WBC Pathology: Gen. Classification

1. WBC Pathology: Gen. Classification Leukopenia a. ineffective granulopoesis suppression of stem cells – aplastic An, drugs ineffective maturation - B12 def Congenital- Kostmann Syndrome b. increased destruction Ig-mediated injury peripheral utilization spleenic sequestration

2. Proliferative states • Reactive • Neoplastic

3. Reactive Proliferation of WBC in Smears • Leukocytosis neutrophilia – Bacterial infection, tissue necrosis lymphocytosis – chr infection, viral, immunologic eosinophilia – asthma, allergy, parasitic monocytosis – chr infection, collagen dis (SLE) 2. Leukemoidreaction • PBS changes: Neutrophils: toxic granules, Döhle bodies, shift to the left Reactive Lymphocytes – Atypical lymphocytes

4. Myelogenous series

5. Stab Döhle Body

6. Toxic Granules Atypical Lymphocyte

7. Reactive Proliferation of WBC in LN Acute Lymphadenitis  Reactive change 2o to microbiologic agents and their toxic prod • Foreign bodies or cell debris Chronic Lymphadenitis 1. Follicular hyperplasia i.e. Toxo, HIV  B- cell stimulation 2. Parafollicular/paracortical hyperplasia i.e. drugs, IM, vaccines  T cell stimulation 3. Sinus histiocytosis = Reticular hyperplasia seen in cancer

12. Follicular Hyperplasia

13. Chronic nonspecficlymphedenitis • Chronic immunological stimuli produce lesions in the lymph nodes • Follicular hyperplasia • Rheumatoid arthritis • HIV • Toxoplasmosis

14. Paracortical hyperplasia • It is T cell mediated immune response • Acute viral infections • Like Infectivous mononucleosis • T cell region contain typical immunoblasts,activated T cell 3 to 4 times the normal round nuclei and several nucleous

15. NEOPLASTIC PROLIFERATIONS • Lymphoid Neoplasms • Plasma cell Dyscracias • Myeloid Neoplasms • Histiocytosis

16. Myeloid neoplasms • arise from stem cells • acute myelogenous leukemias, in which immature progenitor cells accumulate in the bone marrow; • chronic myeloproliferative disorders, in which inappropriately increased production of formed blood elements leads to elevated blood cell counts;

17. myelodysplastic syndromes, which are characteristically associated with ineffective hematopoiesis and cytopenias • Histiocytic neoplasms represent proliferative lesions of histiocytes

18. Leukemias (Acute and Chronic) • Malignant diseases of bone marrow stem cells • Risk factors • a. Chromosomal abnormalities • • Examples—Down syndrome, chromosome instability syndromes, type 1 neuro fibr • b. Ionizing radiation • • Example—nuclear plant explosion • c. Chemicals • Example—benz.ene for myeloid leukemia • d. Alkylating agents • • Particularly busulfan

19. c. Chronic myeloproliferative diseases • • Example—polycythemia vera • f. Paroxysmal nocturnal hemoglobinuria • g. Cigarette smoking • h. Immimodeficieney diseases • • Example—Wiskott-Aldrich syndrome • 4. Age ranges for common leukemias

20. Pathophysiology of Acute Leukemias • The principal pathogenetic problem in acute leukemia is a block in differentiation • accumulation of immature leukemic blasts in the bone marrow • suppress the function of normal hematopoietic stem cells • bone marrow failure

21. NORMAL HEMATOPOESIS

22. B cell Tumors 80% T cell Tumors 20% L Y M P H O I D T U M O R S

23. REAL classif of Lymphoid Tumors 1. Precursor B cell (pre B cell) B lymphoblastic Leu (ALL) / lymphoma 2. Precursor T cell (pre T cell) T lymphoblastic Leu / Lymphoma 3. Peripheral B cell CLL , SLL Hairy cell Leu Burkitts Lymphoma Follicular lymphoma 4. Peripheral T cell or NK cell Adult T cell Lymphoma Anaplastic Large Cell Lymphoma Mycosis Fungoides / Sezary Syndrome 5. Hodgkins Lymphoma

24. Cell Antigens in WBC

25. B cell Tumors 80% T cell Tumors 20% CD1,CD2, CD5, CD7 CD10 CD19 CD10,CD19 CD23 CD5 L Y M P H O I D T U M O R S CD4 CD8 CD19, CD20 CD5, Ig CD 3 CD10,19,20 CD19,20

26. Char. of lymphoid tumors • Mostly B-cells • Each type has its own clinical presentation • Associated with immune abnormalities • Most of them are Bcell origin • The daughter cell of malignant progenitor share the same antigenic receptor gene • Hodgkin lymphoma spread in orderly fashion.

27. Acute lymphoblastic leukemia • Childhood ca • Origin • Immature B or T cell • Presence of Lymphoblast • Immune phenotype terminal deoxynucleotidyltransferaseTdT is a DNA polymerase present for immature B or T cell is positive in 95%

28. The lymphoblasts express B cell marker CD10,19,20 • For T cell CD 2,5,7 • Hyperploidy more the 50 chromosomes • Chrmosomal aberrations in transcrption factors NOTCH1 N PAX5 which is necessary for B or T cell development • Mutations in these leads to development of ALL • Very good response to chemotherapy

29. CLL also called as Small lymphocytic lymphoma also well differentiated lymphocytic lymphoma • Seen in adults also at the age of 60 yrs • I t is mature B cell or T cell origin • Common in Asia and Japan • Male to female 2:1

30. Morhpology • The small lymphocytes of 6to 12 mircmt diameter with mixed with large lymphocytes • Irregular nuclei and scanty cytoplasm increased mitotic rate showing prominent proliferation center • Also SMUDGE cells bec the tumor lymphocyte are fragile give charcterstic of this app

31. BM • Filled with tumor cells also red n white pulp of spllen occupied with tumor cells and hepatic portal system too involved • Immunephenotype • There is a chr deletion of 12q, 13q 11q and 17p • B cell marker CD 19 CD 20 and 23

32. CF • Patients present with anemai,neutropenia and thrombocytopenia • There is hypogammaglobulonemia and prone to infections and asloautoantibodiesagaint red cells

33. They transform to more aggressive form called • DIFFUSE LARGE B CELL LYMPHOMA called Richter syndrome PRO LYMPHOCYTIC LEUKEMIA • Which has poor prognosis

34. Peripheral B cell Neoplasms • Small Lymphocytic Lymphoma/CLL • Follicular Lymphoma • Diffuse large B-Cell lymphoma • Burkitts Lymphoma • Extranodal Marginal zone lymphoma • Mantle Cell Lymphoma • Hairy cell Leukemia • Multiple Myeloma

35. Histology: small cells mixed with “prolymphocytes” ~ proliferative centers

36. Histo: small round lymphocytes with smudge cells

37. FOLLICULAR LYMPHOMAS Most common type in the US (45%) Age: middle age; M ≈ F Chromosomal translocations involving BCL2 CF generalized painless lymphadenopathy w/ BM involvement. Extranodal spread is uncommon Prognosis: 7-9 ys, incurable Waxes & wanes, difficult to cure unaffected by Tx Progress to diffuse DLBL if with c-MYC Immunophenotype: + CD10, C19, CD 20 + Bcl-2 protein (90%)

38. Chronic Lymphocytic Leukemia *Phenotypically & genotypically indistinguishable frSLL differing only in the degree of peripheral lymphocytosis WBC count: ↓ in SLL, ↑in CLL Dx: absolute lymphocyte count >4,000 IR: SLL 4% of NHL CLL Most common Leukemias of adults Chromosomal abn, age, sex, distribution & clinical picture, prognosis: same as SLL

39. Bcl-2 protein Reactive Follicle Follicular Lymphoma

40. Diffuse Large B cell Lymphoma (DLBCL) Age: elderly (median 60y/o); pedia (5%) CF Rapidly enlarging symptomatic mass at a single nodal or extranodal site Prognosis: Aggressive, rapidly fatal if untreated Chemotx complete remission in 60-80% Cytogenetics : bcl6 (30%);t(14:18) (10%) overexpression of BCL2 Immunophenotype: + CD19, CD20; + CD10,

41. Morphology • Large cell with round or oval nuclei • Abudant cytoplasm

42. Burkitt Lymphoma • This common in children young adults • # forms • African or endemic • Non endemic or american • Associated with HIV • Endemic present with mandible or maxillary mass with extranodal involvement like kidney,ovaries and adrenal glands

43. The non endemic involves ileocecal junction and peritoneum • Morphology • Infiltration with intermediate lymphoid cells With multi lobe nucleoli and abundant cytoplasm • Benign macrophages giving app of STARRY SKY

45. Immunephenotype • These B-cell tumors express surface IgM, κ or λ light chain, the pan-B-cell markers CD19 and CD20, and CD10 • Genotype • translocations involving the MYC gene on chromosome 8.

46. Clinical Features • Present with mass in the extranodal are • Aggressive chemotherapy helps for the outcome of the lymphoma • Majoiryt of pt are cured.

47. All endemic tumors are infected with EB virus

48. Histology : Large cell size, multiple nucleoli, irregular nuclei, abundant cytoplasm

49. Endemic pattern Sporadic pattern

50. Starry sky pattern