From the Guidelines
Langerhans cell histiocytosis (LCH) ulcers, also known as Schürger's disease ulcers, are caused by the proliferation of Langerhans cells, which are a type of histiocyte, and are characterized by the presence of BRAF V600E mutation and expression of S100, CD1a, and Langerin. The exact mechanism of ulcer formation is not fully understood, but it is thought to be related to the infiltration of Langerhans cells into various tissues, including the skin, bones, and lymph nodes, leading to tissue damage and ulceration 1. The diagnosis of LCH is often established using a combination of clinical, radiographic, and histopathologic features, including the presence of characteristic lesions, immunohistochemical stains, and molecular testing for BRAF V600E mutation 1.
Key Features of LCH
- Lesions are typically more cellular than those of Erdheim-Chester disease (ECD) and may show overt cytologic atypia 1
- Intermixed eosinophils are commonly present and often numerous 1
- Fibrosis may be present, usually minimal in soft tissues but more pronounced in bone lesions 1
- LCH involves lymph nodes in a distinct sinus pattern, which distinguishes it from the paracortical distribution of reactive Langerhans cells seen in lymphadenopathy due to inflammatory skin conditions 1
Diagnosis and Evaluation
- Immunohistochemical stains, including CD163 or CD68, S100, CD1a, Langerin, and factor XIIIa, may be useful in the diagnosis and classification of LCH 1
- Molecular testing for BRAF V600E mutation may also be demonstrated by IHC analysis 1
- A combination of clinical, radiographic, and histopathologic features is often needed to establish a diagnosis of LCH 1
Clinical Implications
- Early clinical cues that should raise suspicion for LCH include central diabetes insipidus and bony pain in the absence of other etiologies 1
- A thorough evaluation, including radiographic and histopathologic examination, is necessary to establish a diagnosis and guide treatment 1
From the Research
Causes of Schürger's Disease Ulcers
The causes of Schürger's disease ulcers, also known as Langerhans cell histiocytosis (LCH) ulcers, are not fully understood. However, research suggests that LCH is a group of diseases characterized by the proliferation and accumulation of Langerhans cells 2.
Pathogenesis of LCH
The pathogenesis of LCH is thought to involve the activation of the mitogen-activated protein kinase (MAPK) pathway in myeloid precursors, leading to the development of LCH lesions 3. Additionally, mutations in the BRAF V600E and MAP2K1 genes have been identified in approximately 75% of LCH patients, suggesting a neoplastic origin of the disease 4.
Clinical Presentations of LCH
LCH can present with a wide range of clinical manifestations, including skin lesions, bone lesions, and multisystem involvement 2, 5. The disease can occur at any age, but is more common in the pediatric population 4.
Role of Langerhans Cells in LCH
Langerhans cells play a crucial role in the development of LCH lesions. These cells are capable of modulating or halting the inflammatory reaction, and their depletion has been observed in LCH skin lesions 6. The decrease in Langerhans cells is thought to contribute to the development of severe inflammation and skin damage in LCH patients.
Key Factors Contributing to LCH Ulcers
Some key factors that may contribute to the development of LCH ulcers include: