Sarcoidosis complicating anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody biotherapy.

In August 2009, a 57-yr-old male smoker (30 pack-yrs) without medical history was diagnosed as having a melanoma of the left shoulder. A complete surgical excision was performed. The lesion was ulcerated. Breslow’s thickness was 1.034 mm and Clark’s level was III. As the axillary sentinel lymph node was positive for tumour cells, an additional lymphadenectomy was performed. The disease was finally staged at IIIb (pT2b N2a M0), in agreement with the American Joint Committee on Cancer Classification. In December 2009, the patient was included in a placebo-controlled trial to evaluate ipilimumab (a monoclonal antibody anti-cytotoxic T-lymphocyte-associated antigen (CTLA)-4 antibody), after complete resection of a high-risk stage III melanoma. Ipilimumab was administered by intravenously at 10 mg?kg, every 3 weeks for four doses (induction) followed by 10 mg?kg every 12 weeks (maintenance). After two infusions of the maintenance phase, in July 2010, subcutaneous nodules appeared on his left arm and elbow. A concomitant computed tomography (CT) scan showed multiple micronodular, reticulonodular lesions of the lung and bilateral hilar lymph nodes. Positron emission tomography–CT showed an intense fluorodeoxyglucose binding of lung nodules and mediastinal lymph nodes (fig. 1). The skin lesions were biopsied and a pathological study revealed the presence of noncaseating granulomas. Bronchoalveolar lavage showed a mild lymphocytic alveolitis (11%, with a predominance of CD4+ Tcells). Bronchial biopsies were not informative. An additional mediastinoscopy was performed and pathological study demonstrated the presence of epithelioid and gigantocellular granulomas without caseating necrosis or microorganisms. A diagnosis of sarcoidosis was proposed. Pulmonary function tests, ECG and echocardiography were normal. The patient was asymptomatic and he decided to stop the ipilimumab trial. The patient was carefully followed up and 5 months after treatment discontinuation, the skin and nodular pulmonary lesions had disappeared, and the mediastinal lymph nodes had decreased in size.