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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: 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: Summary Background Telomere length is correlated with cellular ageing and immortalization processes. In some human cancers telomere length measurement has proved to be of diagnostic and prognostic value. Results comparable with the traditional terminal restriction fragment length determination by Southern blotting have been obtained in metaphase and interphase cells in some studies by fluorescence in situ hybridization (FISH) analysis; FISH additionally allows for the quantification of telomeres at the cellular level. Objectives In this study, 32 melanocytic lesions were analysed by FISH, aiming at investigating possible telomere differences among various benign and malignant lesions and correlation with telomerase activity (TA) level. Methods FISH was performed on paraffin sections from six common naevi, eight Spitz naevi, 12 melanomas, six melanoma metastases and nine control samples of normal skin. Telomere mean maximum diameter (Feret max), area and number per nuclear area were calculated by image analysis on fluorescent images elaborated through KS400 and in situ imaging system (ISIS) for FISH analysis programs. Mean TA level was also calculated in all lesions and correlated with telomere parameters. Results Telomere number per nuclear area was significantly lower in melanomas and metastases than in benign common and Spitz naevi and in control skin (7·24 ± 3·3; 6·11 ± 3 vs. 14·46 ± 5·6; 16·92 ± 7·8; and 12·59 ± 3·4, respectively; P 〈 0·001). No significant differences were found for the other telomere parameters. In common and Spitz naevi, telomere number was positively correlated with Feret max (P = 0·046 and P 〈 0·0001, respectively). TA was significantly higher in melanomas and metastases than in the other groups (70·18 ± 25·2; 105·07 ± 30 vs. 2·16 ± 2·4; 2·99 ± 2·1; 2 ± 1·2, respectively; P≤0·001) and it was inversely correlated with telomere number per nuclear area in melanomas (P = 0·0041). No other significant correlations were found. Conclusions Encouraging results have been obtained from quantitative telomere evaluation in the diagnosis of melanocytic lesions, although an analysis of a larger number of cases would be necessary to provide more reliable data. An extreme shortening of some telomeres probably results in the decrease of telomeric signals and the lower mean number of detectable telomeres in melanomas and metastases. In melanomas, telomere number per nuclear area is also inversely correlated with TA levels. Quantitative FISH of melanocytic lesions could give more specific information at the cellular level in telomere and telomerase fields of investigation.

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: Abstract · Purpose: To describe a patient with Meige syndrome in whom we observed the coexistence of hereditary lymphedema of the lower legs, conjunctival edema and alopecia of the lateral third of the eyebrows. · Methods: Case report. · Results: Histological examination of the conjunctival and skin specimens showed dermal edema and a slight reduction in the number of severely ectatic lymphatics in the reticular dermis. The vessel were identified as lymphatics on the basis of immunohistochemical evidence of discontinuity and/or absence of basement membrane. · Conclusions: Clinical and histological findings suggest that the etiopathogenesis of the edema in Meige syndrome is related to a structural ectatic defect of lymphatics. This anomaly seems to involve both skin and other sites, such as conjunctival mucosa.