Dutch patients with basal cell carcinoma (BCC). The questionnaire comprised a list of questions related to demographic characteristics, features of BCC, reason for consulting a dermatologist, anxiety, type of treatment and the satisfaction with this treatment and desired benefits of treatment. In total, 220 patients completed the survey. The age of these responders varied between 27 and 89 years (mean 64.6 years). Half of the patient group had already previously experienced a BCC. Most patients (52%) indicated that the diagnosis 'skin cancer' frightened them, but that they knew it could be treated. Accordingly, most patients (70%) indicated that BCC had no or hardly any influence on their quality of life. From the patient's perspective, efficacy, low recurrence rate and no or minor scarring are important features of a BCC treatment. Surgery was the most popular therapy. The number of BCC patients is growing, which will lead to a definite burden for dermatologists in the near future. Our survey demonstrated that patients are mostly interested in the efficacy, low recurrence rates and cosmetic outcome of their therapies. Newly efficacious and non-invasive therapies, such as the recently introduced photodynamic therapy or home treatment with imiquimod, can help to overcome these concerns.

The expression of interleukin-8 receptor in untreated and treated psoriasis.

The expression of IL-8 in psoriasis has been clearly shown with the use of immunocytochemical, RT-PCR and in situ hybridization methods. The presence of its ligand, the IL-8 receptor, has been demonstrated by the RT-PCR technique. We report here a study of the expression of both IL-8 type A and B receptors by immunohistochemical techniques, using one polyclonal and four monoclonal antibodies. By this technique, we found that the neutrophilic granulocytes express the IL-8 type A receptor, whereas the IL-8 type B receptor was present on the keratinocytes. The type B receptor on the keratinocytes was localized in the suprabasal layers of the epidermis. Following therapy, the expression of the IL-8 type B receptor on the keratinocytes was reduced. This could suggest that IL-8 in psoriasis is involved in the disturbed differentiation rather than in proliferation, probably via an autocrine loop.

Relation between expression of adhesion molecules and clinical behavior in cutaneous follicle center cell lymphomas.

BACKGROUND: Primary cutaneous follicle center cell lymphomas (PCFCCLs) of the head or trunk have a much better prognosis than morphologically similar large-cell lymphomas on the legs or follicle center cell lymphomas involving the skin secondarily (SCFCCLs). Recent studies suggest a relation between the expression of adhesion molecules and clinical behavior of malignant B-cell lymphomas. OBJECTIVE: Our purpose was to investigate a potential relation between the expression of adhesion molecules and clinical behavior of these three prognostically different groups of cutaneous B-cell lymphomas. METHODS: Immunohistochemical studies with a selected panel of monoclonal antibodies against adhesion molecules were performed on 10 PCFCCLs on the head or trunk, five PCFCCLs of the legs, and seven SCFCCLs. Expression of adhesion molecules was correlated with clinical and follow-up data. RESULTS: PCFCCLs of the head and trunk expressed ICAM-1 (80%) and LFA-1 (50%) much more frequently than PCFCCLs of the legs (40% and 20%, respectively) and SCFCCLs (14% and 14%, respectively). VLA-4 was expressed in 60% of PCFCCLs of the legs, but not by the PCFCCLs of the head or trunk. Absence of both ICAM-1 and LFA-1 on the neoplastic B cells correlated with a poor prognosis (seven of nine patients died of systemic lymphoma). In contrast, none of the patients with expression of LFA-1 or ICAM-1 have died of lymphoma thus far. CONCLUSION: Our results suggest a relation between the expression of adhesion molecules and the differences in clinical behavior between different groups of primary and secondary cutaneous follicle center cell lymphomas.

The long-term safety and efficacy of cyclosporin in severe refractory atopic dermatitis: a comparison of two dosage regimens.

An open, randomized trial was performed to determine the optimal dosage schedule with regard to the efficacy and safety of cyclosporin in severe atopic dermatitis. The study also provided clinical experience with regard to the efficacy and safety of long-term cyclosporin treatment. During a 2-month dose-finding period, 78 patients with severe, long-standing atopic dermatitis received cyclosporin at a dose of either 5 mg/kg per day, decreasing to 3 mg/kg per day (Group A), or 3 mg/kg per day, increasing to 5 mg/kg per day (Group B), Patients were maintained on their optimal dose for a further 10 months. Patients in Group A showed a significantly greater improvement in efficacy parameters over the first 2 weeks than with patients in Group B, but as the dose was decreased in Group A and increased in Group B, these differences were minimized. After 1 year, cyclosporin showed an efficacy of 59.8% in Group A and 51.7% in Group B, assessed by a severity score. Assessed in terms of an area score, these figures were 48.7% and 40%, respectively. Cyclosporin demonstrated a good safety profile during long-term treatment and was generally well tolerated. The lower starting dosage was not associated with higher dropout rates. This study showed no differences in efficacy or adverse events between the two dosage schedules in long-term treatment.

Distinctive adhesion pathways are involved in epitheliotropic processes at different sites.

Intraepithelial migration of lymphoid cells (epitheliotropism) is a biological process that can be observed under various physiological and pathological conditions. Recently, epitheliotropism was proposed to be a multi-step process, involving interactions of lymphoid cells with both epithelial basement membrane (EBM) and epithelial cells. In the present study we analysed by immunohistochemistry the adhesion mechanisms that are potentially involved in epitheliotropism of lymphoid cells in various disorders, such as tonsillar hyperplasia, coeliac disease, malignant lymphomas of mucosa-associated lymphoid tissue (MALTomas), and mycosis fungoides (MF). The combinations of adhesion molecules expressed on the participating lymphoid and epithelial cells varied among these disorders. These findings suggest that the adhesion pathways utilized in epitheliotropism may be associated with the nature of the lymphoid cell (reactive or neoplastic/B or T) and/or the site of the epithelium involved. In some cases the specificity of the process was determined by the adhesion mechanism involved in the lymphocyte-EBM interaction, as in the case of alpha 3 beta 1 integrin/laminin-5 in MF, and in others by the adhesion mechanisms involved in the interaction between lymphoid and epithelial cells, such as alpha 4 integrin/VCAM-1 in tonsillar hyperplasia and alpha E beta 7/E-cadherin in coeliac disease.

Classification of primary cutaneous T-cell lymphomas.

The term cutaneous T-cell lymphoma designates a group of neoplasms of skin homing T-cells that show considerable variation in clinical presentation, histological appearances, immunophenotype and prognosis. The disadvantages of currently available histological classification schemes are discussed and a new classification is presented. This is based on a combination of clinical, histological and immunophenotypic criteria and it recognizes distinct clinico-pathological entities within this group of diseases.

Classification of primary cutaneous large cell lymphomas.

Primary cutaneous large cell lymphomas represent a heterogeneous group of malignant lymphomas of T- and B-cell origin. Recent studies have been successful in delineating some well-defined clinicopathologic entities within this group. Primary cutaneous follicular (germinal) center cell lymphomas are the most common type of CBCL. These lymphomas generally present with localized skin lesions on the trunk or scalp. They have an indolent clinical course, are highly sensitive to radiotherapy, and have a favorable prognosis. Within the group of primary cutaneous T-LCL, distinction primarily should be made between CD30-positive (> 75% or large clusters of tumor cells) and CD30-negative (no or few scattered positive cells) T-LCL. Primary cutaneous CD30-positive T-LCL, which includes both anaplastic and non-anaplastic subtypes, have recently been defined as a distinct clinicopathologic entity with a favorable prognosis. The overlapping clinical and histological features with LyP suggest that both conditions are part of a broader spectrum of primary cutaneous CD30-positive lymphoproliferative disorders. Primary CD30-negative T-LCL generally are associated with a poor prognosis (4-year-survival, < 25%). Reports on this group are still few, however, and further studies are required to define subgroups with a more favorable prognosis within this heterogeneous group of lymphomas.

Classification of primary cutaneous lymphomas. Historical overview and perspectives.

Primary cutaneous lymphomas represent a heterogeneous group of malignant B- and T-cell lymphomas. In the last two decades, the diagnostic criteria, classification and terminology of these disorders have changed enormously. A historical overview of the subsequent concepts on the classification of this group of disorders is presented. Disadvantages of currently available classification schemes are discussed, and a proposal for a new classification for this group of disorders is formulated.

Primary cutaneous T-cell lymphoma: clinicopathological features and prognostic parameters of 35 cases other than mycosis fungoides and CD30-positive large cell lymphoma.

Within the group of primary cutaneous T-cell lymphomas (CTCLs), mycosis fungoides (MF), Sézary's syndrome (SS), and CD30-positive lymphomas have been delineated as clinicopathological entities. Primary CTCLs that do not belong to one of these entities represent a heterogeneous and ill-defined group of neoplasms. This paper describes the clinical and histological features of 35 of such cases. The object of this study was to define prognostic parameters for this group of primary CTCLs. Using a slightly modified version of the updated Kiel classification, a subdivision was made into CTCL, pleomorphic, small cell type (n = 3); pleomorphic, medium-sized cell type (n = 6); pleomorphic, large cell type (n = 18); and immunoblastic lymphomas (n = 8). Altogether, these lymphomas had a poor prognosis with estimated 2- and 4-year survival rates of 53 and 22 percent, respectively. Patients with pleomorphic, small and medium-sized cell lymphomas (n = 9) proved to have a significantly better survival than those with pleomorphic, large cell lymphomas (P = 0.032) and immunoblastic lymphomas (P = 0.008). Primary cutaneous immunoblastic lymphomas had the worst prognosis with an estimated 2-year survival rate of 14 percent. Other parameters including age (P = 0.345), sex (P = 0.662), extent of skin lesions at presentation (P = 0.0854), and mode of initial treatment (P = 0.609) had no significant effect on the survival time. The results of this study suggest that primary CTCLs other than classical MF, SS, and CD30-positive lymphomas have a poor prognosis in most cases, and that the current classification may be a useful means of predicting the clinical behaviour in these lymphomas.

Differences in clinical behaviour and immunophenotype between primary cutaneous and primary nodal anaplastic large cell lymphoma of T-cell or null cell phenotype.

The histological, immunophenotypic and clinical features of 19 primary cutaneous anaplastic large cell lymphomas (cutaneous ALCL) were compared with those of 18 primary nodal anaplastic large cell lymphomas (nodal ALCL) of T-cell or null cell type. Although cutaneous ALCL and nodal ALCL had identical morphological features, differences in surface marker expression and clinical behaviour were found. Immunophenotypical differences concerned the expression of epithelial membrane antigen (82% of the nodal ALCL were positive v. none of the cutaneous ALCL) and the cutaneous lymphocyte antigen (HECA-452), a possible skin-homing receptor on cutaneous T-lymphocytes (most tumour cells in 44% of cutaneous ALCL cases were positive, whereas nodal ALCL showed expression of HECA-452 on only few tumour cells (< 25%) in 18% of cases tested). Loss of T-cell markers was more pronounced for nodal ALCL. Patients with cutaneous ALCL were generally older (median 61 years) than patients with nodal ALCL (median 24 years) and, in contrast to the latter group, did not show bimodal age distribution. Survival after 4 years, using lymphoma-related death as an end-point, differed significantly between cutaneous ALCL and nodal ALCL; 92% for cutaneous ALCL and 65% for nodal ALCL (P = 0.04). The better survival of cutaneous ALCL patients could not be ascribed to differences in age, stage or initial mode of treatment. These data indicate that differences in immunophenotype and clinical behaviour exist between morphologically identical primary cutaneous and primary node-based ALCL. They indicate that the primary site is an important prognostic factor in predicting the clinical outcome of ALCL.

Spectrum of primary cutaneous CD30 (Ki-1)-positive lymphoproliferative disorders. A proposal for classification and guidelines for management and treatment.

Primary cutaneous CD30 (Ki-1)-positive, large cell lymphomas (LCLs) represent a recently recognized group of cutaneous T-cell lymphomas with a favorable prognosis. The characteristic features of this cutaneous lymphoma are reviewed, differences with primary noncutaneous CD30+ LCLs emphasized, and its relation with other CD30+ cutaneous lymphoproliferative disorders, in particular lymphomatoid papulosis, is discussed. These primary cutaneous CD30+ LCLs, lymphomatoid papulosis, and related conditions represent a clinical and histologic continuum. A classification with practical guidelines for the management and treatment of patients within this spectrum of lymphoproliferative disorders is presented.

Primary cutaneous CD30-positive large cell lymphoma: definition of a new type of cutaneous lymphoma with a favorable prognosis. A European Multicenter Study of 47 patients.

BACKGROUND: CD30 (Ki-1)-positive anaplastic large cell lymphoma (LCL) has been described as a morphologically distinct group of LCL that generally are associated with a poor prognosis. Recent studies indicate that these lymphomas, when confined to the skin, have a favorable prognosis. However, there is no consensus regarding the definition of these primary cutaneous CD30-positive LCL. Reported patients have been selected variously on the basis of morphologic (anaplastic cytology) or immunophenotypical (expression of CD30 antigen) criteria. METHODS: At two recent workshops aimed to achieve consensus on the definition and terminology of these lymphomas, the clinical, histologic, and immunophenotypical data of 47 patients with primary cutaneous CD30-positive LCL from five collaborating European centers were analyzed. RESULTS: Characteristic clinical features were presentation with solitary or localized skin lesions (42 of 47 patients), frequent cutaneous relapses (15 patients), and partial or complete spontaneous remission of skin lesions (11 patients). Twelve of 47 (25%) patients developed extracutaneous disease. The favorable prognosis of these lymphomas is indicated by the follow-up data that show that 36 of 47 patients are alive and in complete remission, only four disease-related deaths have occurred, and the overall median survival is 42 months (range, 2-130 months). There were no differences in clinical presentation, course, or prognosis between anaplastic and nonanaplastic CD30-positive LCL. CONCLUSION: The results of this study indicate that primary cutaneous CD30-positive LCL, regardless of their morphologic classification (anaplastic or nonanaplastic) can be considered as a distinct type of cutaneous T-cell lymphoma. Recognition of this type of cutaneous lymphoma is important because it may prevent patients from unnecessary aggressive treatment.

Oral etoposide in the treatment of cutaneous large-cell lymphomas. A preliminary report of four cases.

The favourable results of oral etoposide as single-agent therapy in four patients with a cutaneous lymphoma other than mycosis fungoides are reported. In all cases other chemotherapeutic options were limited because of prior chemotherapy or the age of the patients. Therapy with etoposide resulted in an initial complete remission in all patients, and was associated with minimal side-effects.

Differential expression of the HECA-452 antigen (cutaneous lymphocyte associated antigen, CLA) in cutaneous and non-cutaneous T-cell lymphomas.

The monoclonal antibody HECA-452 identifies an antigen that is primarily expressed on high endothelial venules, the preferred site of lymphocyte extravasation in lymphoid tissues, and also on a subpopulation of myelomonocytic cells and some T-cells. We investigated the expression of the HECA-452 antigen, also called the cutaneous lymphocyte associated antigen, in primary cutaneous and primary non-cutaneous T-cell non-Hodgkin's lymphomas. The tumour cells of cutaneous T-cell non-Hodgkin's lymphomas were positive in 53% of cases, while only 5% of the non-cutaneous lymphomas were positive. These differences were also present in morphologically identical tumours. Thus, the tumour cells in six out of 10 primary cutaneous anaplastic large cell T-cell lymphomas were positive, while they were positive in none of 24 primary non-cutaneous anaplastic large cell T-cell lymphomas. In general, primary cutaneous and primary nasal T-cell non-Hodgkin's lymphomas were devoid of HECA-452 positive high endothelial venules, whereas most nodal T-cell non-Hodgkin's lymphomas contained HECA-452 positive high endothelial venules. These observations suggest that the HECA-452 antigen might be related to a skin-associated type of lymphoid tissue and to lymphomas originating in the skin. However, the results of HECA-452 expression in secondary sites, and the clinical data of the primary cutaneous large cell lymphomas did not support the concept that HECA-452 is functionally involved in homing to the skin, or that loss of the HECA-452 antigen is related to tumour progression of primary cutaneous T-cell lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS)

The prognosis of patients with lymphomatoid papulosis associated with malignant lymphomas.

Lymphomatoid papulosis (LyP) is a disorder which generally runs a benign course, but can sometimes be associated with a malignant lymphoma. Information about the prognosis of these LyP-associated lymphomas is, however, fragmentary. In this study, the clinical data of 50 LyP-associated malignant lymphomas, including 11 patients of our own group and 39 reported in the literature, are evaluated. Three main groups of LyP-associated malignant lymphomas could be distinguished: cases associated with mycosis fungoides (19/50 cases). Hodgkin's disease (12/50 cases) and (CD30+) large-cell lymphomas (16/50). The results of this study demonstrate that patients with mycosis fungoides. Hodgkin's disease, and (CD30+) large-cell lymphomas limited to the skin have a favourable prognosis. However, the prognosis of patients developing a systemic (CD30+) large-cell lymphoma proved generally poor. The results of this study also indicate that the risk of an individual LyP patient developing systemic lymphoma is less than 5%.

Differential diagnosis of cutaneous large cell lymphomas using monoclonal antibodies reactive in paraffin-embedded skin biopsy specimens.

We studied a large panel of monoclonal antibodies reactive on routinely processed paraffin-embedded tissue to determine their sensitivity and specificity in the diagnosis of 35 primary cutaneous large cell lymphomas of B- (n = 14) and T-cell origin (n = 21). The findings show that differentiation between clinically relevant subgroups can be obtained by a small panel of antibodies including L26, MB2, LN1, MT1, UCHL1, and Ber-H2. Pitfalls in the use of the reagents are discussed.

Solar urticaria and disturbed metabolism of porphyrins.

We report on a case of solar urticaria with elevated protoporphyrin in the stool. No other evidence for an erythropoietic protoporphyria could be found.

Bilateral squamous cell carcinomas arising in long-standing necrobiosis lipoidica.

We describe the second case of bilateral squamous cell carcinoma arising in long-standing necrobiosis lipoidica. The occurrence of squamous cell carcinoma in necrobiosis lipoidica is rare, but should be considered in recalcitrant ulcers, especially when infiltrated.