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Leukocytosis. Leukopenia. Leukosis
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
5. 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
6. 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
7. 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
8. 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
9. 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
11. 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
12.
13. 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
17. 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
18. 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
19. 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
22. 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.
23. 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
24. 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.
25. 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
27. MPS - P. Rubra Vera (PV)MPS - P. Rubra Vera (PV)
28. 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).).
29. 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.
31. 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.
37. 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!!!!
39. 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)
40. 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
41. 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
42. 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.
44. 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
62. 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.
64. • 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
67. 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.
69. 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.
70. 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
71. 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.
72. 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.
73. 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
74. 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
76. 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.
77. 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.
78. 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.
79. 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..
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!
HUGE NUCLEUS
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.