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

Abstract

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.

Cryptococcus‐like changes in the setting of vasculitis

“…Eight cases describing the histological findings of capsule‐like vacuolated spaces mimicking Cryptococcus exist in the literature, all in the setting of neutrophilic dermatoses, and the term “cryptoccoid Sweet syndrome” has been coined . Ko et al described three cases of neutrophilic dermatoses, two in severely ill patients who ultimately succumbed to their disease . Byekova et al reported a case of a patient with clinical and pathological findings suspicious for Cryptococcus ultimately deemed to have Sweet syndrome who suffered a rapidly fatal clinical course similar to our first patient …”

“…Various fungal stains, including mucicarmine, PAS, and GMS, were used to rule out Cryptococcus in the previous cases. Ko et al employed transmission electronic microscopy (TEM) to confirm cells were of human origin, and concluded the cells were probably degrading neutrophils . MPO stains were employed in six of the previously described patients and were noted to be positive, further supporting the cells' neutrophilic origin …”

“…Eight cases describing the histological findings of capsule‐like vacuolated spaces mimicking Cryptococcus exist in the literature, all in the setting of neutrophilic dermatoses, and the term “cryptoccoid Sweet syndrome” has been coined . Ko et al described three cases of neutrophilic dermatoses, two in severely ill patients who ultimately succumbed to their disease .…”

Cryptococcal cellulitis: A rare entity histologically mimicking a neutrophilic dermatosis

“…Recent publications have highlighted neutrophilic dermatoses mimicking cryptococcal infections. In 2013, Ko et al described 3 cases that raised suspicion for Cryptococcus due to the presence of capsule‐like vacuolated spaces. Ultimately, after transmission electron microscopy, these histological findings were found to be compatible with degrading neutrophils.…”

An additional case of neutrophilic dermatosis histopathologically mimicking Cryptococcus in a patient with Sweet's syndrome

“…Mimickers of fungal yeast forms have been previously reported in the setting of neutrophil-and plasma-cell rich inflammatory infiltrates. 1,2 This case adds to the growing body of evidence for a unique histologic presentation of neutrophilic dermatoses that morphologically mimic Cryptococcus. The distinction between these two entities is important for selecting timely and appropriate management since the first-line treatment for Sweet's syndrome includes systemic corticosteroids, while for cryptococcal infection it is important to reduce immunosuppression and institute anti-fungal therapy.…”