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

Sep 29, 2026

Erdheim–Chester disease (ECD) is an ultra-rare non-Langerhans cell histiocytosis with CD68-positive, CD1a/S100-negative histiocytes and frequent BRAFV600E/MAPK pathway mutations. Diagnosis is difficult due to nonspecific manifestations, reliance on invasive biopsies, and multi-year diagnostic delays. Nanoparticle (NP)-enhanced cytology, including surface-enhanced Raman spectroscopy, promises single-molecule sensitivity and multiplexed biomarker detection. NP imaging agents and NP assays for circulating tumor DNA may enable earlier, less invasive, and more precise ECD identification when combined with AI analysis. Standardization and validation remain essential.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages2

Reading Time5 min

AccessFree to download

Abstract

To the Editor

Disease background and diagnostic challenges

NP-enhanced cytology and SERS potential

NP-based imaging and circulating tumor DNA assays

Multiplex biomarker detection

Conclusion

Letter to the Editor Nanoparticle-enhanced cytology: a 2025 breakthrough for rapid diagnosis of Erdheim–Chester disease Awais Butt, MBBSa , Araj Naveed Siddiqui, MBBSb , Maliha Khalid, MBBSb , Muhammad Talha, MBBSc , Aminath Waafira, MBBSd ,* Abstract Erdheim–Chester disease (ECD) is an ultra-rare non-Langerhans cell histiocytosis characterized by CD68-positive, CD1a/S100-negative histiocytes, frequently associated with BRAFV600E 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. Keywords: Erdheim–Chester disease, nanoparticle cytology, rare disease diagnosis, surface-enhanced Raman spectroscopy To the Editor, Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocytosis classified as a neoplastic hematopoietic disorder, characterized by CD68-positive, CD1a/S100-negative and foamy histiocyte infiltrates in multiple organs, such as the retroperitoneum, cardiovascular system, central nervous system (CNS), and long bones. Involvement of these critical structures, such as the periaortic region, right atrium, and CNS, often prompts investigation[1,2]. However, the disease shows no early symptoms, which results in delayed diagnosis. ECD is associated with the genetic mutations in BRAF V600E and MAPK, which are ultimately related to several types of cancers (pulmonary adenocarcinoma, melanoma, etc.), making ECD a malignant disorder. The disease shows both inflammatory and neoplastic symptoms, making its pathophysiology difficult to understand. ECD is extremely rare. It tends to occur in one in a million individuals, providing insufficient data on its exact aDepartment of Medicine, Aziz Fatima Medical and Dental College, Pakistan, bDepartment of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan, cDepartment of Medicine, King Edward Medical University, Lahore, Pakistan, and dDepartment of Medicine, The Maldives National University, Malé, Maldives Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. *Corresponding author. Address: Department of Medicine, The Maldives National University, Rahdhebai Hingun, Malé 20026, Maldives. Tel.: +960 919-5504. [E-mail: wafiagany@gmail.com](E-mail: wafiagany@gmail.com) (A. Waafira). Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Annals of Medicine & Surgery (2026) 88:982–983 Received 11 September 2025; Accepted 4 November 2025 Published online 14 November 2025 [http://dx.doi.org/10.1097/MS9.0000000000004324](http://dx.doi.org/10.1097/MS9.0000000000004324) prevalence. The rarity of the disease produces significant diagnostic challenges and offers a limited understanding of its nature[1]. Current diagnoses depend on tissue biopsy, which may be taken from bone or organs. It requires histology and immunohistochemistry analysis for interpretation of

FAQs

What makes Erdheim–Chester disease difficult to diagnose early?

ECD often lacks early symptoms and presents with nonspecific histiocytic infiltrates. Current diagnosis frequently depends on invasive tissue biopsy plus histology and immunohistochemistry, leading to diagnostic delays of years.

How does nanoparticle-enhanced cytology (including SERS) help with ECD diagnosis?

NP-enhanced cytology using surface-enhanced Raman spectroscopy offers high sensitivity, potentially down to single-molecule detection. It may also allow multiplexed biomarker detection directly on cytology slides.

Which biomarkers and genetic alterations are highlighted for improved detection?

The text highlights CD68, BRAFV600E (MAPK pathway mutations), and Glut-1 as key biomarkers. NP-based assays and imaging agents are discussed as supporting detection of circulating tumor DNA and macrophage-rich lesions.

Sep 29, 2026

Uploaded by eBook King