Sirolimus monotherapy for Erdheim–Chester disease

Figures & data

Figure 1. Typical histopathologic findings of ECD and detection of BRAF^V600E mutation (case 1). Tissue sample of the perinephric mass is characterized by an extensive xanthogranulomatous fibro-inflammatory reaction. Numerous foamy macrophages are present, accompanied by fibrosis and lymphoplasmacytic cell infiltration (A). Immunohistologically, macrophages were strongly positive for CD68 (B) and Factor XIIIa (C) and negative for CD1a (D) and S100 (E). The BRAF^V600E mutation was detected with a BRAF^V600E mutation-specific antibody (Clone VE1, Spring Bioscience, Pleasanton, CA) (F). The mutation was confirmed by PCR amplification at amino acid position 600 with an in house protocol and subsequent sequencing using the Pyromark Q24 (QIAGEN, Hilden, Germany, detection limit 10%). Response to treatment assessed by repeated cardiac MRI scanning in case 1. Cardiac MRI scan at presentation (G) and after 6 months (H) and 12 months (I) of SRL treatment, respectively, showed clear regression of pericardial effusion.

Table 1. Relevant laboratory data of ECD patients on admission.

	Case 1	Case 2	Case 3	Normal range
ESR, mm/h	27	28	74	≤20
CRP, mg/L	5	9	110	≤10
Hemoglobin, mmol/L	8.8	10.3	6.9	8.5–11.0
Platelet count, ×10^9/L	289	436	507	150–400
WBC, ×10^9/L	15.2	18.1	13.0	4.3–10.0
Creatinine, µmol/L	127	80	87	59–104
Albumin, g/L	25	37	24	35–50
Alkaline phosphatase, U/L	103	70	154	30–100
TSH, mU/L	1.3	0.9	1.8	0.4–4.0
FT4, pmol/L	N/A	15	14	10–22
FSH, U/L	32	6	N/A	1–9
LH, U/L	8	3	15	2–12
Oestradiol, pmol/L	47	63	77	≤200
Testosterone, pmol/L	1.9	9.2	3.1	5.0–16.5
Prolactine, pmol/L	0.54	0.17	0.74	0.05–0.38
Cortisol, nmol/L	N/A#	247	337	240–700
IgG4, g/L	0.42	1.18	0.52	≤1.4

ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; WBC: white blood cell count; TSH: thyroid stimulating hormone; FT4: free thyroxine; FSH: follicle-stimulating hormone; LH: luteinizing hormone; IgG4: immunoglobulin G4. N/A: not applicable or not available before start of sirolimus. #This patient used exogenous corticosteroids at the time of referral.

Figure 2. Response to treatment assessed by repeated contrast-enhanced CT scanning in case 2. Abdominal CT scan at presentation (A) and after 6 months of sirolimus (SRL) treatment showed a marked decrease in size and density of the bilateral perirenal soft tissue mass (B). Repeat CT scan 6 months after self-discontinuation of SRL treatment, 8 months after the first follow-up CT scan, showed an increase in size and density of the bilateral perirenal mass (C). Repeat CT scan 6 months after reinstituting SRL treatment again showed a marked decrease in size and density of the bilateral perirenal mass (D). Response to treatment assessed by different imaging modalities in case 3. Thoraco-abdominal CT scan performed at presentation (E,F) and after 6 months of SRL treatment showed a marked decrease in size of the periaortic (I) and perirenal (J) soft tissue mass. ¹⁸FDG-PET scan at presentation (G,H) and after 6 months of SRL treatment showed disappearance of ¹⁸FDG-uptake at the level of the thoracic (aortic arch) and abdominal aorta, pleuropericardium and bilateral perirenal mass (K) and marked decrease of/disappearance in ¹⁸FDG-uptake at the level of the pons and extra-axial lesion near the foramen magna (L), respectively.