Revised diagnostic criteria proposed for ECD, based on recent molecular findings
| Clinical or morphological findings |
| a) Symmetric diaphyseal and metaphyseal osteosclerosis in the legs, best visualized on PET and/or |
| b) Other typical ECD manifestations: perirenal infiltration (hairy kidney) best visualized on CT scan; periaortic sheathing (coated aorta) best seen on CT scan; right atrial pseudo-tumor, best visualized on cardiac MRI; xanthelasma; exophthalmos; osteosclerosis of the facial sinuses |
| Histopathological findings |
| Typical foamy or lipid-laden histiocytes admixed with fibrosis sometimes with Touton giant cells |
| Immunohistochemical staining positive for CD68 or CD163 and negative for CD1a |
| Molecular findings |
| Identification in histiocytosis tissue sample of |
| a) BRAFV600E mutation or |
| b) Activating mutation in the BRAF gene other than BRAFV600E or along the MAPKinase pathway such as KRAS, NRAS, MAP2K1, ARAF, MAP3K1 (nonexhaustive list) or |
| c) Gene fusion activating the MAPKinase pathway or |
| d) Activating mutation in CSF1R |
| Clinical or morphological findings |
| a) Symmetric diaphyseal and metaphyseal osteosclerosis in the legs, best visualized on PET and/or |
| b) Other typical ECD manifestations: perirenal infiltration (hairy kidney) best visualized on CT scan; periaortic sheathing (coated aorta) best seen on CT scan; right atrial pseudo-tumor, best visualized on cardiac MRI; xanthelasma; exophthalmos; osteosclerosis of the facial sinuses |
| Histopathological findings |
| Typical foamy or lipid-laden histiocytes admixed with fibrosis sometimes with Touton giant cells |
| Immunohistochemical staining positive for CD68 or CD163 and negative for CD1a |
| Molecular findings |
| Identification in histiocytosis tissue sample of |
| a) BRAFV600E mutation or |
| b) Activating mutation in the BRAF gene other than BRAFV600E or along the MAPKinase pathway such as KRAS, NRAS, MAP2K1, ARAF, MAP3K1 (nonexhaustive list) or |
| c) Gene fusion activating the MAPKinase pathway or |
| d) Activating mutation in CSF1R |
ECD diagnosis should be made when criterion 1 is associated with criterion A and/or B.