The Diseases of Lymphoid & Hematopoietic system ( 淋巴和造血系统疾病 )

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1 The Diseases of Lymphoid & Hematopoietic system ( 淋巴和造血系统疾病 ) Wei Zhang ( 张伟 ) Ph.D Associate Professor Department of Pathology, Zhejiang University School of Medicine zwei72@zju.edu.cn Tel:

2 髓性组织 骨髓 血液中细胞成分 ( 红细胞 白细胞等 ) 淋巴组织 淋巴造血系统 胸腺脾脏淋巴结广泛分布的淋巴组织

3 Lymph node

4 淋巴结低倍镜结构淋巴小结 皮质区 髓质区

5 淋巴结皮质区与髓质区

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7 淋巴造血系统疾病 淋巴结良性增生 淋巴组织肿瘤 髓系肿瘤 组织细胞和树突状细胞肿瘤

8 Section 1 Benign Lymphoid hyperplasia 淋巴结良性增生

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10 Benign Lymphoid hyperplasia Nonspecific lymphadenitis 淋巴结反应性增生 acute nonspecific lymphadenitis chronic nonspecific lymphadenitis 淋巴滤泡增生 副皮质区淋巴增生 窦组织细胞增生 Distinctive infection 淋巴结特殊感染

11 Distinctive infection 淋巴结特殊感染 Special microorganism Special morphological changes pathogenic microorganism can be detected in lesion tissues, secretion and body fluid. Special drug treatment.

12 Distinctive infection 淋巴结特殊感染 结核性淋巴结炎 淋巴结真菌感染 组织细胞坏死性淋巴结炎 猫抓病 传染性单核细胞增多症

13 Non-specific lymphadenitis

14 Tuberculosis lymph node TB

15 Infection Tumor Nonspecific inflammation distinctive infection metastatic tumors lymphoid neoplasms Lymphoproliferative disorders with unknown reason

16 Section 2 Lymphoid neoplasms Malignant Lymphoma 恶性淋巴瘤 Lymphoma is a malignant tumor which origin from lymph node and other lymphoid tissue.

17 Lymphomas- Definition Clonal tumors of mature and immature lymphocyte including B-cells, T-cells and Natural Killer (NK) cells and so on. Malignant tumors of immune system. Involved organs and tissues: - Lymphoid organs and tissues - Extranodal tissues - Bone marrow - Peripheral blood

18 Leukemia( 白血病 ) is used for lymphoid neoplasms presenting with widespread involvement of the bone marrow, usually accompanied by the presence of large numbers of tumor cells in the peripheral blood. Lymphoma is used to describe proliferations arising as discrete tissue masses. Hence, when applied to particular neoplasms, the terms "leukemia" and "lymphoma" merely describe the usual tissue distribution of the disease at the time of clinical presentation.

19 这一理论成为淋巴瘤分类的基础 淋巴细胞发育转化理论 : 最早由德国病理学家 Lennert 等提出, 近年来不断丰富 主要内容为 : B 和 T 细胞都来自骨髓干细胞, 通过前 B 前 T 细胞 ( 又称淋巴母 细胞 ) 阶段, 发育成为成熟的未受到抗原刺激的 Bl T1 细胞 在 抗原刺激后,B T 细胞都可发生转化, 生成效应细胞 (B2 T2 细 胞和浆细胞 ) 其中 B1 细胞在受到抗原刺激后, 在生发中心先转 化为中心母细胞, 然后才转化为中心细胞, 并在生发中心外发 育成为免疫母细胞和浆细胞 在淋巴细胞转化过程的任何阶段 都可以发生恶变, 形成肿瘤 瘤细胞在形态改变 免疫标记和 功能上与其相应的正常细胞有相似之处, 因此可以用形态学和 免疫学的方法加以识别

20 Lymphomas- Lymphocyte differentiation Phenotypic and genotypic changes in differentiation of B cells and T cells

21 Lymphomas- WHO Classification Hodgkin lymphoma, HL 霍奇金淋巴瘤 Non-Hodgkin lymphoma, NHL 非霍奇金淋巴瘤 B-cell neoplasms T-cell and NK cell neoplasms

22 Lymphomas- staging system

23 Lymphoma-Diagnosis Clinical manifestations Histopathology Immunophenotypes Genetics

24 Lymphoma- Diagnosis Biopsy Histologic classification Immunophenotype analysis Genetic analysis: - Ig and/or TCR Gene rearrangement analysis - Karyotype analysis - Detection of chromosome translocation or fusion genes by FISH or PCR etc

25 Some lymphomas with distinctive genetic abnormalities Types Cytogenetic finding Genetic alteration FL t(14;18)(q32;q21) bcl-2 rearranged* MCL t(11;14)(q13;32) cyclin D1 BL t(8;14)(q24;q32) myc* MALTOMA t( 11;18)(q21;q21) MALT/API2 trisomy 3 ALCL t(2;5)(p23;35) NPM-ALK

26 Lymphoma- Diagnosis Biopsy Histologic classification Immunophenotype analysis Genetic analysis: - Ig and/or TCR Gene rearrangement analysis - Karyotype analysis - Detection of chromosome translocation or fusion genes by FISH or PCR etc

27 Lymphoma-Epidemiology and etiology Chromosome translocation and oncogenes Inherited genetic factors Viruses - Human T-cell leukemia virus-1, HTLV-1 - Epstein-Barr virus, EBV - Kaposi sarcoma herpesvirus / human herpesvirus-8, KSHV/HHV-8 - Hepatitis C virus Bacteria - Helicobacter Pylori, HP - Chlamydia psittaci; C. pneumoniae; C. trachomatis Environment factors

28 Hodgkin lymphoma

29 single to multiple mass, gray-white color, soft, uniform fish-flesh. Hodgkin lymphoma

30 a 5 cm lymph node. The node should normally be soft and pink and less than 1 cm in size. This lymph node is involved with Hodgkin's disease. This gross appearance could pass for a non-hodgkin's lymphoma as well.

31 Hodgkin lymphoma- characteristics A special entity of lymphoma and occupies up to 20% of all lymphomas. Children and young adults are more commonly involved. The tumor arises in a single node or chain of nodes spreads to the anatomically contiguous nodes. the neoplastic cells: Reed-Sternberg (R-S) cell and its variants.

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33 瘤细胞主要有 4 种 : 1. 典型的 Reed-Sternberg(R-S) 细胞这种细胞体大 浆丰 ; 核大, 双核或多核, 核染色质常沿核膜分布 故核膜厚, 而核中央呈空泡状 ; 核内有大而嗜酸性核仁 当双核的 R-S 细胞两核并列, 都有大而嗜酸性核仁 大致对称形似镜中之影, 故称镜影细胞 这种典型的 R-S 细胞是霍奇金淋巴瘤特有的, 故有诊断意义 2. 单核的 R-S 细胞又称霍奇金细胞 此种细胞的形态和典型的细胞相似, 但只有一个核 这种细胞可能是典型的 R-S 细胞的变异型, 它不能作为诊断的依据, 但可作为主要参考指标.

34 瘤细胞主要有 4 种 : 3. 陷窝细胞细胞体大, 浆丰, 但胞浆染色淡或清亮透明分叶状, 核仁较小 在福尔马林固定的标本, 胞浆收缩与周围细胞之间形成透明的空隙, 好似细胞位于陷窝内, 故称陷窝细胞 此种细胞被认为是瘤细胞在机体防御力强的情况下不能完全发育的结果, 此型细胞常在结节性硬化型中见到 4. 多形性或未分化型细胞 此种瘤细胞较典型的 R-S 细胞的形状 大小更不规则, 核巨大, 常呈分叶状扭曲状畸形, 核仁大小不等, 似一般肉瘤细胞 此型瘤细胞常见于淋巴细胞消减型

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36

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38 CHL Nodular sclerosis Lucunar cell

39 Nodular Sclerosing

40 mixed cellularity type

41 Lymphocyte Depleted

42

43 Lymphocyte-rich

44 上述各亚型可以转化, 其规律是淋巴细胞为主型 淋巴细胞消减型 结节硬化型较稳定, 一般不转化为其他类型

45 The first symptom is usually a painless swelling in the neck, armpits or groin. Other symptoms may include any of the following: night sweats or unexplained fever weight loss and tiredness cough or breathlessness persistent itch all over the body

46 Complications The immunity function is lower (reduced). The patient easily suffer from infection of virus and fungus.

47 Prognosis HL is a curable malignancy Overall cure rate approximately 75% With modern therapy, prognosis based more on staging, bulk of disease than morphologic subtype.

48 Non Hodgkin Lymphomas

49 Non-Hodgkin lymphoma- characteristics 80% to 90% of all lymphomas are NHLs Extranodal lymphoma occupies about 1/3 of all NHLs. Histopathologic classification is more complex. Clinical manifestations are closely related to the sites involved. A spectrum from lymphomas to leukemias.

50 常见淋巴细胞标记 T 细胞标记为 :CD2 CD3 CD4 CD7 CD8 B 细胞标记为 :CD10 CD19 CD20 Ig 表面 NK 细胞标记 :CD16 CD56 淋巴母细胞 : 表达 TdT 未端脱氧核苷酸转移酶髓样细胞 :CD13 CD14 CD15 CD64 多潜能 :CD34 CD=Cluster of differentiation

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52

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55 滤泡性淋巴瘤 : 示肿瘤滤泡, 肿瘤淋巴细胞植入

56 WHO classification for tumors of lymphoid tissues - NHL B cell neoplasms precursor B cell neoplasms mature( peripheral ) B cell neoplasms T and NK cell neoplasms precursor T cell neoplasms mature( peripheral ) T and NK cell neoplasms

57 NHL Examples Lymphoblastic leukemia/lymphoma Chronic lymphocytic leukemia / small lymphocytic lymphoma,cll/sll Follicular lymphoma, FL Diffuse large B-cell lymphoma,dlbcl Burkitt lymphoma, BL Plasma cell myeloma Extranodal NK/T-cell lymphoma, nasal type

58 Td T Lymphoblastic leukemia/lymphoma

59 Chronic lymphocytic leukemia / small lymphocytic lymphoma

60 Follicular lymphoma Bcl- 2

61 Diffuse large B-cell lymphoma

62 Burkitt lymphoma

63 Plasma cell myeloma

64 Extranodal NK/T-cell lymphoma, nasal type

65 Clinicopathologic differences between HL and NHL H NHL Patient children/young adults any aged people Stage I / II III / IV Symptoms 40% 15% Site LN, 90% LN, 70% neck/mediastinum extranodal,30% Dissemination predictable random Extranodal uncommon common Leukemia no yes Tumor cell R-S cells lymphocytes

66 Section 3 Myeloid neoplasms 髓系肿瘤 Arise in hematopoietic stem cells and typically give rise to monocolonal proliferations that diffusely replace normal bone marrow. primarily involve the bone marrow and to a lesser degree the secondary hematopoietic organs (the spleen, liver, and lymph nodes) and present with altered hematopoiesis.

67 Myeloid neoplasms : Classification Myeloproliferative neoplasms, MPN Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 Myelodysplastic / myeloproliferative neoplasms, MDS/MPN Myelodysplastic syndromes, MDS Acute myeloid leukemia ( AML) and related precursor neoplasms Acute leukemia of ambiguous lineage

68 Acute myeloid leukemia ( AML) AML are tumors marked by a blockage in the differentiation of early myeloid cells. Immature myeloid cells accumulate in the marrow, replacing normal elements, and frequently circulate in the peripheral blood.

69 AML- clinical manifestations Anemia Hemorrhage Bone pain Fatigue Fever Hepatosplenomegaly Lymphadenopathy

70 AML - Diagnosis Laboratory findings: Peripheral blood increased number of white cells immature white cells BM aspiration immature white cells

71 Peripheral blood Bone marrow biopsy

72 Myeloid sarcoma A myeloid sarcoma is a tumour mass consisting of myeloid blasts with or without maturation occurring at an anatomical site other than the bone marrow. Granulocytic sarcoma, so called choloroma, is the most common type of myeloid sarcoma.

73 Leukemoid reactions Reactive leukocytosis Many immature white cells appear in the blood Response to severe infection, malignant tumor, toxic events or emergencies Reversible

74 MP Granulocyte sarcoma

75 Section 4 Histiocytic and dendritic cell neoplasms

76 Histiocytic and dendritic cell neoplasms - Classification Histiocytic sarcoma Dendritic cell sarcoma Tumors derived from Langerhans cells Interdigitating dendritic cell sarcoma Follicular dendritic cell sarcoma Other rare dendritic cell tumors disseminated juvenile xanthogranuloma

77 Thanks!

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