It is often difficult to diagnose ECD and only a doctor can diagnose this disease. Many patients go years before they get a correct diagnosis. A definitive diagnosis is usually based on clinical symptoms, biopsy, and bone scan.
The diagnostic criteria which have been defined to-date include:
Typical histologic findings:
Typical skeletal findings:
A correct diagnosis relies upon findings of a biopsy of the affected tissue along with imaging studies. The tissue samples should be reviewed by a trained pathologist and imaging by a radiologist who have knowledge of ECD.
When a doctor learns of suggestive symptoms (s)he will often order tests. It is important to make a systematic study of the organs possibly affected: skeleton, lungs, heart, central nervous system, kidneys, eyes, pituitary, skin, and/or teeth.
X-Rays and electrocardiograms (EKG or ECG) are often the initial tests. Non-invasive scans such as CT scan, CT/PET scan, MRI, bone scan, or echocardiogram may be warranted depending upon the symptoms, clinical signs and/or results from previous tests.
If a mass or lesion is found within the body, a tissue biopsy might be performed as part of the diagnostic workup. A pathologist will study the tissue sample that is obtained via the biopsy. ECD affected tissue will usually contain clusters of lipid-laden, foamy histiocytes with signs of chronic inflammation, often with Touton-type giant cells, fibrosis and possible fat necrosis. The pathologist will study the tissue sample further and find the histiocytes expressing positive for CD68, CD163, and Factor XIIIa. The tissue sample will test negative for CD1and Langerin (CD207) and without Birbeck granules. The S-100 protein expression is variable.
A bone biopsy might be warranted. If ECD has affected the bones, the bone biopsy will typically show sclerotic bone.
Although brain lesions are sometimes seen with ECD, it is not always possible to perform a biopsy on these lesions depending on where they appear in the brain. Doctors will normally see these lesions when an MRI of the brain is performed. These lesions will show T2 hyperintensity and often intense gadolinium enhancement. The lesions most often occur in the pons and cerebellum, but they can also occur in the tissue overlying the brain (the meninges) or anywhere else in the brain. These findings might be confused with multiple sclerosis as they mimic a demyelinating process as normally seen in multiple sclerosis.
Increasingly, it is being suggested that ECD patients should be tested for the BRAF V600E mutation. It is reported that more than 50% of ECD patients test positive for this mutation. The genetic mutation is present in ECD lesions only, not in the “germline,” which is to say that it is not a hereditary problem. This testing should be done using immunohistochemistry and an ultrasensitive assay as there have been a large number of false negative findings associated with BRAF testing of ECD patients.
Last updated: November 7, 2016