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1.
Artigo em Inglês | MEDLINE | ID: mdl-31610336

RESUMO

BACKGROUND & AIMS: Cancer therapy with immune checkpoint inhibitors can cause colitis and colon perforation. We investigated whether infection with Epstein Barr virus (EBV) associates with development and severity of colitis in patients receiving immune checkpoint inhibitor therapies. METHODS: We performed a retrospective analysis of fixed colon tissues from 16 patients (12 men, 4 women, median age, 69.5 y) with colitis after immune checkpoint inhibitor therapy (9 patients treated with anti-CTLA4, 3 patients treated with anti-PD1, and 4 patients received a combination). Ten tissue samples were biopsies and 6 were collected during resection (4 surgeries for colon perforation). Patients were treated between 2010 and 2018 in the United Kingdom. The tissues were analyzed by pathology, in situ hybridization (to detect EBV-encoded small RNAs [EBERs]), and immunohistochemistry. Clinical data were also collected. RESULTS: Colon tissues from 4 of the 13 patients who received anti-CTLA4 (alone or in combination, 4 with colon perforation) had EBV-positive lymphoproliferations that manifested as florid ulcers associated with polymorphous infiltrates containing EBV-positive blasts (CD30+ or CD30-negative, CD20+, CD3-negative, and EBER+), plasma cells (CD138+, CD20-negative, and EBER+ or EBER-negative), and small B cells (CD20+, CD3-negative, and EBER+ or EBER-negative), consistent with EBV-positive mucocutaneous ulcers (EBVMCUs). In analyses of biopsies collected from 2 patients with EBVMCUs over multiple time points, we found that earlier biopsies had no or only a few EBV-positive cells, whereas 1 later biopsy had EBVMCU and co-infection with cytomegalovirus. EBVMCUs were associated with steroid-refractory colitis (100% of EBV-positive patients vs 12.5% of EBV-negative patients; P = .008) and colon perforation (100% of EBV-positive patients vs no EBV-negative patients; P = .001). CONCLUSIONS: We found that colon tissues from 4/13 patients with colitis after anti-CTLA4 therapy (4/6 patients who underwent resection and 4/4 patients with colon perforation) contained EBVMCUs. EBVMCUs seem to arise secondarily in areas of inflamed colon due to immunosuppressive treatment for colitis. EBVMCUs are associated with steroid-refractory colitis and colon perforation.

2.
Shoulder Elbow ; 11(2): 137-139, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30936953

RESUMO

We report the case of a middle-age lady who presented following minor trauma, with dominant-sided anterior elbow pain and swelling of 6 months in duration. She was assessed clinically, and underwent investigations, which confirmed features consistent with giant cell tumour (GCT) of distal biceps tendon sheath. She underwent uneventful en-bloc excisional surgery. She did not have radiotherapy. She is now 5 years postoperatively asymptomatic, with full function, and with no signs of recurrence.

3.
Virchows Arch ; 473(6): 749-757, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30151671

RESUMO

Granulysin is a cytolytic protein expressed in cytotoxic T and natural killer (NK) cells. Abnormal serum levels of granulysin in lymphomas with NK and cytotoxic phenotype have been shown to correlate with tumour progression. In this study, we investigated the expression pattern of granulysin in routine sections of normal and reactive lymphoid tissues as well as in a large series of lymphomas. In normal tissues, granulysin labelled a small population of cells that double immunostaining revealed to belong to the pool of cytotoxic T/NK cells. Among lymphoid neoplasms, the highest expression of granulysin (71%) was found in extranodal NK/T cell lymphomas of nasal type (ENKTL). To note is that 29% of ENKTLs, which were negative for one or more of classical cytotoxic markers strongly expressed granulysin. Furthermore, expression of granulysin was observed in rare cases of T cell lymphomas with a cytotoxic phenotype (i.e. ALK-negative anaplastic large cell lymphoma (26%), enteropathy-associated T cell lymphoma (12%) and peripheral T cell lymphoma, NOS (4%)). None of the investigated non-Hodgkin B cell lymphomas, Hodgkin lymphoma and plasma cell myeloma were granulysin positive. The results suggest granulysin as a novel marker for a subset of cytotoxic NK cell derived malignancies and its usefulness is highlighted in those ENKTLs that lack expression of other cytotoxic markers but retain granulysin expression.


Assuntos
Antígenos de Diferenciação de Linfócitos T/biossíntese , Biomarcadores Tumorais/análise , Linfoma Extranodal de Células T-NK/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Diferenciação de Linfócitos T/análise , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Pathogens ; 7(1)2018 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-29518976

RESUMO

The contribution of Epstein-Barr virus (EBV) to the development of specific types of benign lymphoproliferations and malignant lymphomas has been extensively studied since the discovery of the virus over the last 50 years. The importance and better understanding of the EBV-associated lymphoproliferative disorders (LPD) of B, T or natural killer (NK) cell type has resulted in the recognition of new entities like EBV+ mucocutaneous ulcer or the addition of chronic active EBV (CAEBV) infection in the revised 2016 World Health Organization (WHO) lymphoma classification. In this article, we review the definitions, morphology, pathogenesis, and evolving concepts of the various EBV-associated disorders including EBV+ diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), EBV+ mucocutaneous ulcer, DLBCL associated with chronic inflammation, fibrin-associated DLBCL, lymphomatoid granulomatosis, the EBV+ T and NK-cell LPD of childhood, aggressive NK leukaemia, extranodal NK/T-cell lymphoma, nasal type, and the new provisional entity of primary EBV+ nodal T- or NK-cell lymphoma. The current knowledge regarding the pathogenesis of B-cell lymphomas that can be EBV-associated including Burkitt lymphoma, plasmablastic lymphoma and classic Hodgkin lymphoma will be also explored.

5.
Blood ; 130(3): 323-327, 2017 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-28533310

RESUMO

Pediatric-type follicular lymphoma (PTFL) is a B-cell lymphoma with distinctive clinicopathological features. Recently, recurrent genetic alterations of potential importance for its pathogenesis that disrupt pathways associated with the germinal center reaction (TNFRSF14, IRF8), immune escape (TNFRSF14), and anti-apoptosis (MAP2K1) have been described. In an attempt to shed more light onto the pathogenesis of PTFL, an integrative analysis of these mutations was undertaken in a large cohort of 43 cases previously characterized by targeted next-generation sequencing and copy number array. Mutations in MAP2K1 were found in 49% (20/41) of the cases, second in frequency to TNFRSF14 alterations (22/41; 54%), and all together were present in 81% of the cases. Immunohistochemical analysis of the MAP2K1 downstream target extracellular signal-regulated kinase demonstrated its phosphorylation in the evaluable cases and revealed a good correlation with the allelic frequency of the MAP2K1 mutation. The IRF8 p.K66R mutation was present in 15% (6/39) of the cases and was concomitant with TNFRSF14 mutations in 4 cases. This hot spot seems to be highly characteristic for PTFL. In conclusion, TNFRSF14 and MAP2K1 mutations are the most frequent genetic alterations found in PTFL and occur independently in most cases, suggesting that both mutations might play an important role in PTFL lymphomagenesis.


Assuntos
Regulação Neoplásica da Expressão Gênica , Fatores Reguladores de Interferon/genética , Linfoma Folicular/genética , MAP Quinase Quinase 1/genética , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Membro 14 de Receptores do Fator de Necrose Tumoral/genética , Alelos , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Criança , Variações do Número de Cópias de DNA , Feminino , Perfilação da Expressão Gênica , Frequência do Gene , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Fatores Reguladores de Interferon/metabolismo , Linfoma Folicular/diagnóstico , Linfoma Folicular/metabolismo , Linfoma Folicular/patologia , MAP Quinase Quinase 1/metabolismo , Masculino , Análise em Microsséries , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Mutação , Fosforilação , Membro 14 de Receptores do Fator de Necrose Tumoral/metabolismo
6.
Blood ; 128(8): 1101-11, 2016 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-27257180

RESUMO

Pediatric-type follicular lymphoma (PTFL) is a variant of follicular lymphoma (FL) with distinctive clinicopathological features. Patients are predominantly young males presenting with localized lymphadenopathy; the tumor shows high-grade cytology and lacks both BCL2 expression and t(14;18) translocation. The genetic alterations involved in the pathogenesis of PTFL are unknown. Therefore, 42 PTFL (40 males and 2 females; mean age, 16 years; range, 5-31) were genetically characterized. For comparison, 11 cases of conventional t(14:18)(-) FL in adults were investigated. Morphologically, PTFL cases had follicular growth pattern without diffuse areas and characteristic immunophenotype. All cases showed monoclonal immunoglobulin (IG) rearrangement. PTFL displays low genomic complexity when compared with t(14;18)(-) FL (mean, 0.77 vs 9 copy number alterations per case; P <001). Both groups presented 1p36 alterations including TNFRSF14, but copy-number neutral loss of heterozygosity (CNN-LOH) of this locus was more frequently observed in PTFL (40% vs 9%; P =075). TNFRSF14 was the most frequently affected gene in PTFL (21 mutations and 2 deletions), identified in 54% of cases, followed by KMT2D mutations in 16%. Other histone-modifying genes were rarely affected. In contrast, t(14;18)(-) FL displayed a mutational profile similar to t(14;18)(+) FL. In 8 PTFL cases (19%), no genetic alterations were identified beyond IG monoclonal rearrangement. The genetic landscape of PTFL suggests that TNFRSF14 mutations accompanied by CNN-LOH of the 1p36 locus in over 70% of mutated cases, as additional selection mechanism, might play a key role in the pathogenesis of this disease. The genetic profiles of PTFL and t(14;18)(-) FL in adults indicate that these are two different disorders.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Linfoma Folicular/genética , Mutação/genética , Membro 14 de Receptores do Fator de Necrose Tumoral/genética , Adolescente , Adulto , Criança , Pré-Escolar , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 18/genética , Células Clonais , Análise Citogenética , Variações do Número de Cópias de DNA/genética , Análise Mutacional de DNA , Éxons/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Perda de Heterozigosidade/genética , Linfoma Folicular/patologia , Masculino , Pseudolinfoma , Translocação Genética , Adulto Jovem
7.
BMJ Case Rep ; 20152015 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-26002664

RESUMO

Large benign lesions of the breasts are rare in children. We present a case of a 35 cm mass, weighing 2.7 kg in a 13-year-old girl with small developing breasts. Despite the enormity of the lesion, the patient managed to keep it concealed from her parents for 8 months. While initially suspicious of sarcoma a diagnosis of pseudoangiomatous stromal hyperplasia was suggested radiologically and confirmed histologically. Excision with reduction mammoplasty was performed, care taken not to disrupt the remaining breast tissue to facilitate future breast development. 18 months on, the cosmetic appearance of the breasts is good, with healthy underlying breast tissue developing. To the best of our knowledge this case is the largest documented breast tumour of this type in a patient of this age and illustrates the challenge of treating such tumours in the developing breast.


Assuntos
Angiomatose/diagnóstico , Doenças Mamárias/diagnóstico , Neoplasias da Mama/diagnóstico , Mama/patologia , Hiperplasia/diagnóstico , Mamoplastia/métodos , Adolescente , Angiomatose/diagnóstico por imagem , Angiomatose/patologia , Angiomatose/cirurgia , Doenças Mamárias/diagnóstico por imagem , Doenças Mamárias/patologia , Doenças Mamárias/cirurgia , Neoplasias da Mama/patologia , Diagnóstico Diferencial , Feminino , Humanos , Hiperplasia/diagnóstico por imagem , Hiperplasia/patologia , Hiperplasia/cirurgia , Resultado do Tratamento , Ultrassonografia Mamária
8.
Leuk Lymphoma ; 54(5): 959-66, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23020605

RESUMO

We evaluated hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression and their prognostic significance in diffuse large B-cell lymphoma (DLBCL). Expression of HIF-1α and VEGF was studied in 78 patients and results correlated with clinicopathological and prognostic data. HIF-1α and VEGF were expressed in 67% and 84% of patients, respectively, and a significant correlation was demonstrated between them (p < 0.001). Outcome was analyzed according to treatment. HIF-1α positive patients given rituximab demonstrated improved outcome, with 5-year overall survival of 72% for those receiving rituximab versus 65% for those not receiving rituximab, and 5-year progression-free survival (PFS) 76% versus 57%. No correlation was demonstrated between HIF-1α and other prognostic biomarkers including BCL6, CD10 and MUM-1. We demonstrated significantly improved PFS (p = 0.003) in patients receiving rituximab and showing BCL6 overexpression. The results confirm the significant association between HIF-1α and VEGF expression and suggest that HIF-1α expression is a favorable prognostic factor in patients with DLBCL treated with rituximab.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/uso terapêutico , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Feminino , Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Rituximab , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/genética
9.
Virchows Arch ; 461(5): 601-5, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22968924

RESUMO

We describe a case of a 2-week-old male infant who presented with a rapidly enlarging inguinal mass after having received both the bacille Calmette-Guérin (BCG) and hepatitis B vaccines at birth. The clinical picture raised suspicion of a neoplasm, and an excision biopsy was performed. It showed complete effacement of the lymph node architecture by a diffuse proliferation of monomorphic, mitotically active, and medium-sized T-cell blasts with strong expression of CD99. Coalescent necrotizing granulomas were also seen. The lymph node culture was negative for BCG. Upon expert review and additional molecular diagnostics, the initial pathological diagnosis of lymphoblastic T-cell lymphoma was changed to ectopic BCG lymphadenitis and hyperimmune post-vaccinal reaction. The atypical T-cell proliferation was most likely a result of the adjuvant effects of the co-administered vaccines. Post-vaccinal reactions usually involve the injection site or result in localized lymph node enlargements in the areas draining the inoculation site. This case highlights the importance of the clinical context for accurate interpretation of the pathological findings. In the setting of post-vaccinal lymphadenopathy, a biopsy is rarely needed but, when performed, should be interpreted with great caution.


Assuntos
Vacina BCG/efeitos adversos , Vacinas contra Hepatite B/efeitos adversos , Doenças do Sistema Imunitário/diagnóstico , Linfadenite/diagnóstico , Linfoma de Células T/diagnóstico , Vacinas Combinadas/efeitos adversos , Adjuvantes Imunológicos/efeitos adversos , Vacina BCG/imunologia , Diagnóstico Diferencial , Erros de Diagnóstico , Granuloma/etiologia , Granuloma/patologia , Vacinas contra Hepatite B/imunologia , Humanos , Doenças do Sistema Imunitário/etiologia , Recém-Nascido , Linfadenite/etiologia , Linfoma de Células T/etiologia , Masculino , Vacinas Combinadas/imunologia
10.
Blood ; 117(18): 4726-35, 2011 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-21385849

RESUMO

We investigated age-related EBV(+) B-cell lymphoproliferations in the Western population. The clinical features, histology, immunophenotype, EBV-encoded RNA in situ hybridization, and clonality by PCR of T-cell receptor gamma and immunoglobulin genes were categorized in 122 EBV(+) lesions as follows: (1) reactive lymphoid hyperplasia; (2) polymorphic extranodal or (3) polymorphic nodal lymphoproliferative disease (LPD); and (4) diffuse large B-cell lymphoma (DLBCL). Interphase FISH for IG and PAX5 gene rearrangements was performed on 17 cases of DLBCL. The overall median age was 75 years (range, 45-101 years; 67 men, 55 women), and 67, 79, 73, and 77 years, respectively, for groups 1 through 4. Sixteen of 21 cases of polymorphic extranodal LPD were classified as EBV(+) mucocutaneous ulcer. PCR for immunoglobulin genes was polyclonal in reactive lymphoid hyperplasia (84%) and monoclonal in 33%, 63%, and 56% of polymorphic extranodal and nodal LPD cases and DLBCL, respectively. All groups showed restricted/clonal T-cell receptor responses (27%-70%). By FISH, 19% of DLBCLs showed IGH@ rearrangements, but PAX5 was unaffected. Disease-specific 5-year survival was 100%, 93%, 57%, and 25% for groups 1-4, respectively, and 100% for patients with EBV(+) mucocutaneous ulcer. Disease volume was predictive of therapy response (P = .0002), and pathologic subtype was predictive of overall outcome (P = .001). Age-related EBV(+) B-cell LPD encompasses a wider disease spectrum than previously recognized and includes both reactive and neoplastic conditions. Reduction in the T-cell repertoire may contribute to decreased immune surveillance.


Assuntos
Infecções por Vírus Epstein-Barr/etiologia , Linfoma Difuso de Grandes Células B/etiologia , Transtornos Linfoproliferativos/etiologia , Pseudolinfoma/etiologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/imunologia , Países Desenvolvidos , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Rearranjo Gênico de Cadeia Pesada de Linfócito B , Humanos , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/virologia , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Pseudolinfoma/patologia , Pseudolinfoma/virologia
11.
Am J Surg Pathol ; 34(3): 405-17, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20154586

RESUMO

We describe a series of Epstein Barr virus (EBV)-positive circumscribed, ulcerative lesions associated with various types of immunosuppression (IS). The study group (26 patients) comprised 10 males and 16 females, median age 77 years (range 42 to 101). IS in 9 cases included azathioprine (AZA), methotrexate (MTX) or cyclosporin-A (CyA). Seventeen patients had age-related immunosenescence. Patients presented with isolated sharply circumscribed ulcers involving oropharyngeal mucosa (16), skin (6), and gastrointestinal tract (4). Lesions were histologically characterized by a polymorphous infiltrate and atypical large B-cell blasts often with Hodgkin/Reed-Sternberg (HRS) cell-like morphology. The B cells showed strong CD30 and EBER positivity, some with reduced CD20 expression, in a background of abundant T cells. CD15 was positive in 43% of cases (10/23). The pathologic features were identical regardless of the anatomic site or cause of IS. Polymerase chain reaction revealed 39% (7/18) clonal Ig gene rearrangements with 38% (6/16) and 31% (5/16) clonal and restricted T-cell patterns, respectively. Twenty-five percent of patients (5/20) received standard chemotherapy and/or radiotherapy. Forty-five percent (9/20) regressed spontaneously with no treatment and 15% (3/20) were characterized by a relapsing and remitting course. All of the iatrogenic lesions (6/6) with available follow-up responded to reduction of IS. All patients achieved complete remission with no disease-associated deaths over a median follow-up period of 22 months (range 3 to 72). We propose EBV-positive mucocutaneous ulcer as a newly recognized clinicopathologic entity with Hodgkin-like features and a self-limited, indolent course, generally responding well to conservative management. Association with various forms of IS implies a common pathogenetic mechanism. The localized nature of the disease may be owing to a minimal and localized lapse in immunosurveillance over EBV.


Assuntos
Infecções por Vírus Epstein-Barr/etiologia , Gastroenteropatias/virologia , Tolerância Imunológica , Imunossupressores/efeitos adversos , Transtornos Linfoproliferativos/virologia , Úlceras Orais/virologia , Dermatopatias Infecciosas/virologia , Úlcera Cutânea/virologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/virologia , Infecções por Vírus Epstein-Barr/induzido quimicamente , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/terapia , Feminino , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/imunologia , Gastroenteropatias/patologia , Gastroenteropatias/terapia , Rearranjo Gênico do Linfócito T , Genes de Imunoglobulinas , Humanos , Imuno-Histoquímica , Hibridização In Situ , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/terapia , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/imunologia , Mucosa Bucal/virologia , Úlceras Orais/induzido quimicamente , Úlceras Orais/imunologia , Úlceras Orais/patologia , Úlceras Orais/terapia , Reação em Cadeia da Polimerase , Recidiva , Remissão Espontânea , Dermatopatias Infecciosas/induzido quimicamente , Dermatopatias Infecciosas/imunologia , Dermatopatias Infecciosas/patologia , Dermatopatias Infecciosas/terapia , Úlcera Cutânea/induzido quimicamente , Úlcera Cutânea/imunologia , Úlcera Cutânea/patologia , Úlcera Cutânea/terapia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/virologia , Resultado do Tratamento
13.
Br J Haematol ; 123(3): 463-8, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14617006

RESUMO

The All Wales Lymphoma Panel (AWLP) was established in January 1998 to provide a central expert pathological review service for district general hospital pathologists. A discordance rate of 20% between the submitted and reviewed diagnosis has previously been identified. It has not been known whether this change in diagnosis affects clinical management. Ninety-nine patients whose diagnosis was changed as a result of central pathological review are presented. Between January 1998 and August 2000, 125 of 745 (17%) specimens submitted for AWLP review had a consequent change in pathological diagnosis. Of these 125 specimens, 99 (79%) complete case notes were recovered. In all 99 cases, a hypothetical management plan was generated using collected data, clinical protocols and the submitted pathological diagnosis. These plans were compared with the actual management patients received based on the reviewed diagnosis proffered by the AWLP. Forty-six of 99 (46%) cases had a change in management as a result of central pathological review. Overall, management was changed in 8% of cases referred for central pathological review. In conclusion, expert central pathological review has a direct effect on patient management.


Assuntos
Linfoma/tratamento farmacológico , Linfoma/patologia , Patologia Cirúrgica , Planejamento de Assistência ao Paciente , Revisão por Pares , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Linfoma/radioterapia , Masculino , Pessoa de Meia-Idade , País de Gales
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