Disease of lymph- hematopoietic system Maliqin Zhejiang University, School of Medicine Department of Pathology & Pathophysiology Tel: 88208130 Maliqin198@zju.edu.cn
Outline hemopoietic system hematopoietic organ blood Embryonic liver, marrow, spleen, lymphonode
Structure of lymphonode: cortex: peripheral cortical area:lymph nodule+dispersed lymph tissue,b-cell area paracortical area:tymus-dependent zone,dispersed lymph tissue,t-cell area lymphoid sinus:subcapsular sinuses+ peripheral sinus medulla: medullary cord:lymph tissue (B-cell, plasmacyte, macrophage) medullary sinus:macrophage Function: 1filtered lymph 2immune response (T,B cell)
lymphoid sinus 淋巴结低倍镜结构 lymph nodule peripheral cortical area paracortical area cortex medulla medullary cord medullary sinus
Folliculus lymphaticus germinal center
Germinal center Black arrow:centr-parent cell Yellow arrow: plasmablast
Disease of lymph- hematopoietic system
Type Benign: inflammation, reactive hyperplasia, tuberculosis Malignant: primary,secondary
Benign : Inflammation: acute, chronic reactive hyperplasia: Tuberculosis:
stimulus immunereaction Inflammatory B cell-follicular hyperplasia (eg. rheumatoid arthritis) T cell-paracortical hyperplasia (eg. viral infection) Histiocyte hyperplasia (eg. malignant tumor) Mixied hyperplasia (toxoplasmosis, 弓浆虫病 ) granuloma (tuberculosis) purulent (cat-scratch disease)
Follicular hyperplasia
Benign lymphoid hyperplasia Non-specific lymphadenitis 非特异性淋巴结炎 - acute non-specific lymphadenitis - chronic non-specific lymphadenitis follicular hyperplasia parafollicular hyperplasia sinus histiocytosis Distinctive infection 淋巴结的特殊感染
Non-specific lymphadenitis
Distinctive infection 淋巴结的特殊感染 Tuberculous lymphadenitis ( 结核性淋巴结炎 ) fungous infection lymphadenitis( 真菌感染性淋巴结炎 ) Histiocytic necrotizing lymphadenitis( 组织细胞性坏死 性淋巴结炎 -- Kikuchi s disease 菊池病 )
Tuberculosis lymph node TB
caseous necrosis
Infection Tumor Nonspecific inflammation distinctive infection metastatic tumors lymphoid neoplasms Lymphoproliferative disorders with unknown reason
Malignant primary,secondary
黏液湖
Concept of lymphoma 1. malignant lymphoma : Lymphatic tissue s malignant tumor come from primarily inside and outside lymph node 2. lymphocytic monoclonal hyperplasia:t cell and B cell 3. abnormal immune function, such as serum Ig B cell 4. origin of tumour cell T cell NK cell
Type and Degree type degree Hokdkin's disease B non-hokdkin's disease T NK/T Low potential malignancy Midrange potential malignancy Height potential malignancy
Hodgkin Lymphoma (Hodgkin s Disease )
Pathogenesis EBV-EB 病毒 Clinical manifestation lymphadenectasis with without pain early stage:no general symptom advanced stage:fever weight decrease pruritus( 瘙痒 ) anaemia( 贫血 ) Diagnosis:biopsy( 活检 ) Therapy: large dose radiotherapy chemotherapy
Pathological change Early stage: neck and supraclavicular lymph nodes, mediastinal, retroperitoneal and paraaortic lymph node Advanced stage: spleen( 常见, 斑岩脾 ), liver, marrow Gross: size, mobility,adherence,consistency,color, shape Microscopically:Tumor cells and nontumor cells
porphyry spleen 斑岩脾
Hodgkin lymphoma
Hodgkin lymphoma
Tumor cells 1. mirror image cell 2. Single nuclear R-S cell 3. Variant R-S cell lacunar 瘤细胞呈椭圆形 cell:, 胞浆丰 40-50um, 富, 双核, 胞浆丰富空核圆形或椭圆亮形,, 核多叶而皱折彼此对称, 染色质粗 popcorn cell:, 染色质稀疏糙, 沿核膜聚集呈块状, 多核, 核仁多个, 核皱折成, 较典型的核膜厚而清楚 R-S 细胞小 核内有一多叶状, 染色质非常大的 嗜酸性的核细, 核仁大, 胞 polymorph 仁, 周围有空晕 浆淡染 or undiferentiated R-S cell: 瘤细胞及核体积均较大, 不规则, 核内染色质粗, 有明显大核仁 核分裂相多见
Non-tumor cell lymphocyte,plasmocyte inflammatory cell leucocyte neutrophil eosinophilic leukocyte histiocyte,epithelioid cell stroma fibrous tissue Eosinophilic substance
Eosinophilic leukocyte Tumor cell Lymphocyte
Atypical mirror image cell
Single nuclear R-S cell karyomitosis
amphinucleolus Single nucleolus necrotic cell lymphocyte
多倍体型R- S 细胞 胞浆嗜碱性,核呈分叶状 Popcorn cell
Classification of WHO 1. Nodular sclerosis( 结节性硬化型 ) 2. Mixed cellularity ( 混合细胞型 ) 3. Lymphocytic predominance ( 淋巴细胞为主型 ) 4.Lymphocytic depletion ( 淋巴细胞消减型 )
Nodular sclerosis: wide collagen fibers, lacunar cell( 陷窝细胞 ),seldem typical R-S cell Mixed cellularity: various kinds of Hodgkin cells and many typical R-S cell Lymphocytic predominance: popcorn cell( 爆米花细胞 ), seldem typical R-S cell Lymphocytic depletion: a small quantity Lymphocytes and variant multiformity R-S cell
Nodular sclerosis Wide collagen fibers Lucunar cell
lymphocytic predominance lymphocyte popcorn cell Mononuclear R-S cell epithelioid cell
mixed cellularity
lymphocytic depletion Polymorph undifferentiation cell R-S cell lattice fibers
Non-Hodgkin lymphoma (NHL, 非霍奇金淋巴瘤 )
Non Hodgkin Lymphomas
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
B lymphocyte and B lymphocytic predominance 1. Chronic lymphocytic leukemia / small lymphocytic lymphoma 2. Follicular lymphoma( 滤泡性淋巴瘤 ) 3. Diffused big B cell lymphoma ( 弥漫大 B 细胞淋巴瘤 ) 4. Burkitt lymphoma( 伯基特淋巴瘤 ) 5. Plasmacytoid lymphoma( 浆细胞性淋巴瘤 )
Chronic lymphocytic leukemia / small lymphocytic lymphoma
Follicular lymphoma Bcl-2
Differentiation lymphoma hyperplasia Follicle simplex varied cell no macrophagocyte Size of follicle same differ Cell same differ Capsul involve non involve structure disappear normal IH bcl-2 (+) bcl-2 (-)
Diffuse large B-cell lymphoma
Burkitt lymphoma
Burkitt lymphoma(bl, 伯基特淋巴瘤 )
plasmacytoid lymphoma plasmocyte Russell body
Height potential malignancy lymphocyte tumor giant cell polykaryocyte
Height potential malignancy
T cell lymphoma
T cell lymphoma
Extranodal NK/T-cell lymphoma, nasal type
MYELOID NEOPLASM ( 髓性肿瘤 ) NEOPLASM of HISTIOCYTE and DENDRITIC CELL ( 组织细胞与树突状细胞肿瘤 )
Conception : Leukemia ( 白血病 ) malignant tumor which formed by clonal hyperplasia of marrow hemopoietic stem cell. Characteristic: abnormal leucocyte diffuse hyperplasia in marrow peripheral blood and other tissues organ(liver, spleen, lymphonode) anaemia, hemorrhage, infection
MYELOID NEOPLASM Classification According to WHO Myeloproliferative neoplasm (MPN, 骨髓增生性肿瘤 ) Medullary system and Lymph tumor with Eosinophilic cell histiocytosis( 髓系和淋巴肿瘤伴嗜酸性细 胞增多症 ) Myelodysplastic/ MPN ( 骨髓异常增生 / 骨髓增生性肿瘤 ) Myelodysplastic syndrome(mds, 骨髓异常增生综合症 ) acute myeloid leukaemia(aml) and related precursor neoplasm( 急性髓性白血病及其相关前体细胞肿 瘤 )
Type origin, differentiated degree, patient's condition Acute lymphoblasric leukemia acute chronic (ALL, 急性淋巴母细胞白血病 ) Acute myelogenous leukemia (AML, 急性粒细胞 / 髓细胞白血病 ) Chronic myelogenous leukemia ( CML, 慢性粒细胞 / 髓细胞白血病 ) Chronic lymphocytic leukemia ( CLL, 慢性淋巴细胞白血病 )
Classification According to the type of Leukemic cell Myelogenous leukemia ( 髓细胞性白血病 ) Lymphoblasric leukemia( 淋巴母细胞性白血病 ) Monocytic leukemia( 单核细胞性白血病 ) Megakaryocytic leukemia( 巨核细胞性白血病 ) Erythrocytic leukemia( 红细胞性白血病 )
Basic pathological changes Marrow: leucoblast hyperplasia, hematogenesis Peripheral blood: total white cell count (TWBC) juvenile cell( 幼稚细胞 ) thrombocytopenia( 血小板减少 ) Lymphonode: swell, juvenile cell( 幼稚细胞 ) Spleen : swell, oncocyte infiltrating, oppression white pulp Liver:swell, oncocyte infiltrating in sinus hepaticus and portal area
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.
AML- clinical manifestations Anemia Hemorrhage Bone pain Fatigue Fever Hepatosplenomegaly Lymphadenopathy
AML - Diagnosis Laboratory findings: Peripheral blood increased number of white cells immature white cells BM aspiration immature white cells
Peripheral blood Bone marrow biopsy
Myeloid sarcoma ( 髓肉瘤 ) Concentration of immature cells( in other organs out Bone marrow) tumorous mass--myeloid sarcoma( 髓肉瘤 ) 96% --granulocytic sarcoma( 粒细胞肉瘤 ) Fresh granulocytic sarcoma(slight green ) chloroma( 绿色瘤 )
Granulocyte sarcoma MPO
Chloroma
Myeloproliferative neoplasm (MPN, 骨髓增生性肿瘤 ) A tumor which formed by the clonal proliferation of multi-directional differentiation stem cell in marrow. Mature RBC,platelet,granulocyte,monocyte, lymphocyte Chronic myelogenous leukemia (CML, 慢性粒细胞 / 髓细胞性白血病 ) Chronic lymphocytic leukemia (CLL, 慢性淋巴细胞性白血病 )
Differentiation points between CLL and CML CLL CML Age : Origin: >50-year-old 40-50 year old B lymphocyte protocell -segmented neutrocyte peripheral blood: TWBC TWBC 30~100 10 9 /L 100~800 10 9 /L mature small lymphocytes mature granulocyte Marrow : small lymphocytes proliferation granulocyte proliferation Lymphonode : Spleen: Liver : swell no swell 2500g, white pulp 4000~5000g,red pulp portal area sinus hepaticus
Chronic myelogenous leukemia
Chronic myelogenous leukemia 大多数为较成熟的中 晚幼和杆状粒细胞
Classification Chronic myelogenous leukemia,bcr/abl-1( 慢性髓系白血病 ) Chronic neutrophilic leukemia ( 慢性中性粒细胞白血病 ) Polycythemia rubra vera ( 真性红细胞增多症 ) Primary myelofibrosis( 原发性骨髓纤维化 ) Essential thrombocythemia( 特发性血小板增多症 ) Chronic eosinophilic leukemia ( 慢性嗜酸性粒细胞白血病 ) Mastocytosis( 肥大细胞增生症 ) Others
CML Blood smear CML BM biopsy
Clinical manifestation Months-years 30-40 years old Anaemia Weakness Body weight Splenomegaly splenic rupture
Leukemoid reaction( 类白血病反应 ) A clinical blood symptoms which emerge juvenile cell in peripheral blood, number of leucocytes may be increasing,normal, decreasing Severe infection Common cause Some malignant tumor Drug poisoning Massive hemorrhage hemolysis Granulocyte( 粒细胞型 ) Common type Eosinocyte( 嗜酸性细胞型 ) lymphocyte( 淋巴细胞型 ) monocyte( 单核细胞型 ) others( 其它 )
白血病 ( 粒细胞性 ) 与类白血病的区别白血病类白血病 白细胞数 100 10 9 /L 50 10 9 /L 血小板量减少无明显减少 贫血有没有 粒细胞特点无中毒性改变胞浆内有中毒颗粒及空泡 嗜碱性粒细胞较多无 碱性磷酸酶积分降低或消失活性和糖原明显增高 遗传学标记 Ph 1 染色体,t (9;22) 无特征性染色体 转归特点发展迅速, 易恶化病因去除后, 血象恢复
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