RESUMEN
In patients with diffuse large B-cell lymphoma, MYC rearrangement (MYC-R), MYC expression, or concurrent expression of MYC and BCL2 is associated with a poorer prognosis. P53 expression also has been shown to confer inferior survival in diffuse large B-cell lymphoma patients, but less is known about the role of P53 expression in those with MYC-R, MYC expression (MYC+), or MYC&BCL2 co-expression (MYC+/BCL2+). We studied P53 expression in 201 patients with untreated de novo diffuse large B-cell lymphoma. Sixty-seven (33%) cases were P53 positive, 56 (28%) had MYC-R (including 17 MYC/BCL2 double hit lymphoma), 86 (45%) were MYC+/BCL2+, and 47 (24%) were positive for both MYC and P53. Compared with patients with P53 negative lymphoma, the P53 positive group had a poorer overall survival (P=0.004). In patients with lymphoma harboring MYC-R, MYC expression or MYC+/BCL2+, P53 expression was associated with a significantly worse overall survival (P<0.0001, P=0.01, and P=0.035, respectively). Patients with lymphoma showing concurrent P53 expression and MYC-R had a worse prognosis compared with patients with either P53 expression or MYC-R alone (P<0.0001). Similarly, P53 enhanced the negative prognostic effect of MYC expression in DLBCL patients. In addition, among patients with lymphoma with concurrent MYC and P53 expression, MYC and BCL2 or BCL2 & P53 expression, those patients with tumors with MYC and P53 expression had the worst overall survival (P=0.005), regardless of BCL2 expression status. Multivariate analysis demonstrated that both MYC-R and P53 expression were independent prognostic factors in this patient cohort. In conclusion, our data suggest that P53 expression and MYC -R or MYC expression have an additive negative prognostic effect in diffuse large B-cell lymphoma patients. Assessment of P53 expression adds additional prognostic information in de novo diffuse large B-cell lymphoma patients, especially in subgroups with MYC-R, MYC expression and MYC and BCL2 double expression.
Asunto(s)
Linfoma de Células B Grandes Difuso/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Femenino , Reordenamiento Génico , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Pronóstico , Tasa de Supervivencia , Vincristina/uso terapéutico , Adulto JovenRESUMEN
AIMS: Large B cell lymphomas with MYC and BCL6/3q27 rearrangements, designated MYC/BCL6 DHL, are uncommon. Our aim was to better characterize this group of tumours. METHODS AND RESULTS: We studied the clinicopathological features and outcome of 13 patients with MYC/BCL6 DHL and compared this group to a group of 83 MYC/BCL2 DHL patients. There were eight men and five women, with a median age of 63 years. Eleven tumours were classified as diffuse large B cell lymphomas (DLBCL) and two were B cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma (BCLU). Immunohistochemical analysis showed that these tumours were positive for BCL6 (100%), BCL2 (eight of 10; 80%) and CD10 (eight of 10; 80%). Nine of 12 (75%) cases had a germinal centre B cell (GCB) immunophenotype; in one case data were incomplete. All patients were treated with chemotherapy. The clinicopathological features of MYC/BCL6 DHL were similar to MYC/BCL2 DHL, except that MYC/BCL6 DHL had a GCB immunophenotype less often. Patients with MYC/BCL6 DHL had a poor overall survival, similar to patients with MYC/BCL2 DHL (P = 0.32). CONCLUSIONS: MYC/BCL6 DHL is an aggressive B cell lymphoma and patients often have an aggressive clinical course and poor prognosis, similar to patients with MYC/BCL2 DHL.
Asunto(s)
Biomarcadores de Tumor/genética , Linfoma de Burkitt/genética , Linfoma de Células B/genética , Linfoma de Células B Grandes Difuso/genética , Proteínas Proto-Oncogénicas c-bcl-6/genética , Proteínas Proto-Oncogénicas c-myc/genética , Adulto , Anciano , Anciano de 80 o más Años , Linfocitos B/metabolismo , Linfocitos B/patología , Biomarcadores de Tumor/metabolismo , Linfoma de Burkitt/clasificación , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/patología , Femenino , Reordenamiento Génico , Centro Germinal/metabolismo , Centro Germinal/patología , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Linfoma de Células B/clasificación , Linfoma de Células B/diagnóstico , Linfoma de Células B/patología , Linfoma de Células B Grandes Difuso/clasificación , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismoRESUMEN
OBJECTIVE: DLBCL is a heterogeneous disease with 40% of patients presenting as refractory/relapsing disease following R-CHOP treatment. Few recent studies investigating CD30 expression in DLBCL reported various prognostic effects. This study aimed to evaluate CD30 expression and its correlation with MYC rearrangement and to clarify its prognostic significance in DLBCL. METHODS: In 98 patients with de novoDLBCL, we studied CD30 expression by immunohistochemistry using different cutoff values (>0%, ≥20%, and ≥40% lymphoma cells, respectively) and correlated with the corresponding MYC rearrangement status by FISH. RESULTS: The clinicopathologic features were very similar between the CD30+ and CD30- groups. The only major difference was that CD30 expression was nearly exclusively seen in cases without MYC rearrangement. CD30 expression was not predictive of overall survival irrespective of therapy regimens, cell of origin, or MYC rearrangement status (P > 0.05). In the 27 patients receiving aggressive regimens, CD30 expression was associated with better OS (P = 0.008) when all patients were included while the survival advantage was lost (P = 0.21) if MYC rearranged cases were excluded. CONCLUSIONS: CD30 expression was not associated with prognosis in our cohort of de novoDLBCL, including in patients who received aggressive chemotherapy. CD30 expression and MYC rearrangement were mutually exclusive in de novoDLBCL.
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Expresión Génica , Reordenamiento Génico de Linfocito B , Genes myc , Antígeno Ki-1/genética , Linfoma de Células B Grandes Difuso/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Terapia Combinada , Femenino , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Antígeno Ki-1/metabolismo , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
Persistent neutrophilic meningitis presents a diagnostic challenge, because the differential diagnosis is broad and includes atypical infectious causes. We describe a case of persistent neutrophilic meningitis due to Aspergillus fumigatus in an immunocompetent man who had no evidence of sinopulmonary or cutaneous disease. An epidural glucocorticoid injection was identified as a potential route of entry for this organism into the central nervous system, and the case was reported to the state health department.
Asunto(s)
Aspergilosis/diagnóstico , Aspergillus fumigatus/aislamiento & purificación , Encéfalo/patología , Líquido Cefalorraquídeo/parasitología , Contaminación de Medicamentos , Meningitis Fúngica/diagnóstico , Aspergilosis/etiología , Encéfalo/diagnóstico por imagen , Cerebelo/irrigación sanguínea , Infarto Cerebral/etiología , Infarto Cerebral/patología , Diagnóstico Diferencial , Brotes de Enfermedades , Resultado Fatal , Glucocorticoides/administración & dosificación , Cefalea/etiología , Humanos , Inyecciones Epidurales/efectos adversos , Hemorragias Intracraneales/diagnóstico por imagen , Hemorragias Intracraneales/etiología , Dolor de la Región Lumbar/tratamiento farmacológico , Dolor de la Región Lumbar/etiología , Masculino , Meningitis Fúngica/epidemiología , Meningitis Fúngica/etiología , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Estados UnidosRESUMEN
Large B-cell lymphomas with IGH@BCL2 and MYC rearrangement, known as double-hit lymphoma (DHL), are clinically aggressive neoplasms with a poor prognosis. Some large B-cell lymphomas have concurrent abnormalities of MYC and BCL2 other than coexistent translocations. Little is known about patients with these lymphomas designated here as atypical DHL. We studied 40 patients of atypical DHL including 21 men and 19 women, with a median age of 60 years. Nine (23%) patients had a history of B-cell non-Hodgkin lymphoma. There were 30 diffuse large B-cell lymphoma (DLBCL), 7 B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma, and 3 DLBCL with coexistent follicular lymphoma. CD10, BCL2, and MYC were expressed in 28/39 (72%), 33/35 (94%), and 14/20 (70%) cases, respectively. Patients were treated with standard (n=14) or more aggressive chemotherapy regimens (n=17). We compared the atypical DHL group with 76 patients with DHLand 35 patients with DLBCL lacking MYC and BCL2 abnormalities. The clinicopathologic features and therapies were similar between patients with atypical and typical DHL. The overall survival of patients with atypical double-hit lymphoma was similar to that of patients with double-hit lymphoma (P=0.47) and significantly worse than that of patients with DLBCL with normal MYC and BCL2 (P=0.02). There were some minor differences. Cases of atypical double-hit lymphoma more often have DLBCL morphology (P<0.01), less frequently expressed CD10 (P<0.01), and patients less often had an elevated serum lactate dehydrogenase level (P=0.01). In aggregate, these results support expanding the category of MYC/BCL2 DHL to include large B-cell lymphomas with coexistent MYC and BCL2 abnormalities other than concurrent translocations.
Asunto(s)
Genes bcl-2/genética , Genes myc/genética , Linfoma de Células B/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Linfoma de Células B/patología , Masculino , Persona de Mediana Edad , Neprilisina/biosíntesis , Adulto JovenRESUMEN
Schwannomas are benign nerve sheath tumors most commonly found in soft tissue. Intraosseous schwannomas are rare, and account for <0.2 % of primary bone tumors. The typical radiologic findings, a lytic lesion with a thin peripheral rim of sclerosis, are nonspecific. In all reviewed case reports, the diagnosis was made only after microscopic examination. Among previously described intraosseous schwannomas, there have been no reports of tumors arising within cortical bone. It is important to note that while schwannomas are benign tumors, they can be misdiagnosed clinically and radiographically can be potentially mistaken for metastases or other serious skeletal diseases such as osteomyelitis. Tissue sampling is critical for definitive diagnosis as well as to avoid unnecessary treatment. We present the first reported case of an intracortical schwannoma in a 42-year-old man who presented with an incidental radiographic lesion of the diaphyseal femoral cortex.
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Neoplasias Femorales/diagnóstico , Neoplasias Femorales/cirugía , Neurilemoma/diagnóstico , Neurilemoma/cirugía , Adulto , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Tomografía de Emisión de Positrones/métodos , Resultado del TratamientoAsunto(s)
Adenocarcinoma de Células Claras/patología , Biomarcadores de Tumor/análisis , Neoplasias Endometriales/patología , Molécula L1 de Adhesión de Célula Nerviosa/biosíntesis , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/mortalidad , Adulto , Anciano , Supervivencia sin Enfermedad , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Molécula L1 de Adhesión de Célula Nerviosa/análisis , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
OBJECTIVES: Follicular hyperplasias (FHs) with light chain-restricted (LCR) plasmacytoid/plasma cells (PCs) within germinal centers (GCs) based on immunohistochemistry (IHC)/in situ hybridization (ISH) can potentially lead to diagnostic error. This study aims to better characterize such cases, including their clinical implications. METHODS: LC expression by IHC/ISH was quantitatively assessed in GCs of 17 FHs with LCRGCs. BCL2, CD10, BCL6, BCL2, immunoglobulin (Ig) heavy chains, IgG4, and Epstein-Barr encoding region stains were performed. In total, 8 cases had polymerase chain reaction (PCR)-based clonality studies. RESULTS: All cases showed FH, including 4 with progressively transformed GCs (PTGCs); 0.8% to 52% (median, 21%) of the GCs were LCR; 13 of 17 had both κ- and λ-LCRGCs, and 4 of 17 had only κ-LCRGCs; 7 of 16 had prominent intrafollicular IgG4-positive cells. One case demonstrated BCL2-positive cells in focal LCRGCs but lacked BCL2 rearrangement. B-cell monoclonality was demonstrated in 3 of 8 cases (only after microdissection). Seven patients had autoimmune disorders, and 1 had had a transplant. Three patients had a history of lymphoma, 1 developed lymphoma, and 1 developed lymphomatoid granulomatosis subsequently. CONCLUSIONS: FHs with LCRGC by IHC/ISH are typically not associated with the development of lymphoma, even though they can express BCL2 and show monoclonality by PCR. They may be associated with increased intrafollicular IgG4-positive cells, PTGC, and autoimmunity.
Asunto(s)
Centro Germinal/inmunología , Centro Germinal/patología , Cadenas Ligeras de Inmunoglobulina/inmunología , Células Plasmáticas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Hiperplasia/inmunología , Hiperplasia/patología , Linfoma/diagnóstico , Linfoma/inmunología , Linfoma/patología , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/patología , Masculino , Persona de Mediana Edad , Células Plasmáticas/patología , Estudios RetrospectivosRESUMEN
Patients with MYC/BCL2 double-hit lymphoma (DHL) are known to have an aggressive clinical course and to respond poorly to various therapies including intensive chemotherapy and stem cell transplant. Less is known about high-grade B-cell lymphoma with MYC rearrangement without concomitant BCL2 and BCL6 rearrangement, designated here as single-hit lymphoma (SHL). In this study, we assessed 61 cases of SHL and compared them with 83 cases of DHL, all confirmed by MYC, BCL2, and BCL6 fluorescence in situ hybridization studies. Although many clinicopathologic features overlap between patients with SHL and those with DHL, distinct features were observed in SHL. Patients with SHL had tumors with a higher prevalence of p53 overexpression (P=0.047), less frequent expression of CD10, BCL2, and BCL6 (P<0.05), and less often had a history of low-grade B-cell lymphoma (P=0.01). In addition, MYC was more frequently partnered with IGH in SHL than in DHL (P=0.04). With a median follow-up of 25 months, the overall survival of 61 SHL patients was poor and similar to that of DHL patients (2-y overall survival rate of 41% in SHL vs. 48% in DHL; P=0.35) and significantly worse than patients with diffuse large B-cell lymphoma and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, without MYC and BCL2 rearrangements (P<0.0001). In conclusion, patients with SHL have distinct clinicopathologic features but a similar poor prognosis compared with patients with MYC/BCL2 DHL. The poor prognosis of patients with SHL may be partially related to the higher frequency and level of p53 expression in these tumors.
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Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Proteínas de Unión al ADN/genética , Reordenamiento Génico , Linfoma de Células B/diagnóstico , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-myc/genética , Proteína p53 Supresora de Tumor/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Predisposición Genética a la Enfermedad , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Estimación de Kaplan-Meier , Linfoma de Células B/química , Linfoma de Células B/genética , Linfoma de Células B/mortalidad , Linfoma de Células B/patología , Linfoma de Células B/terapia , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Fenotipo , Valor Predictivo de las Pruebas , Proteínas Proto-Oncogénicas c-bcl-6 , Factores de Riesgo , Tennessee , Texas , Resultado del Tratamiento , Regulación hacia Arriba , Adulto JovenRESUMEN
B lymphoblastic leukemia is a B progenitor cell neoplasm with a range of immature immunophenotypes and several associated cytogenetic lesions. In contrast, Burkitt leukemia/lymphoma is a mature B lymphocyte neoplasm with a characteristic germinal center immunophenotype and MYC rearrangement. With modern immunophenotyping and cytogenetic methods, the distinction between these 2 entities is seldom ambiguous. Herein, we report a case of a 9-year-old white boy with circulating leukemic cells that demonstrate morphologic overlap between Burkitt leukemia and B lymphoblastic leukemia. Flow cytometry and immunohistochemical stains demonstrated expression of sets of markers with overlap between immature and mature immunophenotypes. While the leukemic cells tested positive for terminal deoxynucleotidyl transferase (TdT), they expressed CD20, BCL6 (in a subset), and lambda-restricted surface light chain. Molecular studies confirmed a true clonal light chain rearrangement, whereas fluorescent in situ hybridization (FISH) results were negative for MYC rearrangement. Metaphase cytogenetics identified a novel gene rearrangement, t(11;15)(q23;q15), that does not involve the MLL gene. This unique cytogenetic abnormality involves the loss of INO80, an adenosine triphosphatase (ATPase) with DNA binding ability. This cytogenetic abnormality may represent a unique feature of this overlap entity of B lymphoblastic lymphoma that expresses markers of maturity and demonstrates Burkitt-like morphology.
Asunto(s)
Linfoma de Burkitt/genética , Reordenamiento Génico de Linfocito B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Linfoma de Burkitt/inmunología , Niño , Citogenética , Humanos , Inmunofenotipificación , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/inmunologíaRESUMEN
Hairy cell leukemia (HCL) is usually diagnosed by morphology and flow cytometry studies. However, it is challenging sometimes to distinguish HCL from its mimics. Recently, the BRAF V600E mutation has been described as a disease-defining molecular marker for HCL which is present in nearly all cases of HCL but virtually absent in mimics of HCL. In this study, we investigated the possibility of using immunohistochemical detection of the BRAF V600E mutant protein to differentiate HCL from its mimics. A total of twenty-eight FFPE tissue specimens were studied, including HCL (n=12), HCL variant (HCL-v, n=3), splenic marginal zone lymphoma (SMZL, n=6), and other marginal zone lymphomas (MZL, n=7). Immunohistochemical studies were performed using a mouse monoclonal antibody (clone VE1, Spring Bioscience, CA) specific for BRAF V600E mutation. Molecularly confirmed BRAF V600E mutation positive and negative cases were used as the positive and negative controls respectively. All 12 cases of HCL showed cytoplasmic BRAF V600E protein expression in leukemia cells by immunohistochemical study regardless of tumor burden, whereas all cases of HCL mimics including HCL-v, SMZL, and MZL were negative for BRAF V600E protein. Using this BRAF V600E mutation specific antibody, this immunohistochemical study has 100% sensitivity and 100% specificity for the diagnosis of HCL in our cohort. In conclusion, immunohistochemical detection of the BRAF V600E mutant protein is highly sensitive and specific for the diagnosis of HCL. Compared to PCR or sequencing-based methodologies, immunohistochemistry is a relatively rapid and inexpensive alternative for the differential diagnosis between HCL and its mimics.