RESUMEN
Leukemia circulates in the bloodstream and induces various symptoms and complications. Occasionally, these cells accumulate in non-marrow tissues, forming a tumor-like myeloid sarcoma (MS). When the blast-stage leukemia cells invade the brain parenchyma, intracranial MS occurs, leading to a challenging prognosis owing to the limited penetration of cytostatic drugs into the brain and the development of drug resistance. The scarcity of tissue samples from MS makes understanding the phenotypic changes occurring in leukemia cells within the brain environment challenging, thereby hindering development of effective treatment strategies for intracranial MS. This study presents a novel 3D in vitro model mimicking intracranial MS, employing a hydrogel scaffold derived from the brain-decellularized extracellular matrix in which suspended leukemia cells are embedded, simulating the formation of tumor masses in the brain parenchyma. This model reveals marked phenotypic changes in leukemia cells, including altered survival, proliferation, differentiation, and cell cycle regulation. Notably, proportion of dormant leukemia stem cells increases and expression of multidrug resistance genes is upregulated, leading to imatinib resistance, mirroring the pathological features of in vivo MS tissue. Furthermore, suppression of ferroptosis is identified as an important characteristic of intracranial MS, providing valuable insights for the development of targeted therapeutic strategies.
Asunto(s)
Encéfalo , Matriz Extracelular , Sarcoma Mieloide , Humanos , Encéfalo/patología , Encéfalo/metabolismo , Línea Celular Tumoral , Sarcoma Mieloide/metabolismo , Sarcoma Mieloide/patología , Matriz Extracelular/metabolismo , Resistencia a Antineoplásicos , Proliferación Celular/efectos de los fármacos , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Fenotipo , Hidrogeles/química , Andamios del Tejido/química , Diferenciación Celular/efectos de los fármacos , Animales , Ferroptosis/efectos de los fármacosRESUMEN
Erythroblastic sarcoma (ES) (previously called chloroma or granulocytic sarcoma) are rare hematological neoplams characterized by the proliferation of myeloid blasts at extramedullary sites, and primarily involve the skin and soft tissue of middle-aged adults. ES may be concomitant with or secondary to myeloid neoplasms (mostly acute myeloid leukemia (AML)) or in isolated cases (de novo) without infiltration of the bone marrow by blasts. ES share cytogenetic and molecular abnormalities with AML, including RUNX1T1 fusions. Some of these alterations seem to be correlated with particular sites of involvement. Herein, we report an isolated erythroblastic sarcoma with NFIA::RUNX1T1 located in the central nervous system (CNS) of a 3-year-old boy. Recently, two pediatric cases of CNS MS with complete molecular characterization have been documented. Like the current case, they concerned infants (2 and 3 years-old) presenting a brain tumor (pineal involvement) with leptomeningeal dissemination. Both cases also harbored a NFIA::RUNX1T3 fusion. ES constitutes a diagnostic challenge for neuropathologists because it does not express differentiation markers such as CD45, and may express CD99 which could be confused with CNS Ewing sarcoma. CD43 is the earliest pan-hematopoietic marker and CD45 is not expressed by erythroid lineage cells. E-cadherin (also a marker of erythroid precursors) and CD117 (expressed on the surface of erythroid lineage cells) constitute other immunhistochemical hallmarks of ES. The prognosis of patients with ES is similar to that of other patients with AML but de novo forms seem to have a poorer prognosis, like the current case. To conclude, pediatric ES with NFIA::RUNX1T1/3 fusions seem to have a tropism for the CNS and thus constitute a potential pitfall for neuropathologists. Due to the absence of circulating blasts and a DNA-methylation signature, the diagnosis must currently be made by highlighting the translocation and expression of erythroid markers.
Asunto(s)
Neoplasias del Sistema Nervioso Central , Leucemia Mieloide Aguda , Sarcoma Mieloide , Sarcoma , Preescolar , Humanos , Lactante , Masculino , Persona de Mediana Edad , Médula Ósea/patología , Neoplasias del Sistema Nervioso Central/patología , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Factores de Transcripción NFI/genética , Factores de Transcripción NFI/metabolismo , Proteína 1 Compañera de Translocación de RUNX1/metabolismo , Sarcoma/metabolismo , Sarcoma/patología , Sarcoma Mieloide/genética , Sarcoma Mieloide/diagnóstico , Sarcoma Mieloide/metabolismoRESUMEN
The World Health Organization classification and definition of "myeloid sarcoma" is imprecise and misleading. A more accurate term is "extramedullary acute myeloid leukemia tumor (eAML)." The pathogenesis of eAML has been associated with aberrancy of cellular adhesion molecules, chemokine receptors/ligands and RAS-MAPK/ERK signaling. eAML can present with or without synchronous or metachronous intramedullary acute myeloid leukemia (AML) so a bone marrow evaluation is always recommended. Accurate diagnosis of eAML requires tissue biopsy. eAML confined to one or a few sites is frequently treated with local therapy such as radiotherapy. About 75-90% of patients with isolated eAML will develop metachronous intramedullary AML with a median latency period ranging from 4 to 12 months; thus, patients with isolated eAML may also be treated with systemic anti-leukemia therapy. eAML does not appear to have an independent prognostic impact; selection of post-remission therapy including allogeneic hematopoietic cell transplant (alloHCT) is typically guided by intramedullary disease risk. Management of isolated eAML should be individualized based on patient characteristics as well as eAML location and cytogenetic/molecular features. The role of PET/CT in eAML is also currently being elucidated. Improving outcomes of patients with eAML requires further knowledge of its etiology and mechanism(s) as well as therapeutic approaches beyond conventional chemotherapy, ideally in the context of controlled trials.
Asunto(s)
Leucemia Mieloide Aguda , Sistema de Señalización de MAP Quinasas , Proteínas de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Sarcoma Mieloide , Aloinjertos , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mieloide Aguda/clasificación , Leucemia Mieloide Aguda/diagnóstico por imagen , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/terapia , Radioterapia , Sarcoma Mieloide/clasificación , Sarcoma Mieloide/diagnóstico por imagen , Sarcoma Mieloide/metabolismo , Sarcoma Mieloide/terapiaRESUMEN
INTRODUCTION: Myeloid sarcoma (MS) is a rare tumor mass. It may occur at any extramedullary anatomic sites but is uncommon in the sinonasal location.MS commonly presents concurrently with acute myeloid leukemia (AML), but it may predate AML over several months or years, named isolated MS. PATIENT CONCERNS: We report a case of a 15-month-old child who presented with mouth breathing, bilateral rhinorrhea, palpebral edema and proptosis. The routine blood tests were normal for the first few months. Computed tomography scan revealed neoplasm in nasal cavity. DIAGNOSIS: The patient was definitely diagnosed with isolated MS in the nasal cavity through immunohistochemistry combined with clinical features and radiological investigations, and MS further progressed to AML which was confirmed by hematologist. INTERVENTIONS: Endoscopic sinus surgery was performed to acquire specimens. After diagnosis, the patient was promptly treated with systemic chemotherapy. OUTCOMES: All symptoms gradually subsided and the mass of nasal cavity was invisible. No relapse occurred during follow-up. CONCLUSION: Sinonasal MS may be misdiagnosed and should be considered when symptoms persist and worsen. Prompt clinic examinations are essential for cases with suspected MS. Diagnosis of MS is dependent on the immunohistological investigations combined with clinical features, radiological investigations. Early diagnosis and systemic chemotherapy are vital for patients to achieve best prognosis.
Asunto(s)
Leucemia Mieloide Aguda/tratamiento farmacológico , Cavidad Nasal/diagnóstico por imagen , Sarcoma Mieloide/complicaciones , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Errores Diagnósticos/prevención & control , Diagnóstico Precoz , Edema/etiología , Exoftalmia/etiología , Enfermedades de los Párpados/patología , Humanos , Inmunohistoquímica/métodos , Lactante , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/cirugía , Masculino , Cavidad Nasal/patología , Cavidad Nasal/cirugía , Sarcoma Mieloide/diagnóstico por imagen , Sarcoma Mieloide/metabolismo , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoAsunto(s)
Bronquios/patología , Tos/etiología , Sarcoma Mieloide/diagnóstico , Tráquea/patología , Anciano , Médula Ósea/patología , Broncoscopía/métodos , Tos/diagnóstico , Progresión de la Enfermedad , Resultado Fatal , Femenino , Células Precursoras de Granulocitos/patología , Humanos , Recurrencia Local de Neoplasia , Cuidados Paliativos , Sarcoma Mieloide/metabolismo , Sarcoma Mieloide/patología , Tomografía Computarizada por Rayos X/métodosAsunto(s)
Pólipos Adenomatosos/cirugía , Neoplasias del Ciego/cirugía , Colectomía/efectos adversos , Colonoscopía/efectos adversos , Hemorragia Gastrointestinal/etiología , Pólipos Intestinales/cirugía , Hemorragia Posoperatoria/etiología , Sarcoma Mieloide/cirugía , Pólipos Adenomatosos/química , Pólipos Adenomatosos/patología , Anciano , Biomarcadores de Tumor/análisis , Neoplasias del Ciego/química , Neoplasias del Ciego/patología , Humanos , Inmunohistoquímica , Pólipos Intestinales/química , Pólipos Intestinales/patología , Masculino , Sarcoma Mieloide/metabolismo , Sarcoma Mieloide/patología , Resultado del TratamientoRESUMEN
Myeloid sarcoma (MS) is defined as an extramedullary mass-forming lesion composed of immature myeloid cells. It is a rare but well-known manifestation of acute myeloid leukemia. Pediatrics testicular MS may pose a possible diagnostic challenge, an issue that is underscored in the few testicular pediatric MS cases reported in the literature. Herein, we report a series of 5 cases of pediatric testicular MS that are evaluated at the morphologic and immunohistochemical levels with correlation with the KMT2A (MLL) rearrangement status. Three patients presented with no prior history of acute myeloid leukemia. All 5 cases showed monoblastic morphology; positive for CD33, CD43, CD68, CD163, CD4 (dim), and lysozyme; and negative for CD10, CD34, CD117, and myeloperoxidase. KMT2A (MLL) rearrangement was detected in 4 of the 5 cases. In the literature, 8 more cases of pediatric testicular lymphoma were reported. Most of them showed monocytic differentiation and KMT2A (MLL) rearrangement was reported in 3 of the cases. In conclusions, testicular MS in pediatric patients shows monoblastic differentiation which may be attributed to the KMT2A (MLL) rearrangement. We also highlight the importance of using an extended immunohistochemistry panel in the diagnosis of MS.
Asunto(s)
N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Leucemia Mieloide Aguda/complicaciones , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Sarcoma Mieloide/diagnóstico , Sarcoma Mieloide/metabolismo , Neoplasias Testiculares/metabolismo , Antígenos CD/metabolismo , Antígenos CD34/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Antígenos CD4/metabolismo , Niño , Preescolar , Reordenamiento Génico , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Lactante , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Leucosialina/metabolismo , Masculino , Muramidasa/metabolismo , Neprilisina/metabolismo , Peroxidasa/metabolismo , Proteínas Proto-Oncogénicas c-kit/metabolismo , Receptores de Superficie Celular/metabolismo , Sarcoma Mieloide/complicaciones , Sarcoma Mieloide/genética , Lectina 3 Similar a Ig de Unión al Ácido Siálico/metabolismo , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologíaRESUMEN
Recent studies of leukemic tumors in individual extramedullary sites showed they adopt the clinical and metastatic behavior of solid cancers originating in those sites. To elucidate features of leukemic tumors that render them resistant to agents effective against marrow leukemia, we analyzed a series of AML breast tumors by histology, immunohistochemistry, and RNA sequencing. Striking histologic similarities to solid cancers were found: a single-filing architectural pattern virtually identical to that of invasive lobular breast carcinoma and dense desmoplastic keloid-like fibrosis similar to colon, gallbladder, and pancreas carcinomas. Sequencing found 2157 genes significantly downregulated in AML breast tumors compared to normal breast. Comparison to triple-negative breast cancer found 859 genes similarly downregulated. At least 30 of these genes have been associated with poor prognosis in breast cancers. Five were reported in AML marrow studies to correlate with poor prognosis. The findings of this pilot study suggest the seed-and-soil interaction recognized in solid cancer growth may help explain how leukemic cells, in some patients, adopt solid tumor behavior in non-marrow sites. Transformed cells that metastasize from tumor to marrow can impart chemoresistance and be an unrecognized cause of treatment failure and death. Further studies comparing leukemic tumor to simultaneous marrow could potentially identify biomarkers that predict extramedullary resistance and lead to new therapeutic targets. Recognizing the potential for leukemia to adopt solid tumor phenotype, and implementation of body scanning and ablative tumor treatment, could decrease the persistently high rates of marrow resistance and treatment failure.
Asunto(s)
Mama/patología , Leucemia Mieloide Aguda/patología , Sarcoma Mieloide/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor , Mama/química , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Carcinoma/patología , Terapia Combinada , Resistencia a Antineoplásicos , Femenino , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/terapia , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Especificidad de Órganos , Proyectos Piloto , Pronóstico , ARN Mensajero/análisis , ARN Neoplásico/análisis , Sarcoma Mieloide/tratamiento farmacológico , Sarcoma Mieloide/genética , Sarcoma Mieloide/metabolismo , Neoplasias de la Mama Triple Negativas/patologíaAsunto(s)
Neoplasias Cardíacas , Sarcoma Mieloide , Taquicardia Sinusal , Adolescente , Femenino , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/tratamiento farmacológico , Neoplasias Cardíacas/metabolismo , Neoplasias Cardíacas/patología , Humanos , Sarcoma Mieloide/diagnóstico por imagen , Sarcoma Mieloide/tratamiento farmacológico , Sarcoma Mieloide/metabolismo , Sarcoma Mieloide/patología , Taquicardia Sinusal/diagnóstico por imagen , Taquicardia Sinusal/tratamiento farmacológico , Taquicardia Sinusal/metabolismo , Taquicardia Sinusal/patologíaRESUMEN
We report a case of myeloid sarcoma with multifocal skeletal involvement, including the greater wing of the sphenoid bone. A 23-month-old boy presented with left-sided proptosis and fevers, and was found to have an infiltrative mass involving the left sphenoid bone on orbital imaging. Full body imaging further demonstrated multiple bony lesions in the pelvis, thoracic and lumbar vertebrae, bilateral femura, and left humerus, and biopsies of the humerus were consistent with myeloid sarcoma. The patient was started on a standard chemotherapy regimen and is responding well. Myeloid sarcoma presenting with proptosis due to sphenoid bone involvement with simultaneous multifocal skeletal involvement is very uncommon and highlights the importance of biopsy for establishing a definitive diagnosis.
Asunto(s)
Neoplasias Óseas/diagnóstico , Exoftalmia/diagnóstico , Fiebre/diagnóstico , Neoplasias Primarias Múltiples/diagnóstico , Sarcoma Mieloide/diagnóstico , Neoplasias Craneales/diagnóstico , Hueso Esfenoides/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/metabolismo , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Proteínas de Neoplasias/metabolismo , Neoplasias Primarias Múltiples/tratamiento farmacológico , Neoplasias Primarias Múltiples/metabolismo , Sarcoma Mieloide/tratamiento farmacológico , Sarcoma Mieloide/metabolismo , Neoplasias Craneales/tratamiento farmacológico , Neoplasias Craneales/metabolismo , Tomografía Computarizada por Rayos XAsunto(s)
Neoplasias del Mediastino , Neoplasias de Células Germinales y Embrionarias , Sarcoma Mieloide , Adulto , Humanos , Masculino , Neoplasias del Mediastino/diagnóstico por imagen , Neoplasias del Mediastino/metabolismo , Neoplasias del Mediastino/patología , Neoplasias de Células Germinales y Embrionarias/diagnóstico por imagen , Neoplasias de Células Germinales y Embrionarias/metabolismo , Neoplasias de Células Germinales y Embrionarias/patología , Sarcoma Mieloide/diagnóstico por imagen , Sarcoma Mieloide/metabolismo , Sarcoma Mieloide/patologíaRESUMEN
Impaired immunity in patients with late-stage cancer is not limited to antitumor responses, as demonstrated by poor vaccination protection and high susceptibility to infection1-3. This has been largely attributed to chemotherapy-induced impairment of innate immunity, such as neutropenia2, whereas systemic effects of tumors on hematopoiesis and adoptive immunity remain incompletely understood. Here we observed anemia associated with severe deficiency of CD8+ T cell responses against pathogens in treatment-naive mice bearing large tumors. Specifically, we identify CD45+ erythroid progenitor cells (CD71+TER119+; EPCs) as robust immunosuppressors. CD45+ EPCs, induced by tumor growth-associated extramedullary hematopoiesis, accumulate in the spleen to become a major population, outnumbering regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). The CD45+ EPC transcriptome closely resembles that of MDSCs, and, like MDSCs, reactive oxygen species production is a major mechanism underlying CD45+ EPC-mediated immunosuppression. Similarly, an immunosuppressive CD45+ EPC population was detected in patients with cancer who have anemia. These findings identify a major population of immunosuppressive cells that likely contributes to the impaired T cell responses commonly observed in patients with advanced cancer.
Asunto(s)
Anemia/inmunología , Células Precursoras Eritroides/inmunología , Células Supresoras de Origen Mieloide/inmunología , Sarcoma Mieloide/inmunología , Anemia/genética , Anemia/patología , Animales , Antígenos CD/inmunología , Linfocitos T CD8-positivos/inmunología , Modelos Animales de Enfermedad , Células Precursoras Eritroides/metabolismo , Células Precursoras Eritroides/patología , Humanos , Tolerancia Inmunológica , Inmunidad Innata/genética , Antígenos Comunes de Leucocito/inmunología , Ratones , Estadificación de Neoplasias , Especies Reactivas de Oxígeno/metabolismo , Receptores de Transferrina/inmunología , Sarcoma Mieloide/metabolismo , Sarcoma Mieloide/patología , Linfocitos T Reguladores/inmunología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Myeloid sarcoma is a rare presentation of acute leukemia as a solid tumor at various extramedullary sites. It may present concurrently, before or after the onset of systemic bone marrow leukemia. Unusual clinical localization may lead to misdiagnosis, or delayed diagnosis and treatment. We describe the first case, to our knowledge, of de novo myeloid sarcoma of the breast confirmed as acute promyelocytic leukemia. Immunohistochemical analysis, flow cytometry, fluorescent in situ hybridization analysis and molecular analysis using RQ-PCR of tissue samples should be routine in determining the correct diagnosis in this setting.
Asunto(s)
Neoplasias de la Mama/diagnóstico , Leucemia Promielocítica Aguda/diagnóstico , Sarcoma Mieloide/diagnóstico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Médula Ósea/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Diagnóstico Diferencial , Femenino , Citometría de Flujo , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/metabolismo , Imagen por Resonancia Magnética , Mamografía , Sarcoma Mieloide/genética , Sarcoma Mieloide/metabolismo , Resultado del TratamientoAsunto(s)
Biomarcadores de Tumor , Mutación , Proteínas Tirosina Quinasas Receptoras/metabolismo , Sarcoma Mieloide/genética , Sarcoma Mieloide/metabolismo , Transducción de Señal , Proteínas ras/metabolismo , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Myeloid sarcoma is an extramedullary tumor that consists of myeloblasts or immature myeloid cells. The neoplasm can occur in any part of the body, including the bone, periosteum, lymph nodes, skin, and soft tissue and they may occur de novo or in association with acute myeloid leukemia, myeloproliferative neoplasms and myelodysplastic syndromes. Most cases display a myelomonocytic or pure monoblastic morphology. Tumors with megakaryoblastic differentiation are extremely uncommon and may occur in association with transformation of a myeloproliferative disorder. Myeloid sarcoma presenting as a breast mass is very rare and diagnostically challenging. We report a case of myeloid sarcoma with megakaryoblastic differentiation in the breast of a patient with history of essential thrombocythemia. The mass was composed of undifferentiated pleomorphic malignant cells in trabecular cords and nests with many scattered giant malignant cells and brisk abnormal mitoses. On immunohistochemistry, the neoplastic cells were positive for CD61, CD31, CD34, Factor VIII and CD43 which confirmed the diagnosis. To our knowledge, this is the first report of myeloid sarcoma with megakaryoblastic morphology occurring in the breast. Here we discuss the clinicopathologic features of this rare entity and the challenges involved in making this difficult diagnosis.
Asunto(s)
Antígenos de Diferenciación/metabolismo , Neoplasias de la Mama , Diferenciación Celular , Células Progenitoras de Megacariocitos , Proteínas de Neoplasias/metabolismo , Sarcoma Mieloide , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Humanos , Células Progenitoras de Megacariocitos/metabolismo , Células Progenitoras de Megacariocitos/patología , Persona de Mediana Edad , Sarcoma Mieloide/metabolismo , Sarcoma Mieloide/patologíaRESUMEN
Myeloid sarcoma (MS) is a rare condition and is an extramedullary tumour of immature myeloid cells. It is now known that the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway suppresses the host antitumor responses and that these products are expressed on both tumour cells and tumour-infiltrating cells in various malignancies. However, little is known about the significance of PD-1/PD-L1 expression on tumour cells and tumour microenvironmental cells in MS. To investigate the clinicopathological significance of PD-1/PD-L1 expression in MS, we analyzed 98 patients by immunohistochemistry. Of these, 10.2% of cases had neoplastic tumour cells positive for PD-L1 (nPD-L1+ ). However, the rate of nPD-L1+ was <5% (range: 0.27 to 2.97%). On the other hand, PD-L1 expression on 1 or more of stromal cells in the tumour microenvironment (miPD-L1+ ) was observed in 37.8% of cases. Because all nPD-L1+ cases expressed PD-1 on less than 5% of tumour cells, we compared the miPD-L1+ and miPD-L1- groups. There was a correlation between miPD-L1+ status and the number of PD-1-expressing tumour -infiltrating lymphocytes (PD-1+ TILs; P = .0229). miPD-L1+ was found to be associated with poorer overall survival and progression-free survival (P = .00392, P = .00261, respectively). Multivariate analysis also confirmed miPD-L1+ to be an independent poor prognostic factor. In conclusion, our study indicated that the immunotherapy blocking the PD-1/PD-L1 pathway may improve the clinical outcome of MS.
Asunto(s)
Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Linfocitos Infiltrantes de Tumor/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Sarcoma Mieloide/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Linfocitos Infiltrantes de Tumor/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , Sarcoma Mieloide/inmunología , Sarcoma Mieloide/metabolismo , Tasa de Supervivencia , Microambiente Tumoral/inmunología , Adulto JovenAsunto(s)
Bases de Datos Factuales , Sarcoma Mieloide , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Factores de Riesgo , Sarcoma Mieloide/metabolismo , Sarcoma Mieloide/patología , Sarcoma Mieloide/terapia , Tasa de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Myeloid sarcomas (MS) are rare extramedullary tumors composed of blasts of myeloid lineage that either precede, follow or present concomitantly with acute myeloid leukaemia (AML) or myeloproliferative neoplasms. The diagnosis of MS is especially challenging in patients without an antecedent history of leukemia. METHODS: We present 2 cases of intraoral MS that presented as de novo lesions. A detailed review of cases of intraoral MS that either preceded or presented along with leukemia has been done with emphasis on diagnostic criteria used. RESULTS: Two male patients aged 28 and 5 years presented with MS with one patient presenting with concomitant AML. A combination of morphological and immunohistochemical methods was used for diagnosis. A thorough review of world literature revealed 44 cases of intraoral MS that presented as de novo lesions. CONCLUSION: Intraoral MS is a rare tumor with poor prognosis. It may be diagnostically challenging due to its protean clinical manifestations and histological overlap with other tumors.
Asunto(s)
Neoplasias de la Boca/diagnóstico , Sarcoma Mieloide/diagnóstico , Adulto , Preescolar , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Leucemia Mieloide Aguda/complicaciones , Masculino , Neoplasias de la Boca/complicaciones , Neoplasias de la Boca/metabolismo , Peroxidasa/metabolismo , Sarcoma Mieloide/complicaciones , Sarcoma Mieloide/metabolismoRESUMEN
The expression of extracellular matrix protein periostin (POSTN) was attenuated in Med1(-/-) mouse embryonic fibroblasts (MEFs), which exhibited a decreased capability to support hematopoietic progenitor cells (HPCs) in vitro. When bone marrow (BM) cells were cocultured with mitomycin C-treated Med1(+/+) MEFs, or OP-9 or MS-5 BM stromal cells, in the presence of anti-POSTN antibody, the growth of BM cells and number of long-term culture-initiating cells (LTC-ICs) were attenuated. When BM cells were cocultured with Med1(-/-) MEFs in the presence of recombinant POSTN, the growth of BM cells and the number of LTC-ICs were restored. Moreover, antibody-mediated blockage of stromal cells-derived POSTN markedly reduced the growth and cobblestone formation, a leukemic stem cell feature, of stromal cell-dependent MB-1 myeloblastoma cells. POSTN was expressed both in BM cells and variably in different BM stromal cells. Expression in the latter cells was increased by physical interaction with hematopoietic cells. The receptor for POSTN, integrin αvß3, was expressed abundantly in BM stromal cells. The addition of recombinant POSTN to BM stromal cells induced intracellular signaling downstream of integrin αvß3. These results suggest that stromal cell POSTN supports both normal HPCs and leukemia-initiating cells in vitro, at least in part, indirectly by acting on stromal cells in an autocrine or paracrine manner.