RESUMO
Genetic data are becoming increasingly essential in the management of hematological neoplasms as shown by two classifications published in 2022: the 5th edition of the World Health Organization Classification of Hematolymphoid Tumours and the International Consensus Classification of Myeloid Neoplasms and Acute Leukemias. Genetic data are particularly important for acute myeloid leukemias (AMLs) because their boundaries with myelodysplastic neoplasms seem to be gradually blurring. The first objective of this review is to present the latest updates on the most common cytogenetic abnormalities in AMLs while highlighting the pitfalls and difficulties that can be encountered in the event of cryptic or difficult-to-detect karyotype abnormalities. The second objective is to enhance the role of cytogenetics among all the new technologies available in 2023 for the diagnosis and management of AML.
Assuntos
Histiocitose , Leucemia Mieloide Aguda , Humanos , Aberrações Cromossômicas , Análise Citogenética , Células Dendríticas/patologia , Hematologia , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Histiocitose/diagnóstico , Histiocitose/genética , Histiocitose/terapiaRESUMO
INTRODUCTION: Histiocytic disorders pose significant diagnostic and management challenges for the clinicians due to diverse clinical manifestations and often non-specific histopathologic findings. Herein, we report the tumor board experience from the first-of-its-kind Histiocytosis Working Group (HWG). MATERIALS AND METHODS: The HWG was established in June 2017 and consists of experts from 10 subspecialties that discuss cases in a multidisciplinary format. We present the outcome of tumor board case discussions during the first 2 years since its inception (June 2017-June 2019). RESULTS: Forty cases with a suspected histiocytic disorder were reviewed at HWG during this time period. Average number of subspecialties involved in HWG case discussion was 5 (range, 2-9). Histiocytosis Working Group tumor board recommendations led to significant changes in the care of 24 (60%) patients. These included change in diagnosis (n = 11, 27%) and change in treatment (n = 13, 33%). CONCLUSION: Our report highlights the feasibility of a multidisciplinary tumor board and its impact on outcomes of patients with histiocytic disorders.
Assuntos
Histiocitose , Neoplasias , Histiocitose/diagnóstico , Histiocitose/patologia , Histiocitose/terapia , HumanosAssuntos
Histiocitose/diagnóstico , Neoplasias Císticas, Mucinosas e Serosas/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adulto , Feminino , Mãos , Histiocitose/etiologia , Histiocitose/terapia , Humanos , Neoplasias Císticas, Mucinosas e Serosas/etiologia , Neoplasias Císticas, Mucinosas e Serosas/terapia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/terapiaRESUMO
Originally described as a systemic self-limiting disease in infancy, the spectrum of ALK-positive histiocytosis has recently been broadened to include localized diseases in older children and young adults. Despite different manifestations, these tumors share histologic characteristics and a highly recurrent KIF5B-ALK fusion. ALK-positive histiocytosis is poorly characterized in the breast. In this study, we report 3 cases of ALK-positive histiocytosis of the breast. The patients were Asian women, aged 16 to 45 years. Two patients presented with an isolated breast mass, while 1 exhibited multiorgan involvement. The latter patient received ALK inhibitor after surgery, which led to complete remission. Histologically, well-circumscribed tumors displayed fascicular and storiform growth of uniform, nonatypical spindle cells admixed with lymphocytic infiltrates. Fewer conventional epithelioid histiocytes with lobulated or clefted nuclei were observed within the same breast tumors in 2 cases or within a concomitant brain tumor in the third case. Touton-type giant cells were focally present in 2 cases. Immunohistochemically, tumor spindle, and epithelioid cells were diffusely positive for CD163 and ALK in all cases and focally positive for S100 protein in 1 of the cases. CD1a and langerin were negative. Actin-positive myofibroblasts were admixed within the tumor in 2 cases, and their reactive nature was highlighted using double immunostaining. Break-apart fluorescence in situ hybridization assay demonstrated gene rearrangements involving KIF5B and ALK in all the 3 cases. ALK-positive histiocytosis rarely occurs as a spindle cell breast tumor, and should be distinguished from other diseases such as inflammatory myofibroblastic tumors and spindled histiocytic reaction.
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Quinase do Linfoma Anaplásico/análise , Doenças Mamárias/enzimologia , Histiocitose/enzimologia , Adolescente , Adulto , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Quinase do Linfoma Anaplásico/genética , Biomarcadores/análise , Doenças Mamárias/genética , Doenças Mamárias/patologia , Doenças Mamárias/terapia , Quimioterapia Adjuvante , Feminino , Rearranjo Gênico , Histiocitose/genética , Histiocitose/patologia , Histiocitose/terapia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Cinesinas/genética , Mastectomia , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Resultado do TratamentoRESUMO
Patients with pulmonary Langerhans cell histiocytosis (LCH) typically have a benign course but may have extensive cystic lung disease with rare life-threatening complications including multiple and recurrent pneumothoraces and respiratory failure. We report seven severely affected pediatric patients treated with chemotherapy, aggressive chest tube management, and pleurodesis of whom five survived. Patients with extraordinary amounts of pulmonary cystic disease and multiple pneumothoraces due to LCH can have remarkable, curative outcomes with early recognition, optimal LCH-directed therapy, and supportive care.
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Histiocitose/terapia , Pneumopatias/terapia , Pneumotórax/terapia , Adolescente , Tubos Torácicos , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , PleurodeseAssuntos
Doenças Hematológicas/diagnóstico , Histiocitose/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Mastocitose Sistêmica/diagnóstico , Gerenciamento Clínico , Doenças Hematológicas/terapia , Histiocitose/terapia , Humanos , Transtornos Linfoproliferativos/terapia , Mastocitose Sistêmica/terapiaRESUMO
The impact of acute and chronic graft-versus-host disease (GVHD) on clinical outcomes was retrospectively analyzed in 960 patients with non-malignant diseases (NMD) who underwent a first allogeneic hematopoietic stem cell transplantation (HSCT). Grade III-IV acute GVHD (but not grade I-II) was significantly associated with a lower rate of overall survival (OS), and higher non-relapse mortality (NRM) than that seen in patients without acute GVHD. Extensive (but not limited) GVHD was significantly associated with a lower OS rate and higher NRM than that seen in patients without chronic GVHD. Any grade of acute (but not chronic) GVHD was significantly associated with a lower incidence of relapse and a lower proportion of patients requiring a second HSCT or donor lymphocyte infusion for graft failure or mixed chimerism, but its impact on OS was almost negligible. Acute GVHD was significantly associated with lower OS rates in all disease groups, whereas chronic GVHD was significantly associated with lower OS rates in the primary immunodeficiency and histiocytosis groups. In conclusion, acute and chronic GVHD, even if mild, was associated with reduced OS in patients receiving HSCT for NMD and effective strategies should, therefore, be implemented to minimize GVHD.
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Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/mortalidade , Histiocitose/mortalidade , Histiocitose/terapia , Humanos , Síndromes de Imunodeficiência/mortalidade , Síndromes de Imunodeficiência/terapia , Lactente , Masculino , Doenças Metabólicas/mortalidade , Doenças Metabólicas/terapia , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto JovemAssuntos
Histiocitose/terapia , Lasers de Gás/uso terapêutico , Neoplasias Císticas, Mucinosas e Serosas/terapia , Neoplasias Cutâneas/terapia , Anti-Inflamatórios/uso terapêutico , Procedimentos Cirúrgicos Dermatológicos , Feminino , Histiocitose/patologia , Humanos , Pessoa de Meia-Idade , Neoplasias Císticas, Mucinosas e Serosas/patologia , Retratamento , Neoplasias Cutâneas/patologia , Triancinolona Acetonida/uso terapêuticoRESUMO
Histiocytosis describes a group of diseases that have long been considered enigmatic in the history of medicine. Recently, novel genomic analyses have identified somatic oncogenic driver mutations responsible for the pathogenesis of these entities. These discoveries have led to the recharacterization of histiocytoses as neoplastic diseases and have opened a new era of precision medicine approaches for treatment. The histiocytic disorders demonstrate a variety of imaging manifestations involving multiple organ systems, and radiologists play a major role in diagnosis and monitoring. An up-to-date knowledge of the novel genomic discoveries and their implications is essential for radiologists to understand the new approaches to treating histiocytic disorders and to contribute as key members of the multidisciplinary treatment team. This article provides a cutting-edge review of the novel concepts in histiocytosis, with a focus on recent genomic discoveries and precision medicine approaches to treating the disease, and describes imaging manifestations with correlative histologic and genomic findings, with an emphasis on adult-onset cases and uncommon subtypes. ©RSNA, 2018.
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Histiocitose/diagnóstico por imagem , Medicina de Precisão , Feminino , Genômica , Histiocitose/genética , Histiocitose/patologia , Histiocitose/terapia , Humanos , Masculino , Mutação , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidoresRESUMO
The bone marrow is a preferential site for both reactive and neoplastic histiocytic proliferations. The differential diagnosis ranges from reactive histiocyte hyperplasia in systemic infections, vaccinations, storage diseases, post myeloablative therapy, due to increased cell turnover, and in hemophagocytic lymphohistiocytosis, through extranodal Rosai-Dorfman disease to neoplasms derived from histiocytes, including histiocytic sarcomas (HS), Langerhans cell histiocytoses (LCH), Erdheim-Chester disease (ECD), and disseminated juvenile xanthogranuloma (JXG). One of the most important recent developments in understanding the biology of histiocytic neoplasms and in contributing to diagnosis was the detection of recurrent mutations of genes of the Ras/Raf/MEK/ERK signaling pathway, in particular the BRAFV600E mutation, in LCH and ECD. Here, we summarize clinical and pathological findings of 17 histiocytic neoplasms that were presented during the bone marrow symposium and workshop of the 18th European Association for Haematopathology (EAHP) meeting held in Basel, Switzerland, in 2016. A substantial proportion of these histiocytic neoplasms was combined with clonally related lymphoid (n = 2) or myeloid diseases (n = 5, all ECD). Based on the latter observation, we suggest excluding co-existent myeloid neoplasms at initial staging of elderly ECD patients. The recurrent nature of Ras/Raf/MEK/ERK signaling pathway mutations in histiocytic neoplasms was confirmed in 6 of the 17 workshop cases, illustrating their diagnostic significance and suggesting apotential target for tailored treatments.
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Neoplasias da Medula Óssea , Hematologia , Histiocitose , Sociedades Médicas , Substituição de Aminoácidos , Neoplasias da Medula Óssea/genética , Neoplasias da Medula Óssea/metabolismo , Neoplasias da Medula Óssea/patologia , Neoplasias da Medula Óssea/terapia , Congressos como Assunto , Europa (Continente) , Histiocitose/genética , Histiocitose/metabolismo , Histiocitose/patologia , Histiocitose/terapia , Humanos , Sistema de Sinalização das MAP Quinases/genética , Mutação de Sentido Incorreto , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismoRESUMO
Crystal-storing histiocytosis (CSH) is an under-recognized entity with a striking association with lymphoproliferative disorders. To study the typical morphologic features of gastric CSH, all lymphomas diagnosed on in-house gastric specimens at The Ohio State University between January 1, 2008 and January 1, 2017 were retrieved. This search yielded 66 specimens from 51 unique patients. All cases were reviewed with CSH identified in 7 stomach biopsies from 4 patients (2 men:2 women; average age, 69 y; range, 56 to 82 y). Endoscopic findings were all abnormal: diffuse nodularity and white discoloration (n=1), patchy nodularity (n=1), and malignant-appearing fundic mass with lymphadenopathy (n=2). We report the typical gastric CSH lesion displays full-thickness expansion of the lamina propria by a lymphohistiocytic infiltrate that distorts the usual gastric glandular architecture. On high power, all cases were defined by the presence of macrophages with abundant eosinophilic cytoplasm containing nonrefractile, nonpolarizable fibrillary cytoplasmic inclusions. Three of the 4 patients had a kappa-restricted lymphoma; the 1 patient with a lambda-restricted lymphoma had the fewest macrophages. Follow-up data were available up to 228 weeks. All 4 patients had persistent/recurrent lymphoma, and 2 patients died of lymphoma-related complications. None of the CSH cases were prospectively recognized as CSH, and 1 case was initially misdiagnosed as a xanthoma. In summary, CSH is an under-recognized lesion historically associated with lymphoproliferative disorders and we found associated with a high mortality in this small series. Since CSH can be so florid as to obscure the concomitant lymphoma, awareness is crucial for accurate diagnosis.
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Histiocitose/patologia , Corpos de Inclusão/patologia , Linfoma/patologia , Macrófagos/patologia , Gastropatias/patologia , Neoplasias Gástricas/patologia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Erros de Diagnóstico , Feminino , Gastroscopia , Histiocitose/imunologia , Histiocitose/mortalidade , Histiocitose/terapia , Humanos , Imuno-Histoquímica , Corpos de Inclusão/imunologia , Linfoma/imunologia , Linfoma/mortalidade , Linfoma/terapia , Macrófagos/imunologia , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Gastropatias/imunologia , Gastropatias/mortalidade , Gastropatias/terapia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapiaRESUMO
Intralymphatic histiocytosis is a rare disorder associated with a variety of inflammatory conditions. We report the case of an 89-year-old woman with a history of a right knee replacement and a ruptured popliteal cyst who developed an erythematous indurated plaque over the surgical scar. Histopathology revealed fibrosis, chronic inflammation, and histiocytes within the lymphatics consistent with intralymphatic histiocytosis. The plaque flattened following intralesional injection of triamcinolone acetonide 10 mg/cc×1.6 cc once monthly for 2 consecutive months and application of a pressure bandage, with no recurrence after 4 months. This treatment may be useful for recalcitrant disease.
Assuntos
Glucocorticoides/administração & dosagem , Histiocitose/terapia , Doenças Linfáticas/terapia , Triancinolona Acetonida/administração & dosagem , Idoso de 80 Anos ou mais , Bandagens Compressivas , Feminino , Histiocitose/tratamento farmacológico , Humanos , Injeções Intralesionais , Doenças Linfáticas/tratamento farmacológicoRESUMO
Rosai-Dorfman disease (RDD) was first described by the French pathologist Paul Destombes in 1965. It frequently affects children or young adults and is characterized by the presence of large histiocytes with emperipolesis. More than 50 years after this first description, the pathogenesis of this rare disease is still poorly understood. The revised classification of histiocytoses published in 2016 identified various forms of RDD, from familial RDD to IgG4-associated RDD. Almost 90% of the patients with RDD have cervical lymph nodes involvement although all the organs may virtually be involved. Outcomes are typically favorable. Treatments may be necessary in case of compression or obstruction, and are not well codified. The main therapeutic strategies rely on surgery, radiotherapy, steroids, immunosuppressive drugs or interferon-alpha and cladribine.
Assuntos
Histiocitose Sinusal/diagnóstico , Histiocitose Sinusal/terapia , Contratura/diagnóstico , Contratura/epidemiologia , Contratura/terapia , Diagnóstico Diferencial , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/terapia , Histiocitose/diagnóstico , Histiocitose/epidemiologia , Histiocitose/terapia , Histiocitose Sinusal/epidemiologia , HumanosRESUMO
Adult xanthogranulomatous disease of the orbit refers to a heterogeneous group of clinical syndromes with differing degrees of systemic involvement and distinct prognoses. The different syndromes all present clinically with progressively enlarging, yellowish lesions of the orbit. Histologically, the lesions are characterized by an inflammatory infiltrate of foam cells and Touton-type multinucleated giant cells. The xanthomatized histiocytes are CD68+, S100-, and CD1a-. There are 4 clinical forms of xanthogranulomatous disease of the orbit: adult xanthogranulomatous disease of the orbit, adult onset asthma and periocular xanthogranuloma, necrobiotic xanthogranuloma, and Erdheim-Chester disease. The treatment of local lesions are treated with systemic corticosteroids and other immunosuppressors. Vemurafenib, tocilizumab, and sirolimus have shown promising results in systemic disease.
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Histiocitose/patologia , Doenças Orbitárias/patologia , Corticosteroides/uso terapêutico , Adulto , Anticorpos Monoclonais/uso terapêutico , Terapia Combinada , Diagnóstico Diferencial , Gerenciamento Clínico , Doença de Erdheim-Chester/diagnóstico , Doença de Erdheim-Chester/patologia , Doença de Erdheim-Chester/terapia , Histiocitose/diagnóstico , Histiocitose/terapia , Humanos , Imunossupressores/uso terapêutico , Xantogranuloma Necrobiótico/diagnóstico , Xantogranuloma Necrobiótico/patologia , Xantogranuloma Necrobiótico/terapia , Doenças Orbitárias/diagnóstico , Doenças Orbitárias/terapia , Radioterapia AdjuvanteAssuntos
Histiocitose/diagnóstico , Histiocitose/etiologia , Histiocitose/terapia , Síndrome de Ativação Macrofágica/diagnóstico , Síndrome de Ativação Macrofágica/etiologia , Síndrome de Ativação Macrofágica/terapia , Histiocitose/epidemiologia , Humanos , Síndrome de Ativação Macrofágica/epidemiologiaRESUMO
Intravascular/intralymphatic histiocytosis (IV/ILH) is a rare, reactive cutaneous condition, with uncertain pathogenesis. It may be associated with various inflammatory and neoplastic diseases. Although the clinical presentation is various, the biopsies reveal dilated vessels, mostly lymphatics, containing aggregates of histiocytes within their lumina. We described 3 cases of IV/ILH with different clinical presentations. In the first case, the patient presented with lymphedema in the genital region without any underlying disease. However, the second and third cases had reticular erythematous skin lesions. The second case had common variable immunodeficiency disease, rheumatoid arthritis, inflammatory bowel disease, and a history of a lymphoproliferative lesion. The third case had metal prostheses at both his right and left knees. In all these 3 cases, histopathologic and immunohistochemical findings were similar to each other and to those cases reported in the literature. In addition, the third case was admixed with reactive angioendotheliomatosis. In the second case, the endothelium of the ectatic vessels expressed CD31 and CD34, but not D2-40/podoplanin, pointing out that these vessels were blood vessels rather than lymphatics, differing from the other 2 cases. In conclusion, we believe, the most convincing statement about IV/ILH is that it is not a distinct clinicopathologic entity, but a histopathologic feature found as a part of a constellation of inflammatory changes or many other conditions.
Assuntos
Vasos Sanguíneos/patologia , Histiócitos/patologia , Histiocitose/patologia , Vasos Linfáticos/patologia , Adolescente , Adulto , Idoso , Biomarcadores/análise , Biópsia , Vasos Sanguíneos/química , Dilatação Patológica , Feminino , Histiocitose/etiologia , Histiocitose/terapia , Humanos , Imuno-Histoquímica , Vasos Linfáticos/química , Masculino , Fatores de Risco , Resultado do TratamentoRESUMO
We report a rare case of multicentric reticulohistiocytosis (MRH) associated with liver carcinoma. A 36-year-old man who had been diagnosed as having liver carcinoma for 2 years presented with a 2-month history of multiple papulonodules on the face, ears, neck, and upper chest, accompanied by progressive polyarthralgia of the hands, wrists, elbows and knee joints without fever or chills. Skin histology revealed well defined dermal infiltrate consisting of multinucleated giant cells and macrophages having abundant eosinophilic finely granular cytoplasm with ground glass appearance. Further immunohistochemical studies characterized the lesions as positive for CD68, CD45 and Vimentin. A diagnosis of MRH that was associated with liver cancer was made. Treatment with prednisolone for 2 months resulted in a significant improvement of the skin and joint symptoms, but was discontinued due to his significant enlargement and extensive metastases of the liver carcinoma.
Assuntos
Artralgia/etiologia , Carcinoma/complicações , Eritema/etiologia , Glucocorticoides/uso terapêutico , Histiocitose/etiologia , Neoplasias Hepáticas/complicações , Dermatopatias Papuloescamosas/etiologia , Pele/patologia , Adulto , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Artralgia/diagnóstico , Artralgia/tratamento farmacológico , Biópsia , Carcinoma/diagnóstico , Eritema/diagnóstico , Eritema/tratamento farmacológico , Histiocitose/diagnóstico , Histiocitose/terapia , Humanos , Imuno-Histoquímica , Antígenos Comuns de Leucócito/análise , Neoplasias Hepáticas/diagnóstico , Masculino , Prednisolona/uso terapêutico , Indução de Remissão , Pele/química , Pele/efeitos dos fármacos , Dermatopatias Papuloescamosas/diagnóstico , Dermatopatias Papuloescamosas/tratamento farmacológico , Tomografia Computadorizada por Raios X , Vimentina/análiseRESUMO
Histiocytic disorders are rare entities that are becoming more recognized as our understanding of the molecular pathogenesis lead to novel diagnostic tests and targeted drug development. A symposium held at the American Society of Pediatric Hematology/Oncology (ASPHO) 2013 Annual Meeting discussed new insights into histiocytic disorders. This review highlights the symposium presentations, divided into three sections encompassing Langerhans cell histiocytosis (LCH), hemophagocytic lymphohistiocytosis (HLH) and Rosai Dorfman disease (RDD) including subsections on pathogenesis, clinical diagnostic criteria and novel insights into treatment. Details of other histiocytic disorders as well as the standard treatment guidelines have been published elsewhere and are beyond the scope of this discussion [Haupt et al. (2013). Pediatr Blood Cancer 60:175-184; Henter et al. (2007). Pediatr Blood Cancer 48:124-131].
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Histiocitose/diagnóstico , Histiocitose/patologia , Histiocitose/terapia , Congressos como Assunto , Humanos , Guias de Prática Clínica como AssuntoRESUMO
A nationwide survey was conducted to clarify the clinical features and outcomes of Korean children with Langerhans cell histiocytosis (LCH). Korea Histiocytosis Working Party analyzed the data of 603 patients who were diagnosed with LCH between 1986 and 2010 from 28 institutions in Korea. Median age at diagnosis was 65 months (range, 0 to 276 mo). Bone was the most frequently affected organ (79.6%) followed by skin (19.2%). Initially, 419 patients (69.5%) had single-system involvement (SS), 85 (14.1%) with multisystem (MS) disease without risk organ involvement (MS-RO), and 99 (16.4%) multisystem disease with risk organ involvement (MS-RO). The 5-year overall survival (OS) rates in the SS, MS-RO, and MS-RO groups were 99.8%, 98.4%, and 77.0%, respectively (P<0.001), and the 5-year reactivation rates were 17.9%, 33.5%, and 34.3%, respectively (P<0.001). The OS rate was lower in patients with RO involvement (P=0.025) and lack of response to initial treatment (P=0.001). MS involvement (P=0.036) was an independent risk factor for reactivation. Permanent consequences were documented in 99 patients (16.4%). Reactivation of disease, MS involvement, and age at diagnosis ≤ 2 years were associated with higher incidence of permanent consequences. This study emphasized that further efforts are required to improve survival of MS-RO patients and reduce reactivation in younger patients with MS involvement.