The diagnosis and management of sarcoid-like reactions in patients with melanoma treated with BRAF and MEK inhibitors. A case series and review of the literature

Abstract

Sarcoidosis and sarcoid-like reactions (SLR) have been repeatedly reported in patients with melanoma treated with BRAF and MEK inhibitors. In the current study we present three patients that developed SLR under treatment with BRAF and mitogen-activated protein kinase (MEK) inhibitors for melanoma. Two patients developed mediastinal lymphadenitis with histological features of an SLR while on targeted therapy in the adjuvant setting, whereas one patient with metastatic melanoma developed granulomatous nephritis while receiving combination treatment with BRAF/MEK inhibitors and atezolizumab. In addition, we review the published literature on the pathogenesis, clinical characteristics, histologic features, imaging findings, and other potential useful diagnostic tools. We also address the need for a common terminology for these cases and propose an algorithm for the accurate diagnosis of BRAF/MEK inhibitor-induced SLR. We also review the currently available data on the treatment of these patients and suggest a treatment approach for SLR in patients with melanoma, as well as for the management of melanoma when SLR emerges.

Keywords: BRAF inhibitor; melanoma; sarcoid-like reaction; sarcoidosis; targeted therapy.

Figure 1.

Hematoxylin and eosin stain (10×) demonstrates few non-necrotizing sarcoid-like epithelioid granulomas. Multinucleated giant cells are not present.

Figure 2.

Confluent, non-necrotizing, well-formed granulomas in the renal interstitium, composed of epithelioid histiocytes, monocytes, lymphocytes, and a few multinucleated cells.