1. Chapter 12 The diseases of Hematopoietic and Lymphoid System Liu weiping Department of Pathology West China School of Medicine Sichuan University

2. 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.

3. Diseases of hematopoitic and lymphoid system Red cell disorders White cell disorders* Bleeding disorders Disorders that affect the spleen and thymus

4. White cell disorders Non-Neoplastic Disorders - Reactive lymphoid hyperplasia (lymphadenitis) - Reactive leukocytosis Neoplastic Disorders - lymphomas - myeloid neoplasms - Histiocytic and dendritic-cell neoplasms

5. Lymph node

7. Benign lymphoid hyperplasia

8. Non-specific lymphadenitis - acute non-specific lymphadenitis - chronic non-specific lymphadenitis follicular hyperplasia parafollicular hyperplasia sinus histiocytosis Distinctive infection

9. Non-specific lymphadenitis

10. TB Tuberculosis lymph node

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

12. Lymphomas

13. Definition Lymphocyte differentiation WHO Classification Clinical manifestation and staging Diagnosis Genitics Epidemiology and etiology

14. 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

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

16. Hodgkin lymphoma, HL Non-Hodgkin lymphoma, NHL ▲ B-cell neoplasms ▲ T-cell and NK cell neoplasms Lymphomas - WHO Classification

17. Lymphomas - staging system

18. Lymphoma- Diagnosis Clinical manifestations Histopathology Immunophenotypes Genetics

19. 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

20. 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

21. 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

22. Hodgkin lymphoma

24. 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.

25. 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

29. Lucunar cell CHL Nodular sclerosis

30. porphyry spleen

31. Proposed signals mediated “cross talk” between R-S cells and surrounding normal cells in Classical Hodgkin lymphoma

32. Non Hodgkin Lymphomas

33. 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.

34. 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

35. 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

36. Lymphoblastic leukemia/lymphoma TdT

37. Chronic lymphocytic leukemia / small lymphocytic lymphoma

38. Follicular lymphoma Bcl-2

39. Diffuse large B-cell lymphoma

40. Burkitt lymphoma

41. Plasma cell myeloma

42. Extranodal NK/T-cell lymphoma, nasal type

43. Clinicopathologic differences between HL and NHL HL 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

44. Myeloid neoplasms

45. Myeloid neoplasms - Definition Myeloid neoplasms arise within hematopoietic stem cells and typically give rise to monoclonal proliferations that diffusely replace normal bone marrow cells.

46. 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

47. 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.

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

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

51. Peripheral blood Bone marrow biopsy

52. 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.

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

54. Granulocyte sarcoma MPO

55. 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.

56. Myeloproliferative neoplasms : Classification Chronic myelogenous leukemia* BCR-ABL1 positive Chronic neutrophilic leukemia Polycythaemia vera Primary myelofibrosis Essential thrombocythaemia Chronic eosinophilic leukemia Mastcytosis Myeloproliferative neoplasm, unclassifiable

57. Chronic myelogenous leukemia

58. CML Blood smear CML BM biopsy

59. CML- Detection of t(9;21) and ABL/BCR fusion gene

60. Myeloid neoplasms- Etiology Genetic abnormalities - chromosome translocation - gene mutation - gene deletion and gain Radiation exposure Environment factors

61. Treatment Chemotherapy Radiotherapy Antibiotic therapy Bone marrow transplantation Biological therapy

62. Summary Both AML and MPN are all clonal haematopoitic stem cell disorders. Lab findings are important for establishing diagnosis of the tumors. Characteristic genetic abnormalities were found in most of cases. No alternation presented between AML and MPN.

63. Histiocytic and dendritic cell neoplasms

64. 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

65. Tumors derived from langerhans cells Langerhans cell histiocytosis Langerhans cell sarcoma

66. Langerhans cell histiocytosis