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Erdheim-Chester Disease , Heart Atria , Humans , Erdheim-Chester Disease/diagnosis , Heart Atria/pathology , Male , Middle Aged , Female , Heart Neoplasms/diagnosis , AdultSubject(s)
Erdheim-Chester Disease , Myocarditis , Humans , Erdheim-Chester Disease/diagnostic imaging , Erdheim-Chester Disease/complications , Erdheim-Chester Disease/pathology , Erdheim-Chester Disease/diagnosis , Myocarditis/etiology , Myocarditis/diagnostic imaging , Myocarditis/pathology , Male , Middle AgedABSTRACT
INTRODUCTION: Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytic multisystem disorder, deriving from mononuclear phagocytic cells. It is notoriously challenging to diagnose. Here we present a case of a patient with multisystem ECD. CASE PRESENTATION: A 76-year-old female with a history of Hashimoto's thyroiditis who presented with persistent leukocytosis was found to have bilateral renal enlargement with a perinephric mass, a recurrent pericardial effusion, and bilateral pleural effusions. Following biopsies of several sites of involvement, a diagnosis of ECD was made. DISCUSSION: The existing literature on ECD is sparse, and no diagnostic criteria have been put forward due to widely differing presentations, although the most common is skeletal. Definitive diagnosis requires a tissue sample. CONCLUSIONS: In presenting our clinical reasoning and approach, we hope to contribute to the existing body of literature on ECD, with the aim of ultimately having sufficient data to compile a diagnostic framework for other clinicians who encounter ECD.
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Erdheim-Chester Disease , Humans , Erdheim-Chester Disease/diagnosis , Female , Aged , Diagnosis, Differential , Biopsy , Tomography, X-Ray ComputedABSTRACT
OBJECTIVES: To present 4 patients with Erdheim-Chester disease (ECD) based on clinical, radiologic, histopathologic, and molecular genetic findings who had enhancing brainstem lesions and were initially believed to have chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). METHODS: Case series. RESULTS: Although patients with ECD can demonstrate clinical and imaging features similar to CLIPPERS, refractoriness to corticosteroids, lack of fulfillment of specific MRI criteria (i.e., enhancing lesions >3 mm, T2 abnormalities that exceed areas of T1 postgadolinium enhancement), and systemic findings such as "hairy kidney" appearance and metadiaphyseal osteosclerosis on 18F-fluorodeoxyglucose PET-CT help discriminate it from CLIPPERS. DISCUSSION: ECD is a histiocytic neoplasm characterized by multiorgan infiltration of clonal histiocytes carrying activating variants of the MAPK-ERK pathway. Neurologic involvement occurs in up to 40% of ECD with frequent brainstem lesions that can mimic acquired neuroinflammatory disorders, such as CLIPPERS. ECD is an important CLIPPERS mimic with distinct pathophysiology and targeted treatments. We highlight the need to consider histiocytic disorders among other alternate diagnoses when findings are not classic for CLIPPERS.
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Erdheim-Chester Disease , Humans , Erdheim-Chester Disease/diagnosis , Erdheim-Chester Disease/genetics , Middle Aged , Male , Female , Diagnosis, Differential , Aged , Positron Emission Tomography Computed Tomography , Magnetic Resonance Imaging , Adult , Neuroinflammatory Diseases/diagnosis , Neuroinflammatory Diseases/diagnostic imagingABSTRACT
Erdheim-Chester disease (ECD) is a rare histiocytosis that tends to co-exist with other myeloid malignancies. Here, we use genetic and transcriptomic sequencing to delineate a case of co-occurring BRAFV600E-mutated ECD and acute myeloid leukemia (AML), followed by AML remission and relapse. The AML relapse involved the extinction of clones with KMT2A-AFDN and FLT3-ITD, and the predominance of PTPN11-mutated subclones with distinct transcriptomic features. This case report has highlighted the screening for other myeloid malignancies at the diagnosis of ECD and the clinical significance of PTPN11-mutated AML subclones that require meticulous monitoring.
Subject(s)
Erdheim-Chester Disease , Leukemia, Myeloid, Acute , Mutation , Protein Tyrosine Phosphatase, Non-Receptor Type 11 , fms-Like Tyrosine Kinase 3 , Humans , Erdheim-Chester Disease/genetics , Erdheim-Chester Disease/complications , Erdheim-Chester Disease/diagnosis , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/diagnosis , fms-Like Tyrosine Kinase 3/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics , Male , Clonal Evolution/genetics , Female , Proto-Oncogene Proteins B-raf/genetics , Middle AgedSubject(s)
Erdheim-Chester Disease , Interleukin 1 Receptor Antagonist Protein , Proto-Oncogene Proteins B-raf , Humans , Erdheim-Chester Disease/drug therapy , Erdheim-Chester Disease/diagnosis , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Treatment Outcome , Proto-Oncogene Proteins B-raf/genetics , Female , Male , Biopsy , Antirheumatic Agents/therapeutic use , Middle AgedABSTRACT
Histiocytic diseases arise from MAPK mutations in myeloid progenitors. Depending on whether the progenitor follows a dendritic cell or macrophage/monocyte lineage the final histology results in Langerhans cell histiocytosis, Rosai-Dorfman disease or Erdheim-Chester disease. Commentary on: Friedman et al. Mixed histiocytic neoplasms: A multicentre series revealing diverse somatic mutations and responses to targeted therapy. Br J Haematol 2024;205:127-137.
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Mutation , Humans , Erdheim-Chester Disease/genetics , Erdheim-Chester Disease/pathology , Erdheim-Chester Disease/diagnosis , Histiocytosis, Langerhans-Cell/genetics , Histiocytosis, Langerhans-Cell/pathology , Histiocytosis, Langerhans-Cell/diagnosis , Histiocytosis, Sinus/pathology , Histiocytosis, Sinus/diagnosis , Histiocytosis, Sinus/geneticsABSTRACT
OBJECTIVE: To evaluate the heart response of Erdheim-Chester disease (ECD) through continuous follow-up within our large cohort, for which there is a lack of understanding. METHODS: We conducted a retrospective analysis of clinical data from patients with ECD with cardiac involvement diagnosed at our centre between January 2010 and August 2023. We assessed the heart response by integrating pericardial effusion and metabolic responses. RESULTS: A total of 40 patients were included, with a median age of 51.5 years (range: 29-66) and a BRAFV600E mutation rate of 56%. The most common imaging manifestations observed were pericardial effusion (73%), right atrium (70%) and right atrioventricular sulcus infiltration (58%). Among 21 evaluable patients, 18 (86%) achieved a heart response including 5 (24%) complete response (CR) and 13 (62%) partial response (PR). The CR rate of pericardial effusion response was 33%, while the PR rate was 56%. Regarding the cardiac mass response, 33% of patients showed PR. For cardiac metabolic response, 32% and 53% of patients achieved complete and partial metabolic response, respectively. There was a correlation between pericardial effusion response and cardiac metabolic response (r=0.73 (95% CI 0.12 to 0.83), p<0.001). The median follow-up was 50.2 months (range: 1.0-102.8 months). The estimated 5-year overall survival was 78.9%. The median progression-free survival was 59.4 months (95% CI 26.2 to 92.7 months). Patients who received BRAF inhibitors achieved better heart response (p=0.037) regardless of treatment lines. CONCLUSION: We pioneered the evaluation of heart response of ECD considering both pericardial effusion and cardiac metabolic response within our cohort, revealing a correlation between these two indicators. BRAF inhibitors may improve heart response, regardless of the treatment lines.
Subject(s)
Erdheim-Chester Disease , Pericardial Effusion , Humans , Erdheim-Chester Disease/complications , Erdheim-Chester Disease/drug therapy , Erdheim-Chester Disease/diagnosis , Male , Female , Middle Aged , Adult , Retrospective Studies , Aged , Pericardial Effusion/etiology , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Treatment Outcome , MutationABSTRACT
Erdheim Chester Disease (ECD) is a rare histiocytic disorder marked by infiltration of organs with CD68+ histiocytes. ECD stems from mutations of BRAF and MAP2K1 in hematopoietic stem and progenitor cells (HSPCs), which further differentiate into monocytes and histiocytes. Histopathology reveals lipid-containing histiocytes, which test positive for CD68 and CD133 in immunohistochemistry. Signs and symptoms vary and depend on the organ/s of manifestation. Definitive radiological results associated with ECD include hairy kidney, coated aorta, and cardiac pseudotumor. Treatment options primarily include anti-cytokine therapy and inhibitors of BRAF and MEK signaling.
Subject(s)
Erdheim-Chester Disease , Erdheim-Chester Disease/drug therapy , Erdheim-Chester Disease/diagnosis , Erdheim-Chester Disease/genetics , Erdheim-Chester Disease/therapy , Erdheim-Chester Disease/pathology , Erdheim-Chester Disease/metabolism , Humans , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Histiocytes/pathology , Histiocytes/metabolismABSTRACT
RATIONALE: Erdheim-Chester disease (ECD) is a rare multisystemic disease characterized by the infiltration of multiple organs by foamy CD68â +â CD1a-histiocytes. The genetic background consists of gain-of-function somatic mutations in the mitogen-activated protein kinase pathway. The purpose of the present paper is to make a contribution to the scientific literature on ECD by reporting our experience with a complex clinical case report, along with a concise review of the literature. We discussed the unusual clinical presentation, the complex diagnostic process and the comparison with other published cases. PATIENT CONCERNS: A 70-year-old man presented with arthralgia due to multiple bone areas of sclerosis, first diagnosed with metastases of a prostatic neoplasm. Sequential thorax-abdomen, femoral and homer contrast-enhanced computed tomography (CT) showed pericardial effusion, pulmonary fibrosis, and perirenal fibrous tissue as "hairy kidneys." He underwent. Three bone biopsies were unsuccessful to reach diagnosis. DIAGNOSES: A xanthelasma biopsy showed histopathological signs compatible with ECD; genetic analysis showed the mutation BRAFV600E. INTERVENTIONS: The patient underwent targeted therapy with vemurafenib (BRAF-inhibitor), discontinued 2 weeks later due to the onset of a diffuse erythematous papular rash on the trunk and limbs. OUTCOMES: At the 1-year follow-up, there was only progression of chronic kidney disease (CKD). LESSONS: The present case report describes how ECD diagnosis could represent a challenge for clinicians, owing to its heterogeneous clinical presentation. Early diagnosis followed by prompt therapy is essential for modifying the natural history of the disease.
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Erdheim-Chester Disease , Humans , Erdheim-Chester Disease/diagnosis , Erdheim-Chester Disease/genetics , Male , Aged , Proto-Oncogene Proteins B-raf/genetics , Vemurafenib/therapeutic useABSTRACT
Erdheim-Chester disease (ECD) is a rare 'L' (Langerhans) group histiocytic neoplasm that affects a multitude of organ systems, causing osteosclerotic bone lesions, periaortic encasement ('coated' aorta), retroperitoneal fibrosis involving kidneys and ureters ('hairy kidney'), and infiltration of the central nervous system. Cardiovascular involvement can occur in up to 70% of patients and is usually found during computed tomography/magnetic resonance imaging evaluation. When present, cardiovascular symptoms can have wide variability in presentation from asymptomatic to pericarditis, fatal cardiac tamponade, myocardial infarction, conduction abnormalities, heart failure, renal artery stenosis, and claudication. Cardiac involvement found on imaging includes right atrial pseudotumor, right atrioventricular groove infiltration, and pericardial effusions. ECD can involve the large- and medium-sized arteries, often seen as periarterial thickening (commonly coating the aorta) with stenosis/occlusion. Although more cardiovascular ECD cases have begun to be published in the literature, more data are needed on the outcomes of these patients, as well as how cardiovascular manifestations respond to treatment of ECD.
Subject(s)
Erdheim-Chester Disease , Humans , Erdheim-Chester Disease/complications , Erdheim-Chester Disease/diagnosis , Erdheim-Chester Disease/drug therapy , Erdheim-Chester Disease/diagnostic imaging , Male , Middle Aged , Female , Aged , Fatal Outcome , Treatment OutcomeABSTRACT
A radiologically diagnosed tumor in a 29-year-old woman with a fever of around 39⯰C was operated on under the suspicion of cholecystitis or a liver abscess. A solid tumor was found in the adrenal gland and resected. The frozen section findings did not reveal a clear diagnosis of entity and assignment. Histologically, the tumor was found to consist of densely clustered large histiocyte-like cells with expression of vimentin, CD68, and CD163 as well as negativity for keratin, langerin, and SMA. We diagnosed xanthogranulomatous adrenalitis and discussed the differential diagnoses (Langerhans cell histiocytosis, Rosai-Dorfman disease, malakoplakia, Erdheim-Chester disease).
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Adrenal Gland Neoplasms , Xanthomatosis , Humans , Adult , Female , Diagnosis, Differential , Adrenal Gland Neoplasms/diagnosis , Adrenal Gland Neoplasms/pathology , Adrenal Gland Neoplasms/surgery , Xanthomatosis/diagnosis , Xanthomatosis/pathology , Xanthomatosis/surgery , Granuloma/diagnosis , Granuloma/pathology , Granuloma/surgery , Adrenal Gland Diseases/diagnosis , Adrenal Gland Diseases/pathology , Erdheim-Chester Disease/diagnosis , Erdheim-Chester Disease/pathology , Histiocytosis, Sinus/diagnosis , Histiocytosis, Sinus/pathology , Histiocytosis, Sinus/surgeryABSTRACT
Erdheim-Chester disease (ECD) is a rare histiocytosis characterized by the foamy CD68+CD1a- histiocytes infiltrating multiple organs and tissues. ECD might be asymptomatic or present with variable manifestations. The diagnosis of ECD requires characteristic radiological findings and pathological features. Herein, we described a 52-year-old female patient who was admitted to our hospital for recurrent pericardial effusion for two months. She has a medical history of papillary thyroid carcinoma (PTC) and underwent a total thyroidectomy two years before admission. The radiological findings suggested a potential diagnosis of ECD. Cytological analysis of the effusion cytology specimen revealed CD68+CD1a- histiocytes, confirming the ECD diagnosis. The BRAF V600E mutation was identified in the histiocytes, prompting the administration of vemurafenib, a BRAF inhibitor. After two months of standard-dose vemurafenib treatment, the disease was well controlled with pericardial effusion regression.
Subject(s)
Erdheim-Chester Disease , Pericardial Effusion , Proto-Oncogene Proteins B-raf , Vemurafenib , Female , Humans , Middle Aged , Erdheim-Chester Disease/genetics , Erdheim-Chester Disease/drug therapy , Erdheim-Chester Disease/complications , Erdheim-Chester Disease/pathology , Erdheim-Chester Disease/diagnosis , Histiocytes/pathology , Mutation , Pericardial Effusion/pathology , Pericardial Effusion/etiology , Predictive Value of Tests , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins B-raf/genetics , Treatment Outcome , Vemurafenib/therapeutic useABSTRACT
Histiocytoses, including Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD), are inflammatory myeloid tumors in which monocyte lineage cells aggregate in various organs, causing tissue damage. Most of these tumors harbor oncogenic mutations in mitogen-activated protein kinase (MAPK) pathway genes, typified by BRAFV600E. Some patients with LCH develop bilateral symmetrical cerebellar lesions and brain atrophy several years after diagnosis when the initial symptoms disappear, leading to cerebellar ataxia and higher cerebral dysfunction. A similar neurological disorder has also been reported in ECD. This neurological disorder can be improved with MAPK inhibitors. When patients with this neurological disorder are identified among neurodegeneration of unknown etiology or histiocytosis patients and treated early with MAPK inhibitors, the disorder can be reversible.