淋巴造血系统

Chapter 12 The diseases of Hematopoietic and Lymphoid System,Liu weipingDepartment of PathologyWest China School of MedicineSichuan University,Characteristics,The organs and tissues are not confined to a single anatomic site. The cells are constantly in “traffic”.The diseases often appear as systemic involvements.,Diseases of hematopoitic and lymphoid system,Red cell disordersWhite cell disorders*Bleeding disordersDisorders that affect the spleen and thymus,White cell disorders,Non-Neoplastic Disorders - Reactive lymphoid hyperplasia (lymphadenitis) - Reactive leukocytosis Neoplastic Disorders - lymphomas - myeloid neoplasms - Histiocytic and dendritic-cell neoplasms,Lymph node,?,Benign lymphoid hyperplasia,Benign lymphoid hyperplasia,Non-specific lymphadenitis - acute non-specific lymphadenitis - chronic non-specific lymphadenitis follicular hyperplasiaparafollicular hyperplasiasinus histiocytosisDistinctive infection,Non-specific lymphadenitis,TB,Tuberculosis lymph node,Nonspecific inflammation distinctive infection,Infection,Tumor,metastatic tumorslymphoid neoplasms,Lymphoproliferative disorders with unknown reason,Lymphomas,Lymphomas,DefinitionLymphocyte differentiationWHO Classification Clinical manifestation and stagingDiagnosisGeniticsEpidemiology and etiology,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 organsand tissues - Extranodal tissues - Bone marrow - Peripheral blood,Lymphomas- Lymphocyte differentiation,Phenotypic and genotypic changes in differentiation of B cells and T cells,Hodgkin lymphoma, HL Non-Hodgkin lymphoma, NHL B-cell neoplasms T-cell and NK cell neoplasms,Lymphomas- WHO Classification,Lymphomas- staging system,Lymphoma-Diagnosis,Clinical manifestationsHistopathologyImmunophenotypes Genetics,Lymphoma- Diagnosis,BiopsyHistologic classificationImmunophenotype analysis Genetic analysis: - Ig and/or TCR Gene rearrangement analysis - Karyotype analysis - Detection of chromosome translocation or fusion genes by FISH or PCR etc,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 3ALCL t(2;5)(p23;35) NPM-ALK,Lymphoma-Epidemiology and etiology,Chromosome translocation and oncogenesInherited 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 virusBacteria - Helicobacter Pylori, HP - Chlamydia psittaci; C. pneumoniae; C. trachomatisEnvironment factors,Hodgkin lymphoma,Hodgkin lymphoma,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.,Hodgkin lymphoma - Subtypes,Nodular lymphocyte predominance Hodgkin lymphoma, NLPHL Classical Hodgkin lymphoma, CHL Lymphocyte rich, LR Mixed cellularity, MC Lymphocyte deplete, LD Nodular sclerosis, NS,Lucunar cell,CHLNodular sclerosis,porphyry spleen,Proposed signals mediated “cross talk” between R-S cells and surrounding normal cells in Classical Hodgkin lymphoma,Non Hodgkin Lymphomas,Non-Hodgkin lymphoma- characteristics,80% to 90% of all lymphomas are NHLsExtranodal 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.,WHO classification for tumors of lymphoid tissues - NHL,B cell neoplasms precursor B cell neoplasms mature( peripheral ) B cell neoplasmsT and NK cell neoplasms precursor T cell neoplasms mature( peripheral ) T and NK cell neoplasms,NHL Examples,Lymphoblastic leukemia/lymphoma Chronic lymphocytic leukemia / small lymphocytic lymphoma，CLL/SLL Follicular lymphoma, FLDiffuse large B-cell lymphoma，DLBCL Burkitt lymphoma, BLPlasma cell myeloma Extranodal NK/T-cell lymphoma, nasal type,Lymphoblastic leukemia/lymphoma,TdT,Chronic lymphocytic leukemia / small lymphocytic lymphoma,Follicular lymphoma,Bcl-2,Diffuse large B-cell lymphoma,Burkitt lymphoma,Plasma cell myeloma,Extranodal NK/T-cell lymphoma, nasal type,Clinicopathologic differences between HL and NHL,HL NHL Patient children/young adults any aged peopleStage I / II III / IVSymptoms 40% 15% Site LN, 90% LN, 70% neck/mediastinum extranodal,30% Dissemination predictable random Extranodal uncommon commonLeukemia no yesTumor cell R-S cells lymphocytes,Myeloid neoplasms,Myeloid neoplasms - Definition,Myeloid neoplasms arise within hematopoietic stem cells and typically give rise to monoclonal proliferations that diffusely replace normal bone marrow cells.,Myeloid neoplasms : Classification,Myeloproliferative neoplasms, MPNMyeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1Myelodysplastic / myeloproliferative neoplasms, MDS/MPNMyelodysplastic syndromes, MDSAcute myeloid leukemia ( AML) and related precursor neoplasmsAcute leukemia of ambiguous lineage,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,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.,Leukemoid reactions,Reactive leukocytosis Many immature white cells appear in the bloodResponse to severe infection, malignant tumor, toxic events or emergenciesReversible,Granulocyte sarcoma,MPO,Myeloproliferative neoplasms, MPN,Definition: MPN are clonal haematopoitic stem cell neoplasms characterized by proliferation in the bone marrow of one or more of the myeloid lineages.MPN is characterized by hypercellularity of the BM with effective haematopoietic maturation and increased number of granulocytes, red blood cells and/or platelets in the PB.,Myeloproliferative neoplasms : Classification,Chronic myelogenous leukemia* BCR-ABL1 positive Chronic neutrophilic leukemia Polycythaemia veraPrimary myelofibrosisEssential thrombocythaemiaChronic eosinophilic leukemiaMastcytosisMyeloproliferative neoplasm, unclassifiable,Chronic myelogenous leukemia,CML Blood smear,CML BM biopsy,CML- Detection of t(9;21) and ABL/BCR fusion gene,Myeloid neoplasms- Etiology,Genetic abnormalities - chromosome translocation - gene mutation - gene deletion and gainRadiation exposureEnvironment fac