Cyclin D1, B and A expression and cell turnover in psoriatic skin lesions before and after cyclosporin treatment.

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.

Unusual second malignancies following radiation therapy: subcutaneous pleomorphic rhabdomyosarcoma and cutaneous melanoma. Two case reports.

BACKGROUND: Among nonepithelial second neoplasms which are known to be induced by irradiation, rhabdomyosarcomas are extremely rare, and melanomas are infrequent. We report a high-grade sarcoma with rhabdomyoblastic differentiation, which appeared 30 years after megavoltage irradiation for an endometrial adenocarcinoma, and a malignant melanoma which arose after 6 years in the irradiation field of a fibrosarcoma. METHODS: Histology and immunohistochemistry were performed in both cases. In the first case, electron microscopy was also performed. In the second, the previous tumor was re-evaluated. RESULTS: The first case showed histological, immunohistochemical and ultrastructural features of a rhabdomyosarcoma. In the second case, a lentigoid malignant melanoma was histologically and immunohistochemically demonstrated, whereas the previously resected tumor was a fibrosarcoma negative to melanoma markers. CONCLUSIONS: Rare cases of rhabdomyosarcomas and melanomas are induced by irradiation, although in some cases other factors (i.e., genetic risk, chemotherapy) may have a prominent etiopathogenetic role in their development. A close follow-up and a careful examination of the irradiated area should facilitate an early diagnosis of these aggressive postradiation second neoplasms.