Morphologic mimickers of Cryptococcus occurring within inflammatory infiltrates in the setting of neutrophilic dermatitis: a series of three cases highlighting clinical dilemmas associated with a novel histopathologic pitfall

A neutrophil‐predominant inflammatory infiltrate in a cutaneous biopsy can be associated with a broad spectrum of diseases. Here we describe three cases showing a neutrophil‐predominant dermal infiltrate admixed with abundant acellular bodies surrounded by capsule‐like vacuolated spaces, which strikingly mimicked Cryptococcus. Two cases occurred within the settings of underlying hematologic malignancies; the third case was associated with immune dysregulation. Two patients were acutely ill in the medical intensive care unit. Fungal work‐up, including cultures and multiple stains were negative. Because of clinical deterioration in these patients, transmission electron microscopy was pursued to definitively rule out fungal infection. In both cases, characteristics most compatible with autolysing human cells, not Cryptococcus, were identified. Chemotherapy and high‐dose steroids were given, but both patients eventually succumbed to their diseases. To the best of our knowledge, these represent the first reported cases of autolysing human cells mimicking Cryptococcus organisms within neutrophilic infiltrates. They highlight the therapeutic dilemmas arising with histopathologic mimics, as well as the importance of thorough investigation to distinguish mimickers from true infectious organisms. We believe recognition of this microscopic pitfall will be useful to dermatopathologists faced with similar findings in the future, and may prevent unnecessary delay of appropriate therapy in acutely ill patients.