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How I diagnose Erdheim-Chester disease
Aishwarya Ravindran1, Karen L Rech1,
1Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States.
Insights
Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm. Accurate diagnosis requires correlating histology, clinical findings, immunohistochemistry, and genetic studies, especially MAPK pathway mutations.
Area of Science:
- Hematology
- Oncology
- Pathology
Background:
- Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm, distinct from Rosai-Dorfman disease and Langerhans cell histiocytosis.
- Recognized in the 2016 WHO Classification, ECD often involves mutations in the MAPK pathway (80-90% of cases).
Purpose of the Study:
- To discuss ECD diagnosis using illustrative cases.
- To address interpretative challenges in ECD diagnosis.
- To present a diagnostic algorithm for Erdheim-Chester disease.
Main Methods:
- Case study review of three Erdheim-Chester disease patients.
- Histopathological and immunohistochemical analysis.
- Genetic mutational analysis for MAPK pathway mutations.
Main Results:
- ECD is a systemic disease with characteristic organ involvement (bone, perinephric tissue, skin, heart, CNS).
- Histology shows xanthogranulomatous, lymphohistocytic, or fibrohistiocytic infiltrates; neoplastic histiocytes have a macrophage phenotype (CD163+, S100-, CD1a-, langerin-).
- Diagnosis relies on integrating histology, immunohistochemistry (cyclin D1, BRAF V600E), clinical/imaging data, and MAPK pathway mutation analysis.
Conclusions:
- ECD diagnosis is challenging due to overlap with reactive inflammatory conditions.
- Accurate diagnosis necessitates correlating histological features with clinical presentation.
- Immunohistochemistry and genetic studies are crucial for timely and accurate Erdheim-Chester disease diagnosis.
Objectives:
Erdheim-Chester disease (ECD) is one of 3 major types of histiocytic neoplasms, along with Rosai-Dorfman disease and Langerhans cell histiocytosis. It was first recognized as a neoplasm in the 2016 World Health Organization Classification of Haematolymphoid Tumours. About 80% to 90% of cases harbor MAPK pathway mutations.
Methods:
We discuss the diagnosis of ECD using 3 illustrative cases, consider interpretative challenges, and present a diagnostic algorithm.
Results:
Erdheim-Chester disease is a systemic disease that shows a characteristic pattern of organ involvement including bone, perinephric soft tissue, skin, heart, and central nervous system. Histologically, ECD shows a spectrum of xanthogranulomatous, lymphohistocytic, or fibrohistiocytic infiltrates. By immunohistochemistry, the neoplastic histiocytes have a macrophage phenotype with expression of CD163, negative to focal S100, and negative CD1a and langerin. These features alone are not specific and thus insufficient for diagnosis. Immunohistochemistry for cyclin D1 and BRAF V600E, correlation with clinical and imaging findings, and mutational analysis for MAPK pathway mutations all play important roles in establishing an ECD diagnosis.
Conclusions:
The diagnosis of ECD is often challenging due to its clinical and histologic overlap with reactive inflammatory processes. Correlation of histology features with clinical findings, immunohistochemistry, and genetic studies is essential for an accurate and timely diagnosis.
