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Notes: Summary Background Mixed tumours are composed of an admixture of an epithelial/myoepithelial and usually a myxochondroid stromal component. Adipocytes are found more rarely, and account for a minor part of the tumour. To date, only three cases of mixed tumour/pleomorphic adenoma of the salivary gland have been described, showing an extensive adipocyte content of more than 90% of the tumour tissue. Owing to this peculiarity, some authors have defined it as ‘lipomatous pleomorphic adenoma’. We are not aware of previously reported similar lesions in the skin. Objectives We report a case of a tumour that occurred as a 2 × 2 × 1·5 cm nodule in the scalp of a 65-year-old man. Analogies with salivary lipomatous pleomorphic adenoma, as well as histogenesis and differential diagnoses are discussed here. Methods A histological, immunohistochemical and ultrastructural study was performed. Results The tumour was well-circumscribed and showed a substantial mature adipose tissue component intermingled with epithelial cells arranged in ducts and branching tubules, embedded in a fibromyxoid stroma, which was diagnostic of a chondroid syringoma/mixed tumour. Adipocytes strongly expressed S-100 protein and cytokeratin 14. Transitional elements from epithelial/myoepithelial cells into adipocytes were observed. They coexpressed cytokeratin 14, S-100 protein and vimentin, and showed lipid droplets, desmosome-type junctions, cytoplasmic tonofilaments and basal lamina. Conclusions The tumour differed from lipomas with myxoid stroma and from lipoadenomas, which show non-proliferating normal sweat glands admixed with adipose tissue. Because of the similarity to lipomatous pleomorphic adenoma/mixed tumour of salivary glands, we suggest that it should be called ‘lipomatous mixed tumour of the skin’.

Notes: Background Cyclosporin induces a dramatic reversal to normality in psoriatic lesions, with a reduction of inflammatory infiltrate and epidermal proliferation. It is known that the cell cycle and cell proliferation are regulated by the sequential activation of cyclin-dependent kinase/cyclin complexes. Aim We evaluated epidermal cell turnover and thickness, as well as the expression of cyclins D1, B and A in psoriatic skin before and after therapy with cyclosporin. Methods Epidermal thickness, mitotic and apoptotic indices (MI, AI), as well as the percentages of epidermal cell nuclei positive for Ki-67 and cyclins D1, B and A were calculated. Cytoplasmic positivity to cyclin B was also evaluated. Results After 6 weeks of therapy, we observed a clinical improvement of the disease and normalization of the epidermis. Epidermal thickness and Ki-67-, cyclins B- and A-positive nuclei percentage were significantly higher before therapy than after (0·52 ± 0·05 mm vs. 0·21 ± 0·03 mm, P 〈 0·001; 19 vs. 2·6, 19 vs. 3, and 12 vs. 1, respectively; P 〈 0·0005); cytoplasmic positivity to cyclin B was slightly higher before therapy (score 3 vs. 2–3). Cyclin D1 was negative or expressed in a low percentage of nuclei in psoriasis before therapy (0·78), whereas it was always negative after therapy. MI was 0·15 before therapy, whereas mitoses were almost absent afterwards. Apoptoses were undetectable before therapy, whereas a few apoptoses were observed after treatment (AI = 0·4). Conclusions Overexpression of cyclins B and A, rather than D1 seems to characterize psoriasis. Their evaluation could provide further insights in understanding the development of this disorder and could be used to verify the efficacy of currently used therapies as well as future ones.

Notes: Extracorporeal photochemotherapy (ExP) is a well-tolerated new form of chemoimmunotherapy, which is considered to be effective for cutaneous T-cell lymphoma (CTCL) and the treatment of choice for Sézary syndrome. Improvements have also been seen in patients with non-erythrodermic mycosis fungoides (MF) in the early stages, even when tumour cells are not detectable in the peripheral blood. In this study, we used ExP as a monotherapy in seven patients who had early stage (Ib) MF, and who were no longer responsive to or had contraindications for other therapies. We observed a clinical improvement in the disease after 12 months of treatment: one patient showed a complete response, five a partial response, and one remained stable. In each patient we compared skin biopsies of large plaque lesions before and after the treatment. We undertook a histological evaluation of the infiltrate. The lymphoid cell proliferation and death rates were quantified using the following parameters: lymphoid cell density (LCD), Ki67+ lymphoid cell nuclei percentage (Ki67+ Lcn percentage), and apoptotic index (AI). Significant decreases in the lymphoid cell infiltrate and in cell proliferation, and a significant increase in AI were observed after therapy. The mean LCD decreased from 187 ± 33 to 34 ± 17·7, Ki67+ Lcn mean percentage decreased from 16·9 ± 3·9 to 4·9 ± 2·4, and the AI mean value increased from 0·05 ± 0·03 to 2·41 ± 1·54. Our results suggest a role for apoptosis in the improvement of the skin lesions and are in line with some reports on the mode of action of ExP. Although the way in which ExP works needs to be clarified further, it does seem to stimulate a CD8+ cell-mediated anticlonotypic activity against circulating pathogenic clones. Furthermore, a release of tumour necrosis factor α (TNF-α) by circulating monocytes has been demonstrated after ExP. Both are known to induce cell death by apoptosis.

Notes: Background  To date, much confusion exists about the biological significance of dysplastic naevi and about the relationship between melanocytic dysplasia and clinical atypia.Objectives  To use a digital dermoscopy analyser with a series of ‘borderline’ pigmented skin lesions (i.e. dysplastic naevi and in situ melanomas) to find correlation between the studied variables and to determine their discriminating power with respect to histological diagnosis.Methods  The pigmented skin lesions (n = 174) were histologically examined by three experienced dermatopathologists and identified as in situ melanomas (n = 38) and dysplastic naevi (n = 136). The system evaluated 48 parameters as possible discriminant variables, grouped into four categories: geometry, colours, textures and islands of colour. Once the lesions were analysed (stepwise discriminant analysis), sensitivity, specificity and accuracy were calculated.Results  At the end of the stepwise procedure the percentage of cases classified correctly was 71·8%. Of 136 dysplastic naevi only 98 were classified correctly, while 27 of 38 in situ melanomas were recognized correctly.Conclusions  We conclude that there are so far no digital dermoscopic criteria that can clearly distinguish dysplastic naevi from in situ melanomas.

Notes: Summary Background Although the antiproliferative and proapoptotic effects of interferon (IFN)-α are widely recognized, its antitumour mechanisms are not completely known. Recent studies indicate that the derepressed expression of the catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT), and telomerase activity (TA) are involved in the process of human carcinogenesis. Only a few studies have investigated the effects of IFN-α on hTERT and TA, with controversial results. Objectives To study the hTERT mRNA expression, TA and apoptosis in human melanoma cells treated with IFN-α. Methods Five human melanoma cell lines (Me665/2/21, Me665/2/60, HT-144, SK-Mel-28 and SK-Mel-5) were cultured in standard conditions and treated with 20 000 IU mL−1 of human recombinant IFN-α-2b. Apoptosis was evaluated as hypodiploid DNA content determined by flow cytometry, caspase-3/7 activity by enzymatic assay, and poly(adenosine diphosphate-ribose) polymerase cleavage by Western blot analysis. IFN-α receptor (IFNA-R) and hTERT mRNA expression levels were evaluated by semiquantitative reverse transcription–polymerase chain reaction. TA was evaluated by a polymerase chain reaction-based telomerase repeat amplification protocol assay. Results Besides a variable degree of cell proliferation inhibition in all cell lines tested, we found different responses, ranging from no significant effects in SK-Mel-28 cells, to a high degree of apoptosis with no hTERT mRNA expression and TA modification in HT-144 cells, and induction of apoptosis, along with decrease in hTERT mRNA expression and TA in Me665/2/21 cells. No induction of apoptosis was observed in SK-Mel-5 and Me665/2/60 cells, although an early decrease in hTERT mRNA expression, and a minor increase of both hTERT mRNA expression and TA were found, respectively. Conclusions Our results suggest that the effects of IFN-α on hTERT and TA can result from the induction of apoptosis, but they can also occur through a direct modulation of hTERT. We hypothesize that, depending on the cellular context rather than the IFNA-R status of the targeted cells, IFN-α can elicit an apoptotic cell death; furthermore, different pathways of apoptosis, not necessarily involving telomerase, can be put into motion.

Notes: Composite cutaneous haemangioendothelioma is a recently characterized rare tumour of vascular origin. As there are only a few reported cases, the biological behaviour of the tumour and appropriate therapeutic approaches are not yet clear. We report a new case of composite cutaneous haemangioendothelioma and discuss prognostic and therapeutic aspects of this neoplasm.