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Leukocytosis. Leukopenia. Leukosis
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Transcript of Leukocytosis. Leukopenia. Leukosis
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
WBC’sWBC’s
NeutrophNeutrophilil
PMN-PolymorphonuclearPMN-Polymorphonuclear Leucocytes.Leucocytes.
60-70% WBC60-70% WBCAppearance: pink granules in Appearance: pink granules in cytoplasm, nucleus has 3-4 cytoplasm, nucleus has 3-4 lobes lobes 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 are Azurophilic (1°) granules are "lysosomes of PMNs", occur "lysosomes of PMNs", occur in all leukocytesin all leukocytesDÖHLE BODIES and TOXIC DÖHLE BODIES and TOXIC GRANULES are often seen GRANULES are often seen with NEUTROPHILIAwith NEUTROPHILIAAccompanied by a “LEFT” Accompanied by a “LEFT” shiftshift
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
CHEDIAK-HIGASHI SYNDROMECHEDIAK-HIGASHI SYNDROME Also geneticAlso genetic Abnormal LARGE Abnormal LARGE
irregular neutrophil irregular neutrophil granulesgranules
Impaired lysosomal Impaired lysosomal digestion of bacteriadigestion of bacteria
Associated with pigment Associated with pigment and bleeding disordersand bleeding disorders
CAN be serious, CAN be serious, especially in kidsespecially in kids
Eosinophil (Eos)Eosinophil (Eos) Bilobed nucleusBilobed nucleus 2-4% of WBC2-4% of WBC Recruited to sites of Recruited to sites of
inflammationinflammation Function: Involved in Function: Involved in
allergy, parasitic allergy, parasitic infectionsinfections
Contains: eosinophilic Contains: eosinophilic granules granules
Granules contain: major Granules contain: major basic proteinbasic protein
Terminally differentiatedTerminally differentiated
Azurophilic granuels
BasophBasophilil
• Circulating form of mast Circulating form of mast cellscells
• Terminally differentiatedTerminally differentiated• <1% WBC (< 1 x 10*9/L)<1% WBC (< 1 x 10*9/L)• Contains: basophilic Contains: basophilic
granulesgranules• Granules contain: Granules contain:
histamine and heparinhistamine and heparin• IgE receptorsIgE receptors• Involved in allergyInvolved in allergy
Monocyte / MacrophageMonocyte• 3-8% WBC• Circulating form (precursor)
of tissue macrophages• Recruited to sites of
inflammationMacrophages• Phagocytosis, bacterial
killing, antigen presentation• Peritoneal cavity: peritoneal
macrophages• Lung: alveolar macrophages• Spleen: splenic macrophages• Liver: Kupffer cells
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
PrimaryPrimary SecondarSecondaryy
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 leukopoiesis2. Increase of leukocytes transport from bone marrow3. Increase of tumoral type of leukopoiesis during leukosis
1.Hemoconcentrational
2.Redistributional
LeukocytosisLeukocytosis
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
(hepatitis, measles), tuberculosis, CLL
Leukocyte
sBaso-philes
Eosi-nophi-les
NeutrophilesLym-pho-blast
s
Lym-pho-cyte
s
Mo-no-cyte
s
Mye-lo-
blasts
Pro-my-
elocytes
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
/l1% 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/
l3% 2% 0% 0% 0% 2% 3% 7% 4% 75% 4%
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 leukopoiesis2. Increase of leukodieresis3. Increase of leukocyte loss4. 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
Causes of NeutropeniaCauseCause MechanismMechanism
Accelerated removal Accelerated removal ((e.g.e.g., inflammation and , inflammation and infection) infection)
Removal of neutrophils from the circulation exceeds Removal 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 others others
Hydantoinates, primidoneHydantoinates, primidone, and others , and others Immune destructionImmune destruction Aminopyrine Aminopyrine and others and others
• Predictable damage to precursor cells, usually Predictable damage to precursor cells, usually dose dependent dose dependent
• Idiosyncratic depression of bone marrow Idiosyncratic depression of bone marrow functionfunction
• Intramedullary destruction of granulocytesIntramedullary destruction of granulocytes• Immunologic mechanisms with cytolysis or Immunologic mechanisms with cytolysis or
leukoagglutinationleukoagglutination
Periodic or cyclic neutropeniPeriodic or cyclic neutropenia (occurs during a (occurs during infancy and later) infancy and later)
UnknownUnknown
Neoplasms involving bone marrow Neoplasms involving bone marrow (e.g., (e.g., leukemias and lymphomas)leukemias and lymphomas)
Overgrowth of neoplastic cells, which crowd out Overgrowth of neoplastic cells, which crowd out granulopoietic precursors granulopoietic precursors
Idiopathic neutropenia Idiopathic neutropenia that occurs in the absence that occurs in the absence of other disease or provoking influence of other disease or provoking influence
Autoimmune reactionAutoimmune reaction
Felty’Felty’s syndromes syndrome Intrasplenic destruction of neutrophilsIntrasplenic destruction of neutrophils
MyelotoxicMyelotoxic ImmuneImmune
AGRANULOCYTOSISAGRANULOCYTOSIS
1.1. Cytolytic influence, Cytolytic influence, e.g. ionizing radiation e.g. ionizing radiation etc.etc.
2.2. Antimetabolic Antimetabolic influence e.g. influence e.g. cytostatics etc. cytostatics etc.
1.1. Autoimmune e.g. Autoimmune e.g. lupus erythematosus, lupus erythematosus, rheumatoid arthritisrheumatoid arthritis
2. Heteroimmune 2. Heteroimmune
Leukemias Bone marrow, blood, blast cellsAcute / Chronic & Myeloid / LymphoidAML / ALL & CML / CLL
Lymphomas – Lymph nodes, tumorHodgkins - Non-Hodgkins. MyelomaHigh grade & Low gradePremalignant conditions:Myeloproliferative syndromes (MPS)Myelodysplastic syndromes (MDS)
WBC Neoplastic disorders :
Mechanisms of bone Mechanisms of bone marrow neoplasiamarrow neoplasia Blast cells (malignant)Blast cells (malignant) overpopulate the bone marrow overpopulate the bone marrow
and replace the normal cells causing bone destruction and 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 the or their descendents may appear in the peripheral blood (leukemia), in extramedullary sites such peripheral 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 by may 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: Malignant Malignant transformation of hematopoietic and lymphoid cell transformation 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 as Malignant cells are classified as myeloid, lymphoid or myeloid, lymphoid or plasmacyticplasmacytic. The characteristic behavior of particular . The characteristic behavior of particular malignant stem cells determines the presentation of the malignant stem cells determines the presentation of the disease.disease.
Types of bone marrow neoplasia1. 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
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 MalignanMalignant t
LeukemiasLeukemias LymphomaLymphoma
s s
PremalignantPremalignant::
MyeloproliferativMyeloproliferativee
Myelodysplastic Myelodysplastic Sy.Sy.
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 age2. Marrow hypercellularity, except myelofibrosis which is
dominated by fibrosis3. Splenomegaly due to extramedullary hematopoiesis4. Peripheral blood abnormalities and hyperviscosity,
except for myelofibrosis
MPS: ClassificationMPS: Classification
MPS - P. Rubra Vera (PV)MPS - P. Rubra Vera (PV)
Myelodysplastic syndromesMyelodysplastic syndromes Myelodysplastic syndromesMyelodysplastic syndromes (MDS, formerly known as (MDS, formerly known as
""preleukemiapreleukemia") are a diverse collection of hematological conditions ") are a diverse collection of hematological conditions united by ineffective production of blood cells and united by ineffective production of blood cells and varying risks of varying risks of transformation to acute myelogenous leukemia (AML)transformation to acute myelogenous leukemia (AML). Anemia . Anemia requiring chronic blood transfusion is frequently present. requiring chronic blood transfusion is frequently present.
Myelodysplastic syndromes (MDS)Myelodysplastic syndromes (MDS) are bone marrow stem cell are bone marrow stem cell disorders resulting in disorderly and ineffective hematopoiesis disorders resulting in disorderly and ineffective hematopoiesis manifested by manifested by irreversible quantitative and qualitative defects in irreversible quantitative and qualitative defects in hematopoietic cellshematopoietic cells. In a majority of cases, the course of disease is . In a majority of cases, the course of disease is chronic with gradually worsening cytopenias due to progressive chronic with gradually worsening cytopenias due to progressive bone marrow failure.bone marrow failure.
Approximately one-third of patients with MDS progress to AML Approximately one-third of patients with MDS progress to AML within months to a few years.within months to a few years.
The median age at diagnosis of a MDS is between 60 and 75 years; The median age at diagnosis of a MDS is between 60 and 75 years; a few patients are less than 50; a few patients are less than 50; MDS are rare in childrenMDS are rare in children. Males are . Males are slightly more commonly affected than females. Signs and slightly more commonly affected than females. Signs and symptoms are nonspecific and generally related to the symptoms are nonspecific and generally related to the blood blood cytopeniascytopenias (anemia, neutropenia, thrombocytopenia). (anemia, neutropenia, thrombocytopenia).
A significant proportion of the morbidity and mortality attributable A significant proportion of the morbidity and mortality attributable to MDS results not from transformation to AML but rather from the to MDS results not from transformation to AML but rather from the cytopenias seen in all MDS patients. Anemia is most common and cytopenias seen in all MDS patients. Anemia is most common and responds to transfusion, patients often suffer from iron overload. responds to transfusion, patients often suffer from iron overload. The two most serious complications in MDS patients resulting from The two most serious complications in MDS patients resulting from their cytopenias are their cytopenias are bleedingbleeding ( (due to lack of plateletsdue to lack of platelets) or ) or infectioninfection ((due to lack of white blood cellsdue to lack of white blood cells). ).
Myelodysplastic Syndromes:Myelodysplastic Syndromes: Excess proliferation in marrow.Excess proliferation in marrow. But functional & Structural But 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.
MPS : E.T. Bleeding MPS : E.T. Bleeding
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.
Leukemia Leukemia ClassificationClassification
Acute Leukemias:Acute Leukemias: Acute Myeloid Leukemia - Acute Myeloid Leukemia - AMLAML
AML AML 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
Leukemia – Leukemia – Clinical Clinical FeaturesFeatures Anemia Anemia (low RBC)(low RBC) Fever - Infections Fever - Infections (low WBC)(low WBC) Bleeding tendency Bleeding tendency (low PLT)(low PLT) Tender bones, lymphadenopathy, Tender bones, lymphadenopathy,
spleenomegaly etc. spleenomegaly etc. (Leukemic (Leukemic infiltration)infiltration)
IntoxicationIntoxication Autosensitization (esp. lymphogenic L.)Autosensitization (esp. lymphogenic L.)
AML-M5 - Gum Hypertrophy:AML-M5 - Gum Hypertrophy:
AML- Marked Purpura:AML- Marked Purpura:
ALL:Cervical ALL:Cervical LymphadenopathyLymphadenopathy
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 normal All 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!!!!
BLASTBLAST
WHITE CELL NEOPLASMS WHITE CELL NEOPLASMS Leuk/LymphLeuk/Lymph
Many have chromosomal translocationsMany have chromosomal translocations Can arise in inherited and/or genetic Can arise in inherited and/or genetic
diseases:diseases: Downs Syndrome (Trisomy 21)Downs Syndrome (Trisomy 21) Fanconi’s anemia (hereditary aplastic Fanconi’s anemia (hereditary aplastic
anemia)anemia) Ataxia telangiectasia Ataxia 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 Human Herpesvirus-8 (B-Cell
Lymphomas) (also KS)Lymphomas) (also KS)
WHITE CELL NEOPLASMS WHITE 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 disease Can follow celiac disease T-Cell lymphomasT-Cell lymphomas Are common in HIV, B-Cell Are common in HIV, B-Cell
lymphomas, CNS lymphomaslymphomas, CNS lymphomas
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.
AML ALL
Types of LeukemiasTypes of Leukemias 3. 3. Chronic lymphocytic leukemia (CLL)Chronic lymphocytic leukemia (CLL) Peak incidence is in Peak incidence is in
elderly males >60years old. Bone marrow has >40% lymphoid elderly males >60years old. Bone marrow has >40% lymphoid cells, peripheral blood has >15 X10↑6. Neoplastic cells cells, 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 closely 10 years, it responds poorly to chemotherapy. It is closely related to small cell lymphoma and lymphadenopathy is related to small cell lymphoma and lymphadenopathy is common.common.
4. 4. Chronic myelogenous leukemias (CML)Chronic myelogenous leukemias (CML) Peak incidence is Peak 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 WBC functioning; anemia, bleeding & infection. Peripheral WBC counts in the 20-50,000 range with large component of myeloid counts in the 20-50,000 range with large component of myeloid precursors. Frequently terminates in a “blast” crisis with precursors. 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.
Leukocyte
sBaso-philes
Eosi-nophi-les
NeutrophilesLym-pho-blast
s
Lym-pho-cyte
s
Mo-no-cyte
s
Mye-lo-
blasts
Pro-my-
elocytes
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
/l1% 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/
l3% 2% 0% 0% 0% 2% 3% 7% 4% 75% 4%
ALL-Acute Lymphoid Leuk.ALL-Acute Lymphoid Leuk. Common in Children.Common in Children. FAB classification L1, L2 FAB classification L1, L2
& L3& L3 B cell, T cell & histiocytic B cell, T cell & histiocytic
types.types. CD10 +ve, Pre B cell type CD10 +ve, Pre B cell type
common.common. Lymphadenopathy, Lymphadenopathy,
bleeding tendencybleeding tendency Moderate Moderate
HepatosplenomegalyHepatosplenomegaly
ALL-L1ALL-L1
ALL-L2ALL-L2
ALL-L3ALL-L3
AML-Acute Myeloid Leuk.AML-Acute Myeloid Leuk.
Malignancy of myeloid progenitor Malignancy of myeloid progenitor cells.cells.
Adults commonAdults common Hepatosplenomegaly moderateHepatosplenomegaly moderate No significant lymphadenopathyNo significant lymphadenopathy Bleeding tendency Bleeding tendency Gum bleeding common in M5/M4Gum bleeding common in M5/M4 FAB classification - M0 to M7.FAB classification - M0 to M7.
AML-Acute Myeloid Leuk.AML-Acute Myeloid Leuk.►M0 - AML No maturation M0 - 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 maturation M2 - 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.
AML-M0 - Undifferentiated:AML-M0 - Undifferentiated:
AML-M1 - without AML-M1 - without maturationmaturation
AML-M2 - with maturationAML-M2 - with maturation
AML-M3 - Auer RodsAML-M3 - Auer Rods
M3M3
AML-M3 - Promyeloid
AML-M4 - MyelomonocyticAML-M4 - Myelomonocytic
AML-M5b - Monoblastic Leuk
AML-M6 : Erythroleukemia
AML-M7 : Megakaryocytic
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.
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.
Chronic Myelomonocytic Leukemia
• Circulating promonocytes are present (A and B) in a sample from a patient with chronic myelomonocytic leukemia (A and B, blood sample.
• 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
• HYPO-gammaglobulinemia• 15% have antibodies against
RBC’s or PLATS• CANNOT be classified as
separate from lymphomas
LymphomasNeoplasms of lymphoid cells may be divided into two major
groups:• Non-Hodgkin’s lymphoma ~70%• Hodgkins lymphoma ~30%Predisposing factors1. 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.
(MALIGNANT) (MALIGNANT) LYMPHOMASLYMPHOMAS
► Terms in historic classifications:Terms in historic classifications: Diffuse/Follicular, Small/Large, Cleaved/Non-cleavedDiffuse/Follicular, Small/Large, Cleaved/Non-cleaved Hodgkins (REED-STERNBERG CELL) /NON-HodgkinsHodgkins (REED-STERNBERG CELL) /NON-Hodgkins Lukes, Rappaport, etc.Lukes, Rappaport, etc. Working Formulation, WHO, NIH, FAB, Intl., etc.Working Formulation, WHO, NIH, FAB, Intl., etc. BB TT PRECURSOR (less mature looking)PRECURSOR (less mature looking) PERIPHERAL (more mature looking)PERIPHERAL (more mature looking)
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, firm Lymphadenopathy, 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.
Non-Hodgkins Lymphoma:Non-Hodgkins Lymphoma: Non-Hodgkin’s lymphomas represent a group of Non-Hodgkin’s lymphomas represent a group of
heterogeneous lymphocytic cancers that are heterogeneous lymphocytic cancers that are multicentric in origin and spread to various tissues multicentric in origin and spread to various tissues throughout the body, including the bone marrow.throughout the body, including the bone marrow.
According to cell type According to cell type T cell NHLT cell NHL B cell NHL B cell NHL Miscellaneous NHL Miscellaneous 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 grade According to Clinical grade •Low grade NHLLow grade NHL•High grade NHL High grade NHL •Intermediate grade NHLIntermediate grade NHL
Non-Hodgkin lymphomasBurkitt 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.
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.
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
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 left with shift to the left
oror lower counts with considerable lower counts with considerable
numbers of immature granulocytesnumbers of immature granulocytes quantitative or qualitative changes quantitative or qualitative changes
in lymphocytes or monocytesin lymphocytes or monocytes
Leukemoid ReactionLeukemoid Reaction
neutrophiliceosinophilic
lymphocytic
hemolysishemolysishemorrhagehemorrhagemalignancymalignancyHodgkin diseaseHodgkin diseasemyelofibrosismyelofibrosisTBTBburnsburnseclampsiaeclampsia
parasiteparasite
infectious infectious lymphocytosislymphocytosispertussispertussisTBTB
Plasma cell disordersPlasma cell disordersMain typesMain types
Multiple myelomaMultiple myeloma Waldenstrom macroglobulinemia: A malignancy of Waldenstrom macroglobulinemia: A malignancy of
plasmacytoid lymphocytes that secrete IgM resulting in a plasmacytoid lymphocytes that secrete IgM resulting in a hyperviscosity syndrome with renal, retinal and cerebral hyperviscosity 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: often Monoclonal gammopathy of unknown significance: often diagnosed in asymptomatic elderly patients. It is present in diagnosed 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 monoclonal Neoplastic plasma cells produce a monoclonal
immunoglobulin component that can be identified by serum immunoglobulin component that can be identified by serum electrophoresiselectrophoresis
Deposition of light chain immunoglobulin may form amyloid Deposition of light chain immunoglobulin may form amyloid deposits in the kidneys, vessels and other organs.deposits in the kidneys, vessels and other organs.
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.
Multiple MyelomaMultiple MyelomaClinical Presentation:Clinical Presentation: - Pts present in their middle fifties or - Pts present in their middle fifties or
older (60-70 yr)older (60-70 yr)- Constitutional symptoms, anemia, - Constitutional symptoms, anemia,
thrombocytopenia, and renal thrombocytopenia, and renal failure;failure;
- Approx 80% of pts have chief - Approx 80% of pts have chief complaint of bone pain w/ diffuse complaint of bone pain w/ diffuse bone tenderness, particularly over bone 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 as - Symptoms range in duration from as short as few wks to as long as 2 yrs.short as few wks to as long as 2 yrs.
Neoplastic cells secrete Neoplastic cells secrete a a monoclonal monoclonal immunoglobulin: IgG 60%, immunoglobulin: IgG 60%, IgA 20% and IgD, IgE or the IgA 20% and IgD, IgE or the heavy or light chain 20%. heavy or light chain 20%. Normal immunoglobulins Normal immunoglobulins are suppressed increasing are suppressed increasing the risk of infection.the risk of infection.
Multiple bone lesions Multiple bone lesions are are composed of nests of composed of nests of neoplastic cells and appear neoplastic cells and appear as “punch” lesions in bones. as “punch” lesions in bones. Bony lesions may cause Bony lesions may cause symptomatic symptomatic hypercalcemia, metastatic hypercalcemia, metastatic calcification also occurs.calcification also occurs.
Excess immunoglobulin Excess immunoglobulin may be deposited in may be deposited in peripheral tissue forming peripheral tissue forming amyloid. They may be amyloid. They may be secreted secreted in the urine as in the urine as Bence-Jones proteinsBence-Jones proteins, , occasionally proteins occasionally proteins obstruct renal tubules obstruct renal tubules resulting in resulting in renal failurerenal failure..
SUMMARYSUMMARY
Dexter star Michael C. Hallfights against Hodgkin’s Lymphoma