Diagnostic Heterogeneity in Langerhans Cell Histiocytosis: A Retrospective Series Emphasizing Morphologic Mimicry and Diagnostic Challenges

Abstract

Introduction: Langerhans Cell Histiocytosis (LCH) is a rare disease of Langerhans-type dendritic cells. It is insidious in onset and shows a wide range of clinical manifestations, from solitary bone lesions to aggressive multisystem disease. The rarity of LCH, its multifaceted presentations, and histological similarities to other conditions frequently result in diagnostic delays. The aim of this study was to assess the clinical, radiological, histomorphological and immunohistochemical characteristics and to highlight diagnostic challenges faced along with factors influencing patient outcomes of LCH in our cohort.

Materials and Methods: This is a retrospective case series where thirteen histopathologically confirmed cases of LCH were retrieved from patient medical records and histopathology reports from September 2018 to August 2025. Data were collected, tabulated, and analyzed by descriptive statistics using Microsoft Excel 2016.

Results: In this study, LCH cases showed an age range of 11 months to 55 years with a median of 5 years. The male-to-female ratio was 3.3:1. Mean lesion size was 2.51cm. The majority of cases 6/13 (46.2%) were single-system unifocal. The most commonly involved site was bone 9/21 (42.9%). Lytic lesion on imaging was indicated in 100% of our cases with bone lesions. Immunohistochemistry (IHC) markers like Langerin, CD1a, S100, Fascin and CD68 were positive in 100% of the cases in which they were performed. The Ki-67 proliferation index varied across our cases, indicating variability in proliferative activity and showed median positivity of 20% (range of 10-70%).

Conclusion: LCH can occur in diverse age groups and varied anatomic sites. An integrated diagnostic approach including clinicoradiological, histopathological and IHC correlation is required. A combination of IHC panel (Langerin, Fascin, CD1a, S100 supported by CD68 and a negative marker LCA) should be used rather than relying on a single marker, particularly in diagnostically challenging cases. Disease extent and risk-organ involvement were the main factors influencing clinical outcome, with multisystem diseases including risk organs having worse survival.