Involvement In Erdheim-Chester Disease Research Articles

Complete remission of critical neurohistiocytosis by vemurafenib.

Objective:To describe a patient with life-threatening brainstem neurohistiocytosis who recovered completely upon targeted treatment with the V600E mutation-specific BRAF inhibitor vemurafenib.Methods:We report clinical, histiologic, genetic, and sequential imaging findings, including fluorodeoxyglucose (FDG)-PET, over a follow-up period of 11 months.Results:The patient presented with central hyperventilation, skeletal and perirenal Erdheim-Chester disease, and cutaneous Langerhans cell histiocytosis. A BRAF V600E hotspot mutation was detected in all afflicted tissues. Therapy with vemurafenib led to complete and stable clinical remission of CNS lesions and systemic disease that could be demonstrated by brain MRI and whole-body FDG-PET.Conclusions:Neurologic involvement in Erdheim-Chester disease usually confers a poor prognosis. In this patient, vemurafenib was well-tolerated and highly efficacious for severe brainstem involvement in Erdheim-Chester disease with overlapping Langerhans cell histiocytosis. This case illustrates the heterogeneous phenotypic spectrum of neurohistiocytosis and underscores the importance of genetic testing.Classification of evidence:This article provides Class IV evidence. This is a single observational study without controls.

Thoracic, abdominal and musculoskeletal involvement in Erdheim-Chester disease: CT, MR and PET imaging findings.

BackgroundErdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis with characteristic radiological and histological features. This entity is defined by a mononuclear infiltrate consisting of lipid-laden, foamy histiocytes that stain positively for CD68 and negatively for CD1a. Osseous involvement is constant and characteristic. Extra-osseous lesions may affect the retroperitoneum, lungs, skin, heart, brain and orbits.MethodsBoth radiography and technetium-99m bone scintigraphy may reveal osteosclerosis of the long bones, which is a typical finding in ECD. For visceral involvement, computed tomography (CT) is most useful, while magnetic resonance (MR) imaging is more sensitive for cardiovascular lesions; 2-[fluorine-18] fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/CT scanning is useful in assessing the extension of ECD lesions.ResultsThe prognosis is extremely variable and is often worse when there is cardiovascular system involvement. Diagnosis is based on the combination of radiographic, CT, MR imaging and nuclear medicine features and a nearly pathognomonic immunohistochemical profile.ConclusionThe aims of this work are to perform a systematic review of Erdheim-Chester disease as seen on imaging of the chest, abdomen and musculoskeletal system and to discuss the diagnostic workup and differential diagnoses according to the imaging presentation. Teaching points • Bone involvement is usually present in patients, and the imaging findings are pathognomonic of ECD. • The circumferential periaortic infiltration may extend to its branches, sometimes becoming symptomatic. • Cardiac involvement—the pericardium, right atrium and auriculoventricular sulcus—worsens its prognosis. • Perirenal infiltration extending to the proximal ureter is highly suggestive of this disease.

Cardiac involvement in Erdheim-Chester disease: a case report

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis of unknown etiology characterized by proliferation of lipid-containing foamy histiocytes affecting bones and potentially every organ. There is a wide clinical spectrum of the disease, ranging from asymptomatic bone or soft-tissue lesions to life-threatening systemic involvement. Although the initial descriptions published by Jakob Erdheim and William Chester in 1930 included a patient with right atrial infiltration on autopsy, cardiovascular involvement in ECD has only gained more recognition recently. In the present report, we describe a case with cardiac involvement, presenting with symptomatic heart failure and a cardiac mass assessed with echocardiogram and cardiac magnetic resonance imaging.

Commentary on "A Case of Erdheim-Chester Disease with Asymptomatic Renal Involvement"

We read with interest the article written by Dr. Lee et al. [1] on renal involvement in Erdheim-Chester disease (ECD). We agree with the authors on the long asymptomatic period of obstructive nephropathy that occurs in ECD. In our experience, a 60-year-old female, suffering from diabetes mellitus, who was treated with metformin, was admitted for fever, abdominal pain, diarrhoea, and acute renal failure (creatinine, 19 mg/dL). For two years, she had suffered from ECD, diagnosed in another medical ward. She had undergone interferon therapy with stability of her clinical status. Since the diagnosis, she had bilateral hydronephrosis, however, she had never suffered from impaired renal function. At admission, laboratory examinations showed: leukocytes, 21,500/µL; platelet, 54,000/µL; Hb, 11 g/dL; pH, 7.05; HCO3-, 9 mEq/L; serum lactates, 6 mEq/L. Findings on other routine laboratory examinations were within the normal range. Renal ultrasound showed a bilateral hydronephrosis, more to the right side. A percutaneous nephrostomy was placed to the right side; the patient received antibiotic and saline solution therapy with progressive improvement of her clinical status (remission of fever, recovery of diuresis; normalization of renal function and acid-base balance); blood and urine cultures were negative for bacterial growth. We diagnosed intestinal discomfort and lactic acidosis metformin associated with acute renal failure secondary to dehydration. Upon the complete normalization of renal function (creatinine, 1.16 mg/dL), it was possible to perform a computed tomography scan with contrast, which showed a slight hydronephrosis on the right side (Fig. 1) and a marked hydronephrosis on the left side (Fig. 2). We decided to remove the percutaneous nephrostomy, and, as in the case reported by Dr. Lee et al. [1], we counseled a wait-and-see policy in the outpatient clinic. We counseled ureteral stenting in cases of hydronephrosis or deterioration of renal function. Fig. 1 Computed tomography abdomen scan: slight hydronephrosis of right kidney with percutaneous nephrostomy. Fig. 2 Computed tomography abdomed scan: marked hydronephrosis of left kidney.

Cardiac involvement in Erdheim-Chester disease: echocardiographic appearance and value of cardiac MRI

Erdheim-Chester disease (ECD) is a rare non-Langerhans form of cell histiocytosis characterized by xanthogranulomatous infiltrates of long bones and potentially every organs. It has been found by MRI and CT studies that cardiac involvement occurs more often than expected, in different forms, and that cardiovascular manifestations are underdiagnosed. A 43-year-old man with known ECD, asymptomatic, was screened for cardiac involvement by transthoracic echocardiography. …

Cerebral, Facial, and Orbital Involvement in Erdheim-Chester Disease: CT and MR Imaging Findings

Cerebral, Facial, and Orbital Involvement in Erdheim-Chester Disease: CT and MR Imaging Findings

Cerebral, Facial, and Orbital Involvement in Erdheim-Chester Disease: CT and MR Imaging Findings

To retrospectively review the brain magnetic resonance (MR) imaging and computed tomographic (CT) findings in patients with Erdheim-Chester disease (ECD). The ethics committee required neither institutional review board approval nor informed patient consent for retrospective analyses of the patients' medical records and imaging data. The patients' medical files were retrospectively reviewed in accordance with human subject research protocols. Three neuroradiologists in consensus analyzed the signal intensity, location, size, number, and gadolinium uptake of lesions detected on brain MR images obtained in 33 patients with biopsy-proved ECD. Thirty patients had intracranial, facial bone, and/or orbital involvement, and three had normal neurologic imaging findings. The hypothalamic-pituitary axis was involved in 16 (53%) of the 30 patients, with six (20%) cases of micronodular or nodular masses of the infundibular stalk. Meningeal lesions were observed in seven (23%) patients. Three (10%) patients had bilateral symmetric T2 high signal intensity in the dentate nucleus areas, and five (17%) had multiple intraaxial enhancing masses. Striking intracranial periarterial infiltration was observed in three (10%) patients. Another patient (3%) had a lesion in the lumen of the superior sagittal sinus. Nine (30%) patients had orbital involvement. Twenty-four (80%) patients had osteosclerosis of the facial and/or skull bones. At least two anatomic sites were involved in two-thirds (n = 20) of the patients. Osteosclerosis of the facial bones associated with orbital masses and either meningeal or infundibular stalk masses was seen in eight (27%) patients. Lesions of the brain, meninges, facial bones, and orbits are frequently observed and should be systematically sought on the brain MR and CT images obtained in patients with ECD, even if these patients are asymptomatic. Careful attention should be directed to the periarterial environment.

Intérêt de la tomographie par émission de positons couplée au scanner dans la maladie d'Erdheim-Chester

Erdheim-Chester disease is a rare non-Langerhans form of histiocytosis. We report the use of combined fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET-CT) in this disease. Three men, aged from 55 to 74 years with confirmed Erdheim-Chester disease were included. 18F-FDG PET-CT allowed to detect visceral and vascular involvement of the disease which were overlooked with CT-scan or magnetic resonance imaging: left common carotid and ilio-femoral artery in one patient, coronary, femoral and tibia in the second, aortic, common carotid, femoral and mandibula in the remaining patient. Also, sequential 18F-FDG PET-CT was useful to appreciate treatment efficiency (decrease hyperfixation) and decide treatment modification (interferon alpha). 18F-FDG PET-CT combined imaging allows to assess the extent of involvement in Erdheim-Chester disease. 18F-FDG PET-CT may be also a useful tool in the management of Erdheim-Chester disease.

Diagnóstico radiológico de la enfermedad de Erdheim Chester. A propósito de un caso

Erdheim-Chester disease is a rare disorder, belonging to the group of histiocytoses, in which diffuse infiltration of histiocytes affects various organs and systems. Bone involvement in Erdheim-Chester disease manifests as generalized sclerosis of the bone marrow and cortex of the long bones, and this peculiar radiologic characteristic differentiates it from other histiocytoses. Diagnostic suspicion of the disease derives from the pulmonary and bone radiologic findings as well as from the clinical findings. Histological study reveals histiocyte infiltration affecting the soft tissues, musculoskeletal system, and central nervous system. The definitive diagnosis is reached by immunohistochemistry. Like other histiocytoses, such as Langerhans cell histiocytosis, immunohistochemical techniques reveal lipid-laden histiocytes; however, unlike the other types, Erdheim-Chester histiocytes stain negatively for S 100 protein and do not contain Birbeck granules.

Bone Involvement in Erdheim-Chester Disease: Imaging Findings including Periostitis and Partial Epiphyseal Involvement

To retrospectively review the bone findings at radiography, scintigraphy, computed tomography (CT), and magnetic resonance (MR) imaging in 11 patients with immunohistochemical and histologic proof of Erdheim-Chester disease. This study was designed as a retrospective review; approval of the institutional review board and patient consent were not required for this type of study. Eleven patients (eight men and three women; mean age, 49 years; range, 17-68 years) with Erdheim-Chester disease underwent conventional radiography of the skeleton and bone scintigraphy. Two patients underwent CT of the femora and 10 underwent CT of the skull. Eight patients underwent MR imaging. Conventional radiographs, bone scintigrams, CT scans, and MR images were reviewed in consensus by four musculoskeletal radiologists. All 11 patients had involvement of the long bones and normal axial skeleton, hands, and feet. Bilateral and symmetric osteosclerosis of the diaphysis of the long bones was present in 52 (26 pairs) (98%) of the 53 bone lesions visible on conventional radiographs. Osteosclerosis was heterogeneous in 65% of the patients and homogeneous in 35%. Diaphysis was involved in 100% and metaphysis in 44 (83%) lesions. Partial epiphyseal involvement sparing the subchondral bone was present in 24 (45%) lesions. Periostitis was seen in 35 (66%) and endosteitis in 50 (94%) of the 53 long bones involved. Bone scintigraphy depicted tracer uptake in all bone lesions visible on radiographs. Skull and face bone lesions were present in two patients. MR imaging depicted a replacement of the normal fatty bone marrow by heterogeneous signal intensity on T1- and T2-weighted spin-echo images. Lesion extent, epiphyseal involvement, and periostitis were clearly depicted at MR imaging. This series provides a detailed description of bone involvement in Erdheim-Chester disease. Periostitis and partial epiphyseal involvement of the long bones are also features of this disease. (c) RSNA, 2005.

Imaging of Thoracoabdominal Involvement in Erdheim-Chester Disease

Imaging of Thoracoabdominal Involvement in Erdheim-Chester Disease

Bilateral orbital involvement in Erdheim-Chester disease: case report

Purpose: To report a case of Erdheim-Chester disease with bilateral orbital involvement and to inform ophthalmologists about this uncommon condition. Methods: Case report. A 41-year-old man presented with proptosis, lid xanthelasmas, disc edema and extraocular muscle restrictions. He was suspected of having a systemic lymphoma and had already been submitted to a retroperitoneal biopsy, however, the diagnosis was still uncertain. Results: The patient was evaluated by computed tomography and magnetic resonance imaging of the orbit. Orbital pseudotumor was suspected and a biopsy of the orbital lesion initially failed to provide the correct diagnosis which was only made after detailed analysis of the clinical and imaging findings, and review of the histopathologic studies. The systemic diagnosis was made after the orbital diagnosis although the patient had been extensively investigated for more than one year. Conclusions: Erdheim-Chester disease is a rare idiopathic systemic condition characterized by a xanthogranulomatous process involving retroperitoneum, heart, lungs, bone and other tissues. The condition is often fatal due to renal or cardiovascular complications. Ocular findings are rare but may be very helpful for the diagnosis. Therefore, ophthalmologists should be aware of the clinical manifestations and imaging findings of this rare disease in order to establish an early diagnosis.

Erdheim-Chester disease: clinical, radiologic, and histopathologic findings in five patients with interstitial lung disease.

Erdheim-Chester disease is a clinicopathologic entity defined by a characteristic pattern of symmetric osteosclerosis caused by an infiltrate of mononuclear cells that include prominent numbers of foamy histiocytes. About half of patients have extraskeletal manifestations, including involvement of the hypothalamus/posterior pituitary, orbit, retroperitoneum, skin, lung, and heart. Pulmonary involvement is an uncommon but important manifestation of Erdheim-Chester disease because it causes significant morbidity and mortality. A review of the Mayo Clinic files produced four patients with confirmed Erdheim-Chester disease in whom lung biopsy had been performed. One additional patient was included from the University of Pittsburgh. Four patients were women. The mean age was 53.6 years (range 25-70 years). All patients had bilateral and symmetric sclerotic bone lesions characteristic of Erdheim-Chester disease, although in three the skeletal abnormalities were discovered only after lung biopsy. Four patients had dyspnea, and one also had a dry cough. One patient died 17 months after diagnosis. Chest radiographs showed diffuse interstitial infiltrates in all patients, with an upper zone predominance in three. Thoracic computed tomography (CT) scans showed thickening of the visceral pleura and interlobular septa with patchy associated fine reticular and centrilobular opacities and ground glass attenuation. Lung biopsy specimens showed an infiltrate of foamy histiocytes, lymphocytes, and scattered Touton giant cells with associated fibrosis in a striking lymphatic distribution. The infiltrate involved visceral pleura, interlobular septa, and bronchovascular bundles. Immunohistochemical stains were positive for CD68 in all cases and S-100 protein in four cases. Stains for CD1a were consistently negative. Ultrastructural studies in one case showed no Birbeck granules. Although in bone the histologic features of Erdheim-Chester disease may overlap with Langerhans' cell histiocytosis, its expression in the lung is distinct. Lung involvement in Erdheim-Chester disease has emerged as a unique radiographic and histologic entity.

Bilateral orbital involvement in Erdheim-Chester disease

Erdheim-Chester disease is an idiopathic condition characterized by a xanthogranulomatous process infiltrating the bones, lungs, heart, retroperitoneum and other tissues. This condition is often fatal. Ocular findings are rare. The authors report a case of bilateral xanthelasmas and bilateral massive orbital infiltration in a 61-year-old man with severe retroperitoneal fibrosis, renal and cardiovascular problems. The ophthalmic manifestations and differential diagnosis of this peculiar pathologic condition are discussed.

Pulmonary involvement in Erdheim-Chester disease: high-resolution CT findings

Erdheim-Chester disease is a distinctive pathological radiographic entity, most commonly characterised by a typical skeletal involvement resulting from histiocytic infiltration of the bone marrow. Although lung involvement is often absent, we report a case of diffuse infiltrative lung disease characterised by a wide-spread reticular pattern on high-resolution CT scans associated with cystic airspaces and mild honeycombing observed throughout both lungs. Interstitial infiltration with lipid-laden histiocytes was histologically confirmed by means of transbronchial biopsy.