RESUMEN
The accurate diagnosis and classification of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) are challenging due to the overlapping pathological and molecular features of myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN). We investigated the genomic landscape in different MDS/MPN subtypes, including chronic myelomonocytic leukemia (CMML; n = 97), atypical chronic myeloid leukemia (aCML; n = 8), MDS/MPN-unclassified (MDS/MPN-U; n = 44), and MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T; n = 12). Our study indicated that MDS/MPN is characterized by mutations commonly identified in myeloid neoplasms, with TET2 (52%) being the most frequently mutated gene, followed by ASXL1 (38.7%), SRSF2 (34.7%), and JAK2 (19.7%), among others. However, the distribution of recurrent mutations differs across the MDS/MPN subtypes. We confirmed that specific gene combinations correlate with specific MDS/MPN subtypes (e.g., TET2/SRSF2 in CMML, ASXL1/SETBP1 in aCML, and SF3B1/JAK2 in MDS/MPN-RS-T), with MDS/MPN-U being the most heterogeneous. Furthermore, we found that older age (≥65 years) and mutations in RUNX1 and TP53 were associated with poorer clinical outcomes in CMML (p < 0.05) by multivariate analysis. In MDS/MPN-U, CBL mutations (p < 0.05) were the sole negative prognostic factors identified in our study by multivariate analysis (p < 0.05). Overall, our study provides genetic insights into various MDS/MPN subtypes, which may aid in diagnosis and clinical decision-making for patients with MDS/MPN.
Asunto(s)
Mutación , Enfermedades Mielodisplásicas-Mieloproliferativas , Proteínas Proto-Oncogénicas , Humanos , Anciano , Masculino , Femenino , Persona de Mediana Edad , Enfermedades Mielodisplásicas-Mieloproliferativas/genética , Enfermedades Mielodisplásicas-Mieloproliferativas/clasificación , Anciano de 80 o más Años , Proteínas Proto-Oncogénicas/genética , Adulto , Dioxigenasas , Factores de Empalme Serina-Arginina/genética , Janus Quinasa 2/genética , Proteínas de Unión al ADN/genética , Genómica/métodos , Leucemia Mielomonocítica Crónica/genética , Leucemia Mielomonocítica Crónica/patología , Síndromes Mielodisplásicos/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/diagnóstico , Proteínas Represoras/genética , Factores de Empalme de ARN/genética , Proteínas Portadoras , Proteínas NuclearesRESUMEN
BACKGROUND: Immunosuppressed bone marrow transplant patients with pulmonary infiltrates routinely undergo bronchoscopy with bronchoalveolar lavage (BAL) to investigate potential etiologies. Cytokine release syndrome after BAL is unreported in the literature in general and in this patient population. CASE PRESENTATION: We report on an allogeneic bone marrow transplant patient with non-infectious organizing pneumonia of the lungs who developed delayed and rapidly progressive shock and hypoxia post-procedure over the course of 12 h resulting in intensive care unit admission for supportive care. BAL was characterized by a marked lymphocytic, cytotoxic T cell infiltrate on pathology and flow cytometry without clear evidence of infection. The patient's clinical status improved quickly only after the initiation of high dose intravenous steroids and returned to baseline as an outpatient. CONCLUSION: The patient's clinical data and course suggest a cytotoxic T cell response from the lung and BAL as the etiology. With an increasing number of cellular therapies for cancer entering the clinic, the potential for unusual but morbid complications from routine bronchoscopy should be considered.
Asunto(s)
Enfermedades Pulmonares , Neoplasias , Humanos , Líquido del Lavado Bronquioalveolar , Síndrome de Liberación de Citoquinas , Lavado Broncoalveolar/métodos , Broncoscopía/métodosRESUMEN
Classic Hodgkin lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and T cell/histiocyte-rich large B cell lymphoma form a unique set of lymphomas with similar morphologic growth patterns (occasional neoplastic cells within a prominent cellular cell background) that are pathobiologically related. Distinguishing these entities has been historically difficult by flow cytometry; however, our laboratory has developed antibody-fluorochrome combinations capable of immunophenotyping these lymphomas. Additionally, characterization of the background reactive lymphocytes can aid in narrowing the differential diagnosis. This review summarizes the immunophenotypic features and insights of the neoplastic and reactive populations found in this unique group of lymphomas.
Asunto(s)
Enfermedad de Hodgkin , Linfoma Folicular , Linfoma de Células B Grandes Difuso , Humanos , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/patología , Linfocitos T , Linfoma Folicular/diagnóstico , Linfoma Folicular/patología , Histiocitos/patología , Citometría de Flujo , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/patología , Linfocitos , Inmunofenotipificación , Diagnóstico DiferencialRESUMEN
Our understanding of the genetics and biology of lymphoblastic leukemia/lymphoma (acute lymphoblastic leukemia, ALL) has advanced rapidly in the past decade with advances in sequencing and other molecular techniques. Besides recurrent chromosomal abnormalities detected by karyotyping or fluorescence in situ hybridization, these leukemias/lymphomas are characterized by a variety of mutations, gene rearrangements as well as copy number alterations. This is particularly true in the case of Philadelphia-like (Ph-like) ALL, a major subset which has the same gene expression signature as Philadelphia chromosome-positive ALL but lacks BCR-ABL1 translocation. Ph-like ALL is associated with a worse prognosis and hence its detection is critical. However, techniques to detect this entity are complex and are not widely available. This chapter discusses various subsets of ALL and describes our approach to the accurate classification and prognostication of these cases.