Summary of organ manifestations of ECD
| Organ . | Clinical and radiographic features . |
|---|---|
| Bones | Lower-extremity bone pain is the most common presenting symptom (50%)6 ; full-body (skull-to-toes) FDG-PET-CT scan or 99mTc bone scintigraphy shows bilateral symmetric osteosclerosis of metadiaphysis of femur, tibia, and fibula in >95% cases and is pathognomonic; skull and axial skeleton less commonly involved than LCH, which typically shows lytic punched-out lesions rather than sclerotic lesions that are seen in ECD30 |
| Nervous system | Seen in 25% to 50% patients, with predilection toward brain parenchyma of the posterior cranial fossa and dura, although infiltrations can occur throughout the neuraxis39 ; these abnormalities often but do not invariably demonstrate gadolinium enhancement; rarely, may present with nontumorous neurodegenerative-like (atrophic) changes in the brainstem and cerebellum Retinal involvement has been reported as well96 Clinical manifestations depend on the site of involvement, and may include ataxia, dysarthria, cognitive impairment, headaches, or peripheral neuropathy6 ; some patients may present with mood lability111 |
| Endocrine | Anterior and posterior pituitary abnormalities (40% to 70%); most commonly central DI (25% to 50%) and may precede the diagnosis of ECD by several years, sometimes decades6,35,39,109 ; other pituitary hormone deficiencies that are commonly seen are growth hormone, gonadotropin, thyrotropin, and corticotropin; hyperprolactinemia can be seen in 15% to 30% patients35,109 ; although normal pituitary imaging does not exclude hormonal deficiency, an abnormal pituitary stalk MRI is commonly associated with hypopituitarism; primary hypothyroidism (20%), hypogonadism (19%), and adrenal insufficiency (6%) can be seen as well35 |
| Orbit | Unilateral or bilateral infiltration seen in 25% to 30% of patients; clinical manifestations include exophthalmos, retro-orbital pain, oculomotor nerve palsy or vision loss6,36 ; differential diagnosis includes xanthogranuloma,36 RDD, Graves disease, granulomatous disease, and IgG4-related disease |
| Respiratory | Lung involvement in ECD is mostly asymptomatic and seen radiologically in ∼50% of cases, involving either the lung parenchyma or pleura6,7 ; unlike pulmonary LCH, no association with cigarette smoking has been reported; although plain chest radiographs can be normal, findings on CT of the chest may include mediastinal infiltration, pleural thickening or effusions, interlobular septal thickening, ground-glass opacities, or centrilobular opacities34,38,41 ; pulmonary function tests commonly reveal a more restrictive as compared with an obstructive pattern6,34 ; ECD may also involve facial sinuses, with maxillary sinus thickening in ∼50% patients6 |
| Cardiovascular | Cardiovascular involvement may be asymptomatic but can be seen in 50% to 70% patients at imaging evaluation by CT and/or MRI31,33,75 ; most common findings include pericardial infiltration with effusion (which may be complicated by tamponade) or myocardial infiltration in the form of right atrioventricular pseudotumor (40%)6,75 ; circumferential soft tissue sheathing of the thoracic/abdominal aorta and its branches may be seen as “coated” aorta may be seen on CT scan (50% to 60%)6,42 ; periarterial involvement of renal vessels may lead to renovascular hypertension (20%), is responsive to stenting,112 and can be monitored with renal artery dopplers; involvement of other visceral vessels has been reported as well; coronary arteries may be involved in 30% to 50% of patients31,38 |
| Retroperitoneum, including kidney | Manifesting as infiltrative perinephric soft tissue thickening, or “hairy kidney” (50% to 60%)7 ; perinephric infiltrates can rarely extend to involve the renal pelvis and/or renal ureters causing hydronephrosis and renal failure requiring dialysis and nephrostomy with stent placement6 ; in some cases, it may also extend to involve the adrenal glands32 ; longstanding perinephric ECD may lead to atrophy of kidneys; differential diagnosis includes retroperitoneal fibrosis and IgG4-related disease |
| Cutaneous | Seen in 20% to 30% patients, with one-half of the patients manifesting skin lesions as initial ECD presentation6,7,37 ; most common cutaneous manifestation is xanthelasma, occurring as yellowish plaques around the eyelids but can occur as yellowish-brown papules or plaques on the face, neck, axilla, trunk or groin as well37 ; it may also present as subcutaneous nodules or granuloma annulare-like lesions37 |
| Reticuloendothelial and hematopoietic system | In one study, 11% of ECD patients had liver and spleen involvement, respectively, although the prevalence has been lower in other series6,40 ; ECD rarely involves the lymph nodes, but may involve bone marrow in 8% of cases113 ; ECD may also be associated with concomitant myeloid neoplasms in 10% of cases, specifically myeloproliferative neoplasm, myelodysplastic syndrome, or mixed myelodysplastic/myeloproliferative overlap syndrome including chronic myelomonocytic leukemia21 |
| Organ . | Clinical and radiographic features . |
|---|---|
| Bones | Lower-extremity bone pain is the most common presenting symptom (50%)6 ; full-body (skull-to-toes) FDG-PET-CT scan or 99mTc bone scintigraphy shows bilateral symmetric osteosclerosis of metadiaphysis of femur, tibia, and fibula in >95% cases and is pathognomonic; skull and axial skeleton less commonly involved than LCH, which typically shows lytic punched-out lesions rather than sclerotic lesions that are seen in ECD30 |
| Nervous system | Seen in 25% to 50% patients, with predilection toward brain parenchyma of the posterior cranial fossa and dura, although infiltrations can occur throughout the neuraxis39 ; these abnormalities often but do not invariably demonstrate gadolinium enhancement; rarely, may present with nontumorous neurodegenerative-like (atrophic) changes in the brainstem and cerebellum Retinal involvement has been reported as well96 Clinical manifestations depend on the site of involvement, and may include ataxia, dysarthria, cognitive impairment, headaches, or peripheral neuropathy6 ; some patients may present with mood lability111 |
| Endocrine | Anterior and posterior pituitary abnormalities (40% to 70%); most commonly central DI (25% to 50%) and may precede the diagnosis of ECD by several years, sometimes decades6,35,39,109 ; other pituitary hormone deficiencies that are commonly seen are growth hormone, gonadotropin, thyrotropin, and corticotropin; hyperprolactinemia can be seen in 15% to 30% patients35,109 ; although normal pituitary imaging does not exclude hormonal deficiency, an abnormal pituitary stalk MRI is commonly associated with hypopituitarism; primary hypothyroidism (20%), hypogonadism (19%), and adrenal insufficiency (6%) can be seen as well35 |
| Orbit | Unilateral or bilateral infiltration seen in 25% to 30% of patients; clinical manifestations include exophthalmos, retro-orbital pain, oculomotor nerve palsy or vision loss6,36 ; differential diagnosis includes xanthogranuloma,36 RDD, Graves disease, granulomatous disease, and IgG4-related disease |
| Respiratory | Lung involvement in ECD is mostly asymptomatic and seen radiologically in ∼50% of cases, involving either the lung parenchyma or pleura6,7 ; unlike pulmonary LCH, no association with cigarette smoking has been reported; although plain chest radiographs can be normal, findings on CT of the chest may include mediastinal infiltration, pleural thickening or effusions, interlobular septal thickening, ground-glass opacities, or centrilobular opacities34,38,41 ; pulmonary function tests commonly reveal a more restrictive as compared with an obstructive pattern6,34 ; ECD may also involve facial sinuses, with maxillary sinus thickening in ∼50% patients6 |
| Cardiovascular | Cardiovascular involvement may be asymptomatic but can be seen in 50% to 70% patients at imaging evaluation by CT and/or MRI31,33,75 ; most common findings include pericardial infiltration with effusion (which may be complicated by tamponade) or myocardial infiltration in the form of right atrioventricular pseudotumor (40%)6,75 ; circumferential soft tissue sheathing of the thoracic/abdominal aorta and its branches may be seen as “coated” aorta may be seen on CT scan (50% to 60%)6,42 ; periarterial involvement of renal vessels may lead to renovascular hypertension (20%), is responsive to stenting,112 and can be monitored with renal artery dopplers; involvement of other visceral vessels has been reported as well; coronary arteries may be involved in 30% to 50% of patients31,38 |
| Retroperitoneum, including kidney | Manifesting as infiltrative perinephric soft tissue thickening, or “hairy kidney” (50% to 60%)7 ; perinephric infiltrates can rarely extend to involve the renal pelvis and/or renal ureters causing hydronephrosis and renal failure requiring dialysis and nephrostomy with stent placement6 ; in some cases, it may also extend to involve the adrenal glands32 ; longstanding perinephric ECD may lead to atrophy of kidneys; differential diagnosis includes retroperitoneal fibrosis and IgG4-related disease |
| Cutaneous | Seen in 20% to 30% patients, with one-half of the patients manifesting skin lesions as initial ECD presentation6,7,37 ; most common cutaneous manifestation is xanthelasma, occurring as yellowish plaques around the eyelids but can occur as yellowish-brown papules or plaques on the face, neck, axilla, trunk or groin as well37 ; it may also present as subcutaneous nodules or granuloma annulare-like lesions37 |
| Reticuloendothelial and hematopoietic system | In one study, 11% of ECD patients had liver and spleen involvement, respectively, although the prevalence has been lower in other series6,40 ; ECD rarely involves the lymph nodes, but may involve bone marrow in 8% of cases113 ; ECD may also be associated with concomitant myeloid neoplasms in 10% of cases, specifically myeloproliferative neoplasm, myelodysplastic syndrome, or mixed myelodysplastic/myeloproliferative overlap syndrome including chronic myelomonocytic leukemia21 |
DI, diabetes insipidus; IgG4, immunoglobulin G4.