Abstract

A 39-year-old man with a two-year history of nivolumab and ipilimumab treatment for metastatic colon cancer presented with pruritic red indurated plaques in areas of red tattoo pigment with overlying areas of serous crusting and mild erosion. Interval worsening of the rash occurred following a month of treatment with clobetasol 0.05% ointment, so a punch biopsy was performed. Sections showed dense interstitial, perivascular, and periadnexal, non-necrotizing granulomatous inflammation, centered in the upper dermis with areas of deep dermal and upper subcuticular extension, in association with exogenous red tattoo pigment primarily within granulomas and multinucleated cells. The granulomas displayed tuberculoid characteristics, composed of epithelioid histiocytes and scattered multinucleated giant cells with peripheral rimming by lymphocytes and plasma cells. Abundant background eosinophils were noted. The epidermis showed acanthosis with mild spongiosis, focal vacuolar change, and exocytosis. Special stains were negative for microorganisms amidst the dermal inflammation and within the granulomas. Granulomatous inflammation associated with interface dermatitis has been described with cutaneous reactions to red tattoo ink. Sarcoidosis-like granulomas have also been reported in patients receiving immune checkpoint inhibitor (ICI) therapy. Taken together, the histopathological findings in this case raise a differential diagnosis that includes a granulomatous reaction to red tattoo pigment or an ICI-induced tattoo reaction, with the possibility of a component of allergic contact dermatitis given the epidermal changes and presence of eosinophils.