TheDiseaseofHematopoieticandLymphoidSystems(淋.ppt

1、,The Disease of Hematopoietic and Lymphoid Systems,Hematopoietic and Lymphoid Systems,Myeloid tissueBone marrowRBC, platelets, granulocytes, monocytesLymphoid tissuelymph nodes thymus spleen,Disorders encompass a wide range of diseases, involving its any organs or tissues.RBC: usually anemiaWBC: ove

2、rgrowth, usually malignant common and lethal,Neoplastic proliferations of white cells,Be defined briefly as follows:Myeloid neoplasms 髓样组织肿瘤Lymphoid neoplasms 淋巴样组织肿瘤HistiocytosisMan-made classification The distinction in some cases may be blurred.,Myeloid neoplasms,Arise within hematopoietic stem c

3、ells Three general categories:Acute myelogenous leukemia (AML 急性髓性白血病) Chronic myeloproliferative disorders （慢性骨髓增生性疾病）Chronic myelogenous leukemia 慢性髓性白血病Polycythemia vera 真性红细胞增生症Myeloid metaplasia with myelofibrosis 伴骨髓纤维化的髓样增生Essential thrombocythemia 真性血小板增生症Myelodysplastic syndromes（骨髓增生异常综合症）

4、,Myeloid neoplasms: CD13,CD14,CD15,CD64,8 types: FAB classification M18,Lymphoid neoplasms,A group of entities that vary widely in terms of their clinical presentation and behaviorClassification scheme that relies on a combination of clinical, morphologic, phenotypic and genotypic features the relat

5、ionship between lymphoma and lymphocytic leukemiaCertain important relevant principles most: B Cell origin neoplasms are often composed of cells that arrest at specific stages,A. Precursor B-cell neoplasmsB. Peripheral B-cell neoplasms A. Precursor T-cell neoplasmsB. Peripheral T-/NK-cell neoplasms.

6、 Hodgkin lymphoma,Lymphoid neoplasms,NHL,A. Precursor B-cell neoplasms 1. Precursor B-cell leukemia/lymphomaA. Precursor T-cell neoplasms 1. Precursor T-cell leukemia/lymphomapre-B-lymphoblastic tumor: first leukemia lymphoma pre-T-lymphoblastic tumor: mediastinal masses involved the thymus leukemia

7、 Both tumors usually have the clinical appearance of an acute lymphoblastic leukemia (ALL),Common features of acute leukemias ALL +AML,Clinical features1. Abrupt stormy onsetwithin 3 months2. Symptoms related to depression of normal marrow functionPathophysiology Block in differentiation blasts accu

8、mulate in marrow normal hematopoietic stem cells,Anemiafatigue,Mature leukocytes infection,Thromobocytopeniableeding,Clinical features3. Bone pain and tenderness4. Generalized lymphadenopathy splenomegaly, and hepatomegaly More common in ALL5.Central nervous system manifestations Headache, vomiting,

9、 and nerve palsies children adults, ALLAML,Common features of acute leukemias,Laboratory findingsAnemiaPlatelet count is usually depressedWBC count is variably elevatedMuch more important: blasts in the circulating blood and the bone marrow,Common features of acute leukemias,Clinical treatment Chemo

10、therapy Bone marrow stem cell(MSCs) transplantation,Common features of acute leukemias,Different features between AML and ALL,Morphology,coarse and clumped chromatin1-2 nucleoli,AML ALL,Age,adults; median age : 50 yrs,Peroxidase +,Fine chromatin; 3-5 nucleoli, more cytoplasmcontaining granules,Auer

11、rods,Pre-B(85% ): children, 4 years;Pre-T(15%): adolescent males, 15-20years,PAS+,histochemistry,Clinical features,As described previously,immunophenotyping,CD13,CD14,CD15, CD64,TdT (95% +)B: CD19T: CD2,AML ALL,Karyotypic changes,Pre-B: Hyperdiploidy t (12;21) ; Ph,prognosis,Good:2-10 yrs, pre-B,Dev

12、astating disease,M2: t(8;21)M3:t(15;17) 维甲酸治疗M4: inv(16) /del(16),Age 25-60 years Peak incidence : 40-50 yearsClinical features 1. Onset is slow; 2. nonspecific initial symptoms Easy fatigability, weakness, and weight loss 3. Extreme splenomegaly infarct pains,Chronic myelogenous leukemia, CML,Patho

13、logy changesLeukocyte countand bone marrow is hypercellular Predominantly: neutrophils and myelocytes Basophils and eosinophils myeloblasts10%Spleen infarcts acute onset left upper quadrant pain,Chronic myelogenous leukemia, CML,Chronic myelogenous leukemia, CML,Karyotypic changes Ph (Philadelphia)

14、chromosome: t(9;22)(q34;q11) c-abl-ber fusion genes/P210protein: increased, dysregulated tyrosine kinase activityPrognosisSlow progressionwithout treatment, median survival is 3 yearsBone marrow transplantationSTI-571: the exciting concept of designer drugs that specifically target oncoproteins,B. P

15、eripheral B-cell neoplasms,Small lymphocytic lymphoma/chronic lymphocytic leukimia(慢性淋巴细胞性白血病/小淋巴细胞性淋巴瘤）B-cell prolymphocytec leukemia B细胞性前淋巴细胞白血病Lymphoplasmacytic lymphoma 淋巴细胞、桨细胞性淋巴瘤Mantle cell lymphoma 套细胞性淋巴瘤Follicular Lymphoma 滤泡性淋巴瘤Extranodal marginal zone lymphoma(MALT lymphoma) 节外边缘带淋巴瘤7.

16、Splenic marginal zone lymphoma 脾边缘带淋巴瘤8. Nodal marginal zone lymphoma 淋巴结边缘带淋巴瘤9. Hairy cell leukemia 毛细胞性白血病10. Plasmacytoma/plasma cell myeloma 浆细胞瘤/骨髓瘤11. Diffuse Large B-cell Lymphoma 弥漫性大细胞性淋巴瘤12. Burkitt Lymphoma 伯基特淋巴瘤,Peripheral Lymphoid Cell Tumors,Small lymphocytic lymphoma/chronic lymphoc

17、ytic leukimia,Age 50 yearsClinical features 1. Often asymptomatic or nonspecific (easy fatigability, weight loss, and anorexia) 2. Hypogammaglobulinemia susceptibility to bacterial infections 3. Generalized lymphadenopathy, splenohepatomegaly 4. Total leukocyte count,Lymph nodes, the bone marrow, sp

18、leen, liverMorphologyLow power: sheets of tumor cells diffusely efface involved lymph nodes,Small lymphocytic lymphoma/chronic lymphocytic leukimia,MorphologyPredominant cells compact, small, dark-staining round nuclei, Scanty cytoplasm, and little variation in sizeProliferation centers-Pseudofollic

19、le foci of mitotically active prolymphocytes,Small lymphocytic lymphoma/chronic lymphocytic leukimia,Immunophenotyping: mature B cells Pan-B-cell markers:CD19,CD20, SIgPrognosis the course and prognosis are extremely variable The median survival is 46years. To transform to more aggressive tumors, su

20、ch as diffuse large B-cell lymphoma: less than 1 year,Small lymphocytic lymphoma/chronic lymphocytic leukimia,Age Older persons (rarely before age 20 years)Clinical characteristics Painless lymphadenopathy, frequently generalized Morphologylymph nodes are effaced by a nodular or follicular architect

21、ure,Follicular Lymphoma,MorphologyPredominant neoplastic cells-centrocyte, CC 1. slight larger than resting lymphocytes 2. Coarse and condensed chromatin prominent indentations and linear infoldings Nucleoli are indistinctOther cells -Centroblast,CB 1.3-4 times the size of resting lymphocytes 2. Ves

22、icular chromatin several nucleoli modest amounts of cytoplasm,Follicular Lymphoma,Immunophenotyping,Pan-B-cell markers: CD19, CD20, BCL2,BCL2,14: IgH gene; 18:BCL2 geneTranslocation t(14,18) Bcl-2 protein antiapoptotic effect,Prognosis,Indolent course, median survival,7 to 9 yearsnot easily curable4

23、0% of patients progress to a diffuse large B-cell lymphoma,diffuse large B-cell lymphoma,Age Most important type of lymphoma in adults approximatelly 50% of all adult NHLsMorphology its nuclei is large and varible (3-4 times the size of resting lymphocytes),Immunophenotype Pan-B-cell marker: CD19, C

24、D20Subtypes: epstein-Barr virus(EBV) associated acquired immunodeficiency syndrome and iatrogenic immunosuppression human herpes type 8( HHV-8) infections a rare group mediastinal large B-cell lymphoma usually in young adults a predilection for spread to abdominal viscera and CNS,diffuse large B-cel

25、l lymphoma,Karyotype30% t(14;18) BCL2 arrangement1/3 3q27 BCL6 arrangementPrognosisAggressive , Rapidly fatal if untreatedWith intensive combination chemotherapy, complete remission can be achieved in 60%-80% of the patients,Burkitt Lymphoma,Age Children or young adults endemic in some parts of Afri

26、ca and sporadic in other areas. Common sites Africa : Maxilla(上颌骨） or mandible （下颚骨） other areas: abdominal (bowel, retroperitoneum, ovaries)Pathogenesis Correlated with EBV infection,MorphologyStarry sky: macrophages with ingested nuclear debrisMonotonous round or oval nuclei containing 2-5 promine

27、nt nucleoli Active mitosis,Immunophenotype SIgM, pan-B-cell markers: CD19, CD10Karyotype t(8;14) et al Translocations involving MYC gene 8 MYC 14 IgH or 2、22 ，Prognosis It may be the fastest growing human neoplasm, however, with very aggressive chemotherapy, the majority of patients can be cured.,Bu

28、rkitt Lymphoma,. Hodgkin Lymphoma,10%20%, Tomas HodgkinIt was separated from NHLs for several reasonsIt arises almost invariably in a single node or a chain of nodes distinctive neoplastic giant cells called Read-Sternberg (RS) cells mixed with a variable infiltrate of reactive inflammatory cells.Sy

29、stemic manifestations, such as feverWith a relatively good prognosis.,RS cellsAbundant cytoplasm, d=15 to 45umMultilobate nucleus or multinucleate with large, round, prominent nucleoliMirror-image nuclei,. Hodgkin Lymphoma,Variant of RS cellsMononuclear variantsLacunar cell A large folded or hyperlo

30、bate nucleus with multiple small nucleoli Abundant, pale-staining cytoplasm,. Hodgkin Lymphoma,Variant of RS cells3.Lymphocytic and histocytic variants,(L&H cell or Popcorn cell ) have twisted , multilobate nuclei, resembling popcorn kernels,. Hodgkin Lymphoma,1. Nodular lymphocyte predominant Hodgk

31、in lymphomaCD45 +; CD15, CD30 2. Classical Hodgkin lymphoma CD45 -; CD15, CD30 +,Hodgkin lymphoma,Nodular lymphocyte predominant Hodgkin lymphoma,Morphology L 35yrsGood prognosis,Classical Hodgkin lymphoma,Nodular sclerosisMixed cellularityLymphocyte richLymphocyte depleted,1. Nodular sclerosis Hodg

32、kin lymphomaThe most common, young femaleMorphology Collagen bands divide the lymphoid tissue into circumscribed nodules Lacunar cell Lymphocytes, eosinophils, HistiocytesPrognosis is good.,Classical Hodgkin lymphoma,2. Mixed cellularity Hodgkin lymphoma More common in older male Typical RS and mono

33、nuclear cells are plentifulLymphocytes, eosinophils, plasma cells, histiocytes,Classical Hodgkin lymphoma,3. Lymphocyte predominance young maleA large number of small, mature-looking reactive lymphocytes admixed with a variable number of benign histiocytes, often within large, poorly defined nodulesL&H is common and typical RS is rare,Classical Hodgkin lymphoma,4. Lymphocyte depletionVary rareRS cells: diffusely proliferateLymphocytes: greatly reduceOld people, HIV infectionPoor prognosis,Classical Hodgkin lymphoma,