Immunohistochemical evidence of cytokine networks during progression of human melanocytic lesions.

Melanoma cells in culture express a variety of growth factors and cytokines and some of their autocrine and paracrine roles have been investigated. However, less information is available on the potential dynamic changes in expression of these molecules on cells during melanoma development and progression in situ. Using immunohistochemistry, we tested 40 nevi and primary and metastatic melanoma lesions for the expression of 10 growth factors and cytokines and the respective receptors representing 10 cell surface molecules. Nevi and thin (< 1 mm) primary melanomas showed little expression of ligands except weak reactivity of tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), interleukin-8 (IL-8) and reactivity of TGF-betaR and c-kit. Marked up-regulation of growth factors, cytokines and receptor expression was observed in thick (> 1 mm) primary melanomas, which were stained with polyclonal or monoclonal antibodies (MAbs) for IL-1alpha, IL-1beta, IL-6, IL-8, TNF-alpha, TGF-beta, granulocyte-macrophage colony-stimulating factor (GMCSF) and stem cell factor (SCF), but not IL-2. Metastases showed similar expression patterns except that SCF was absent. Co-expression of ligand and receptor was observed for TGF-beta, GM-CSF and IL-6, suggesting an autocrine role for these ligands. TNF-alpha appears to be a marker of benign lesions; IL-6 and IL-8 expression is associated with biologically early malignancy; TGF-beta, GM-CSF and IL-1alpha are highly expressed in biologically late lesions; and TNF-beta is an apparent marker of metastatic dissemination. Our results indicate that melanoma cells utilize cascades of growth factors and cytokines for their progression.

[Echography applied in dermatologic diseases. A comparative preliminary study of the use of high-frequency transducers]. / L'ecografia applicata alle malattie dermatologiche. Studio preliminare comparativo sull'impiego delle sonde con elevata frequenza.

Ultrasonography (US) was first used in dermatology in 1979. During the last few years, US has evolved thanks to technological progress and its use has been on the increase, in dermatology, to study both localized and diffuse skin diseases. In this paper, the authors review and compare the results obtained with a 20 MHz transducer with those obtained with 7.5 MHz and 10 MHz transducers in the study of skin alterations. Three parameters were considered: lesion identification, spatial evaluation and US structure. Fifty-eight cases of localized and 48 of diffuse skin diseases were examined. The localized forms were benign in nature in 18 patients (3 nevi, 2 seborrheic keratoses, 3 ulcus cruris cases, 6 sebaceous and 2 liquid cysts). The other 40 patients had malignant neoplastic lesions (16 epitheliomas, 13 primitive melanomas, 1 metastatic melanoma, 8 lymphomas and 2 Kaposi's sarcomas). The 48 cases of diffuse conditions included 27 systemic sclerosis, 18 psoriasis and 3 lichen planus cases. The comparative analysis of the results obtained using the different types of transducers in the study of localized dermatoses showed no differences in lesion identification and in the depiction of their US features. On the other hand, the 20 MHz transducer was much more accurate than the others as regards the spatial evaluation of the lesions measurable in millimeters, whereas it poorly demonstrated the lesions > 1.5 cm. However, only the 20 MHz transducer could demonstrate the US features of diffuse conditions.

Cell kinetics of melanocytes in common and dysplastic nevi and in primary and metastatic cutaneous melanoma.

The 3H-thymidine labelling (LI) and mitotic (MI) indexes were calculated in 29 cutaneous melanocytic lesions: 6 common nevi (CN), 11 dysplastic nevi, subclassified as nevi with architectural atypia (NAA = 4) and nevi with cyto-architectural atypia (NCAA = 7), 2 melanomas in situ (MIS), 4 invasive superficial spreading melanomas (IM) and 6 metastatic melanomas (MM). The LI mean values resulted to be: CN = 0.23%, NAA = 0.98%, NCAA = 1.79%, MIS = 5.75%, IM = 5.16%, MM = 3.80%. In CN, NAA, NCAA and MIS, these values were calculated at epidermal level; in IM and MM at dermal level. At dermal level, the LI mean values of CN, NAA and NCAA were: 0.20%, 0.20%, 0.23% respectively. The MI mean value was close to 0 in CN, NAA, NCAA, MIS; 0.18% in IM, 0.16% in MM. Confirming a low proliferative activity in CN and a high activity in melanomas (MIS, IM, MM), the results showed that dysplastic nevi (NAA, NCAA) had a proliferative activity intermediate between common nevi and melanomas. The lesions with melanocytic atypia (NCAA) resulted to have a higher proliferative activity than those without this histological feature (NAA).

[Malignant acrospiroma with "zoster-like" clinical expression]. / Acrospiroma maligno ad espressione clinica "zosteriforme".

The diagnostic category "malignant acrospiroma" includes acrosiryngeal-derived sweat gland malignant neoplasms. Many terms are usually employed to indicate different histologic types of such tumours, lacking a definitive classification. We describe a patient suffering from malignant acrospiroma (malignant poroma) with unusual clinico-evolutive presentation.

In situ immunologic characterization of cutaneous involvement in Hodgkin's disease.

The current study assesses in situ the antigenic phenotype of cutaneous infiltrate in two cases of Hodgkin's disease affecting the skin. Immunostaining utilized monoclonal antibodies for T-lymphocyte and B-lymphocyte and mononuclear phagocyte markers. The same immunophenotypic pattern of cutaneous infiltrate was observed in both cases, despite a different histopathologic subtype (mixed cellularity in case one, nodular sclerosis in case two). The majority of infiltrating cells expressed T-lymphocyte markers, with a predominance of CD8+ phenotype. Few cells bore B-lymphocyte markers or had DRC-1+ phenotype. No CD1a+ dendritic cell was found in the dermal infiltrate. Variable numbers of cells reacted with mononuclear phagocyte markers. The authors believe that the antigenic phenotype of cutaneous Hodgkin's disease has not previously been reported. The immunophenotypic pattern of skin infiltrate is different from that described in lymphoid tissues. Such findings could be related to the previous therapy or to the possible influence of skin microenvironment.

Primary cutaneous follicular centre-cell lymphoma--a lymphoproliferative disease with favourable prognosis.

In this study the clinico-pathological and immuno-histological features, the methods of treatment and follow-up data of 11 patients with follicular centre-cell (B-cell) lymphoma primarily presenting in the skin are reported. All the patients had nodular, tumorous and/or papulonodular skin lesions on the trunk. In nine patients the disease was confined to a circumscribed area of the back. Small papulonodular or plaque-like lesions, as well as large nodules or tumours, were biopsied in six of 11 patients. No clear-cut correlation between the age and clinical morphology of the lesions and their histological growth pattern was found. Interestingly, however, a different immuno-architectural pattern was observed in large, late lesions compared to small, early lesions. Initial treatment consisted of orthovolt radiotherapy (in two patients associated with surgical excision), resulting in complete remission in all patients. Only one patient developed extracutaneous disease, which was limited to a single drainage lymph node appearing simultaneously with a cutaneous relapse. Five other patients had recurrent disease in the skin close to the initial site. The median disease-free period was 15.5 months. On relapse, radiotherapy alone or in combination with short courses of chemotherapy was performed. This resulted in a second complete remission. All the patients are still alive and in complete remission, with a median survival of 37 months. These results confirm the favourable prognosis of patients affected with primary cutaneous follicular centre-cell lymphoma limited to the trunk. Orthovolt radiotherapy proved to be the most suitable treatment for both initial lesions and relapses limited to the skin.

Pre-neoplastic lesions of vulvar cancer.

The monitoring of potentially neoplastic lesions is based on the determination of the histopathologic characteristics of the lesion, which is done either by large surgical resection of the lesions "in toto" or by biopsy of the lesion. Chronic vulvar dystrophy may develop into carcinoma, the supposed likelihood varying according to the various Authors. The lesion which is histologically defined as atypical keratoacanthoma is the most frequent precursor of carcinoma. Most Authors agree in believing that lichen scleroatrophic does not often develop into carcinoma. It is, nevertheless, the most frequent precursor of leukoplakia which is, on the other hand, a risk lesion. However, any chronic vulvar irritation may increase the risk of cancer and must therefore be carefully monitored by multiple biopsies to be examined at regular intervals.

Comparison between lymphographic findings and clinical follow-up in malignant melanoma.

The clinical developments in 23 patients with stage I melanoma of the lower limbs were followed over a 2 year period. The subjects were divided into two groups based on lymphographic findings (14 negative, 9 positive or dubious). All underwent excision of the primary tumor, but none underwent prophylactic lymphadenectomy. At the end of the 2 year period there were no significant differences in the clinical developments in the two groups.