Part I Neoplastic Proliferation Of Wbc
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Part I Neoplastic Proliferation Of Wbc

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Part I Neoplastic Proliferation Of Wbc Presentation Transcript

  • 1. NEOPLASTIC PROLIFERATION OF WBC
    1
  • 2. LYMPHOID NEOPLASM
    MYELOID NEOPLASM - Hematopoietic stem cells
    MYELOID LINEAGE
    1. ERYTHROID
    2. GRANULOCYTIC
    AML
    MYELODYSPLASTIC
    CHRONIC MYELOPROLIFERATIVE D/O
    3. THROMBOCYTIC
    HISTIOCYTOSES
    2
    CATEGORIES:
  • 3. Acute Myelogenous
    Immature progenitor cells accumulate in BM
    Myelodysplastic Syndromes
    Ineffective Hematopoiesis
    Peripheral Cytopenias
    Chronic Myeloproliferative D/O
    Increased production
    1 or more terminally differentiated myeloid elements
    GRANULOCYTES
    Leads to elevated peripheral blood counts
    3
    Granulocytic Lineage
  • 4. 4
    Pathogenetic factors
  • 5. Mutated genes  Produce Negative protein
    Interfere with its normal function/ or Inapropriate increase in some normal activity ( MALTomas )
    Translocation of either MALT1 or BCL10 protein  Upregulation of NF-kB
    Normally Bind to form complex  regulate NF-kB
    NF-kB has important pro-survival function in normal lymphocytes
    Oncoprotein created by genomic abberations
    Often Block normal maturation  Affect rapidly proliferating cells
    Acute Leukemias
    Proto-Oncogenes
    Often activated in lymphocytes by errors that occur during attempted antibody diversification
    5
    Chromosomal Translocation & Other Acquired Mutations
  • 6. 6
    Pathogenetic factors
  • 7. 7
    Pathogenetic factors
  • 8. 8
    Pathogenetic factors
  • 9. 9
    Pathogenetic factors
  • 10. 10
    Smoking
  • 11. LYMPHOID NEOPLASMS
    11
  • 12. CLASSIFICATION:
    Lymphocytic Leukemia
    Lymphoma
    Plasma cell Neoplasm
    12
  • 13. Lymphoid neoplasm
    Widespread Bone Marrow Involvement
    Usually (+) Large Numbers of Tumor cells in Peripheral smear
    13
    Lymphocytic leukemia
  • 14. Proliferations arising as Discrete tissue masses
    2 Types
    1. Non-HodgkinsLmphoma
    2. HodgkinsLymhoma
    Many types present with Leukemia
    Term used – Tissue distribution of the disease at time of clinical presentation
    14
    lymphoma
  • 15. Most commonly arise in Bone Marrow
    Rarely present as Leukemia
    R/T Secretion of Antibodies by tumor cells
    15
    Plasma cell Neoplasm
  • 16. Vast majority are B cell in origin
    Markers recognized by Antibodies help in characterization into 5 categories
    Often disrupt normal architecture & function of Immune system
    Susceptibility to infection
    Autoimmune
    16
    FEATURES- Lymphoid Neoplasm
  • 17. Inherited or acquired Immunedeficiency High risk certain lymphoid neoplasm
    Particularly caused by oncogenic virus eg. EBV
    17
    FEATURES- Lymphoid Neoplasm
  • 18. Tend to home to a particular tissue sites
    Follicular Lymphoma – Germinal center
    T-cell Lymphomas – Skin
    Some recirculate through the lymphatics & peripheral blood  Distant sites
    Except Hodgkins, Marginal zone lymphoma ( MALToma )
    18
    FEATURES- Lymphoid Neoplasm
  • 19. Determined by Anatomic distribuation of disease
    2/3 NHL and 100% of Hodgkin Lymphomas
    Enlarged Nontender LN
    Often > 2 cm
    Remaining 1/3 NHL
    Symptoms r/t to involvement of Extranodal sites
    Skin, Stomach, Brain
    19
    Clinical PresentationLymphoma
  • 20. Abrupt stormy onset
    Present w/in days to few weeks
    S/S related to Suppression of normal Hematopoiesis by tumor cells in BM
    Characteristic is Infiltrate in Spleen & Liver
    20
    LYMPHOCYTICLEUKEMIA
  • 21. Involve the skeleton
    Local bone destruction
    Pain
    Pathologic Fractures
    Addendum
    Secretion of whole Ab or Ig fragments
    21
    PLASMA CELL NEOPLASM
  • 22. Precursor B cell Neoplasm
    Immature B cells
    Peripheral B cell Neoplasms
    Mature B cells
    Percursor T-cell Neoplasm
    Immature T cells
    Peripheral T-cell & NK cell Neoplasm
    Mature T cell & NK cells
    Hodgkin Lymphoma
    22
    WHO 5 CATEGORIES
  • 23. Precursor B and T –Cell Neoplasms
    - Neoplasm of Immature B cells
    Acute Lymphoblastic Leukemia/Lymphoma
    23
  • 24. Group of Neoplasm composed of Immature pre-B or Pre-T LYMPHOBLASTS
    Most common cancer of Children
    Slightly higher in boys
    2 Types:
    1. Pre-B cell
    2. Pre-T cell
    Both tumors types are morphologically indistinguishable
    Features :
    24
  • 25. 85% are B-ALLs
    Manifest as Childhood Acute Leukemia
    Peak age is 3 y/o
    Extensive BM involvement
    Variable Peripheral involvement
    Uncommonly present as Lymphoma
    Less common is T-ALLs
    Adolescent males
    As Thymic Lymphoma
    Many evolve to Leukemia
    Features :
    25
  • 26. B-ALL
    Leukemic Presentation
    Marrow Hyperplasia and packed with Lymphoblast
    T-ALL
    Mediastinalthymic mass
    Often with LNadenopathy & Splenomegaly
    26
    Morphology
  • 27. Lymphoblast in PBS
    DefinitveDx based on Lymphocyte –specific markers with Antibodies
    Histochemical stain
    Negative for myeloperoxidase
    Often (+) PAS in cytoplasmic aggregates
    Immunophenotype
    (+) TdT in > 95% of cases
    DNA polymerase
    Expressed only in pre-B and pre-T lymphoblast
    Morphology :
    27
  • 28. 28
    Acute Lymphoblastic Leukemia
  • 29. B-ALL lymphoblast (+)
    CD19, CD10, CD19, CD20
    T-ALL lymphoblast (+)
    CD1, CD2, CD5, CD7
    Arrest in normal Maturation of Lymphoblast
    Dysregulation in epxression and function of transcription factors
    29
  • 30. About 90% ALL have numerical or structural chromosomal changes
    Most commonly – Hyperploidy
    > 50 chromosomes
    Hypoploidy
    Translocation
    Hyperploidy & Hypoploidy are seen only in B-ALL
    B & T ALL are associated wuth completely different sets of translocation
    30
    Molecular Pathogenesis
  • 31. 70% of T-ALL
    Have gain-of-function mutations in NOTCH1
    NOTCH1 is essential for T-cell development
    High Fraction of B-ALL
    Have loss-of-function mutations in genes for B cell development
    NET EFFECT:
    1. Disturb differentiation of Lymphoid precursor
    2. Promote Maturation arrest
    Single mutations are not sufficient to produce ALL  Must Acquire additional mutation before ALL develop
    31
    Molecular Pathogenesis
  • 32. Abrupt stormy onset
    Present w/in days to few weeks
    Symptoms r/t bone marrow suppression
    Anemia , Infection, Bleeding episodes
    Clinical Features :
    32
  • 33. Mass Effects
    Bone pain & tenderness
    Generalized Lymphadenopathy, Splenomegaly, Hepatomegaly
    T-ALL
    Complications R/T complression of large vessels and Airways in mediastinum
    Both may have CNS manifestation
    Due to meningeal spread
    Headache, Vomiting, Nerve palsies
    Clinical Features :
    33
  • 34. 34
  • 35. Aggressive ChemoTx often w/ prophylactic CNS treatment
    > 95% of children achieve complete remission
    75-85% of choldren are Cured
    Still the leading cause of cancer death in children
    Treatment & Prognosis :
    35
  • 36. Unfavorable Prognostic Factors
    < 2y/o
    Presentation in adolescence or childhood
    Peripheral blast count > 100,000
    Presence of Ph’ chromosome
    T(9;22)
    Commonly seen in adult patients
    ALLOGENIC BM TRANSPLANT – POOR PROGNOSTIC CATEGORIES
    36
  • 37. Age 2-10 y/o
    Low WBC count
    Early pre-B phenotype
    Hyperploidy or t(12;21)
    Favorable Prognostic Factor
    37
  • 38. Peripheral B cell Neoplasm- Neoplasm of Mature B cells
    38
    Chronic Lymphocytic Leukemia & Small Lymphocytic Lymphoma
    2. Follicular Lymphoma
    3. Diffuse Large Cell Lymphoma
    4. Extranodal marginal zone Lymphoma
    5. Burkitts Lymphoma
  • 39. CHRONIC LYMPHOCYTIC LEUKEMIA –CLLand SMALL LYMPHOCYTIC LYMPHOMA- SLL
    39
  • 40. Features
    Similar - Morphological, Phenotype, Genotype
    Differ only in degree of peripheral blood Lymphocytosis
    40
  • 41. Features
    CLL – Chronic Lymphocytic Leukemia
    Most common leukemia of Adults in Western countries
    Median age 60 y/o
    2:1 male preponderance
    Diagnostic Criteria
    Absolute Lymphocytosis > 4000 per mm3
    PERIPHERAL BLOOD
    WBC counts is High
    Increased numbers of Small Lymphocytes
    Smudge cell
    41
  • 42. Chronic Lymphocytic Leukemia
    42
  • 43. Features
    SLL – Small Lymphocytic Lymphoma.
    Represent 4% of Non-Hodgkin Lymphoma
    Total WBC count is Variable
    If w/ Bone Marrow Involvement can present as Leukopenia
    LYMPH NODE
    Diffusely Effaced , Predominant Small Lymphocytes
    Variable large Prolymphocytes
    CREATE PROLIFERATION CENTERS
    PATHOGNOMONIC FOR CLL/SLL
    43
  • 44. Small Cell Lymphoma
    44
  • 45. Immunophenotype/ Molecular Genetics
    CD5 – present in tumor cells
    T-cell marker
    Expressed by small subset of normal B lymphos
    Chromosomal translocation is rare
    Most are Deletions
    13q14
    11q
    17p
    45
  • 46. Clinical Features
    Mostly over 50 y/o
    Male > Female 2:1
    Often Asymptomatic
    Nonspecific symptoms when manifest
    BONE MARROW INVOLVEMENT
    All cases of CLL
    Most cases of SLL
    46
  • 47. Clinical Features
    50-60% show
    Generalized Lymphadenopathy
    Hepatosplenomegaly
    VARIABLE INVOLVEMENT OF SPLEEN & HEPATIC PORTAL TRATS
    47
  • 48. Clinical Features
    Disrupts Immune function
    Hypogammaglobulinemia – Susceptible to INFXN
    Autoimmune
    Auto-Antibodies produced by non-neoplastic B cells
    10-15% develop Hemolytic anemia /Thrombocytopenia
    48
  • 49. Prognosis
    Extremely Variable
    Depend mostly on Stage
    Overall Median is 4-6 years
    Minimal Tumor burden  10 years
    49
  • 50. Poor Prognostic Factors
    Presence of Deletions 11q & 17p
    Usually higher stage
    Transformation to higher grades
    Prolymphocytic 15%-30%
    Worsening cytopenias
    Increasing Splenomegaly
    Diffuse Large cell 5%-10%
    Rapidly enlarging mass w/in LN or spleen
    Richter syndrome
    Survival < 1 year
    50