RESUMO
BACKGROUND: Surgery plus peri-operative/adjuvant chemotherapy is the standard of care for locally advanced GC/GEJC, though with unsatisfactory results. dMMR/MSI-high tumors have better prognosis and scant benefit from chemotherapy as compared to pMMR/MSS ones. The differential outcome of therapies in terms of safety and efficacy according to sex is still debated in GC/GEJC patients. METHODS: We previously performed an individual patient data pooled analysis of MAGIC, CLASSIC, ITACA-S, and ARTIST trials including GC/GEJC patients treated with surgery alone or surgery plus peri-operative/adjuvant chemotherapy to assess the value of MSI status. We performed a secondary analysis investigating the prognostic and predictive role of sex (female versus male) in the pooled analysis dataset in the overall population and patients stratified for MSI status (MSI-high versus MSS/MSI-low). Disease-free (DFS) and overall survival (OS) were calculated. RESULTS: Patients with MSI-high tumors had improved survival as compared to MSS/MSI-low ones irrespective of sex, whereas in those with MSS/MSI-low tumors, females had numerically longer OS and DFS (5-year OS was 63.2% versus 57.6%, HR 0.842; p = 0.058, and 5-year DFS was 55.8% versus 50.8%, HR 0.850; p = 0.0504 in female versus male patients). The numerical difference for the detrimental effect of chemotherapy in MSI-high GC was higher in females than males, while the significant benefit of chemotherapy over surgery alone was confirmed in MSS/MSI-low GC irrespective of sex. CONCLUSIONS: This pooled analysis including four randomized trials highlights a relevant impact of sex in the prognosis and treatment efficacy of MSI-high and MSS/MSI-low non-metastatic GC/GEJC.
Assuntos
Junção Esofagogástrica , Instabilidade de Microssatélites , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas , Humanos , Masculino , Feminino , Junção Esofagogástrica/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Prognóstico , Fatores Sexuais , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Quimioterapia AdjuvanteAssuntos
Neoplasias Esplênicas , Proteína Supressora de Tumor p53 , Humanos , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/genética , Proteína Supressora de Tumor p53/genética , Linfoma de Células B/patologia , Linfoma de Células B/genética , Linfoma de Células B/diagnóstico , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , FemininoAssuntos
Linfoma de Células T Associado a Enteropatia , Transtornos Linfoproliferativos , Pólipos Nasais , Feminino , Humanos , Diagnóstico Diferencial , Linfoma de Células T Associado a Enteropatia/diagnóstico , Linfoma de Células T Associado a Enteropatia/patologia , Antígeno Ki-1/metabolismo , Linfoma de Células T/diagnóstico , Linfoma de Células T/patologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/patologia , Pólipos Nasais/diagnóstico , Pólipos Nasais/patologia , Idoso de 80 Anos ou maisAssuntos
Implante Mamário , Implantes de Mama , Neoplasias da Mama , Linfoma Anaplásico de Células Grandes , Humanos , Feminino , Implantes de Mama/efeitos adversos , Linfoma Anaplásico de Células Grandes/etiologia , Linfoma Anaplásico de Células Grandes/patologia , Implante Mamário/efeitos adversos , Reino Unido/epidemiologia , Neoplasias da Mama/etiologia , Neoplasias da Mama/cirurgiaRESUMO
BACKGROUND: Treatment with CHOP-based chemotherapy with consolidative radiotherapy (CRT) for primary mediastinal B cell lymphoma (PMBCL) has been the standard approach in the pre-rituximab era. Overtreatment with CRT for patients who may have already been cured by primary immunochemotherapy in the rituximab era is a significant concern due to the long-term toxicity associated with radiotherapy. Positron emission tomography (PET) may help to identify patients who may not benefit from further CRT. METHODS: We conducted a retrospective review of patients treated at the Royal Marsden Hospital between 2003 and 2020 for PMBCL to assess CRT use and survival outcomes. RESULTS: Forty-three patients were identified, with 95% of the patients receiving R-CHOP. CRT was given in 5 patients. Five-year event-free survival was 79% (95% confidence interval: 64%-89%) and 5-year overall survival was 88% (95% confidence interval: 73%-95%). Seven of 9 patients with DS4 did not receive CRT and instead monitored with serial PET scans. None of these 7 patients relapsed in the mediastinum. CONCLUSION: CRT may be omitted in patients with a negative end of treatment PET scans; however, careful observation may also obviate the need for CRT in PET positive patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Humanos , Rituximab/uso terapêutico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Tomografia por Emissão de Pósitrons/métodos , Ciclofosfamida/uso terapêutico , Vincristina/efeitos adversos , Prednisona/efeitos adversos , Doxorrubicina/efeitos adversos , Linfoma Difuso de Grandes Células B/tratamento farmacológicoRESUMO
Follicular lymphoma (FL) develops through a stepwise acquisition of cooperative genetic changes with t(14;18)(q32;q21)/IGH::BCL2 occurring early at the pre-B stage of B-cell development. Patients with FL typically show an indolent clinical course, remitting and relapsing with the eventual development of resistance to treatments. Interestingly, the majority of transformed FL do not progress directly from FL but originate from their clonally related lymphoma precursor (CLP) cells. To examine whether such divergent tumour evolution also underpins the relapses in patients with early-stage FL, we investigated by targeted next-generation sequencing 13 cases (stage I = 9, stage II = 4), who showed complete remission (mean: 5 years; range: 1-11.5 years) following local radiotherapy but subsequently relapsed (≥2 in 5). A clonal relationship between the diagnostic FL and relapses was confirmed in 11 cases. In six cases, common and distinct variants were seen between the paired diagnostic and relapsed lymphomas, indicating their divergent evolution from a CLP. In two cases, different B-cell clones were involved in the diagnostic and relapsed lymphomas, including one case involving two different BCL2 translocations. In the remaining five cases, the relapsed lymphoma developed via a linear progression (n = 4) or a mixed evolutionary path (n = 1). These findings may bear important implications in the routine diagnosis and management of relapsed FL. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Assuntos
Linfoma Folicular , Humanos , Linfoma Folicular/genética , Linfoma Folicular/terapia , Linfoma Folicular/patologia , Recidiva Local de Neoplasia/genética , Translocação Genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Reino UnidoRESUMO
Session 3 of the lymphoma workshop of the XXI joint meeting of the European Association for Haematopathology and the Society for Hematopathology took place in Florence, Italy, on September 22, 2022. The topics of this session were splenic and nodal marginal zone lymphomas, transformation in marginal zone lymphomas, and pediatric nodal marginal zone lymphomas and their differential diagnosis as well as related entities. Forty-two cases in these categories were submitted to the workshop, including splenic lymphomas (marginal zone and diffuse red pulp lymphomas), transformed marginal zone lymphomas (splenic and nodal), nodal marginal zone lymphomas with increased TFH-cells, and pediatric nodal marginal zone lymphomas. The case review highlighted some of the principal problems in the diagnosis of marginal zone lymphomas, including the difficulties in the distinction between splenic marginal zone lymphoma, splenic diffuse red pulp lymphoma, and hairy cell leukemia variant/splenic B-cell lymphoma with prominent nucleoli which requires integration of clinical features, immunophenotype, and morphology in blood, bone marrow, and spleen; cases of marginal zone lymphoma with markedly increased TFH-cells, simulating a T-cell lymphoma, where molecular studies (clonality and mutation detection) can help to establish the final diagnosis; the criteria for transformation of marginal zone lymphomas, which are still unclear and might require the integration of morphological and molecular data; the concept of an overlapping spectrum between pediatric nodal marginal zone lymphoma and pediatric-type follicular lymphoma; and the distinction between pediatric nodal marginal zone lymphoma and "atypical" marginal zone hyperplasia, where molecular studies are mandatory to correctly classify cases.
Assuntos
Leucemia Linfocítica Crônica de Células B , Linfoma de Zona Marginal Tipo Células B , Linfoma Folicular , Neoplasias Esplênicas , Humanos , Criança , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma Folicular/patologia , Leucemia Linfocítica Crônica de Células B/diagnóstico , Baço/patologia , Medula Óssea/patologia , Hiperplasia/patologia , Neoplasias Esplênicas/patologiaRESUMO
Emerging entities and molecular subgroups in large B-cell lymphomas (LBCLs) were discussed during the 2022 European Association for Haematopathology/Society for Hematopathology workshop in Florence, Italy. This session focused on newly recognized diseases and their diagnostic challenges. High-grade/large B-cell lymphoma with 11q aberration (HG/LBCL-11q) is defined by chromosome 11q-gains and telomeric loss. FISH analysis is recommended for the diagnosis. HG/LBCL-11q can occur in the setting of immunodeficiency, including ataxia-telangiectasia, and predominates in children. The morphological spectrum of these cases is broader than previously thought with often Burkitt-like morphology and coarse apoptotic bodies. It has a Burkitt-like immunophenotype (CD10+, BCL6+, BCL2-) but MYC expression is weak or negative, lacks MYC rearrangement, and is in contrast to Burkitt lymphoma 50% of the cases express LMO2. LBCL with IRF4 rearrangement (LBCL-IRF4) occurs mainly in the pediatric population but also in adults. LBCL-IRF4 has an excellent prognosis, with distinguishing molecular findings. IRF4 rearrangements, although characteristic of this entity, are not specific and can be found in association with other chromosomal translocations in other large B-cell lymphomas. Other molecular subgroups discussed included primary bone diffuse large B-cell lymphoma (PB-DLBCL), which has distinctive clinical presentation and molecular findings, and B-acute lymphoblastic leukemia (B-ALL) with IGH::MYC translocation recently segregated from Burkitt lymphoma with TdT expression. This latter disorder has molecular features of precursor B-cells, often tetrasomy 1q and recurrent NRAS and KRAS mutations. In this report, novel findings, recommendations for diagnosis, open questions, and diagnostic challenges raised by the cases submitted to the workshop will be discussed.
Assuntos
Linfoma de Burkitt , Linfoma Difuso de Grandes Células B , Adulto , Humanos , Criança , Linfoma de Burkitt/genética , Linfoma de Burkitt/patologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Aberrações Cromossômicas , Translocação Genética , MutaçãoRESUMO
The 2022 European Association for Haematopathology/Society for Hematopathology lymphoma workshop session on cavity-based lymphomas included sixty-eight cases in seven sections. The disease entities discussed include primary effusion lymphomas (PEL), extracavitary primary effusion lymphomas and confounding entities (ECPEL), HHV8-negative B-lineage lymphomas-effusion based (EBV-negative, EBV-positive, and plasmablastic types), diffuse large B-cell lymphoma associated with chronic inflammation, fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL), breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), and other lymphomas presenting as an effusion. All entities above are discussed; however, three are delved into greater detail given the challenges with classification: ECPEL, HHV8-negative effusion-based lymphomas, and FA-DLBCL. Cases exemplifying the diagnostic difficulty in differentiating ECPEL from HHV8-positive diffuse large B-cell lymphoma and germinotropic lymphoproliferative disorder were discussed. The more recently recognized effusion-based HHV8-negative large B-cell lymphoma is explored, with several cases submitted raising the question if this subset should be carved out as a specific entity, and if so, what should be the refining diagnostic criteria. Case submissions to the FA-DLBCL section yielded one of the largest case series to date, including classic cases, cases furthering the discussion on disease sites and prognosis, as well as novel concepts to be considered in this entity. The 2022 EA4HP/SH workshop cases allowed for further confirmation of the characteristics of some of the more historically accepted cavity-based lymphomas, as well as further inquiry and debate on relatively new or evolving entities.
Assuntos
Herpesvirus Humano 8 , Linfoma Difuso de Grandes Células B , Linfoma Anaplásico de Células Grandes , Linfoma de Efusão Primária , Transtornos Linfoproliferativos , Humanos , Linfoma de Efusão Primária/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/patologiaRESUMO
Cytotoxic peripheral T-cell lymphomas and EBV-positive T/NK-cell lymphoproliferative diseases were discussed at the 2022 European Association for Haematopathology/Society for Hematopathology lymphoma workshop held in Florence, Italy. This session focused on (i) primary nodal EBV-positive T and NK-cell lymphomas (primary nodal-EBV-TNKL), (ii) extranodal EBV-positive T/NK lymphoproliferative diseases (LPD) in children and adults, (iii) cytotoxic peripheral T-cell lymphomas, NOS (cPTCL-NOS), EBV-negative, and (iv) miscellaneous cases. Primary nodal-EBV-TNKL is a newly recognized entity which is rare, aggressive, and associated with underlying immune deficiency/immune dysregulation. All cases presented with lymphadenopathy but some demonstrated involvement of tonsil/Waldeyer's ring and extranodal sites. The majority of tumors are of T-cell lineage, and the most frequent mutations involve the epigenetic modifier genes, such as TET2 and DNMT3A, and JAK-STAT genes. A spectrum of EBV-positive T/NK LPD involving extranodal sites were discussed and highlight the diagnostic challenge with primary nodal-EBV-TNKL when these extranodal EBV-positive T/NK LPD cases demonstrate predominant nodal disease either at presentation or during disease progression from chronic active EBV disease. The majority of cPTCL-NOS demonstrated the TBX21 phenotype. Some cases had a background of immunosuppression or immune dysregulation. Interestingly, an unexpected association of cPTCL-NOS, EBV-positive and negative, with TFH lymphomas/LPDs was observed in the workshop cases. Similar to a published literature, the genetic landscape of cPTCL-NOS from the workshop showed frequent mutations in epigenetic modifiers, including TET2 and DNMT3A, suggesting a role of clonal hematopoiesis in the disease pathogenesis.
Assuntos
Infecções por Vírus Epstein-Barr , Linfoma de Células T Periférico , Adulto , Criança , Humanos , Linfoma de Células T Periférico/genética , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/patologia , Hematopoiese Clonal , Linfócitos T/patologiaRESUMO
INTRODUCTION: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon type of non-Hodgkin lymphoma, associated with breast implant capsules. Despite improvements in our understanding of BIA-ALCL, communicating the prognosis to patients remains challenging due to limited long-term follow-up data. This has important implications for decision-making, including recommendations for subsequent reconstructive procedures. The aim of this study was to assess the longer-term oncological outcomes of patients receiving multidisciplinary treatment for BIA-ALCL. METHODS: This was a retrospective cohort study of BIA-ALCL patients treated at a tertiary referral unit. The data are presented using simple descriptive statistics. RESULTS: Between 2015 and 2022, 18 BIA-ALCL patients were treated at our institution. The median age at diagnosis was 48.5 (IQR 41-55) years. Ten patients developed BIA-ALCL after cosmetic breast augmentation, and 8 after breast reconstruction following mastectomy for cancer. All patients had a history of textured implant insertion. The median time from first implant surgery to diagnosis was 8.5 (IQR 7-12) years. All patients underwent en-bloc total capsulectomy with implant removal, and 2 received systemic therapy. Fifteen patients had Stage I (IA-IC) disease, 2 had Stage IIA and 1 Stage III BIA-ALCL, based on the TNM classification system. At a median follow-up of 45 (IQR 15-71) months, there were no episodes of local or systemic relapse or death. CONCLUSIONS: Surgical management for BIA-ALCL is sufficient in early-stage disease, and associated with excellent oncological outcomes. This information is reassuring for patients when discussing recurrence risk.
Assuntos
Implante Mamário , Implantes de Mama , Neoplasias da Mama , Linfoma Anaplásico de Células Grandes , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Implantes de Mama/efeitos adversos , Linfoma Anaplásico de Células Grandes/etiologia , Linfoma Anaplásico de Células Grandes/terapia , Estudos Retrospectivos , Neoplasias da Mama/etiologia , Neoplasias da Mama/cirurgia , Mastectomia/métodos , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/cirurgia , Implante Mamário/efeitos adversos , Implante Mamário/métodosRESUMO
Follicular helper T-cell lymphomas (TFH lymphomas) were discussed in session V of the lymphoma workshop of the European Association for Haematopathology (EA4HP)/Society for Hematopathology (SH) 2022 meeting in Florence, Italy. The session focused on the morphologic spectrum of TFH lymphoma, including its three subtypes: angioimmunoblastic-type (AITL), follicular-type, and not otherwise specified (NOS). The submitted cases encompassed classic examples of TFH lymphoma and unusual cases such as those with early or indolent presentations, associated B-cell proliferations, or Hodgkin/Reed-Sternberg-like cells. The relationship between TFH lymphoma and clonal hematopoiesis was highlighted by several cases documenting divergent evolution of myeloid neoplasm and AITL from shared clonal mutations. The distinction between TFH lymphoma and peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), was stressed, and many challenging examples were presented. Various cases highlighted the difficulties of differentiating TFH lymphoma from other established types of lymphoma and reactive conditions. Cutaneous T-cell lymphoma expressing TFH markers, particularly when resulting in lymph node involvement, should be distinguished from TFH lymphomas. Additional immunophenotyping and next-generation sequencing studies were performed on various cases in this session, highlighting the importance of these technologies to our current understanding and classification of TFH lymphomas.
Assuntos
Linfoma de Células T Periférico , Neoplasias Cutâneas , Humanos , Hematopoiese Clonal , Linfócitos T Auxiliares-Indutores/patologia , Linfoma de Células T Periférico/patologia , Linfonodos/patologia , Neoplasias Cutâneas/patologiaRESUMO
The translocation t(14;18)(q32:q21)/IGH::BCL2 occurs at the pre-B stage of B-cell development in the bone marrow and is insufficient for malignant transformation, although it leads to the formation of in situ follicular B-cell neoplasia (ISFN). Despite that, the translocation is the genetic hallmark of follicular lymphoma (FL), it occurs infrequently in metachronous/synchronous lymphomas, including extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL), mantle cell lymphoma, and Hodgkin's lymphoma. In each of these scenarios, the two lymphomas often appear to be clonally related by analyses of IGH::BCL2 and/or rearranged IG genes. However, it remains largely unknown whether one lymphoma originates from the other or they develop independently. We studied five cases of metachronous EMZL and FL. In four cases, the two lymphomas were clonally related, as shown by identical IGH::BCL2 and/or rearranged IG genes or shared mutations. There were common and unique mutations between the paired EMZL and FL, indicating that they developed independently from a common premalignant cell population, harbouring IGH::BCL2 in three cases. Furthermore, case 1 presented with three metachronous FLs, and all of them originated from a common precursor cell population via divergent evolution. Our findings highlight the multi-malignant potential of IGH::BCL2-positive B-cells. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Assuntos
Linfoma de Zona Marginal Tipo Células B , Linfoma Folicular , Humanos , Adulto , Linfoma Folicular/genética , Linfoma de Zona Marginal Tipo Células B/genética , Translocação Genética , Mutação , Proteínas Proto-Oncogênicas c-bcl-2/genéticaAssuntos
Linfoma Difuso de Grandes Células B , Humanos , Estudos Retrospectivos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Organização Mundial da Saúde , Proteínas Proto-Oncogênicas c-bcl-2 , PrognósticoRESUMO
The European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL) was established 25 years ago with the goal to facilitate clinical trials and research collaborations in the field both within Europe and worldwide. Since its inception, much progress has been made whereby major improvements in outcomes have been achieved. In this Review, we describe the different diagnostic entities of non-Hodgkin lymphoma in children and young adults describing key features of each entity and outlining clinical achievements made in the context of the EICNHL framework. Furthermore, we provide an overview of advances in biopathology with an emphasis on the role of biological studies and how they have shaped available treatments. Finally, for each entity, we describe future goals, upcoming clinical trials, and highlight areas of research that require our focus going forward.