病理学课件：淋巴造血(2009)

1、The Disease of Hematopoietic and Lymphoid Systems Hematopoietic and Lymphoid Systems nMyeloid tissue nBone marrow nRBC, platelets, granulocytes, monocytes nLymphoid tissue nlymph nodes n thymus n spleen Disorders n encompass a wide range of diseases, involving its any organs or tissues. nRBC: usuall

2、y anemia nWBC: overgrowth, usually malignant common and lethal Neoplastic proliferations of white cells Be defined briefly as follows: 1.Myeloid neoplasms 髓样组织肿瘤髓样组织肿瘤 2.Lymphoid neoplasms 淋巴样组织肿瘤淋巴样组织肿瘤 3.Histiocytosis Man-made classification The distinction in some cases may be blurred. Myeloid ne

3、oplasms nArise within hematopoietic stem cells nThree general categories: nAcute myelogenous leukemia (AML 急性髓性白血病急性髓性白血病) nChronic myeloproliferative disorders （慢性骨髓增生性疾病）慢性骨髓增生性疾病） nChronic myelogenous leukemia 慢性髓性白血病慢性髓性白血病 nPolycythemia vera 真性红细胞增生症真性红细胞增生症 nMyeloid metaplasia with myelofibros

4、is 伴骨髓纤维化的髓样增生伴骨髓纤维化的髓样增生 nEssential thrombocythemia 真性血小板增生症真性血小板增生症 nMyelodysplastic syndromes（骨髓增生异常综合症）（骨髓增生异常综合症） 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 behavior C

5、lassification scheme that relies on a combination of clinical, morphologic, phenotypic and genotypic features the relationship between lymphoma and lymphocytic leukemia Certain important relevant principles most: B Cell origin neoplasms are often composed of cells that arrest at specific stages A. P

6、recursor B-cell neoplasms B. Peripheral B-cell neoplasms A. Precursor T-cell neoplasms B. Peripheral T-/NK-cell neoplasms . Hodgkin lymphoma Lymphoid neoplasms NHL A. Precursor B-cell neoplasms 1. Precursor B-cell leukemia/lymphoma A. Precursor T-cell neoplasms 1. Precursor T-cell leukemia/lymphoma

7、pre-B-lymphoblastic tumor: first leukemia lymphoma pre-T-lymphoblastic tumor: mediastinal masses involved the thymus leukemia Both tumors usually have the clinical appearance of an acute lymphoblastic leukemia (ALL) Common features of acute leukemias ALL +AML nClinical features 1. Abrupt stormy onse

8、twithin 3 months 2. Symptoms related to depression of normal marrow function Pathophysiology Block in differentiation blasts accumulate in marrow normal hematopoietic stem cells Anemia fatigue Mature leukocytes infection Thromobocytopenia bleeding nClinical features 3. Bone pain and tenderness 4. Ge

9、neralized lymphadenopathy splenomegaly, and hepatomegaly More common in ALL 5.Central nervous system manifestations Headache, vomiting, and nerve palsies children adults, ALLAML Common features of acute leukemias nLaboratory findings 1.Anemia 2.Platelet count is usually depressed 3.WBC count is vari

10、ably elevated Much more important: blasts in the circulating blood and the bone marrow Common features of acute leukemias nClinical treatment Chemotherapy Bone marrow stem cell(MSCs) transplantation Common features of acute leukemias Different features between AML and ALL Morphology coarse and clump

11、ed chromatin 1-2 nucleoli AML ALL Age adults; median age : 50 yrs Peroxidase + Fine chromatin; 3-5 nucleoli, more cytoplasm containing granules, Auer rods Pre-B(85% ): children, 4 years; Pre-T(15%): adolescent males, 15-20years PAS+ histochemistry Clinical features As described previously immunoph e

12、notyping CD13,CD14, CD15, CD64 TdT (95% +) B: CD19 T: CD2 AML ALL Karyotypic changes Pre-B: Hyperdiploidy t (12;21) ; Ph prognosis Good:2-10 yrs, pre-B Devastating 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 years Clinical features 1. Onset is sl

13、ow; 2. nonspecific initial symptoms Easy fatigability, weakness, and weight loss 3. Extreme splenomegaly infarct pains Chronic myelogenous leukemia, CML Pathology changes Leukocyte countand bone marrow is hypercellular Predominantly: neutrophils and myelocytes Basophils and eosinophils myeloblasts10

14、% Spleen infarcts acute onset left upper quadrant pain Chronic myelogenous leukemia, CML Chronic myelogenous leukemia, CML Karyotypic changes Ph (Philadelphia) chromosome: t(9;22)(q34;q11) c-abl-ber fusion genes/P210protein: increased, dysregulated tyrosine kinase activity Prognosis Slow progression

15、 without treatment, median survival is 3 years Bone marrow transplantation STI-571: the exciting concept of designer drugs that specifically target oncoproteins B. Peripheral B-cell neoplasms 1.Small lymphocytic lymphoma/chronic lymphocytic leukimia(慢性淋巴细胞性白血病慢性淋巴细胞性白血病/小淋巴细胞性淋巴瘤）小淋巴细胞性淋巴瘤） 2.B-cell

16、 prolymphocytec leukemia B细胞性前淋巴细胞白血病细胞性前淋巴细胞白血病 3.Lymphoplasmacytic lymphoma 淋巴细胞、桨细胞性淋巴瘤淋巴细胞、桨细胞性淋巴瘤 4.Mantle cell lymphoma 套细胞性淋巴瘤 5.Follicular Lymphoma 滤泡性淋巴瘤滤泡性淋巴瘤 6.Extranodal marginal zone lymphoma(MALT lymphoma) 节外边缘带淋巴瘤节外边缘带淋巴瘤 7. Splenic marginal zone lymphoma 脾边缘带淋巴瘤脾边缘带淋巴瘤 8. Nodal margi

17、nal zone lymphoma 淋巴结边缘带淋巴瘤淋巴结边缘带淋巴瘤 9. Hairy cell leukemia 毛细胞性白血病毛细胞性白血病 10. Plasmacytoma/plasma cell myeloma 浆细胞瘤浆细胞瘤/骨髓瘤骨髓瘤 11. Diffuse Large B-cell Lymphoma 弥漫性大细胞性淋巴瘤弥漫性大细胞性淋巴瘤 12. Burkitt Lymphoma 伯基特淋巴瘤伯基特淋巴瘤 Peripheral Lymphoid Cell Tumors Small lymphocytic lymphoma/ chronic lymphocytic leu

18、kimia Age 50 years Clinical 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, spleen, l

19、iver Morphology Low power: sheets of tumor cells diffusely efface involved lymph nodes Small lymphocytic lymphoma/chronic lymphocytic leukimia Morphology Predominant cells compact, small, dark-staining round nuclei, Scanty cytoplasm, and little variation in size Proliferation centers-Pseudofollicle

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

21、 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 Morphology lymph nodes are effaced by a nodular or follicular architec

22、ture Follicular Lymphoma Morphology Predominant neoplastic cells-centrocyte, CC 1. slight larger than resting lymphocytes 2. Coarse and condensed chromatin prominent indentations and linear infoldings Nucleoli are indistinct Other cells -Centroblast,CB 1.3-4 times the size of resting lymphocytes 2.

23、Vesicular chromatin several nucleoli modest amounts of cytoplasm Follicular Lymphoma Immunophenotyping Pan-B-cell markers: CD19, CD20, BCL2 BCL2 14: IgH gene; 18:BCL2 gene Translocation t(14,18) Bcl-2 protein antiapoptotic effect Prognosis Indolent course, median survival,7 to 9 years not easily cur

24、able 40% 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 NHLs Morphology its nuclei is large and varible (3-4 times the size of resting lymphocytes) Immunophenotype Pan-B-cell marker:

25、CD19, CD20 Subtypes: 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 lar

26、ge B-cell lymphoma Karyotype 30% t(14;18) BCL2 arrangement 1/3 3q27 BCL6 arrangement Prognosis Aggressive , Rapidly fatal if untreated With intensive combination chemotherapy, complete remission can be achieved in 60%-80% of the patients Burkitt Lymphoma Age Children or young adults endemic in some

27、parts of Africa 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 Morphology Starry sky: macrophages with ingested nuclear debris Monotonous round or oval nuclei contai

28、ning 2-5 prominent nucleoli Active mitosis Immunophenotype SIgM, pan-B-cell markers: CD19, CD10 Karyotype 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 patient

29、s can be cured. Burkitt Lymphoma . Hodgkin Lymphoma 10%20%, Tomas Hodgkin It was separated from NHLs for several reasons nIt arises almost invariably in a single node or a chain of nodes ndistinctive neoplastic giant cells called Read- Sternberg (RS) cells mixed with a variable infiltrate of reactiv

30、e inflammatory cells. nSystemic manifestations, such as fever nWith a relatively good prognosis. RS cells Abundant cytoplasm, d=15 to 45um Multilobate nucleus or multinucleate with large, round, prominent nucleoli Mirror-image nuclei . Hodgkin Lymphoma Variant of RS cells 1.Mononuclear variants 2.Lacunar cell A large folded or hyperlobate nucleus with multiple small nucleoli Abundant, pale-staining cytoplasm . Hodgkin Lymphoma Variant of RS cells 3.Lymphocytic and histocytic variants,(L CD15, CD30 2. Classical Hodgkin lymphoma CD45 -; CD15, CD30 + Hodgkin lymphoma Nodular lymphoc