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1.
Ann R Coll Surg Engl ; 102(2): e42-e44, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31538800

RESUMO

Erdheim-Chester disease is a rare infiltrative histiocytic disorder with around 800 cases being reported worldwide. Patients most commonly present with skeletal pain, but the condition has been shown to affect multiple other organs. We describe a rare presentation in which the disease infiltrated the sinuses and affected an ex-RAF pilot's vision. After extensive investigation of the elusive diagnosis, repeating of a molecular test using polymerase chain reaction analysis allowed for identification of a mutation (BRAF V600) ultimately leading to the diagnosis of Erdheim-Chester disease.


Assuntos
Cegueira/etiologia , Doença de Erdheim-Chester/diagnóstico , Sinusite/etiologia , Cegueira/terapia , Análise Mutacional de DNA , Diagnóstico Diferencial , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/genética , Doença de Erdheim-Chester/terapia , Osso Etmoide/diagnóstico por imagem , Osso Etmoide/patologia , Osso Etmoide/cirurgia , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia , Pilotos , Proteínas Proto-Oncogênicas B-raf/genética , Sinusite/terapia , Osso Esfenoide/diagnóstico por imagem , Osso Esfenoide/patologia , Osso Esfenoide/cirurgia , Tomografia Computadorizada por Raios X
2.
Rinsho Ketsueki ; 60(9): 1308-1316, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597857

RESUMO

Whether Langerhans cell histiocytosis (LCH) is an inflammatory disorder or a neoplasm is an ongoing debate. On the basis of the identification of the BRAF V600E mutation in 2010, LCH should be defined as an inflammatory myeloid neoplasia. Mutually exclusive BRAF V600E (50-60%) and MAP2K1 (12-25%) mutation renders the ERK activation. BRAF V600E mutations were detected in approximately 50-60% of patients with Erdheim-Chester disease (ECD), and these patients are being treated with vemurafenib, a selective BRAF V600 kinase inhibitor, approved by the US Food and Drug Administration. The Japan Langerhans cell histiocytosis study group-02 protocol study showed five-year overall survival rate of 92% and event-free survival of 46% in risk-organ involvement of positive multi-system LCH. We aimed to improve the quality of life by reducing relapses and development of late complications. It is essential to achieve a close cooperation between hematologists catering to pediatric and adult patients with LCH. Furthermore, novel targeted therapies of MAPK inhibitors are required along with intensified chemotherapy to achieve better outcomes in patients with LCH in Japan.


Assuntos
Histiocitose de Células de Langerhans/genética , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Criança , Intervalo Livre de Doença , Doença de Erdheim-Chester/tratamento farmacológico , Doença de Erdheim-Chester/genética , Humanos , Japão , Mutação , Qualidade de Vida , Taxa de Sobrevida , Vemurafenib/uso terapêutico
3.
Exp Mol Pathol ; 111: 104320, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31639332

RESUMO

BRAF V600E is the predominant oncogenic driver of L-group histiocytoses, which includes Erdheim-Chester disease (ECD); however, limited data exist on the prevalence of this mutation in sporadic XG family lesions. This study sought to determine the incidence of BRAF V600E mutation in a clinically annotated cohort of patients with xanthogranulomas (XG) and reticulohistiocytomas (RH). A retrospective review of 58 lesions was performed, including 41 XG and 17 RH. Immunohistochemistry (HC) and PCR-based methods were performed to evaluate for the BRAF V600E mutation. The BRAF V600E mutation was detected by IHC/PCR in 3 RH from an adult who had no history of arthritis, malignancy, xanthelasma, diabetes insipidus or bone pain. All other XG and RH were negative for the BRAF V600E mutation. No associated systemic diseases were identified in this cohort. Our findings suggest that BRAF V600E mutations are not an oncogenic driver of sporadic XG and solitary RH. Therefore, identification of such a mutation in a patient with multiple lesions should raise consideration for ECD. We also report the first known BRAF V600E mutation in a patient with multiple reticulohistiocytomas.


Assuntos
Biomarcadores Tumorais/genética , Doença de Erdheim-Chester/genética , Doença de Erdheim-Chester/patologia , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Adolescente , Adulto , Idoso , Carcinogênese , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
4.
Orphanet J Rare Dis ; 14(1): 11, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30630516

RESUMO

BACKGROUND: Erdheim-Chester disease (ECD) is a rare multi-systemic form of histiocytosis. Treatment with BRAF inhibitors has markedly improved outcomes of ECD; however, this targeted therapy is expensive (estimated annual cost is $50,000). Since estimated annual cost of interferon-α (IFN-α) is only approximately $1600 in China, we retrospectively evaluated the long-term therapeutic efficacy of IFN-α and the value of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) as an assessment method among 32 ECD patients who received high dose IFN-α therapy at Peking Union Medical College Hospital. RESULTS: The median age at diagnosis was 48 years (range, 6-66 years). The median duration of treatment was 18.5 months (range, 1-51 months). The overall clinical response rates were 80.0%, including 33.3% complete response, 36.7% partial response and 10.0% stable disease. Thirty-one patients underwent a total of 81 scans by FDG-PET. Seventeen patients had serial FDG-PET results, nine patients had experienced a partial metabolic response at the last follow-up. The median reduction of ratios between the most active target lesion standardized uptake value (SUV) and liver SUV from baseline to last FDG-PET scan was 61.4% (range, 8.8-86.6%). Eight of thirteen patients who experienced continuous clinical improvement during follow-up had at least one target lesion SUV increased by FDG-PET which decreased in subsequent scans without changing treatment strategy. The estimated 3-year progression-free survival (PFS) and overall survival (OS) were 64.1 and 84.5%, respectively. Central nervous system (CNS) involvement was the only predictor for poor PFS and OS. CONCLUSIONS: High-dose IFN-α treatment is a cost-effective option, especially for patients without CNS involvement. Single target lesion SUV elevation according to FDG-PET do not accurately demonstrate disease progression, but serial FDG-PET imaging effectively discriminate treatment response.


Assuntos
Doença de Erdheim-Chester/diagnóstico por imagem , Doença de Erdheim-Chester/tratamento farmacológico , Interferon-alfa/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Adolescente , Adulto , Idoso , Criança , Doença de Erdheim-Chester/genética , Doença de Erdheim-Chester/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Adulto Jovem
5.
Diagn Pathol ; 13(1): 94, 2018 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-30474563

RESUMO

BACKGROUND: Erdheim Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis characterized by widespread tissue infiltration by CD68-positive, CD1a-negative foamy histiocytes. ECD can be difficult to identify, and diagnosis relies on the presence of histiocytes with certain histologic and immunophenotypic features in an appropriate clinical and radiologic setting. Clinical signs and symptoms are variable depending on which organ systems are involved. Most patients have at least skeletal involvement with bone pain as well as fatigue. Other common manifestations include diabetes insipidus, cardiac, periaortic, or retro-orbital infiltration/fibrosis, kidney impairment, xanthelasmas, among others. CASE PRESENTATION: Herein, we describe a case of BRAF-mutation positive ECD in a patient with Burkitt lymphoma, and we review recent literature. CONCLUSION: Underlying BRAF and other MAPK pathway mutations are identified in approximately 50% of cases of ECD, which aids in diagnosis as well as enables novel targeted treatments. ECD patients have an increased risk of myeloid neoplasms; however, unlike other histiocytoses, an association with lymphoproliferative disorders has not been recognized.


Assuntos
Linfoma de Burkitt/terapia , Doença de Erdheim-Chester/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Biópsia , Linfoma de Burkitt/complicações , Linfoma de Burkitt/diagnóstico , Análise Mutacional de DNA , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/diagnóstico , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes
6.
J Clin Exp Hematop ; 58(4): 161-165, 2018 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-30305475

RESUMO

Erdheim-Chester disease (ECD), a rare form of non-Langerhans cell histiocytosis, is characterized by the infiltration of foamy CD68+ and CD1a- histiocytes into multiple organ systems. Central nervous system (CNS) involvement has recently been reported to be a poor prognostic factor when treating ECD with interferon alpha. We report the case of a 66-year-old Japanese patient with ECD involving the CNS who harbored the BRAF V600E mutation and also concomitantly developed polycythemia vera with the JAK2 V617F mutation. We confirmed 2-chlorodeoxyadenosine (cladribine) therapy to be effective for the patient in this case.


Assuntos
Doenças do Sistema Nervoso Central , Cladribina/administração & dosagem , Doença de Erdheim-Chester , Janus Quinase 2 , Mutação de Sentido Incorreto , Policitemia Vera , Proteínas Proto-Oncogênicas B-raf , Idoso , Substituição de Aminoácidos , Doenças do Sistema Nervoso Central/diagnóstico por imagem , Doenças do Sistema Nervoso Central/tratamento farmacológico , Doenças do Sistema Nervoso Central/enzimologia , Doenças do Sistema Nervoso Central/genética , Doença de Erdheim-Chester/diagnóstico por imagem , Doença de Erdheim-Chester/tratamento farmacológico , Doença de Erdheim-Chester/enzimologia , Doença de Erdheim-Chester/genética , Humanos , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Masculino , Policitemia Vera/diagnóstico por imagem , Policitemia Vera/tratamento farmacológico , Policitemia Vera/enzimologia , Policitemia Vera/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo
7.
Neurochirurgie ; 64(6): 439-441, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30274919

RESUMO

Erdheim-Chester disease is a rare form of non-Langerhans cell histiocytosis. It is an inflammatory disorder associated with BRAF V600E mutation in 50% of cases. This multisystem disease is rarely associated with spinal involvement. Neurological involvement is an independent predictive factor of poor prognosis. The diagnosis is histopathological based on CD68-positive and CD1A-negative histiocytes. Treatment with interferon-alpha is an independent predictor of survival in Erdheim-Chester disease and vemurafenib has also been shown to be effective for BRAF V600E mutation. We report a clinical case of a 51-year-old patient with multiple and rare locations of Erdheim-Chester disease, particularly at the sphenoid sinus.


Assuntos
Doença de Erdheim-Chester/genética , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Compressão da Medula Espinal/genética , Doença de Erdheim-Chester/diagnóstico , Humanos , Interferon-alfa/metabolismo , Pessoa de Meia-Idade , Seio Esfenoidal/cirurgia , Compressão da Medula Espinal/diagnóstico
8.
J Neurosurg Pediatr ; 23(1): 48-53, 2018 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-30265230

RESUMO

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell form of histiocytosis that can affect the central nervous system. ECD predominantly affects adults, and only a few pediatric cases have been reported. The co-occurrence of ECD and Langerhans cell histiocytosis (LCH) is exceedingly rare. An 11-year-old boy, who was diagnosed with LCH 7 years previously, presented with multiple giant intracranial lesions. At the time of his initial diagnosis, only one intracranial lesion was observed, and it began to enlarge. Currently, up to 7 intracranial lesions can be observed in this patient. However, the diagnosis of ECD was not confirmed until this most recent open resection. The BRAF V600E mutation was detected in both LCH and ECD lesions. Dabrafenib therapy exhibited dramatic efficacy in this pediatric patient. This case represents the first successful application of dabrafenib in a pediatric patient with intracranial ECD lesions as well as mixed ECD and LCH. In this article, the authors describe the intricate diagnosis and treatment processes in this patient. Recent studies regarding treatment with BRAF inhibitors for neurological involvement in mixed ECD and LCH are also reviewed.


Assuntos
Encefalopatias/tratamento farmacológico , Doença de Erdheim-Chester/tratamento farmacológico , Histiocitose de Células de Langerhans/tratamento farmacológico , Imidazóis/uso terapêutico , Oximas/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Encefalopatias/diagnóstico por imagem , Encefalopatias/genética , Encefalopatias/patologia , Criança , Doença de Erdheim-Chester/diagnóstico por imagem , Doença de Erdheim-Chester/genética , Doença de Erdheim-Chester/patologia , Histiocitose de Células de Langerhans/diagnóstico por imagem , Histiocitose de Células de Langerhans/genética , Histiocitose de Células de Langerhans/patologia , Humanos , Masculino , Mutação , Tomografia por Emissão de Pósitrons , Proteínas Proto-Oncogênicas B-raf/genética , Tomografia Computadorizada por Raios X
10.
Haematologica ; 103(11): 1815-1824, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29976744

RESUMO

Erdheim-Chester disease is a rare histiocytosis with insufficient clinical data. To clarify the clinical features and prognostic factors of Erdheim-Chester disease, we conducted a nationwide survey to collect the detailed data of 44 patients with Erdheim-Chester disease in Japan. The median age of onset of the participants was 51 (range: 23-76) years, and the median number of involved organs per patient was 4 (range: 1-11). The existence of central nervous system disease was correlated with older age (P=0.033), the presence of cardiovascular lesions (P=0.015), and an increased number of involved organs (P=0.0042). The median survival from the onset was 10.4 years, and >3.0 mg/dL C-reactive protein level at onset was associated with worse outcome (median survival, 14.6 vs. 7.4 years; P=0.0016). In a multivariate analysis, age >60 years (hazard ratio, 25.9; 95% confidence interval, 2.82-237; P=0.0040) and the presence of digestive organ involvement (hazard ratio, 4.74; 95% confidence interval, 1.05-21.4; P=0.043) were correlated with worse survival. Fourteen patients had available histological samples of Erdheim- Chester disease lesions. BRAFV600E mutation was detected in 11 patients (78%) by Sanger sequencing. A correlation between BRAF mutation status and clinical factors was not observed. Our study revealed that age and digestive organ involvement influence the outcome of Erdheim-Chester disease patients, and an inflammatory marker, such as C-reactive protein, might reflect the activity of this inflammatory myeloid neoplasm.


Assuntos
Doença de Erdheim-Chester/genética , Doença de Erdheim-Chester/mortalidade , Mutação de Sentido Incorreto , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Fatores Etários , Idoso , Substituição de Aminoácidos , Intervalo Livre de Doença , Doença de Erdheim-Chester/patologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
11.
Arterioscler Thromb Vasc Biol ; 38(8): 1913-1925, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29930009

RESUMO

Objective- Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by the infiltration of multiple tissues with lipid-laden histiocytes. Cardiovascular involvement is frequent in ECD and leads to a severe prognosis. The objective of this study was to determine whether an alteration of lipid metabolism participates in the lipid accumulation in histiocytes and the cardiovascular involvement in ECD. Approach and Results- An analysis of plasma lipid levels indicated that male ECD patients carrying the BRAFV600E (B-Raf proto-oncogene, serine/threonine kinase) mutation exhibited hypoalphalipoproteinemia, as demonstrated by low plasma HDL-C (high-density lipoprotein cholesterol) levels. Capacity of sera from male BRAFV600E ECD patients to mediate free cholesterol efflux from human macrophages was reduced compared with control individuals. Cardiovascular involvement was detected in 84% of the ECD patients, and we reported that the presence of the BRAFV600E mutation and hypoalphalipoproteinemia is an independent determinant of aortic infiltration in ECD. Phenotyping of blood CD14+ cells, the precursors of histiocytes, enabled the identification of a specific inflammatory signature associated with aortic infiltration which was partially affected by the HDL phenotype. Finally, the treatment with vemurafenib, an inhibitor of the BRAFV600E mutation, restored the defective sera cholesterol efflux capacity and reduced the aortic infiltration. Conclusions- Our findings indicate that hypoalphalipoproteinemia in male ECD patients carrying the BRAFV600E mutation favors the formation of lipid-laden histiocytes. In addition, we identified the BRAF status and the HDL phenotype as independent determinants of the aortic involvement in ECD with a potential role of HDL in modulating the infiltration of blood CD14+ cells into the aorta.


Assuntos
Aorta/metabolismo , Doenças da Aorta/genética , HDL-Colesterol/sangue , Doença de Erdheim-Chester/genética , Histiócitos/metabolismo , Hipoalfalipoproteinemias/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta/efeitos dos fármacos , Aorta/patologia , Doenças da Aorta/tratamento farmacológico , Doenças da Aorta/enzimologia , Biomarcadores/sangue , Estudos de Casos e Controles , Doença de Erdheim-Chester/sangue , Doença de Erdheim-Chester/diagnóstico , Doença de Erdheim-Chester/tratamento farmacológico , Feminino , Predisposição Genética para Doença , Histiócitos/efeitos dos fármacos , Histiócitos/patologia , Humanos , Hipoalfalipoproteinemias/sangue , Hipoalfalipoproteinemias/diagnóstico , Hipoalfalipoproteinemias/tratamento farmacológico , Receptores de Lipopolissacarídeos/sangue , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Fatores de Risco , Fatores Sexuais , Células THP-1 , Vemurafenib/uso terapêutico , Adulto Jovem
12.
Eur Radiol ; 28(11): 4635-4642, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29736852

RESUMO

OBJECTIVES: To investigate the computed tomography (CT) thoracic findings in Erdheim-Chester disease (ECD) and evaluate the association of these findings with the BRAFV600E mutation. METHODS: This was a prospective study of patients with ECD (n=61, men=46) who underwent thoracic CT imaging. CT examinations were independently interpreted by two experienced radiologists. Association of imaging findings with BRAFV600E was achieved via the Chi-square or Fisher's exact test and odds ratios (OR) with 95% confidence intervals (CI), as appropriate. RESULTS: Fifty-five ECD patients (90%) showed pulmonary findings, which included interlobular septal thickening (69%), pulmonary nodules (62%), airway thickening (13%) and ground glass opacities (36%). Pulmonary nodules were classified by the pattern of distribution: subpleural regions (36%), lung parenchyma (13%) and both regions (13%). Pleural and mediastinal involvement were present in 15% and 62% of cases, respectively. The most common mediastinal finding was sheathing of the right coronary artery (34%), followed by sheathing of the thoracic aorta (30%). The BRAFV600E mutation, positive in 31 patients, was associated with the frequency of sheathing of the coronary arteries (p = 0.01). CONCLUSIONS: Of the thoracic findings reported in this study, we found a statistically significant positive association between the BRAFV600E mutation and presence of coronary artery sheathing. KEY POINTS: • To assess the degree of thoracic involvement in ECD with CT. • BRAF V600E mutation has a high association with right coronary artery sheathing. • BRAF V600E genetic testing detects patients at high risk of developing RCA sheathing.


Assuntos
Doença de Erdheim-Chester/genética , Doença de Erdheim-Chester/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Tórax/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta Torácica/patologia , Criança , Pré-Escolar , Vasos Coronários/patologia , Doença de Erdheim-Chester/diagnóstico por imagem , Feminino , Humanos , Pulmão/patologia , Masculino , Mediastino/patologia , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/patologia , Mutação , Pleura/patologia , Estudos Prospectivos , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto Jovem
14.
Eur Radiol ; 28(9): 3751-3759, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29556768

RESUMO

OBJECTIVES: To use magnetic resonance imaging (MRI) and computed tomography (CT) to define abdominal involvement in Erdheim-Chester disease (ECD), and to investigate the association between these findings and the BRAFV600E mutation. METHODS: This prospective study was performed on 61 ECD patients (46 men). The MRI and CT imaging studies were reviewed independently by two experienced radiologists. The association between BRAFV600E mutation and imaging findings was analysed using Fisher's exact test, and odds ratios with 95% confidence intervals. RESULTS: Perinephric infiltration was the most common finding (67%), followed by involvement of proximal ureters (61%). In 56% of cases, infiltration extended to the renal sinuses, and in 38% caused hydronephrosis. Adrenal gland infiltration was present in 48% of patients. Infiltration of renal artery (49%) and aorta (43%) were the most common vascular findings, followed by sheathing of celiac, superior mesenteric artery (SMA) or inferior mesenteric artery (IMA) (23%). The BRAFV600E mutation was positive in 53% of patients with interpretable BRAF sequencing. There was a statistically significant association between this mutation and perinephric infiltration (p = 0.003), renal sinus involvement (p < 0.001), infiltration of proximal ureters (p < 0.001), hydronephrosis (p < 0.001), adrenal gland involvement (p < 0.001), periaortic infiltration (p = 0.03), sheathing or stenosis of renal artery (p < 0.001) and sheathing of other aortic branches (p = 0.04). CONCLUSIONS: Renal and vascular structures are the most commonly affected abdominal organs in ECD patients. Some of these findings have significant positive association with the BRAFV600E mutation. KEY POINTS: • Abdominal imaging plays a crucial role in management of Erdheim-Chester disease. • Significant associations exist between BRAF V600E mutation and several abdominal imaging findings. • Considering several associations, evaluating BRAFV600E mutation status is recommended in ECD patients.


Assuntos
Abdome/patologia , Doença de Erdheim-Chester/diagnóstico por imagem , Doença de Erdheim-Chester/genética , Imagem por Ressonância Magnética/métodos , Proteínas Proto-Oncogênicas B-raf/genética , Tomografia Computadorizada por Raios X/métodos , Abdome/diagnóstico por imagem , Adulto , Idoso , Doença de Erdheim-Chester/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Estudos Prospectivos , Adulto Jovem
19.
J Nucl Med ; 59(5): 774-779, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29097410

RESUMO

The purpose of this study was to evaluate 18F-FDG PET/CT for the diagnosis, management, and treatment of Erdheim-Chester disease (ECD). Methods: Our institutional database (2007-2017) was retrospectively reviewed for patients with pathologically proven ECD. A chart review yielded demographics, clinical information, and 5 categories of clinical impact. Two radiologists in consensus interpreted the images. Imaging findings were correlated with clinical data. Results: Seventy-one 18F-FDG PET/CT examinations were performed for 32 patients. The average SUVmax of the most active disease site was 9.2 (SD, 6.1). The most common sites involved were the skeleton (90.6% of patients, including 47% with axial and pelvic skeletal involvement), kidneys (81.3%), and central nervous system (CNS) (46.9%). Twenty-six patients were tested for a proto-oncogene B-Raf V600E (BRAF) mutation (18 had the mutation and 8 did not). The presence of a BRAF mutation was associated with 18F-FDG-avid CNS disease (P = 0.0357), higher SUVmax (P = 0.0044), and greater mortality (P = 0.0215). The presence of CNS disease had 88% specificity and a 92% positive predictive value for predicting the presence of a BRAF mutation. PET/CT examination results influenced patient management in 48% of cases (34/71). Conclusion:18F-FDG PET/CT results may act as a biomarker for the presence of a BRAF mutation, aid in establishing a diagnosis, guide biopsies, and gauge the treatment response in ECD patients. Axial and pelvic skeletal involvement is greater than previously reported.


Assuntos
Doença de Erdheim-Chester/diagnóstico por imagem , Doença de Erdheim-Chester/genética , Mutação , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Bases de Dados Factuais , Feminino , Fluordesoxiglucose F18 , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Sensibilidade e Especificidade , Software
20.
Mod Pathol ; 31(4): 581-597, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29192649

RESUMO

Erdheim-Chester disease is a rare, non-Langerhans cell histiocytosis histologically characterized by multi-systemic proliferation of mature histiocytes in a background of inflammatory stroma. The disease can involve virtually any organ system; most commonly the bones, skin, retroperitoneum, heart, orbit, lung, and brain are affected. Although a histiocytic proliferation is the histological hallmark of the disease, a wide range of morphological appearances have been described as part of case studies or small series. A comprehensive review of histopathological features in clinically and molecularly defined Erdheim-Chester disease has yet to be characterized. To address this issue and help guide clinical practice, we comprehensively analyzed the pathological spectrum of Erdheim-Chester disease in a clinically and molecularly defined cohort. We reviewed 73 biopsies from 42 patients showing involvement by histiocytosis from a variety of organ systems, including bone (16), retroperitoneum (11), skin (19), orbit (6), brain (5), lung (6), cardiac structures (2), epidural soft tissue (3), oral cavity (2), subcutaneous soft tissue (2), and testis (2). In eight patients, one or more bone marrow biopsies were performed due to clinical indication and an accompanying myeloid neoplasm was detected in six of them. Thirty-eight cases were investigated for genetic abnormalities. Somatic mutations involving BRAF (25/38), MAP2K1 (6/38), ARAF (2/38), MAP2K2 (1/38), KRAS (1/38), and NRAS (1/38) genes were detected. One of the cases with a MAP2K1 mutation also harbored a PIK3CA mutation. We have observed marked heterogeneity in histology and immunophenotype, identified site-specific features, overlap with other histiocytic and myeloid disorders and potential diagnostic pitfalls. We hope that broadening the spectrum of recognized pathologic manifestations of Erdheim-Chester disease will help practicing clinicians and pathologists to diagnose Erdheim-Chester disease early in the disease course and manage these patients effectively.


Assuntos
Doença de Erdheim-Chester/genética , Doença de Erdheim-Chester/patologia , Estudos de Coortes , Humanos
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