Ulcerating nodules on a background of lower leg lymphoedema.

A patient presented with a 3-month history of a rapidly enlarging ulcerated tumour on his lower leg, occurring on a background of chronic idiopathic lymphoedema of approximately 10 years' duration. Histology revealed extensive infiltration of the dermis by a vascular tumour with pleomorphic and hyperchromatic endothelial cells, which stained positive for vascular markers CD31, CD34 and ERG. A diagnosis of lymphoedema-associated angiosarcoma was reached and our patient was treated with isolated limb perfusion with high-dose melphalan and tumour necrosis factor-alfa.

Evaluation of follicular T-helper cells in primary cutaneous CD4+ small/medium pleomorphic T-cell lymphoma and dermatitis.

BACKGROUND: CD4+ small/medium-sized pleomorphic T-cell lymphoma (SMPTCL) is a controversial primary cutaneous lymphoma, in which the candidate neoplastic cells express a follicular T-helper phenotype. We describe 16 cases of SMPTCL and compare expression of PD-1, CXCL-13 and ICOS in these tumors with 40 dermatitis cases. METHODS: Histopathologic examination and immunocytochemistry were performed for 16 tumors and 40 assorted dermatitis cases. RESULTS: All but one patient presented with solitary lesions. Each biopsy revealed a dense nodular non-epitheliotropic infiltrate of atypical T-cells. Neoplastic cells were CD3+/CD4+/CD8(-)/CD30(-). Cutaneous recurrence occurred in one patient over a median follow up of 8 months (range 5-36). All tumors widely expressed PD-1 and ICOS to a lesser extent. CXCL-13 stained much fewer cells. Of the dermatitis cases, PD-1 (most numerous) and ICOS labeled lymphoid cells in all cases, albeit fewer than in the tumors, and CXCL-13 was negative in 32. A rosette pattern of PD-1 expression was identified in all the SMPTCL cases but not in dermatitis. CONCLUSIONS: There remains uncertainty about the appropriate nosological status of SMPTCL, which some authors consider to be a pseudolymphoma. However, this study suggests a significant difference in the prevalence and pattern of follicular T-helper cell markers between this tumor and lymphoid proliferations known to be reactive.

UVA photosensitization of thiopurines and skin cancer in organ transplant recipients.

The thiopurines azathioprine, 6-mercaptopurine and 6-thioguanine (6-TG) are important medications for cancer and inflammatory disorders. They are also widely prescribed as immunosuppressants in organ transplant patients. Their metabolism results in the incorporation of 6-TG into patients' DNA, and this increases skin sensitivity to incident UVA. Unlike the canonical DNA bases, which do not absorb UVA to a significant degree, DNA 6-TG is a strong UVA chromophore. It acts as a Type II UVA photosensitizer, and the combination of 6-TG and UVA treatment induces a synergistic toxicity in cultured human cells. Here, we review some of the damage that this interaction causes. Photochemical activation of DNA 6-TG triggers DNA and protein oxidation; it induces DNA breakage, DNA crosslinking, oxidation of DNA bases and the covalent attachment of proteins to DNA. Many of these photochemical DNA lesions are difficult for cells to deal with, and we review the evidence linking thiopurine immunosuppression with genome instability and the high incidence of skin cancer in organ transplant recipients.

Thiopurines in current medical practice: molecular mechanisms and contributions to therapy-related cancer.

Thiopurines have diverse clinical applications and their long-term use as anti-rejection drugs in transplant patients has been associated with a significantly increased risk of various types of cancer. Although they are slowly being replaced by a new generation of non-thiopurine immunosuppressants, it is anticipated that their use in the management of inflammatory and autoimmune diseases will continue to increase. Therapy-related cancer will remain a potential consequence of prolonged treatment for these generally non-life-threatening conditions. Understanding how thiopurines contribute to the development of cancer will facilitate clinical decisions about the potential risks to patients of long-term treatment for chronic inflammatory disorders.