Case Report: Neutrophil extracellular trap formation in palisaded neutrophilic granulomatous dermatitis

Palisaded neutrophilic granulomatous dermatitis (PNGD) is an uncommon reactive granulomatous dermatosis frequently associated with rheumatoid arthritis (RA). Histopathologically, PNGD is characterized by neutrophilic infiltrates, degenerated collagen bundles, and surrounding palisading histiocytes; however, the contribution of neutrophils to lesion formation remains poorly understood. We report two patients with RA-associated PNGD who presented with chronic erythematous papules and nodules on the elbows. Histopathological examination revealed characteristic palisaded granulomatous inflammation with dense neutrophilic aggregates and degenerated collagen. Immunofluorescence studies demonstrated abundant neutrophil extracellular trap (NET) formation within the neutrophilic aggregates. NETs are extracellular chromatin structures released by activated neutrophils that can promote sterile inflammation and tissue injury. In both cases, CD68-positive macrophages surrounded the NET-rich structures. As reported, M2 macrophages were observed throughout the lesions; however, macrophages directly contacting NET-rich aggregates showed little or no expression of the M2- and M1-associated markers, suggesting that they did not exhibit a conventional M1 or M2 macrophage profile. Further characterization revealed that these peri-NET cells exhibited a CD68-dominant/CD14-low/HLA-DR-low phenotype. To our knowledge, these findings provide the first documentation of NET formation within PNGD lesions. Comparative studies are required to determine whether this finding is enriched in or specific to PNGD. We hypothesize that repetitive mechanical stress, together with RA-associated alterations in NET formation and clearance, may favor the persistence of NET-rich inflammatory foci. Overall, the documentation of NET formation and its spatial association with macrophages expands the histopathological characterization of PNGD.