face while hepatic lesions remained perfectly stable. The facial lesion was then biopsied, and pathology revealed a noncaseating granuloma consistent with sarcoidosis. Bronchial biopsy was also performed and disclosed sarcoidosis lesions. The angiotensinconverting enzyme level was elevated (103 IU/l, normal below 67). The bronchoalveolar lavage showed a moderate lymphocyte count (5%) with a predominance of CD4; however, the CD103/CD4 ratio was 0.97. Counts of the regulatory CD4+ CD25+ cells in the peripheral blood as well as in the bronchoalveolar lavage were normal. The phenotype of circulating lymphocytes was normal. We reestablished the diagnosis as sarcoidosis associated with stable metastatic disease. A CT scan performed 3 months after discontinuation of the anti-CTLA4 therapy revealed a decrease in size of the mediastinal masses.

The cytotoxic-T-lymphocyte-associated antigen CTLA4 is expressed on the surface of most T cells only after activation. Its binding to B7 family receptors on antigen-presenting cells antagonizes T-cell activation, inhibits IL-2 production and receptor expression and interferes with cell-cycle regulation. CTLA4 downregulates T-cell responses and is involved in the immune tolerance of self-antigens. It is thought that use of anti-CTLA4 antibody could enhance the response of tumor-reactive T cells against tumor ‘self’-antigens. In animal models, anti-CTLA4 enhanced antitumor immunity. Anti-CTLA4 antibodies have been used in human melanoma, and preliminary results showed cases of regression of this cancer. This therapeutic agent has autoimmune adverse effects (dermatitis, hepatitis, hypophysitis, diarrhea and colitis). Response appears to be significantly associated with the onset of autoimmune reactions. However, the use of corticosteroids to treat severe induced autoimmune manifestations does not seem to affect the antitumor effect [1, 2]. Sarcoidosis is a multisystem granulomatous disorder of unclear etiology. It is thought that exaggerated cellular immunity could play a key role through a Th1 T-cell-mediated response to an unknown antigen. IL-2 synthesis and the expression of IL-2 receptors is found increased, and it is thought that the activation of CD4+ T cells is associated with-interferon production and macrophage activation that lead to the granuloma formation [3]. This is the first report of pulmonary and cutaneous sarcoidosis induced by an anti-CTLA4 antibody in the treatment of a metastatic melanoma. We can hypothesize that anti-CTLA4 antibody made possible the enhanced T-cell response implicated in the constitution of the granuloma. The etiological diagnosis of mediastinal lymphadenopathies in metastatic melanoma cases can be very difficult; a differential diagnosis with sarcoidosis is indeed extremely difficult to estab-