Hematopathology diagnosis and education

血液病理学诊断和教育

• 批准号: 7733466
• 负责人: Elaine Jaffe
• 金额: $ 73.68万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7733466
• 关键词: Adopted; Age; Area; Autoimmune Diseases; B cell differentiation; B-Cell Lymphomas; B-Lymphocytes; Basic Science; Biological Factors; Biological Markers; Burkitt Lymphoma; CD8B1 gene; Categories; Cell Differentiation process; Cells; Childhood; Childhood Lymphoma; Chronic; Chronic Lymphocytic Leukemia; Classification; Clinical; Clinical Research; Communicable Diseases; Communication; Communities; Consensus; Cutaneous; Cutaneous Lymphoma; Cytotoxic T-Lymphocytes; Depth; Development; Diagnosis; Diagnostic; Diagnostic Services; Diffuse; Diffuse Lymphoma; Disease; Duodenum; Education; Elderly; Essential Genes; European; Evolution; Exposure to; Extranodal; Follicular Lymphoma; Functional disorder; Gene Expression Profiling; Goals; Growth; Hairy Cell Leukemia Variant; Hematopathology; Hematopoietic and Lymphoid Tissue; Hodgkin Disease; Homing; Human Herpesvirus 4; Human Herpesvirus 8; Hyperplasia; Immunohistochemistry; Immunophenotyping; In Situ; In Situ Hybridization; Individual; Indolent; Inflammation; International; Investigation; Ki-1 Large-Cell Lymphoma; Knowledge; Laboratories; Large-Cell Immunoblastic Lymphoma; Large-Cell Lymphomas; Lesion; Lymphoblastic Leukemia; Lymphocyte Function; Lymphocytosis; Lymphoid Cell; Lymphoma; Lymphomagenesis; Lymphomatoid Granulomatosis; Lymphoproliferative Disorders; Malignant lymphoid neoplasm; Mantle Cell Lymphoma; Mediastinal; Minor Planets; Mission; Molecular; Molecular Genetics; Molecular Profiling; Morphology; Multicentric Angiofollicular Lymphoid Hyperplasia; Neoplasms; Nodal; Panniculitis; Pathogenesis; Pathologic; Pathologist; Pathology; Pathway interactions; Patient Care; Patients; Peripheral; Phenotype; Philosophy; Physicians; Physiology; Procedures; Process; Reporting; Research; Research Training; Role; Services; Site; Skin; Societies; Solid; Splenic Red Pulp; Staging; Standards of Weights and Measures; Stratification; Structure of germinal center of lymph node; T-Cell Lymphoma; T-Cell and NK-Cell Neoplasm; T-Lymphocyte; Techniques; Thinking; Training Programs; Transplantation; United States National Institutes of Health; Update; Variant; Waldenstrom Macroglobulinemia; World Health Organization; age related; autoimmune lymphoproliferative syndrome; base; clinical Diagnosis; clinically relevant; concept; disease classification; host neoplasm interaction; in vivo; interest; large cell Diffuse non-Hodgkin' s lymphoma; lymphoid neoplasm; neoplastic; outcome forecast; prevent; promoter; skills; sound; subcutaneous; success; tool; translational study; tumor

The World Health Organization (WHO) Classification of Tumours of the Haematopoietic and Lymphoid Tissues has been revised and updated for a new edition (4th Edition) under the auspices of the Society of Hematopathology (SH) and the European Association for Haematopathology (EAHP). This initiative is a continuation of 2001 WHO classification that represented a major advance in terms of broad acceptance and general use during the last years by pathologists and clinicians from all over the world. The successes of this classification was due to the major consensus built among all the players based on a proposal that was biologically sound, clinically relevant and practically ease to use worldwide in different clinical settings. The major principles of the current WHO classification, stratification of the neoplasms primarily according to their lineage and the definition of distinct clinically relevant diseases based on a combination of morphology, immunophenotype, genetic and molecular features and clinical manifestations, are considered a solid framework in which the new knowledge and perspectives should be incorporated. The new knowledge generated over the last years has highlighted several aspects of the current WHO classification that need revision and update, including the need for the clarification of some poorly defined categories, the inclusion of new defined entities, and the consideration of new concepts and information Refinement in definitions, advances in old controversies, and new categories The new classification has refined the definition of well established diseases such as chronic lymphocytic leukemia (CLL) lymphoplasmacytic lymphoma and Waldestrom macroglobulinemia and T-cell lymphomas such as anaplastic large cell lymphoma (ALCL) and subcutaneous panniculitis-like T-cell lymphoma. Consensus on old controversies includes the recognition that it is not clinically relevant to distinguish between grades 1 and 2 of follicular lymphoma (FL) but it is important to segregate grade 3b from 3a since it may correspond to a category that may be closer to diffuse large B-cell lymphoma (DLBCL) than conventional FL. The category of diffuse large B-cell lymphoma has recognized the important contribution of gene expression profiling accepting the two molecular subtypes of germinal center and activated B-cell derived DLBCL. However, the difficulties to diagnose these subtypes with reliable tools other than microarray expression profiling prevents from recommending the use of these categories in the clinical practice. Different subtypes and new entities have been accepted, particularly among DLBCL with a terminal B-cell differentiation such as ALK positive DLBCL, DLBCL associated with chronic inflammation, plasmablastic lymphoma, large cell lymphoma arising in HHV-8 associated multicentric Castleman disease, and EBV+ DLBCL of the elderly. Among peripheral T-cell lymphomas, Anaplastic large cell lymphoma (ALCL) ALK positive is a specific entity that should be distinguished from tumors with similar morphology and phenotype but ALK negative, that are considered a different provisional category. The diagnosis of subcutaneous panniculitis-like T-cell lymphoma is now restricted to the cases with an alpha/beta phenotype since similar tumours with gamma/delta phenotype are reclassified as primary cutaneous gamma/delta T-cell lymphoma, a category that appears to be more aggressive with frequent systemic dissemination. New concepts The classification has recognized early lesions and indolent forms of lymphomas that may correspond to early stages of lymphomagenesis such as Monoclonal B-cell lymphocytosis, or follicular lymphoma and mantle cell lymphoma in situ. The identification of these situations are of conceptual interest to investigate the early mechanisms in lymphomagenesis but also of clinical importance since these patients may need a more conservative management approach. Several new categories have been included in which the age of the patients is a major identifier. Thus, pediatric follicular lymphomas and nodal marginal zone lymphomas or the EBV-positive lymphomas of the childhood and the EBV-positive large cell lymphoma of the elderly are clinico-pathologic situations that suggest the potential influence of age-related biological factors in the pathogenesis and manifestations of certain lymphoid neoplasms. The importance of specific topographic sites as an important feature of certain lymphomas had been recognized previously in certain extranodal lymphomas such as MALT, primary mediastinal, splenic, and certain primary cutaneous lymphomas. This idea has been now expanded incorporating additional B and T-cell primary cutaneous, CNS DLBCL, and also recognizing that follicular lymphomas originated in the duodenum or skin are categories with specific clinicopathologic features and management requirements. This relationship between topography and specific disease entities may be related to specific etiopathogenic mechanisms (infectious diseases), particular lymphoid cells of origin (asteroid cells), site related immunological functions (immunological santuaries) or tumor-host interactions (homing of lymphoid cells). The new classification has also recognized two categories that correspond to lymphomas with overlapping features between different entities, the B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma and the B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma. These categories may not correspond probably to specific entities but are important to be recognized clinically because these patients may need to be distinguished form the more conventional categories for the different clinical evolution and treatment strategies. These patients need further investigations and interestingly, these tumours may represent clinical examples of the plasticity of the lymphoid cells that may be broader than initially thought. Unresolved issues and provisional entities Some issues are not resolved in the new classification. Several categories are still considered provisional or emerging because it is not clear if they may correspond to peculiar variants of other entities. These categories include the diffuse B-cell lymphomas of the splenic red pulp and their possible relationship to hairy cell leukemia variant, primary cutaneous aggressive epidermotropic CD8 positive cytotoxic T-cell lymphoma, primary cutaneous small/medium CD4 positive T-cell lymphoma, and the ALCL ALK-negative among others. Finally, new challenging perspectives have been discussed during the process of updating the classification but it was felt that they require further investigations before being adopted for routine diagnostic use. These topics include the role of biomarkers in the prognosis lymphoma, and the information generated by microarray expression profiling studies in the identification new lymphoma subtypes or the potential clinical value of specific molecular pathogenetic pathways.

在血液病理学会 (SH) 和欧洲血液病理学会 (EAHP) 的支持下，世界卫生组织 (WHO) 造血和淋巴组织肿瘤分类已修订和更新为新版本（第 4 版）。该倡议是 2001 年 WHO 分类的延续，该分类代表了过去几年世界各地病理学家和临床医生在广泛接受和普遍使用方面的重大进步。该分类的成功归功于所有参与者基于生物学合理、临床相关且易于在全球不同临床环境中实际使用的提案而达成的主要共识。目前世界卫生组织分类的主要原则，主要根据肿瘤的谱系进行分层，以及基于形态学、免疫表型、遗传和分子特征以及临床表现的组合的不同临床相关疾病的定义，被认为是应纳入新知识和观点的坚实框架。过去几年产生的新知识突出了当前世界卫生组织分类中需要修订和更新的几个方面，包括需要澄清一些定义不明确的类别、纳入新定义的实体以及考虑新概念和信息定义的细化、旧争议的进展和新类别新分类完善了慢性淋巴细胞白血病等既定疾病的定义 (CLL) 淋巴浆细胞淋巴瘤和 Waldestrom 巨球蛋白血症以及 T 细胞淋巴瘤，例如间变性大细胞淋巴瘤 (ALCL) 和皮下脂膜炎样 T 细胞淋巴瘤。对旧争议的共识包括认识到区分滤泡性淋巴瘤 (FL) 1 级和 2 级在临床上并不相关，但区分 3b 级和 3a 级很重要，因为它可能对应于比传统 FL 更接近弥漫性大 B 细胞淋巴瘤 (DLBCL) 的类别。弥漫性大 B 细胞淋巴瘤类别已认识到基因表达谱的重要贡献，接受生发中心和活化 B 细胞衍生的 DLBCL 两种分子亚型。然而，使用微阵列表达谱以外的可靠工具来诊断这些亚型的困难阻碍了在临床实践中推荐使用这些类别。不同的亚型和新实体已被接受，特别是具有终末B细胞分化的DLBCL，例如ALK阳性DLBCL、与慢性炎症相关的DLBCL、浆母细胞淋巴瘤、HHV-8相关的多中心Castleman病引起的大细胞淋巴瘤以及老年人的EBV+ DLBCL。 在外周 T 细胞淋巴瘤中，间变性大细胞淋巴瘤 (ALCL) ALK 阳性是一种特殊实体，应与形态和表型相似但 ALK 阴性的肿瘤区分开来，后者被视为不同的临时类别。皮下脂膜炎样 T 细胞淋巴瘤的诊断现在仅限于具有 α/β 表型的病例，因为具有 γ/δ 表型的类似肿瘤被重新分类为原发性皮肤 γ/δ T 细胞淋巴瘤，这一类别似乎更具侵袭性，且经常发生全身播散。新概念 该分类已识别出淋巴瘤的早期病变和惰性形式，可能对应于淋巴瘤发生的早期阶段，例如单克隆 B 细胞淋巴细胞增多症或滤泡性淋巴瘤和套细胞原位淋巴瘤。这些情况的识别对于研究淋巴瘤发生的早期机制具有概念上的意义，而且也具有临床重要性，因为这些患者可能需要更保守的治疗方法。已纳入几个新类别，其中患者的年龄是主要标识符。因此，小儿滤泡性淋巴瘤和淋巴结边缘区淋巴瘤或儿童期 EBV 阳性淋巴瘤和老年人 EBV 阳性大细胞淋巴瘤的临床病理情况表明，年龄相关的生物学因素对某些淋巴肿瘤的发病机制和表现具有潜在影响。先前在某些结外淋巴瘤（例如 MALT、原发性纵隔、脾和某些原发性皮肤淋巴瘤）中，已认识到特定地形部位作为某些淋巴瘤的重要特征的重要性。 这一想法现已扩展到其他 B 细胞和 T 细胞原发皮肤、中枢神经系统 DLBCL，并且还认识到起源于十二指肠或皮肤的滤泡性淋巴瘤是具有特定临床病理特征和管理要求的类别。地形和特定疾病实体之间的这种关系可能与特定的病因机制（传染病）、特定的淋巴细胞起源（小行星细胞）、位点相关的免疫功能（免疫庇护所）或肿瘤-宿主相互作用（淋巴细胞归巢）有关。新分类还识别了与不同实体之间具有重叠特征的淋巴瘤相对应的两个类别：不可分类的 B 细胞淋巴瘤，其特征介于 DLBCL 和伯基特淋巴瘤之间；以及不可分类的 B 细胞淋巴瘤，其特征介于 DLBCL 和经典霍奇金淋巴瘤之间。这些类别可能不对应于特定实体，但对于临床识别很重要，因为可能需要将这些患者与不同临床演变和治疗策略的更常规类别区分开来。这些患者需要进一步的研究，有趣的是，这些肿瘤可能代表了淋巴细胞可塑性的临床例子，其可塑性可能比最初想象的更广泛。未解决的问题和临时实体 新分类中的一些问题未得到解决。有几个类别仍然被认为是临时的或新兴的，因为尚不清楚它们是否可能对应于其他实体的特殊变体。这些类别包括脾红髓弥漫性 B 细胞淋巴瘤及其与毛细胞白血病变异体的可能关系、原发性皮肤侵袭性表皮性 CD8 阳性细胞毒性 T 细胞淋巴瘤、原发性皮肤小/中 CD4 阳性 T 细胞淋巴瘤和 ALCL ALK 阴性等。最后，在更新分类的过程中讨论了新的具有挑战性的观点，但人们认为在将其用于常规诊断用途之前需要进一步研究。 这些主题包括生物标志物在淋巴瘤预后中的作用，以及微阵列表达谱研究在识别新的淋巴瘤亚型中产生的信息或特定分子发病途径的潜在临床价值。