Leukocytosis. Leukopenia. Leukosis


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Prepared By MD, PhD. Marta R. Gerasymchuk, pathophysiology department of Ivano-Frankivsk National Medical University, Ukraine
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  • ALL blasts look the same on routine stains, whether they are myeloblasts, lymphoblasts, monoblasts, etc.
    A blast is a blast!
    Please remember you have all been conditioned to think a NUCLEOLUS is darker than the rest of the NUCLEUS, as it is on H&E, but in the usual stains we stain bone marrow smears or peripheral smears with, the nucleoli are LIGHTER!!!
  • MYELOPEROXIDASE stains are often use to identify cells believed to be of MYELOID origin, such as blastic looking cells, but you cannot really tell for sure on Wright’s or Giemsa stains.
  • TOXIC GRANULES are EXAGGERATIONS of the marrow’s normal granularity, DOHLE bodies are fragments of remaining dilated rough ER.
    Neutrophilia can be viewed as a NONSPECIFIC index of acute infection, especially bacterial, but also tissue necrosis.
  • Not only are basophils RARE to find normally, but pure “basophilia” is also VERY rare.
  • Why would monocytosis be linked to granulomatous diseases? Answer: Monocytes are macrophages in circulation, and granulomatous diseaseas are macrophage diseases. Is it surprising that many classical granulomatous diseases are also characterized by monocytosis, because macrophages are the CHIEF cells of granulomas? Answer: NO, not surprizing, it would be logical even!
  • Would it be a fair statement to say that whereas, neutrophilia is characterized by bacterial infections, lymphocytosis can be an index of many viral infections? Answer: Yes, it is fair, but there are many exceptions.
  • The most life saving thing you can learn today is how to recognize a blast!
    NUCLEOLI (stain LIGHTER not DARKER than the rest of the nucleus on Wright stain), How many nucleoli does that one blast cell have? Answer: 3
    NO cytoplasmic differentiation
  • Ataxia-Telangiectasia is characterised by:
    Early-onset progressive cerebellar ataxia (difficulty with control of movement)
    Ocular apraxia (difficulty following objects across visual field)
    Telangiectasias of the eyes and skin
    Immunodeficiency, low immunoglobulin concentrations
    Chromosomal instability
    Hyper-sensitivity to ionizing radiation
    Increased incidence of malignancies (primarily hematologic).
    Raised alpha-fetoprotein levels.[4]
    Absent thymic shadow on X-ray.
    Ovarian dysgenesis
  • Acute promyelocytic leukemia, remember promyelocytes have BOTH nucleoli AND nonspecific granules, true BLASTS do NOT have granules.
    Do you remember that M3 has a high degree of association with DIC?
  • You can usually diagnose CLL simply from a CBC printout, but should verify the cells visually.
  • Many cells from CLL have a “smudge” or “basket” appearance
  • Note the “lytic” lesions. Often the term “punched out” is used also.
  • Leukocytosis. Leukopenia. Leukosis

    1. 1. By M.D., PhD., Associate ProfessorBy M.D., PhD., Associate Professor Marta R. GerasymchukMarta R. Gerasymchuk,, Pathophysiology DepartmentPathophysiology Department Ivano-Frankivsk National Medical UniversityIvano-Frankivsk National Medical University
    2. 2. WBC’sWBC’s
    3. 3. NeutrophilNeutrophil PMN-PolymorphonuclearPMN-Polymorphonuclear Leucocytes.Leucocytes. 60-70% WBC60-70% WBC Appearance: pink granules inAppearance: pink granules in cytoplasm, nucleus has 3-4cytoplasm, nucleus has 3-4 lobeslobes Function:Function: ♦♦ MarginationMargination ♦♦ RollingRolling ♦♦ AdhesionAdhesion ♦♦ Transmigration (Diapedesis)Transmigration (Diapedesis) ♦♦ ChemotaxisChemotaxis ♦♦ Phagocytosis: Recognition,Phagocytosis: Recognition, Engulfment, Killing (digestion)Engulfment, Killing (digestion) ♦♦Equilibrium with splenic poolEquilibrium with splenic pool Azurophilic (1°) granules areAzurophilic (1°) granules are "lysosomes of PMNs", occur"lysosomes of PMNs", occur in all leukocytesin all leukocytes DÖHLE BODIES and TOXICDÖHLE BODIES and TOXIC GRANULES are often seenGRANULES are often seen with NEUTROPHILIAwith NEUTROPHILIA Accompanied by a “LEFT”Accompanied by a “LEFT” shiftshift
    4. 4. PELGER-HUET ANOMALYPELGER-HUET ANOMALY  GeneticGenetic  Sometimes ACQUIRED (Pseudo-PELGER-HUET)Sometimes ACQUIRED (Pseudo-PELGER-HUET)  All neutrophils look like BANDSAll neutrophils look like BANDS  NOT serious, mostly a cute incidental findingNOT serious, mostly a cute incidental finding
    5. 5. CHEDIAK-HIGASHI SYNDROMECHEDIAK-HIGASHI SYNDROME  Also geneticAlso genetic  Abnormal LARGEAbnormal LARGE irregular neutrophilirregular neutrophil granulesgranules  Impaired lysosomalImpaired lysosomal digestion of bacteriadigestion of bacteria  Associated with pigmentAssociated with pigment and bleeding disordersand bleeding disorders  CAN be serious,CAN be serious, especially in kidsespecially in kids
    6. 6. Eosinophil (Eos)Eosinophil (Eos)  Bilobed nucleusBilobed nucleus  2-4% of WBC2-4% of WBC  Recruited to sites ofRecruited to sites of inflammationinflammation  Function: Involved inFunction: Involved in allergy, parasiticallergy, parasitic infectionsinfections  Contains: eosinophilicContains: eosinophilic granulesgranules  Granules contain: majorGranules contain: major basic proteinbasic protein  Terminally differentiatedTerminally differentiated Azurophilic granuels
    7. 7. BasophilBasophil• Circulating form of mastCirculating form of mast cellscells • Terminally differentiatedTerminally differentiated • <1% WBC (< 1 x 10*9/L)<1% WBC (< 1 x 10*9/L) • Contains: basophilicContains: basophilic granulesgranules • Granules contain:Granules contain: histamine and heparinhistamine and heparin • IgE receptorsIgE receptors • Involved in allergyInvolved in allergy
    8. 8. Monocyte / Macrophage Monocyte • 3-8% WBC • Circulating form (precursor) of tissue macrophages • Recruited to sites of inflammation Macrophages • Phagocytosis, bacterial killing, antigen presentation • Peritoneal cavity: peritoneal macrophages • Lung: alveolar macrophages • Spleen: splenic macrophages • Liver: Kupffer cells
    9. 9. LymphocyteLymphocyte •Appearance: small (same size as RBCs), little visible cytoplasm •NO specific granules • 20-25% of WBC •T cells: CMI (for viral infections) • B cells: humoral (antibody) • Natural Killer Cells T B T B
    10. 10. PrimaryPrimary SecondarySecondary Absolute RelativeAbsolute Relative LeukocytosisLeukocytosis Stimulation of leukopoiesis - Leukocytosis of pregnant (5- 6 mounts of pregnancy) Redistribution of leukocytes in vascular bed - alimentary, - emotional, - myogenic, - static 1. Stimulation of leukopoiesis 2. Increase of leukocytes transport from bone marrow 3. Increase of tumoral type of leukopoiesis during leukosis 1.Hemoconcentra tional 2.Redistributional
    11. 11. LeukocytosisLeukocytosis
    12. 12. LeukocytosisLeukocytosis 4000-9000 • Neutrophylia – Acute bacterial infection, sterile inflammation Eosinophylia – Allergy (allergic rhinitis, other hypersensitivity reactions,including drug reactions), parasites (ascaris, hookworm, strongiloides), certain skin diseases, cancer (adenocarcinoma) • Basophilia – rare (leukemia) • Monocytosis – chronic infections, bacterial endocarditis, rickettsiosis, malaria, collagen vascular disorders, inflammatory bowel diseases • Lymphocytosis – some viral infections
    13. 13. Leuko cytes Baso- philes Eosi- nophi -les Neutrophiles Lym- pho- blasts Lym- pho- cytes Mo- no- cytes Mye- lo- blasts Pro- my- elocyt es Mye- lo- cytes Meta- mye- lo- cytes Stab- nuc- leonic Seg- men- tonuc- lenic 12 1% 2% 0% 0% 0% 1 % 15% 57% 0% 20% 4% 100* 109 /l 1% 0% 0% 0% 1% 2% 5% 8% 80% 1% 2% 60* 109 /l 2% 0% 90% 0% 1% 0% 2% 1% 0% 3% 1% 22* 109 /l 2% 1% 3% 14% 10% 6% 7% 39% 0% 10% 8% 48* 109 /l 3% 2% 0% 0% 0% 2% 3% 7% 4% 75% 4%
    14. 14. Leukopenias Primary (hereditary) Secondary (Acquired) 1. Deficit of maturity factors - constant hereditary neutropenia -periodic hereditary neutropenia 2. Deficit of myeloperoxidase, G-6-PhDG - hereditary monocytopenia with phagocytic insufficiency deficit (disease of Chediak- Higashi) 1. Inhibition of leukopoiesis 2. Increase of leukodieresis 3. Increase of leukocyte loss 4. Decrease of leukocyte emigration from bone morrow 1. Redistributional e.g. shock, severe muscular work etc. 2. Hemodilutional e.g. blood plasma, transfusion of blood substitutes, hydremia etc. Absolute Relative
    15. 15. Causes of Neutropenia CauseCause MechanismMechanism Accelerated removalAccelerated removal ((e.g.e.g., inflammation and, inflammation and infection)infection) Removal of neutrophils from the circulation exceedsRemoval of neutrophils from the circulation exceeds productionproduction Drug-induced granulocytopeniaDrug-induced granulocytopenia Defective productionDefective production Cytotoxic drugs used in cancer therapyCytotoxic drugs used in cancer therapy Phenothiazine, thiouracil,Phenothiazine, thiouracil, chloramphenicol, phenylbutazonechloramphenicol, phenylbutazone, and, and othersothers Hydantoinates, primidoneHydantoinates, primidone, and others, and others Immune destructionImmune destruction AminopyrineAminopyrine and othersand others • Predictable damage to precursor cells, usuallyPredictable damage to precursor cells, usually dose dependentdose dependent • Idiosyncratic depression of bone marrowIdiosyncratic depression of bone marrow functionfunction • Intramedullary destruction of granulocytesIntramedullary destruction of granulocytes • Immunologic mechanisms with cytolysis orImmunologic mechanisms with cytolysis or leukoagglutinationleukoagglutination Periodic or cyclic neutropeniPeriodic or cyclic neutropenia (occurs duringa (occurs during infancy and later)infancy and later) UnknownUnknown Neoplasms involving bone marrowNeoplasms involving bone marrow (e.g.,(e.g., leukemias and lymphomas)leukemias and lymphomas) Overgrowth of neoplastic cells, which crowd outOvergrowth of neoplastic cells, which crowd out granulopoietic precursorsgranulopoietic precursors Idiopathic neutropeniaIdiopathic neutropenia that occurs in the absencethat occurs in the absence of other disease or provoking influenceof other disease or provoking influence Autoimmune reactionAutoimmune reaction Felty’Felty’s syndromes syndrome Intrasplenic destruction of neutrophilsIntrasplenic destruction of neutrophils
    16. 16. MyelotoxicMyelotoxic ImmuneImmune AGRANULOCYTOSISAGRANULOCYTOSIS 1.1. Cytolytic influence, e.g.Cytolytic influence, e.g. ionizing radiation etc.ionizing radiation etc. 2.2. Antimetabolic influenceAntimetabolic influence e.g. cytostatics etc.e.g. cytostatics etc. 1.1. Autoimmune e.g. lupusAutoimmune e.g. lupus erythematosus,erythematosus, rheumatoid arthritisrheumatoid arthritis 2. Heteroimmune2. Heteroimmune
    17. 17.  Leukemias Bone marrow, blood, blast cells Acute / Chronic & Myeloid / Lymphoid AML / ALL & CML / CLL  Lymphomas – Lymph nodes, tumor Hodgkins - Non-Hodgkins. Myeloma High grade & Low grade Premalignant conditions: Myeloproliferative syndromes (MPS) Myelodysplastic syndromes (MDS) WBC Neoplastic disorders :
    18. 18. Mechanisms of boneMechanisms of bone marrow neoplasiamarrow neoplasia  Blast cells (malignant)Blast cells (malignant) overpopulate the bone marrowoverpopulate the bone marrow and replace the normal cells causing bone destructionand replace the normal cells causing bone destruction and/or blood or lymphoid cell deficiencies.and/or blood or lymphoid cell deficiencies.  Malignant cellsMalignant cells or their descendents may appear in theor their descendents may appear in the peripheral blood (leukemia), in extramedullary sites suchperipheral blood (leukemia), in extramedullary sites such as the spleen and liver (as the spleen and liver (hepatosplenomegalyhepatosplenomegaly) and in) and in lymph nodes (lymph nodes (lymphadenopathylymphadenopathy).).  Bone marrow malignancyBone marrow malignancy may be accompanied bymay be accompanied by myelofibrosis (the extensive deposition of collagen by non-myelofibrosis (the extensive deposition of collagen by non- neoplastic fibroblasts).neoplastic fibroblasts).  Types of bone marrow neoplasia:Types of bone marrow neoplasia: MalignantMalignant transformation of hematopoietic and lymphoid celltransformation of hematopoietic and lymphoid cell precursors may occur at any point in their maturation.precursors may occur at any point in their maturation. Malignant cells are classified asMalignant cells are classified as myeloid, lymphoid ormyeloid, lymphoid or plasmacyticplasmacytic. The characteristic behavior of particular. The characteristic behavior of particular malignant stem cells determines the presentation of themalignant stem cells determines the presentation of the disease.disease.
    19. 19. Types of bone marrow neoplasia 1. Myeloproliferative disorders: Characterized by the malignant transformation of developmentally pluripotent myeloid stem cells and their linage- restricted descendants. 2. Myelodysplastic syndromes: Characterized by ineffective hematopoiesis and pancytopenia. 3. Leukemia: Characterized by the appearance of neoplastic WBCs in the peripheral circulation. 4. Plasma cell disorders: Characterized by the monoclonal proliferation of neoplastic plasma cells and plasmacytoid lymphocytes usually in the bone marrow
    20. 20. Neoplastic WBC Disorders:Neoplastic WBC Disorders:  No Benign Neoplasms – All are considered malignant or premalignant.  Cells flood blood stream – Leukemia.  Arise in marrow(myeloid/lymphoid) or Lymph node (lymphoid), then spread to blood & other organs  MalignantMalignant  LeukemiasLeukemias  LymphomasLymphomas  Premalignant:Premalignant:  MyeloproliferativeMyeloproliferative  Myelodysplastic Sy.Myelodysplastic Sy.
    21. 21. Myeloproliferative Disorders These disorders include: • polycythemia rubra vera (proliferation of RBC precursors), • essential thrombocytemia (proliferation of platelet precursors) • chronic myelocytic leukemia (proliferation of neutrophil precursors) and • myelofibrosis (proliferation of fibroblasts). These entities are interrelated and may transform one into another or into acute myeloblastic leukemia (AML). Features common to all myeloproliferative disorders: 1. Peak incidence in 40-70 years of age 2. Marrow hypercellularity, except myelofibrosis which is dominated by fibrosis 3. Splenomegaly due to extramedullary hematopoiesis 4. Peripheral blood abnormalities and hyperviscosity, except for myelofibrosis
    22. 22. MPS: ClassificationMPS: Classification
    23. 23. MPS - P. Rubra Vera (PV)MPS - P. Rubra Vera (PV)
    24. 24. Myelodysplastic syndromesMyelodysplastic syndromes  Myelodysplastic syndromesMyelodysplastic syndromes (MDS, formerly known as "(MDS, formerly known as "preleukemiapreleukemia")") are a diverse collection of hematological conditions united by ineffectiveare a diverse collection of hematological conditions united by ineffective production of blood cells andproduction of blood cells and varying risks of transformation to acutevarying risks of transformation to acute myelogenous leukemia (AML)myelogenous leukemia (AML). Anemia requiring chronic blood. Anemia requiring chronic blood transfusion is frequently present.transfusion is frequently present.  Myelodysplastic syndromes (MDS)Myelodysplastic syndromes (MDS) are bone marrow stem cell disordersare bone marrow stem cell disorders resulting in disorderly and ineffective hematopoiesis manifested byresulting in disorderly and ineffective hematopoiesis manifested by irreversible quantitative and qualitative defects in hematopoietic cellsirreversible quantitative and qualitative defects in hematopoietic cells. In. In a majority of cases, the course of disease is chronic with graduallya majority of cases, the course of disease is chronic with gradually worsening cytopenias due to progressive bone marrow failure.worsening cytopenias due to progressive bone marrow failure.  Approximately one-third of patients with MDS progress to AML withinApproximately one-third of patients with MDS progress to AML within months to a few years.months to a few years.  The median age at diagnosis of a MDS is between 60 and 75 years; a fewThe median age at diagnosis of a MDS is between 60 and 75 years; a few patients are less than 50;patients are less than 50; MDS are rare in childrenMDS are rare in children. Males are slightly. Males are slightly more commonly affected than females. Signs and symptoms aremore commonly affected than females. Signs and symptoms are nonspecific and generally related to thenonspecific and generally related to the blood cytopeniasblood cytopenias (anemia,(anemia, neutropenia, thrombocytopenia).neutropenia, thrombocytopenia).  A significant proportion of the morbidity and mortality attributable toA significant proportion of the morbidity and mortality attributable to MDS results not from transformation to AML but rather from theMDS results not from transformation to AML but rather from the cytopenias seen in all MDS patients. Anemia is most common andcytopenias seen in all MDS patients. Anemia is most common and responds to transfusion, patients often suffer from iron overload. Theresponds to transfusion, patients often suffer from iron overload. The two most serious complications in MDS patients resulting from theirtwo most serious complications in MDS patients resulting from their cytopenias arecytopenias are bleedingbleeding ((due to lack of plateletsdue to lack of platelets) or) or infectioninfection ((due to lackdue to lack of white blood cellsof white blood cells).).
    25. 25. Myelodysplastic Syndromes:Myelodysplastic Syndromes:  Excess proliferation in marrow.Excess proliferation in marrow.  But functional & StructuralBut functional & Structural abnormalityabnormality  Ineffective Myelopoiesis.Ineffective Myelopoiesis.  Peripheral pancytopenia.Peripheral pancytopenia.  Also known as Refractory Anemia’sAlso known as Refractory Anemia’s  Not responding to hematenics.Not responding to hematenics.
    26. 26. MPS : E.T. BleedingMPS : E.T. Bleeding
    27. 27. LEUKEMIAS  ■ Leukemias are malignant neoplasms arising from the transformation of a single blood cell line derived from hematopoietic stem cells.  ■ The leukemias are classified as acute and chronic lymphocytic (lymphocytes) or myelogenous (granulocytes, monocytes) leukemias, according to their cell lineage.  ■ Because leukemic cells are immature and poorly differentiated, they proliferate rapidly and have a long life span; they do not function normally; they interfere with the maturation of normal blood cells; and they circulate in the bloodstream, cross the bloodbrain barrier, and infiltrate many body organs.
    28. 28. LeukemiaLeukemia ClassificationClassification  Acute Leukemias:Acute Leukemias:  Acute Myeloid Leukemia -Acute Myeloid Leukemia - AMLAML  AMLAML M0, M1, M2, M3M0, M1, M2, M3,, M4, M5, M6 & M7M4, M5, M6 & M7  Acute Lymphoid Leukemia -Acute Lymphoid Leukemia - ALLALL  ALL -ALL - L1, L2 & L3L1, L2 & L3 - maturity- maturity  Chronic Leukemias:Chronic Leukemias:  Chronic Myeloid Leukemia-Chronic Myeloid Leukemia- CMLCML  Chronic Lymphoid Leukemia -Chronic Lymphoid Leukemia - CLLCLL
    29. 29. Leukemia –Leukemia – ClinicalClinical FeaturesFeatures  AnemiaAnemia (low RBC)(low RBC)  Fever - InfectionsFever - Infections (low WBC)(low WBC)  Bleeding tendencyBleeding tendency (low PLT)(low PLT)  Tender bones, lymphadenopathy,Tender bones, lymphadenopathy, spleenomegaly etc.spleenomegaly etc. (Leukemic infiltration)(Leukemic infiltration)  IntoxicationIntoxication  Autosensitization (esp. lymphogenic L.)Autosensitization (esp. lymphogenic L.)
    30. 30. AML-M5 - Gum Hypertrophy:AML-M5 - Gum Hypertrophy:
    31. 31. AML- Marked Purpura:AML- Marked Purpura:
    32. 32. ALL:Cervical LymphadenopathyALL:Cervical Lymphadenopathy
    33. 33. LEUKEMIASLEUKEMIAS Acute or ChronicAcute or Chronic  Myeloid or LymphocyticMyeloid or Lymphocytic  Childhood or AdultChildhood or Adult  All involve marrowAll involve marrow  All ACUTE leukemias suppress normalAll ACUTE leukemias suppress normal hematopoesis, i.e., have anemia,hematopoesis, i.e., have anemia, thrombocytopeniathrombocytopenia  Most have chromosomal aberrationsMost have chromosomal aberrations  Some can respond DRASTICALLY to chemo,Some can respond DRASTICALLY to chemo, most notably ALL in children, even be cured!!!!most notably ALL in children, even be cured!!!!
    34. 34. BLASTBLAST
    35. 35. WHITE CELL NEOPLASMS Leuk/LymphWHITE CELL NEOPLASMS Leuk/Lymph  Many have chromosomal translocationsMany have chromosomal translocations  Can arise in inherited and/or genetic diseases:Can arise in inherited and/or genetic diseases:  Downs Syndrome (Trisomy 21)Downs Syndrome (Trisomy 21)  Fanconi’s anemia (hereditary aplastic anemia)Fanconi’s anemia (hereditary aplastic anemia)  Ataxia telangiectasiaAtaxia telangiectasia  May have a STRONG viral relationship:May have a STRONG viral relationship:  HTLV-1 (lymphoid tumors)HTLV-1 (lymphoid tumors)  EBV (Burkitt Lymphoma)EBV (Burkitt Lymphoma)  Human Herpesvirus-8 (B-Cell Lymphomas)Human Herpesvirus-8 (B-Cell Lymphomas) (also KS)(also KS)
    36. 36. WHITE CELL NEOPLASMSWHITE CELL NEOPLASMS Leuk/LymphLeuk/Lymph  Can be caused by H. Pylori (Can be caused by H. Pylori (gastric B-gastric B- Cell lymphomasCell lymphomas))  Can follow celiac diseaseCan follow celiac disease  T-Cell lymphomasT-Cell lymphomas  Are common in HIV, B-CellAre common in HIV, B-Cell lymphomas, CNS lymphomaslymphomas, CNS lymphomas
    37. 37. 1. Acute1. Acute Lymphoblastic leukemia (ALL)Lymphoblastic leukemia (ALL) ~30% of all leukemias, the most common among children under 5 years old. The marrow contains more than 30% lymphoblasts. The prognosis is inversely proportional to age. 2. Acute myelogenous leukemia (AML)2. Acute myelogenous leukemia (AML) ~80% of acute leukemias in adults. Marrow has >20% myeloblasts. Overall prognosis is poor with relapse after chemotherapy and most do not survive more than 5 years after diagnosis. Two forms; acute denovo AML or as an end-stage of CML and myelofibrosis. AMLALL
    38. 38. Types of LeukemiasTypes of Leukemias 3.3. Chronic lymphocytic leukemia (CLL)Chronic lymphocytic leukemia (CLL) Peak incidence is inPeak incidence is in elderly males >60years old. Bone marrow has >40% lymphoidelderly males >60years old. Bone marrow has >40% lymphoid cells, peripheral blood has >15 X10↑6. Neoplastic cellscells, peripheral blood has >15 X10↑6. Neoplastic cells resemble B-lymphocytes. CLL has an indolent course over 7-resemble B-lymphocytes. CLL has an indolent course over 7- 10 years, it responds poorly to chemotherapy. It is closely10 years, it responds poorly to chemotherapy. It is closely related to small cell lymphoma and lymphadenopathy isrelated to small cell lymphoma and lymphadenopathy is common.common. 4.4. Chronic myelogenous leukemias (CML)Chronic myelogenous leukemias (CML) Peak incidence isPeak incidence is ~60years old. Symptoms are related to loss of normal marrow~60years old. Symptoms are related to loss of normal marrow functioning; anemia, bleeding & infection. Peripheral WBCfunctioning; anemia, bleeding & infection. Peripheral WBC counts in the 20-50,000 range with large component of myeloidcounts in the 20-50,000 range with large component of myeloid precursors. Frequently terminates in a “blast” crisis withprecursors. Frequently terminates in a “blast” crisis with peripheral WBCs of >100,000 with immature myeloid cells.peripheral WBCs of >100,000 with immature myeloid cells. Prognosis is poor despite chemotherapy.Prognosis is poor despite chemotherapy.
    39. 39. Leuko cytes Baso- philes Eosi- nophi -les Neutrophiles Lym- pho- blasts Lym- pho- cytes Mo- no- cytes Mye- lo- blasts Pro- my- elocyt es Mye- lo- cytes Meta- mye- lo- cytes Stab- nuc- leonic Seg- men- tonuc- lenic 12 1% 2% 0% 0% 0% 1 % 15% 57% 0% 20% 4% 100* 109 /l 1% 0% 0% 0% 1% 2% 5% 8% 80% 1% 2% 60* 109 /l 2% 0% 90% 0% 1% 0% 2% 1% 0% 3% 1% 22* 109 /l 2% 1% 3% 14% 10% 6% 7% 39% 0% 10% 8% 48* 109 /l 3% 2% 0% 0% 0% 2% 3% 7% 4% 75% 4%
    40. 40. ALL-Acute Lymphoid Leuk.ALL-Acute Lymphoid Leuk.  Common in Children.Common in Children.  FAB classification L1, L2FAB classification L1, L2 & L3& L3  B cell, T cell & histiocyticB cell, T cell & histiocytic types.types.  CD10 +ve, Pre B cell typeCD10 +ve, Pre B cell type common.common.  Lymphadenopathy,Lymphadenopathy, bleeding tendencybleeding tendency  ModerateModerate HepatosplenomegalyHepatosplenomegaly
    41. 41. ALL-L1ALL-L1
    42. 42. ALL-L2ALL-L2
    43. 43. ALL-L3ALL-L3
    44. 44. AML-Acute Myeloid Leuk.AML-Acute Myeloid Leuk.  Malignancy of myeloid progenitor cells.Malignancy of myeloid progenitor cells.  Adults commonAdults common  Hepatosplenomegaly moderateHepatosplenomegaly moderate  No significant lymphadenopathyNo significant lymphadenopathy  Bleeding tendencyBleeding tendency  Gum bleeding common in M5/M4Gum bleeding common in M5/M4  FAB classification - M0 to M7.FAB classification - M0 to M7.
    45. 45. AML-Acute Myeloid Leuk.AML-Acute Myeloid Leuk. ►M0 - AML No maturationM0 - AML No maturation (<3% Peroxidase +ve)(<3% Peroxidase +ve) ►M1 - AML Min.MaturationM1 - AML Min.Maturation(>3% Peroxidase +ve)(>3% Peroxidase +ve) ►M2 - AML With full maturationM2 - AML With full maturation ►M3 - A.Promyelocytic leukemiaM3 - A.Promyelocytic leukemia ►M4 - A.Myelomonocytic leukemiaM4 - A.Myelomonocytic leukemia ►M5 - A.Monocytic LM5 - A.Monocytic L(a-Monocytic, b-M.blastic)(a-Monocytic, b-M.blastic) ►M6 - A. ErythroleukemiaM6 - A. Erythroleukemia ►M7 - A. Megakaryocytic leukemia.M7 - A. Megakaryocytic leukemia.
    46. 46. AML-M0 - Undifferentiated:AML-M0 - Undifferentiated:
    47. 47. AML-M1 - without maturationAML-M1 - without maturation
    48. 48. AML-M2 - with maturationAML-M2 - with maturation
    49. 49. AML-M3 - Auer RodsAML-M3 - Auer Rods
    50. 50. M3M3
    51. 51. AML-M3 - Promyeloid
    52. 52. AML-M4 - MyelomonocyticAML-M4 - Myelomonocytic
    53. 53. AML-M5b - Monoblastic Leuk
    54. 54. AML-M6 : Erythroleukemia
    55. 55. AML-M7 : Megakaryocytic
    56. 56. Chronic Myeloid Leukemia • Middle age 40-60y • Philadelphia chromosome, t(9:22) • Leucocytosis (>50x109 /L), abnormal cells • Marked splenomegaly • Anemia, Bleeding • Hypermetabolism, • Hyperuricemia- gout, renal impairment.
    57. 57. Chronic Myelogenous Leukemia, BCR-ABL1+ • Chronic myelogenous leukemia presenting in blast phase including lymph node involvement. • A, Peripheral blood smear with leukocytosis, massive left shift with “myelocyte bulge” and 7% blasts (Wright- Giemsa). • B, Inguinal lymph node with sheets of blasts (H&E). • C, Blasts positive for CD3 antigen. Contributed by N. Vajpayee and colleagues.
    58. 58. Chronic Myelomonocytic Leukemia • Circulating promonocytes are present (A and B) in a sample from a patient with chronic myelomonocyti c leukemia (A and B, blood sample.
    59. 59. • Unexplained sustained (months) lymph count of > 4000/mm3 is CLL, usually picked up on CBC • M>F • Lymphs look normal and are NOT blasts • No need for marrow exam for dx, but progressive involvement of marrow, nodes, and other organs is the usual biologic behavior • Liver can be involved portally or sinusoidally • Translocations RARE, but trisomies and deletions common
    60. 60. • HYPO-gammaglobulinemia • 15% have antibodies against RBC’s or PLATS • CANNOT be classified as separate from lymphomas
    61. 61. Lymphomas Neoplasms of lymphoid cells may be divided into two major groups: • Non-Hodgkin’s lymphoma ~70% • Hodgkins lymphoma ~30% Predisposing factors 1. Oncogenes, both lymphomas & leukemias may share the same oncogenes. 2. Radiation increases the risk of lymphomas particularly radiation therapy for neoplastic disorders. 3. Environmental factors, Burkitt lymphoma is related to EBV infection. 4. Immunodeficiency states (congenital or acquired) are associated with an increased incidence of lymphomas; HIV is associated with CNS lymphoma.
    62. 62. (MALIGNANT)(MALIGNANT) LYMPHOMASLYMPHOMAS ► Terms in historic classifications:Terms in historic classifications:  Diffuse/Follicular, Small/Large, Cleaved/Non-Diffuse/Follicular, Small/Large, Cleaved/Non- cleavedcleaved  Hodgkins (REED-STERNBERG CELL) /NON-Hodgkins (REED-STERNBERG CELL) /NON- HodgkinsHodgkins  Lukes, Rappaport, etc.Lukes, Rappaport, etc.  Working Formulation, WHO, NIH, FAB, Intl., etc.Working Formulation, WHO, NIH, FAB, Intl., etc.  BB  TT  PRECURSOR (less maturePRECURSOR (less mature looking)looking)
    63. 63. Hodgkins Lymphoma:Hodgkins Lymphoma:  Hodgkin’s disease is a group of cancers characterized by Reed-Sternberg cells that begins as a malignancy in a single lymph node and then spreads to contiguous lymph nodes  Lymphadenopathy, painless, firmLymphadenopathy, painless, firm  Pel-Ebstein fever, Eosinophilia,Pel-Ebstein fever, Eosinophilia,  Reed-Sternberg cells - B lymphocytesReed-Sternberg cells - B lymphocytes  Histological Types:Histological Types: – Lymphocyte predominant.Lymphocyte predominant. – Nodular Sclerosis.Nodular Sclerosis. – Mixed cellularity.Mixed cellularity. – Lymphocyte depleted.Lymphocyte depleted.
    64. 64. Non-Hodgkins Lymphoma:Non-Hodgkins Lymphoma:  Non-Hodgkin’s lymphomas represent a group ofNon-Hodgkin’s lymphomas represent a group of heterogeneous lymphocytic cancers that areheterogeneous lymphocytic cancers that are multicentric in origin and spread to various tissuesmulticentric in origin and spread to various tissues throughout the body, including the bone marrow.throughout the body, including the bone marrow.  According to cell typeAccording to cell type  T cell NHLT cell NHL  B cell NHLB cell NHL  Miscellaneous NHLMiscellaneous NHL  Ex: Lennert’s lymphoma is a low grade Tcell NHL.Ex: Lennert’s lymphoma is a low grade Tcell NHL.  Burkitt’s lymphoma is a high grade B cell NHLBurkitt’s lymphoma is a high grade B cell NHL According to Clinical gradeAccording to Clinical grade •Low grade NHLLow grade NHL •High grade NHLHigh grade NHL •Intermediate grade NHLIntermediate grade NHL
    65. 65. Non-Hodgkin lymphomas Burkitt lymphoma is a rapidly growing B-cell lymphoma affecting children and adults. It is related to EB virus infection. Solid tumors are often located in extranodal tissue. Response to chemotherapy is inversely related to age.
    66. 66. Hodgkin’s disease comprise several closely related neoplastic lymph node disorders that resemble lymphoma Areas of involvement: This usually involves a neoplastic process in contiguous lymph nodes usually in the neck and mediastinum. Extranodal involvement and disease above and below the diaphragm portend poor prognosis.
    67. 67. Clinical Differences Between Hodgkin and Non-Hodgkin Lymphomas Hodgkin Lymphoma Non-Hodgkin Lymphoma More often localized to a single axial group of nodes (cervical, mediastinal, para-aortic) More frequent involvement of multiple peripheral nodes Orderly spread by contiguity Noncontiguous spread Mesenteric nodes and Waldeyer ring rarely involved Waldeyer ring and mesenteric nodes commonly involved Extranodal involvement uncommon Extranodal involvement common
    68. 68. Leukemoid ReactionLeukemoid Reaction an excessive leukocytic responsean excessive leukocytic response leukocytosis of 50 x10leukocytosis of 50 x1099 /L or higher/L or higher with shift to the leftwith shift to the left oror lower counts with considerable numberslower counts with considerable numbers of immature granulocytesof immature granulocytes quantitative or qualitative changes inquantitative or qualitative changes in lymphocytes or monocyteslymphocytes or monocytes
    69. 69. Leukemoid ReactionLeukemoid Reaction neutrophiliceosinophilic lymphocytic hemolysishemolysis hemorrhagehemorrhage malignancymalignancy Hodgkin diseaseHodgkin disease myelofibrosismyelofibrosis TBTB burnsburns eclampsiaeclampsia parasiteparasite infectiousinfectious lymphocytosislymphocytosis pertussispertussis TBTB
    70. 70. Plasma cell disordersPlasma cell disorders Main typesMain types  Multiple myelomaMultiple myeloma  Waldenstrom macroglobulinemia: A malignancy ofWaldenstrom macroglobulinemia: A malignancy of plasmacytoid lymphocytes that secrete IgM resulting in aplasmacytoid lymphocytes that secrete IgM resulting in a hyperviscosity syndrome with renal, retinal and cerebralhyperviscosity syndrome with renal, retinal and cerebral ischemia as a result of microvascular occlusion.ischemia as a result of microvascular occlusion.  Monoclonal gammopathy of unknown significance: oftenMonoclonal gammopathy of unknown significance: often diagnosed in asymptomatic elderly patients. It is present indiagnosed in asymptomatic elderly patients. It is present in ~1% of patients over 60 years old and 3% of patients over 70.~1% of patients over 60 years old and 3% of patients over 70. There is a 1% risk of developing multiple myelomaThere is a 1% risk of developing multiple myeloma.. Clinical featuresClinical features  Tend to occur in those >45 years old.Tend to occur in those >45 years old.  Neoplastic plasma cells produce a monoclonalNeoplastic plasma cells produce a monoclonal immunoglobulin component that can be identified by serumimmunoglobulin component that can be identified by serum electrophoresiselectrophoresis  Deposition of light chain immunoglobulin may form amyloidDeposition of light chain immunoglobulin may form amyloid deposits in the kidneys, vessels and other organs.deposits in the kidneys, vessels and other organs.
    71. 71. Multiple MyelomaMultiple Myeloma • A neoplasm of mature plasma cells that respond poorly to chemotherapy and usually survive ~3 years after diagnosis. Renal damage due to protein deposition is the most common cause of death. Infection, systemic amyloidosis, anemia, hyperviscosity and metabolic disorders contribute to the poor outcome.
    72. 72. Multiple MyelomaMultiple Myeloma Clinical Presentation:Clinical Presentation: - Pts present in their middle fifties- Pts present in their middle fifties or older (60-70 yr)or older (60-70 yr) - Constitutional symptoms, anemia,- Constitutional symptoms, anemia, thrombocytopenia, and renalthrombocytopenia, and renal failure;failure; - Approx 80% of pts have chief- Approx 80% of pts have chief complaint of bone pain w/ diffusecomplaint of bone pain w/ diffuse bone tenderness, particularly overbone tenderness, particularly over the sternum and pelvis.the sternum and pelvis. - Pathological fracture of spine or- Pathological fracture of spine or femur may be heralding event;femur may be heralding event; - Symptoms range in duration from- Symptoms range in duration from as short as few wks to as long as 2as short as few wks to as long as 2 yrs.yrs.
    73. 73.  Neoplastic cells secreteNeoplastic cells secrete aa monoclonal immunoglobulin:monoclonal immunoglobulin: IgG 60%, IgA 20% and IgD, IgEIgG 60%, IgA 20% and IgD, IgE or the heavy or light chain 20%.or the heavy or light chain 20%. Normal immunoglobulins areNormal immunoglobulins are suppressed increasing the risksuppressed increasing the risk of infection.of infection.  Multiple bone lesionsMultiple bone lesions areare composed of nests of neoplasticcomposed of nests of neoplastic cells and appear as “punch”cells and appear as “punch” lesions in bones. Bony lesionslesions in bones. Bony lesions may cause symptomaticmay cause symptomatic hypercalcemia, metastatichypercalcemia, metastatic calcification also occurs.calcification also occurs.  Excess immunoglobulinExcess immunoglobulin may bemay be deposited in peripheral tissuedeposited in peripheral tissue forming amyloid. They may beforming amyloid. They may be secretedsecreted in the urine as Bence-in the urine as Bence- Jones proteinsJones proteins, occasionally, occasionally proteins obstruct renal tubulesproteins obstruct renal tubules resulting inresulting in renal failurerenal failure..
    75. 75. Dexter star Michael C. Hall fights against Hodgkin’s Lymphoma