Main characteristics of the enrolled patients at study entry
| . | . | . | Involved sites and/or main disease manifestations . | Mutations . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient # . | Age (y), gender . | Previous therapies . | Bone . | Cardiovascular system . | Retroperitoneum . | Endocrine system . | CNS . | Lung . | Other . | BRAF . | NRAS . | KRAS . | PIK3CA . |
| 1 | 68, M | PDN + CYC | Long bones (lower limbs) | Coated aorta | Peri-renal and peri-aortic fibrosis, bilateral HDN, and mesenteric fibrosis with repeat bowel occlusion | — | — | — | Bilateral leg edema and systemic symptoms | Negative (by IHC) | N/A | N/A | N/A |
| 2 | 47, M | — | Long bones (upper and lower limbs) | Pericarditis with tamponade, atrial mass, and coated aorta | Peri-renal and peri-aortic fibrosis | Hyper-prolactinemia (pituitary involvement on MRI) | — | — | Skin nodules | V600E | WT | WT | WT |
| 3 | 37, F | — | Long bones (upper and lower limbs) | — | Peri-aortic and mesenteric fibrosis | Pituitary enlargement (on MRI) | Supratentorial parenchymal nodules | — | Skin nodule | WT | WT | WT | WT |
| 4 | 44, M | IFN-α | Long bones (lower limbs), skull and facial bones, and left clavicle | — | Peri-renal and peri-aortic fibrosis, and bilateral HDN | Diabetes insipidus, (central) hypothyroidism and hypogonadism; and MRI evidence of pituitary stalk involvement | — | Interstitial lung disease | — | N/A | N/A | N/A | N/A |
| 5 | 69, M | — | Long bones (lower limbs), and facial bones | — | Peri-aortic and peri-renal fibrosis, and left-sided HDN | Peripheral hypogonadism | — | — | — | V600E | WT | WT | WT |
| 6 | 75, M | — | Long bones (lower limbs), facial bones, right clavicle, ribs, and spine | — | — | — | Diffuse involvement of midbrain, pons, cerebellar peduncles, supra-tentorial nodules | Interstitial lung disease | — | N/A | N/A | N/A | N/A |
| 7 | 43, M | — | Long bones (lower limbs) | — | — | — | Cortical and pons nodules, and bulky emispheric mass in the parieto-occipital left lobes | — | Xanthelasma, soft-tissue masses (para-vertebral, Achille's tendons, nose, and right thigh) | NA | NA | NA | NA |
| 8 | 42, F | PDN + colchicine | Long bones (upper and lower limbs) and facial bones | Coated aorta, myocardial infiltration with coronary involvement, and atrial mass | Peri-aortic and peri-renal fibrosis, bilateral HDN, and mesenteric fibrosis with ascites | (Peripheral) hypogonadism | — | Interstitial lung disease | Exophthalmos, xanthelasmas, digital ischemia, diffuse lymph-node enlargement, and bilateral leg edema | V600E | WT | WT | WT |
| 9 | 71, M | — | — | — | Peri-renal fibrosis | — | — | — | Exophthalmos | N/A | N/A | N/A | N/A |
| 10 | 46, M | — | Long bones (upper and lower limbs) and facial bones | Pericarditis with massive pericardial effusion, myocardial infiltration with coronary involvement, and coated aorta | Peri-aortic and peri-renal fibrosis, bilateral HDN, and mesenteric fibrosis | (Peripheral) hypogonadism | — | — | Exophthalmos | WT | WT | WT | WT |
| . | . | . | Involved sites and/or main disease manifestations . | Mutations . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient # . | Age (y), gender . | Previous therapies . | Bone . | Cardiovascular system . | Retroperitoneum . | Endocrine system . | CNS . | Lung . | Other . | BRAF . | NRAS . | KRAS . | PIK3CA . |
| 1 | 68, M | PDN + CYC | Long bones (lower limbs) | Coated aorta | Peri-renal and peri-aortic fibrosis, bilateral HDN, and mesenteric fibrosis with repeat bowel occlusion | — | — | — | Bilateral leg edema and systemic symptoms | Negative (by IHC) | N/A | N/A | N/A |
| 2 | 47, M | — | Long bones (upper and lower limbs) | Pericarditis with tamponade, atrial mass, and coated aorta | Peri-renal and peri-aortic fibrosis | Hyper-prolactinemia (pituitary involvement on MRI) | — | — | Skin nodules | V600E | WT | WT | WT |
| 3 | 37, F | — | Long bones (upper and lower limbs) | — | Peri-aortic and mesenteric fibrosis | Pituitary enlargement (on MRI) | Supratentorial parenchymal nodules | — | Skin nodule | WT | WT | WT | WT |
| 4 | 44, M | IFN-α | Long bones (lower limbs), skull and facial bones, and left clavicle | — | Peri-renal and peri-aortic fibrosis, and bilateral HDN | Diabetes insipidus, (central) hypothyroidism and hypogonadism; and MRI evidence of pituitary stalk involvement | — | Interstitial lung disease | — | N/A | N/A | N/A | N/A |
| 5 | 69, M | — | Long bones (lower limbs), and facial bones | — | Peri-aortic and peri-renal fibrosis, and left-sided HDN | Peripheral hypogonadism | — | — | — | V600E | WT | WT | WT |
| 6 | 75, M | — | Long bones (lower limbs), facial bones, right clavicle, ribs, and spine | — | — | — | Diffuse involvement of midbrain, pons, cerebellar peduncles, supra-tentorial nodules | Interstitial lung disease | — | N/A | N/A | N/A | N/A |
| 7 | 43, M | — | Long bones (lower limbs) | — | — | — | Cortical and pons nodules, and bulky emispheric mass in the parieto-occipital left lobes | — | Xanthelasma, soft-tissue masses (para-vertebral, Achille's tendons, nose, and right thigh) | NA | NA | NA | NA |
| 8 | 42, F | PDN + colchicine | Long bones (upper and lower limbs) and facial bones | Coated aorta, myocardial infiltration with coronary involvement, and atrial mass | Peri-aortic and peri-renal fibrosis, bilateral HDN, and mesenteric fibrosis with ascites | (Peripheral) hypogonadism | — | Interstitial lung disease | Exophthalmos, xanthelasmas, digital ischemia, diffuse lymph-node enlargement, and bilateral leg edema | V600E | WT | WT | WT |
| 9 | 71, M | — | — | — | Peri-renal fibrosis | — | — | — | Exophthalmos | N/A | N/A | N/A | N/A |
| 10 | 46, M | — | Long bones (upper and lower limbs) and facial bones | Pericarditis with massive pericardial effusion, myocardial infiltration with coronary involvement, and coated aorta | Peri-aortic and peri-renal fibrosis, bilateral HDN, and mesenteric fibrosis | (Peripheral) hypogonadism | — | — | Exophthalmos | WT | WT | WT | WT |
Unless stated otherwise, the mutations were assessed using molecular techniques (see text for details); only in 1 patient (patient #1) did we assess it by IHC only.
“Coated aorta” indicates perivascular infiltration of the thoraco-abdominal aorta (Diamond et al27 ).
CYC, cyclophosphamide; HDN, hydronephrosis; N/A, biopsy not available (or not enough to allow sufficient nucleic acid amplification); V600E, mutation V600E of BRAF; WT, wild-type.