Assuntos
Doença de Erdheim-Chester , Miocardite , Humanos , Doença de Erdheim-Chester/diagnóstico por imagem , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/patologia , Doença de Erdheim-Chester/diagnóstico , Miocardite/etiologia , Miocardite/diagnóstico por imagem , Miocardite/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Doença de Erdheim-Chester , Leucemia Mieloide Aguda , Mutação , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Tirosina Quinase 3 Semelhante a fms , Humanos , Doença de Erdheim-Chester/genética , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Tirosina Quinase 3 Semelhante a fms/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Masculino , Evolução Clonal/genética , Feminino , Proteínas Proto-Oncogênicas B-raf/genética , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Doença de Erdheim-Chester , Derrame Pericárdico , Humanos , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/tratamento farmacológico , Doença de Erdheim-Chester/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Idoso , Derrame Pericárdico/etiologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Resultado do Tratamento , MutaçãoRESUMO
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.
Assuntos
Doença de Erdheim-Chester , Humanos , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/diagnóstico , Doença de Erdheim-Chester/tratamento farmacológico , Doença de Erdheim-Chester/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Evolução Fatal , Resultado do TratamentoRESUMO
ABSTRACT: A 36-year-old man who was at follow-up for histiocytosis had sudden-onset symptoms of unilateral ophthalmic increased pressure. The patient was referred to the FDG PET/CT for determination of involvement with suspicion of Erdheim-Chester disease. The reduction of the FDG uptake in all of the lesions (medial temporal lobes, nasal septum, medulla spinalis in sacral region, as well as perinephritic infiltrations), which were determined by the first PET/CT, was achieved at second imaging.
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Doença de Erdheim-Chester , Masculino , Humanos , Adulto , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Transporte Biológico , Medula EspinalRESUMO
Erdheim-Chester disease is a rare histiocytosis that primarily affects the skeletal system, but cardiovascular manifestations occur in 75% of cases and are associated with a poor prognosis. Given the small number of cases, the evolution and management of the disease are uncertain. Therefore, it is important to report and share Erdheim-Chester cases. This report presents the case of a young patient with constrictive pericarditis and mitral valve regurgitation resulting from Erdheim-Chester disease.
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Doença de Erdheim-Chester , Insuficiência da Valva Mitral , Humanos , Valva Aórtica , Doença de Erdheim-Chester/complicações , Insuficiência da Valva Mitral/complicações , PericardiectomiaRESUMO
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.
Assuntos
Doença de Erdheim-Chester , Derrame Pericárdico , Proteínas Proto-Oncogênicas B-raf , Vemurafenib , Humanos , Doença de Erdheim-Chester/genética , Doença de Erdheim-Chester/tratamento farmacológico , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/patologia , Doença de Erdheim-Chester/diagnóstico , Feminino , Derrame Pericárdico/patologia , Derrame Pericárdico/etiologia , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/genética , Vemurafenib/uso terapêutico , Resultado do Tratamento , Mutação , Histiócitos/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Valor Preditivo dos Testes , CitologiaRESUMO
OBJECTIVE: To describe the cerebrospinal fluid (CSF) metabolomic pattern of pituitary stalk lesions. METHODS: CSF was collected from patients with different pituitary stalk lesions treated at Peking Union Medical College Hospital: germ cell tumor (GCT, n = 27); hypophysitis (n = 10); and Langerhans cell histiocytosis (LCH) or Erdheim-Chester disease (ECD) (LCH + ECD, n = 10). The CSF metabolome profiles were characterized by liquid chromatography-mass spectrometry (LC-MS). RESULTS: There were 44 metabolites that significantly differed between patients with GCT and those with hypophysitis (P < .05). Between patients with GCT with CSF level of beta subunit of human chorionic gonadotrophin (ß-hCG) < 5â mIU/mL and those with hypophysitis, there were 15 differential metabolites (P < .05, fold change > 1.5 or < 1/1.5). All of the metabolites had an area under the curve (AUC) above 0.7. There were 9 metabolites that significantly differed between patients with GCT and those with LCH + ECD (P < .05) and 7 metabolites had significant differences between GCT (CSF ß-hCG < 5â mIU/mL) and LCH + ECD (P < .05, fold change > 1.5 or < 1/1.5). We found 6 metabolites that were significantly different between patients with hypophysitis and those with LCH + ECD (P < .05) and 5 of these had fold change more than 1.5 or less than 1/1.5. Three metabolites, 5-deoxydiplosporin, cloversaponin I, and phytosphingosine, showed excellent capabilities to differentiate the 3 disease categories. Furthermore, we identified 67 metabolites associated with clinical test results (ρ > 0.2, P < .05) and 29 metabolites showed strong correlation (ρ > 0.4, P < .05). CONCLUSION: Our study is the first to systematically investigate the metabolomics of CSF in different pituitary stalk lesions. CSF metabolomics is a useful strategy for biomarker discovery.
Assuntos
Doença de Erdheim-Chester , Histiocitose de Células de Langerhans , Hipofisite , Neoplasias Embrionárias de Células Germinativas , Humanos , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/tratamento farmacológico , Doença de Erdheim-Chester/patologia , Hipófise/patologiaRESUMO
OBJECTIVE: To analyze the body distribution of Erdheim-Chester disease (ECD) and determine the utility of 2-[18â¯F]FDG PET/CT compared to other imaging techniques. Additionally, to assess the aggressiveness and extent of the disease based on the presence/absence of the BRAFV600E mutation. MATERIALS AND METHODS: The 2-[18F]FDG-PET/CT scans of all patients diagnosed with ECD between 2008 and 2021 were reviewed, including 19 patients. The affected territories were classified as detectable by PET/CT or detectable only by other imaging techniques (bone scintigraphy, contrast-enhanced CT, or MRI). Descriptive analysis and correlation of the BRAF mutation with the affected organs and maximum SUV were performed using the Student's t-test. RESULTS: Out of the 19 patients (14 males; mean age 60.3 years), 11 had the BRAFV600E mutation. A total of 127 territories (64 organ-systems) affected were identified using different imaging modalities, of which 112 were detected by PET/CT, and an additional 15 territories were solely identified by cerebral and cardiac MRI. The presence of BRAFV600E mutation was associated with greater organ involvement (pâ¯<â¯0.05) without differences in SUVmax (pâ¯>â¯0.05). CONCLUSION: 2-[18F]FDG PET/CT is a highly effective diagnostic tool in patients with ECD, detecting the majority of affected territories. MRI was the only imaging modality with additional findings in territories showing high physiological uptake of 2-[18F]FDG (cerebral and cardiac). The presence of the BRAFV600E mutation correlated with a higher extent of the disease.
Assuntos
Doença de Erdheim-Chester , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Masculino , Humanos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Doença de Erdheim-Chester/diagnóstico por imagem , Doença de Erdheim-Chester/genética , Doença de Erdheim-Chester/complicações , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , MutaçãoRESUMO
BACKGROUND: Erdheim-Chester disease (ECD) is a rare progressive non-Langerhans' cell histiocytic multisystem disorder with a broad spectrum of clinical manifestations, including infiltrative perinephric with ureteral involvement resulting in hydronephrosis, renal atrophy, and eventual renal failure. OBJECTIVE: To present a patient with ECD with bilateral renal/ureteral involvement managed with bilateral percutaneous nephrostomy tubes (PCNT) and trametinib who underwent bilateral robotic upper tract reconstruction, the first such published report. The video demonstrates only the left-sided repair, which posed specific challenges and demonstrates reconstructive techniques useful in complex upper tract repairs with limited tissue availability. MATERIALS AND METHODS: A 35-year-old male initially presented with baseline creatinine of 1.62 and split renal function; 30% right and 70% left by Lasix renogram. Extra-genitourinary manifestations of disease included cardiac hypertrophy and skin ulcers/lesions. Bilateral retrograde pyeloureterography showed proximal ureteral obliteration â¼4 cm bilaterally. Multiple management options were discussed including PCNTs, but patient elected for definitive repair. He was seen by Cardiology and Anesthesia and deemed to be optimized. He held his trametinib for 1week before surgery. We demonstrate a difficult ureteral dissection with fibrotic hilum preventing separation. Simultaneous ureteroscopy identified the distal extent of stricture which was excised, leaving a â¼15 cm gap. Downward nephropexy was performed with ultrasound guidance to identify an inferior calyx. Partial nephrectomy was then performed without vascular control due to hilar fibrosis. Ileal interposition was chosen to bridge the remaining â¼8 cm gap. Proximal ileo-calyceal and distal ileo-ureteral anastomoses were performed. We then placed a 30 cm × 7 Fr double-J ureteral stent in standard fashion. The ileum was secured to the renal pelvis to maintain a straight lie and an omental flap was secured in place. RESULTS: Immediate postoperative course was complicated by partial small bowel obstruction leading to a negative exploratory laparotomy and a subsequent episode of urosepsis. The patient is now voiding well without stents or PCNTs, without infections and with improving renal function, now with GFR (glomerular filtration rate) of 62 from 43 preoperatively. With aggressive hydration, patient has had no obstruction of the distal ureter with mucus. MRI Abdomen/Pelvis 6months later showed irregularity of the calyces with stable mild hydronephrosis. The patient continues to be medically managed on trametinib for his underlying disease, with surveillance for recurrent fibrosis and obstruction which has not yet occurred. CONCLUSION: Robotic ureterolysis and ureterocalycostomy with possible bowel interposition is a reasonable option for upper tract reconstruction in select patients with ECD.
Assuntos
Doença de Erdheim-Chester , Hidronefrose , Fibrose Retroperitoneal , Ureter , Obstrução Ureteral , Masculino , Humanos , Adulto , Ureter/cirurgia , Obstrução Ureteral/etiologia , Obstrução Ureteral/cirurgia , Obstrução Ureteral/patologia , Fibrose Retroperitoneal/complicações , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/cirurgia , Pelve Renal/patologia , Hidronefrose/cirurgia , Hidronefrose/complicações , Íleo , FibroseRESUMO
Erdheim-Chester disease (ECD) is a rare and probably fatal multisystemic non-Langerhans cell histiocytosis (LCH). To comprehensively investigate the clinical features, genomic analysis, treatments, and prognostic factors of ECD, we retrospectively analyzed the clinical data of 75 ECD patients and 10 mixed LCH and ECD patients in our center. The median age at diagnosis was 46 years (range, 5-70). ECD patients were older at diagnosis (p = 0.006) and had more cardiac involvement (p = 0.011) as well as vascular (p = 0.031) involvement compared to mixed LCH and ECD patients. 64.8% of ECD patients and 87.5% of mixed LCH and ECD patients carried BRAFV600E mutation. The BRAFV600E mutation correlated with a greater number of affected organs (p = 0.030) and was associated with lung involvement (p = 0.033) as well as pleural involvement (p = 0.002). The median follow-up time was 38 months (range, 1-174). The estimated 5-year progression-free survival (PFS) and overall survival (OS) were 48.9% and 84.7%, respectively. In a multivariate analysis, right atrial pseudotumor (p = 0.013) and pancreatic involvement (p = 0.005) predicted worse OS, while pleural (p = 0.042) and central nervous system (CNS) involvement (p = 0.043) predicted worse PFS. Our study described the clinical spectrum of ECD and mixed LCH and ECD, while also revealed the prognostic value of right atrial pseudotumor and pancreatic, pleural, and CNS involvement for worse survival.
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Fibrilação Atrial , Doença de Erdheim-Chester , Histiocitose de Células de Langerhans , Humanos , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Doença de Erdheim-Chester/genética , Doença de Erdheim-Chester/complicações , Prognóstico , Estudos Retrospectivos , Proteínas Proto-Oncogênicas B-raf/genética , Fibrilação Atrial/complicações , Histiocitose de Células de Langerhans/patologiaRESUMO
BACKGROUND Erdheim-Chester disease (ECD), a form of non-Langerhans-cell histiocytosis, is extremely rare. The mean age of individuals with ECD is in their 50s. Histiocytic infiltration of vital organ systems is a potential cause of substantial morbidity, which is associated with the multisystemic form of ECD. This report presents the first case of ECD with renal abnormalities in Palestine. CASE REPORT A 54-year-old woman with no medical or surgical history presented with 6 months of bilateral flank pain with no radiation or fever. A physical examination revealed only bilateral flank pain. Urine tests showed microhematuria. Laboratory test results showed increased serum creatinine levels (1.21 mg/dL) and microcytic anemia. A CT scan revealed significant multi-organ abnormalities, including renal abnormalities with a hairy kidney sign, pericardial effusion, and an osteolytic lesion of the spine. The hairy kidney sign is pathognomonic for ECD, so the renal mass was biopsied to confirm the diagnosis. The biopsy showed foamy histiocytes, lymphocytes, and plasma cells. Foamy histiocytes were CD68-positive and negative for S100, CD1a, and HMB45. PAx5 and CD3 immunostaining showed T-predominant B-lymphocyte mixtures. CONCLUSIONS In the setting of systemic symptoms and imaging abnormalities such as presence of the hairy kidney sign, pericardial effusion, and osteolytic lesion of the spine, it is necessary to examine the possibility of ECD and proceed with a biopsy for confirmation. This is the first case in Palestine to be reported and the second case worldwide with a renal mass as an atypical presentation.
Assuntos
Doença de Erdheim-Chester , Derrame Pericárdico , Feminino , Humanos , Pessoa de Meia-Idade , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/diagnóstico , Doença de Erdheim-Chester/patologia , Derrame Pericárdico/etiologia , Dor no Flanco , Biópsia/efeitos adversos , Tomografia Computadorizada por Raios XRESUMO
Oculofacial myorhythmia (OFM) is a movement disorder characterized by slow, rhythmic, and repetitive movement that affects the periorbital and perioral muscles. This abnormal movement is classified as a tremor and is highly suggestive of brainstem lesions. Unlike the oculomasticastory myorhythmia, the oculofacial pattern has rarely been reported to date. We present a patient diagnosed with Erdheim Chester disease who two years after the diagnosis developed an oculofacial myorhythmia. We additionally provide a pathological framework based on evolutionary changes on neuroimaging which could explain the appearance of this very rare movement disorder. No cases of OFM have been described in patients with ECD to date. To our knowledge we are reporting the first case of oculofacial myorhythmia secondary to Erdheim Chester disease. To conclude, oculofacial myorhytmia could be a late-onset clinical manifestation of ECD with brainstem involvement.
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Doença de Erdheim-Chester , Transtornos dos Movimentos , Humanos , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/diagnóstico , Doença de Erdheim-Chester/patologia , Transtornos dos Movimentos/complicações , Fenótipo , Tremor/complicações , Masculino , AdultoRESUMO
We report a case of BRAF-mutation positive Erdheim-Chester disease presenting with a cerebellar ataxia. This is the first such case to be reported without structural MRI abnormalities but with a single intrathecally produced oligoclonal band. Now that the histiocytoses have been recharacterised as neoplastic, we speculate that the mechanism of the ataxia in our case is paraneoplastic. We highlight the importance of searching for BRAF mutations in this disease, as their presence leads to effective personalised treatments.
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Ataxia Cerebelar , Doença de Erdheim-Chester , Humanos , Ataxia Cerebelar/etiologia , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/diagnóstico , Proteínas Proto-Oncogênicas B-raf/genética , Ataxia , AutoanticorposRESUMO
BACKGROUND: Erdheim-Chester disease (ECD) is a rare histiocytic disorder characterized by multisystem xanthogranulomatous infiltration by lipid-laden histiocytes. We report two cases of ECD involving the orbit and describe their clinicopathologic factors, treatments, and prognosis. One was a rare case of ECD complicated with primary thrombocytosis. CASE PRESENTATION: This study describes two patients with bilateral orbital ECD. Both presented with proptosis and visual loss; imaging findings showed bilateral intraorbital masses. Both had different degrees of systemic symptoms (pleural effusion, pericardial effusion, ascites, and heart failure) before the ocular symptoms and did not find the cause before ophthalmic tumor resection and pathological biopsy. The diagnosis of ECD was confirmed after pathological biopsy and detection of BRAFV600E mutation. Patient 2 also with primary thrombocytosis and had a CALR mutation as well as the BRAFV600E mutation. Both patients were recommended to receive targeted therapy. Patient 1 refused targeted therapy for financial reasons and was discharged after local radiotherapy only. The patient had no light perception in either eye and no improvement in systemic symptoms. Patient 2 began targeted treatment after diagnosis and reached the discharge criteria 2 weeks later. He is in good condition at present, but unfortunately, his eyesight has not improved because of the irreversible damage to his visual function. CONCLUSION: ECD is easily misdiagnosed and missed because of its rarity and diverse clinical manifestations. Orbital involvement is common in ECD, and surgery is the most frequently employed approach. Despite the surgical resection is not curative, its significance lies in biopsy to establish diagnosis and/or surgical debulking to relieve mass effect, minimizing further impairment of visual function. Targeted therapy is the most effective treatment for patients with a positive BRAF mutation gene. Evaluation of a concomitant myeloid neoplasm is also critical before initiating targeted therapies for refractory ECD.
Assuntos
Doença de Erdheim-Chester , Trombocitemia Essencial , Masculino , Humanos , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/diagnóstico , Doença de Erdheim-Chester/genética , Proteínas Proto-Oncogênicas B-raf/genética , Trombocitemia Essencial/complicações , Resultado do Tratamento , BiópsiaRESUMO
Background: Erdheim Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis of unknown etiology that occurs in multiple organs. The clinical characteristics of ECD are unknown, making it difficult to diagnose. Case presentation: A 61-year-old woman presented with left knee pain and contracture. She had recent medical problems such as recurrent urinary tract infection, pericardial effusion, and pleural effusion. Simple radiography and magnetic resonance imaging of the knee revealed an osteosclerotic lesion. Under suspicion of malignancy, other radiologic modalities were performed, but there were no significant results showing malignancy. A bone biopsy of the knee lesion led to a final diagnosis of ECD. The patient was treated with systemic steroids and was ultimately tried on PEG-interferon. Conclusion: This report describes an unusual presentation of ECD involving the skeletal system and multiple extraskeletal organs. Owing to its non-specific nature, ECD was notably difficult to diagnose. Therefore, if a patient has knee pain and other multiorgan presentations without malignancy, clinicians should suspect ECD.