Melanoma associated with tumour necrosis factor-α inhibitors: a Research on Adverse Drug events And Reports (RADAR) project.

BACKGROUND: Tumour necrosis factor-α inhibitors (TNFαIs) are used for treatment of inflammatory disorders. There is evidence linking these agents with occurrence of malignancies. For four out of five TNFαIs the Food and Drug Administration (FDA) label states, 'melanoma has been reported in patients treated with these agents'. OBJECTIVES: To determine whether a statistically significant association exists between administration of TNFαIs and development of malignant melanoma. METHODS: We searched the FDA Adverse Event Reporting System (FAERS) database for terms related to melanoma and TNFαIs for detection of safety signals. We also searched a large urban academic electronic medical record (EMR) database for which we calculated the relative risk (RR) of melanoma in subjects exposed to TNFαIs vs. nonexposed subjects. RESULTS: There were 972 reports of melanoma associated with a TNFαI identified in the FAERS database, with 69 reports among individuals using more than one TNFαI. A safety signal was detected for infliximab, golimumab, etanercept and adalimumab, but not certolizumab pegol. For TNFαIs as a class of drugs, a safety signal was detectable in the FAERS database, and RR was significant in the EMR database. For the EMR cohort, 6045 patients were exposed to TNFαIs and 35 cases of melanoma were detected. Significance for RR was detected for adalimumab (RR 1·8, P = 0·02) and etanercept (RR 2·35, P = 0·0004 < 0·001). CONCLUSIONS: We identified a significant association between exposure to TNFαIs and malignant melanoma in two different analyses. Our findings add to existing evidence linking these agents with the occurrence of malignant melanoma. Additional investigations are required to explore this association further along with the risk of melanoma with TNFαI therapy.

Primary malignant fibrous histiocytoma of the pleura. A case report.

A rare primary malignant fibrous histiocytoma of the pleura is described. The tumor was found in an elderly male and was followed for more than ten years without treatment. At the terminal stage, the patient developed a malignant pleural effusion, which contained mainly histiocytelike, rounded forms with many bizarre and multinucleated giant tumor cells. The main tumor mass was characterized by dual fibroblastlike and histiocytelike cellular components and a storiform growth pattern. In the solid areas, the tumor cells were mainly fibroblastlike spindle-shaped forms, which produced collagen. The tumor cells in the loose, vascular areas and in the effusion were predominantly histiocytelike, with some exhibiting phagocytic activity. We believe that this is the first reported case of a malignant fibrous histiocytoma of the pleura with a malignant effusion showing a preferential histiocytelike differentiation of tumor cells in the fluid environment.