Nanoparticle-enhanced cytology: a 2025 breakthrough for rapid diagnosis of Erdheim–Chester disease

Erdheim-Chester disease (ECD) is an ultra-rare non-Langerhans cell histiocytosis characterized by CD68-positive, CD1a/S100-negative histiocytes, frequently associated with BRAF V600E and MAPK pathway mutations. Diagnosis remains challenging due to its nonspecific presentation, reliance on invasive biopsies, and frequent diagnostic delays of several years. Nanoparticle (NP)-enhanced cytology, including surface-enhanced Raman spectroscopy, represents a promising breakthrough in 2025, enabling single-molecule sensitivity and multiplexed biomarker detection on cytology slides. NP-based imaging agents, such as Cu-Macrin for positron emission tomography, demonstrate high specificity for macrophage-rich lesions, while NP assays improve capture of circulating tumor DNA, including BRAF V600E. When integrated with AI-driven image analysis, NP-based approaches may overcome current diagnostic barriers, enabling earlier, less invasive, and more precise identification of ECD. Standardization of NP-based diagnostic protocols and continued research are essential to validate these emerging technologies and translate them into clinical practice.