RESUMO
OPINION STATEMENT: Myeloid sarcoma, a rare malignant tumor characterized by the invasion of extramedullary tissue by immature myeloid cells, commonly occurs concomitantly with acute myeloid leukemia, myelodysplastic syndromes, or myeloproliferative neoplasms. The rarity of myeloid sarcoma poses challenges for diagnosis and treatment. Currently, treatments for myeloid sarcoma remain controversial and primarily follow protocols for acute myeloid leukemia, such as chemotherapy utilizing multi-agent regimens, in addition to radiation therapy and/or surgery. The advancements in next-generation sequencing technology have led to significant progress in the field of molecular genetics, resulting in the identification of both diagnostic and therapeutic targets. The application of targeted therapeutics, such as FMS-like tyrosine kinase 3(FLT3) inhibitors, isocitrate dehydrogenases(IDH) inhibitors, and the B cell lymphoma 2(BCL2) inhibitors, has facilitated the gradual transformation of traditional chemotherapy into targeted precision therapy for acute myeloid leukemia. However, the field of targeted therapy for myeloid sarcoma is relatively under-investigated and not well-described. In this review, we comprehensively summarize the molecular genetic characteristics of myeloid sarcoma and the current application of targeted therapeutics.
Assuntos
Leucemia Mieloide Aguda , Sarcoma Mieloide , Humanos , Sarcoma Mieloide/etiologia , Sarcoma Mieloide/genética , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
This report describes a 56-year-old man who was diagnosed with myeloid sarcoma (MS) of the testis and right shoulder after receiving allogenic stem cell transplantation (allo-SCT) at the age of 47 for acute myeloid leukemia (AML) with inv (16) (p13.1;q22). Nine years after allo-SCT, he complained of a painful right testicular mass. He underwent orchiectomy, and the pathologic diagnosis was MS. Inv (16) was identified by fluorescence in situ hybridization (FISH) using testicular tumor specimens. 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) revealed FDG accumulation in the right shoulder. FISH analysis of bone marrow aspirate revealed no increase in blasts and ruled out CBFB-MYH11 fusion. Reinduction chemotherapy, consolidation, and local radiation therapy for the left testis and right shoulder were administered to him. After that, he received a second allo-SCT from an unrelated donor who was HLA-matched. As of 2 years after the second allo-SCT, recurrence of neither AML nor myeloid sarcoma has been observed. The recurrence of MSs without bone marrow involvement is frequently reported in single, multiple single organs, or multiple single regions. Even if MSs recur in a distant location, combining systemic and local treatment may be a better treatment strategy.
Assuntos
Leucemia Mieloide Aguda , Sarcoma Mieloide , Fluordesoxiglucose F18 , Humanos , Hibridização in Situ Fluorescente , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Recidiva , Sarcoma Mieloide/etiologia , Sarcoma Mieloide/terapia , Ombro/patologia , Transplante de Células-Tronco , Testículo/patologia , Transplante HomólogoAssuntos
Crise Blástica/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Sarcoma Mieloide/diagnóstico , Idoso , Compostos de Anilina/administração & dosagem , Compostos de Anilina/uso terapêutico , Humanos , Imuno-Histoquímica , Imunofenotipagem , Hibridização in Situ Fluorescente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Linfonodos/patologia , Masculino , Mutação , Nitrilas/administração & dosagem , Nitrilas/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Sarcoma Mieloide/etiologiaAssuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Sarcoma Mieloide , Neoplasias Testiculares , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Sarcoma Mieloide/etiologia , Sarcoma Mieloide/terapia , Neoplasias Testiculares/terapia , Resultado do TratamentoRESUMO
Myeloid sarcoma is a rare ocular manifestation of acute myeloid leukemia. Bilateral manifestation preceding any clinical signs of leukemia is even rarer. We here report the case of a 16-month-old patient with rapidly progressive, inflammatory, acute bilateral exophthalmos associated with exposure keratitis. Computed tomography (CT) scan of the orbit and of the brain showed bilateral tissue-like infiltration into the orbital cavity. Blood tests showed biologic inflammatory syndrome, bicytopenia and circulating blasts 83%. Myelogram was performed based on the presence of circulating blasts; it showed acute myeloid leukemia (grade 4). Clinicians should suspect myeloid sarcoma in patients with bilateral exophthalmos and conduct a careful interpretation of blood test results.
Assuntos
Exoftalmia/etiologia , Leucemia Mieloide Aguda/diagnóstico , Neoplasias Orbitárias/diagnóstico , Sarcoma Mieloide/diagnóstico , Humanos , Lactente , Leucemia Mieloide Aguda/complicações , Masculino , Mielografia , Neoplasias Orbitárias/etiologia , Sarcoma Mieloide/etiologia , Tomografia Computadorizada por Raios XAssuntos
Crise Blástica/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Mutação de Sentido Incorreto , Proteínas de Neoplasias/genética , Nucleofosmina/genética , Algoritmos , Antineoplásicos/uso terapêutico , Basófilos/patologia , Dasatinibe/uso terapêutico , Diagnóstico Diferencial , Proteínas de Fusão bcr-abl/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Cromossomo Filadélfia , Inibidores de Proteínas Quinases/uso terapêutico , Sarcoma Mieloide/etiologiaRESUMO
OBJECTIVE: Intracranial myeloid sarcomas (IMS) are rare central nervous system manifestations of malignant hematopoietic neoplasms of myeloid origin such as acute myeloid leukemia and chronic myeloid leukemia. Reported cases in the literature are limited to primarily case reports. We present a systematic review of this rare central nervous system tumor, characterizing the clinical presentation, tumor location, histopathology, and available treatment modalities. We correlate these variables with mortality, recurrence, and complications to suggest optimal management strategies for IMS. METHODS: A systematic literature search was performed across Ovid MEDLINE, Scopus, and Embase using 14 search terms in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This systematic review examines variables such as patient age, tumor location, size, presenting symptoms, treatment modality, extent of resection, and mortality. We performed descriptive analyses to identify bivariate associations between patient characteristics, treatment, and outcomes. RESULTS: The mean age at diagnosis was 34.8 years, and the most common etiology was acute myeloid leukemia (68.8%). The most common presenting symptoms were headache (45.5%), vision complaints (27.3%), and weakness/motor symptoms (21.2%). IMS were most commonly located in the temporal lobe (10.1%), cerebellum (10.1%), or falcine/parasagittal (10.1%) region. Patients who received radiotherapy (P < 0.001) or chemotherapy (P < 0.001) had lower rates of mortality versus those who did not. Surgical treatment and extent of resection were not significantly associated with mortality (P > 0.05). CONCLUSION: The use of adjuvant radiotherapy or chemotherapy for IMS significantly reduces mortality, confirming IMS as a cranial manifestation of a systemic disease. Although surgical treatment is indicated for histopathologic diagnosis and to relieve mass effect, the extent of resection does not predict overall survival.
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Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/terapia , Procedimentos Neurocirúrgicos/métodos , Radioterapia/métodos , Sarcoma Mieloide/terapia , Neoplasias Encefálicas/etiologia , Neoplasias Encefálicas/fisiopatologia , Quimioterapia Adjuvante , Cefaleia/fisiopatologia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mieloide Aguda/complicações , Debilidade Muscular/fisiopatologia , Recidiva Local de Neoplasia , Radioterapia Adjuvante , Sarcoma Mieloide/etiologia , Sarcoma Mieloide/fisiopatologia , Taxa de Sobrevida , Resultado do Tratamento , Transtornos da Visão/fisiopatologiaAssuntos
Antineoplásicos/administração & dosagem , Transplante de Rim/efeitos adversos , Sarcoma Mieloide/etiologia , Sarcoma Mieloide/genética , Adulto , Trióxido de Arsênio/administração & dosagem , Humanos , Masculino , Insuficiência Renal Crônica/terapia , Sarcoma Mieloide/tratamento farmacológico , Sarcoma Mieloide/patologia , Doadores de Tecidos , Transplantados , Tretinoína/administração & dosagemRESUMO
Myeloid sarcoma (MS) as a solid extra-medullary (EM) manifestation of acute myeloid leukemia (AML), myeloproliferative or myelodysplastic syndromes is a rare presentation of relapse after allogeneic hematopoietic stem cell transplantation (HSCT). The databases of the Departments of Hematology and Oncology of the University Hospitals of Jena and Rostock were screened for patients aged 18 years or older for onset of MS after HSCT for myeloid malignancies between 2002 and 2019. Nineteen patients with MS were identified, the majority of whom had received reduced-intensity conditioning (RIC). The median onset of MS was 425 days after HSCT and the median overall survival since MS was 234 days. Although MS is associated with a poor prognosis, three patients survived more than two years and one more than 11 years after MS onset. These results indicate that RIC protocols may be associated with a higher risk of EM relapse. Since EM relapse occurred in the presence of Graft-versus-host-disease, these observations also demonstrate the limitations of graft-versus-tumor effects after HSCT. In conclusion, occurrence of MS after HSCT is associated with a poor prognosis, as multimodal curative concepts including intensive chemotherapy and another HSCT are often not viable.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Sarcoma Mieloide , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda/terapia , Recidiva , Estudos Retrospectivos , Sarcoma Mieloide/etiologia , Sarcoma Mieloide/terapia , Condicionamento Pré-Transplante/efeitos adversos , Transplante HomólogoRESUMO
Spontaneous myeloid leukemia is rarely reported in non-human primates. We report a case of myeloproliferative disorder suggestive of acute myeloid leukemia with intraoral lesions in an olive baboon (Papio anubis). Clinical pathology, radiology, gross examination (pre-mortem and post-mortem), histopathology, and immunohistochemistry findings are provided.
Assuntos
Leucemia Mieloide Aguda/veterinária , Doenças dos Macacos/diagnóstico , Transtornos Mieloproliferativos/veterinária , Papio anubis , Sarcoma Mieloide/veterinária , Animais , Feminino , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patologia , Doenças dos Macacos/etiologia , Doenças dos Macacos/patologia , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/etiologia , Transtornos Mieloproliferativos/patologia , Sarcoma Mieloide/diagnóstico , Sarcoma Mieloide/etiologia , Sarcoma Mieloide/patologiaAssuntos
Neoplasias Gastrointestinais/diagnóstico , Leucemia Mieloide Aguda/complicações , Sarcoma Mieloide/diagnóstico , Duodeno/patologia , Endoscopia do Sistema Digestório , Neoplasias Gastrointestinais/patologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Sarcoma Mieloide/etiologia , Estômago/patologiaRESUMO
PURPOSE OF REVIEW: The purpose of this review is to summarize the current literature on the presentation, diagnosis, and treatment options available for extramedullary (EM) manifestations of leukemia including myeloid sarcoma (MS) and leukemia cutis (LC). RECENT FINDINGS: Advanced imaging using 18FDG-PET/CT is an effective screening tool for EM manifestations of leukemia. The role of radiation therapy has been more clearly delineated in the treatment of both MS and LC. FDA-approved targeted agents have improved outcomes in patients with AML but have not demonstrated improvements specifically for EM; however, a checkpoint inhibitor, Ipilimumab, holds promise in impacting local control for the treatment of AML-related EM. EM manifestations of leukemia pose significant therapeutic challenges. Treatment of EM is predicated on multiple factors including the presence of concomitant bone marrow involvement, AML-risk classification, and timing of presentation at initial diagnosis or relapse following systemic therapy.
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Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Sarcoma Mieloide/diagnóstico , Sarcoma Mieloide/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Humanos , Prognóstico , Sarcoma Mieloide/etiologiaAssuntos
Neoplasias Renais/diagnóstico , Transplante de Rim , Leucemia Promielocítica Aguda/diagnóstico , Sarcoma Mieloide/diagnóstico , Idoso , Biópsia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Rim/diagnóstico por imagem , Rim/patologia , Rim/ultraestrutura , Neoplasias Renais/etiologia , Neoplasias Renais/terapia , Transplante de Rim/efeitos adversos , Leucemia Promielocítica Aguda/genética , Masculino , Sarcoma Mieloide/etiologia , Sarcoma Mieloide/terapia , Doadores de Tecidos , Tomografia Computadorizada por Raios XRESUMO
Splenomegaly is a key clinical manifestation of myelofibrosis, and splenectomy is currently indicated in patients with drug refractory, symptomatic splenomegaly or with the aim of improving refractory cytopenias. Transformation to acute myeloid leukemia occurs in up to 20% of patients with myelofibrosis, while cases of myeloid sarcoma have been reported very unfrequently. In this manuscript, we report the case of a 60-year-old man with a history of primary myelofibrosis who underwent splenectomy because of drug-refractory massive splenomegaly, systemic symptoms and anemia. At the opening of the peritoneal cavity, the spleen resulted massively enlarged and tenaciously entrapped by a pervasive neoplastic-like tissue. The extensive involvement of the abdomen fatally complicated the surgical procedure. At postmortem examination, the spleen showed a diffuse infiltration of immature cells that were also found in the peritoneum, bowel, liver, lungs and myocardium. After immunohistochemical, cytogenetic, flow cytometric and molecular characterization of neoplastic population, a diagnosis of disseminated myeloid sarcoma of the spleen was made. This case report highlights a very unusual case of myeloid sarcoma originating from the spleen in a patient with myelofibrosis who had no evidence of bone marrow or peripheral blood involvement by leukemic cells. Molecular characterization showed that leukemic cells originated from the founding clone of the chronic phase. The sarcoma could not be suspected based on clinical findings and was diagnosed only at the time of surgical procedure and autopsy. This case suggests that leukemic transformation of myelofibrosis can originate outside the bone marrow and, presumably rarely, present as a granulocytic sarcoma.
Assuntos
Mielofibrose Primária/patologia , Sarcoma Mieloide/patologia , Esplenomegalia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/tratamento farmacológico , Sarcoma Mieloide/etiologia , Esplenomegalia/etiologia , Esplenomegalia/cirurgiaRESUMO
Myeloid sarcoma is a rare, architecture-effacing proliferation of myeloid blasts localized to an extramedullary site, with or without concurrent bone marrow involvement. Clonal heterogeneity results from acquisition of somatic mutations within different subclones of leukemic cells. It was hypothesized that clonal heterogeneity between myeloid sarcomas and concurrent bone marrow biopsies might be present, given their differing biological features and microenvironment. High-throughput sequencing of the largest series (n = 24) of paired myeloid sarcomas and bone marrow biopsies was performed. One third of myeloid sarcomas (8/24) showed discordant molecular profiles, and 75% (n = 6) of these cases had discordant mutations in genes with prognostic significance or molecularly targeted therapies. Patients with molecularly discordant myeloid sarcoma had significantly worse overall survival (median survival, 195 days versus not reached, hazard ratio, 3.3, P < 0.05). Further investigation into molecular discordance between myeloid sarcoma and concurrent bone marrow biopsies may help in understanding clonal evolution of myeloid neoplasms and mechanisms regulating extramedullary blast localization.
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Biomarcadores Tumorais/genética , Medula Óssea/patologia , Oncogenes , Sarcoma Mieloide/diagnóstico , Sarcoma Mieloide/etiologia , Adulto , Idoso , Biópsia , Feminino , Perfilação da Expressão Gênica , Frequência do Gene , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunofenotipagem , Cariótipo , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Sarcoma Mieloide/mortalidadeRESUMO
RATIONALE: Granulocytic sarcoma (GS), also known as chloroma, is a tumor comprising myeloblasts or monoblasts, potentially occurring as an extramedullary mass. Systemic chemotherapy should be used to induce complete remission. However, such patients with chloroma have a poorer treatment outcome than those without extramedullary myeloid sarcomas. PATIENT CONCERNS: A 30-year-old woman who initially presented with bilateral ovarian masses and splenomegaly was admitted to hospital. Also, her complete blood cell counts showed pancytopenia and blood smear revealed a few immature cells (3%). DIAGNOSES: A bone marrow biopsy demonstrated acute myelomonocytic leukemia, and the chromosomal analysis revealed a 46, XX, del18 (p11) [20] karyotype and cytogenetics and molecular markers showed all negative results. INTERVENTIONS: Since this diagnosis, she received remission-inducing chemotherapy comprising anthracycline and cytarabine, which is a standard regimen for acute myeloid leukemia (AML), and followed by allogenic hematopoietic stem cell transplantation from Human leukocyte antigen (HLA)-identical sibling donor. OUTCOMES: After transplantation, the bone marrow engrafted successfully without complications. She visited our clinic regularly with no evidence of leukemia relapse or graft-versus host disease. LESSONS: This report represents the first case of ovarian GS, wherein treatment was successful with high-dose chemotherapy, followed by allogenic hematopoietic stem cell transplantation without oophorectomy.