12 White Blood Cell Disorders

Benign Qualitative White Blood Cell (WBC) Disorders

Pathogenesis
1. Defects in leukocyte structure
o Example-membrane fusion defect in Chdiak-Higashi syndrome
. Defects in leukocyte function
a. !eukocyte adhesion defect
Example-deficient selectin or CD11a"CD1#
b. Phagocytosis defect
Example-decreased opsonins in $ruton%s agammaglobulinemia
c. &icrobicidal defect
Example-deficiency of myeloperoxidase
Benign Qualitative White Blood Cell (WBC) Disorders
Pathogenesis
1. Defects in leukocyte structure
o Example-membrane fusion defect in Chdiak-Higashi syndrome
. Defects in leukocyte function
a. !eukocyte adhesion defect
Example-deficient selectin or CD11a"CD1#
b. Phagocytosis defect
Example-decreased opsonins in $ruton%s agammaglobulinemia
c. &icrobicidal defect
Example-deficiency of myeloperoxidase
Pathogenesis
1. Defects in leukocyte structure
o Example-membrane fusion defect in Chdiak-Higashi syndrome
. Defects in leukocyte function
a. !eukocyte adhesion defect
Example-deficient selectin or CD11a"CD1#
b. Phagocytosis defect
Example-decreased opsonins in $ruton%s agammaglobulinemia
c. &icrobicidal defect
Example-deficiency of myeloperoxidase
Clinical findings
1. 'nusual pathogens (e.g.) coagulase-negati*e Staphylococcus+
. ,re-uent infections and gro.th failure in children
/. !ack of an inflammatory response (e.g.) production of 0cold0 abscesses+
1. 2e*ere gingi*itis
3ob%s syndrome is an autosomal recessi*e disorder of neutrophils) characteri4ed by
abnormal chemotaxis leading to 0cold0 soft tissue abscesses due to Staphylococcus
aureus. Patients ha*e red hair) a leonine face) chronic ec4ema) and increased 5gE
(hyperimmune E syndrome+.
'nusual benign leukocyte reactions
1. !eukemoid reaction
a. 6bsolute leukocyte count usually abo*e 78)888"9!.
&ay in*ol*e neutrophils) lymphocytes) or eosinophils
b. Etiology
ii Perforating appendicitis (neutrophils+
iii :hooping cough (lymphocytes+
iiii Cutaneous lar*a migrans (eosinophils+
b. Pathogenesis
Exaggerated response to infection
ii !eukoerythroblastic reaction
a. 5mmature bone marro. cells enter the peripheral blood
b. Pathogenesis
ii $one marro. infiltrati*e disease
iii Examples-fibrosis) metastatic breast cancer
b. Peripheral blood findings
ii &yeloblasts) progranulocytes
iii ;ucleated <$Cs) tear drop <$Cs
Benign Quantitative WBC Disorders
Disorders in*ol*ing neutrophils
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1. ;eutrophilic leukocytosis
a. 6bsolute neutrophil count abo*e >888"9!
b. Etiology
i. 5nfection (e.g.) acute appendicitis+
ii. 2terile inflammation .ith necrosis (e.g.) acute myocardial infarction+
iii. Drugs (e.g.) corticosteroids+
c. Pathogenesis
i. 5ncreased bone marro. production or release of neutrophils
ii. Decreased acti*ation of neutrophil adhesion molecules
!ess neutrophils adhere to endothelial cells
Examples-corticosteroids) catecholamines) lithium
. ;eutropenia
a. 6bsolute neutrophil count belo. 1788"9!
b. Etiology
i. 6plastic anemia
ii. 5mmune destruction
Example-systemic lupus erythematosus (2!E+
iii. 2eptic shock
c. Pathogenesis
i. Decreased production
ii. 5ncreased destruction (e.g.) complement) macrophages+
iii. 6cti*ation of neutrophil adhesion molecules (e.g.) endotoxins+
5ncrease the number of neutrophils adhering to endothelium
Disorders in*ol*ing neutrophils
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1. ;eutrophilic leukocytosis
a. 6bsolute neutrophil count abo*e >888"9!
b. Etiology
i. 5nfection (e.g.) acute appendicitis+
ii. 2terile inflammation .ith necrosis (e.g.) acute myocardial infarction+
iii. Drugs (e.g.) corticosteroids+
c. Pathogenesis
i. 5ncreased bone marro. production or release of neutrophils
ii. Decreased acti*ation of neutrophil adhesion molecules
!ess neutrophils adhere to endothelial cells
Examples-corticosteroids) catecholamines) lithium
. ;eutropenia
a. 6bsolute neutrophil count belo. 1788"9!
b. Etiology
i. 6plastic anemia
ii. 5mmune destruction
Example-systemic lupus erythematosus (2!E+
iii. 2eptic shock
c. Pathogenesis
i. Decreased production
ii. 5ncreased destruction (e.g.) complement) macrophages+
iii. 6cti*ation of neutrophil adhesion molecules (e.g.) endotoxins+
5ncrease the number of neutrophils adhering to endothelium
Disorders in*ol*ing eosinophils
1. Eosinophilia
a. 6bsolute eosinophil count o*er >88"9!
b. Etiology
i. ?ype 5 hypersensiti*ity reaction
Examples-bronchial asthma) reaction to penicillin) hay fe*er
ii. 5n*asi*e helminthic infection
Examples-strongyloidiasis) hook.orm infection
Pin.orms and adult ascariasis do not ha*e eosinophilia (nonin*asi*e+.
iii. Polyarteritis nodosa) 6ddison%s disease (cortisol deficiency+
c. Pathogenesis
i. <elease of eosinophil chemotactic factor from mast cells (e.g.) type 5
hypersensiti*ity+
ii. ;o se-uestering of eosinophils in lymph nodes (e.g.) hypocortisolism+
. Eosinopenia
a. Hypercortisolism (e.g.) Cushing syndrome) corticosteroids+
b. Corticosteroids se-uester eosinophils in lymph nodes.
Disorders in*ol*ing basophils@ basophilia
1. 6bsolute basophil count o*er 118"9!
. Etiology
o Chronic myeloproliferati*e disorders (e.g.) polycythemia *era+
Disorders in*ol*ing lymphocytes
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1. !ymphocytosis
a. 6bsolute lymphocyte count o*er 1888"9! in adults or o*er #888"9! in children
b. Etiology
i. Airal (e.g.) mononucleosis+ or bacterial (e.g.) .hooping cough+
ii. Drugs (e.g.) phenytoin+
iii. Bra*es% disease
c. Pathogenesis
i. 5ncreased production
ii. Decreased entry into lymph nodes
Example-lymphocytosis-promoting factor produced by Bordetella
pertussis
. 6typical lymphocytosis
a. Etiology
i. 5nfection
Examples-mononucleosis) *iral hepatitis) cytomegalo*irus infection)
toxoplasmosis
ii. Drugs (e.g.) phenytoin+
b. Pathogenesis
i. 6ntigenically stimulated lymphocytes
ii. Prominent nucleoli and abundant blue cytoplasm
/. 5nfectious mononucleosis
a. Caused by Epstein-$arr *irus (E$A+
b. Pathogenesis
i. Primarily transmitted by kissing
E$A initially replicates in the sali*ary glands and then disseminates.
ii. E$A attaches to CD1 receptors on $ cells.
Causes $-cell proliferation and increased synthesis of antibodies
iii. Airus remains dormant in $ cells.
<ecurrences may occur.
c. Clinical findings
i. ,atigue) tonsillitis
ii. Hepatosplenomegaly) generali4ed lymphadenopathy
Danger of splenic rupture in contact sports
iii. <ash de*elops if treated .ith ampicillin.
d. !aboratory findings
i. 6typical lymphocytosis
'sually more than 8C of the total :$C count
6typical lymphocytes are antigenically stimulated ? cells
ii. Positi*e heterophil antibody test
Detects 5g& antibodies against horse (most common+) sheep) and bo*ine
<$Cs
iii. Positi*e anti*iral capsid antigen test
&ost sensiti*e test
i*. 5ncreased serum transaminases from hepatitis
3aundice is rare.
1. !ymphopenia
a. 6bsolute lymphocyte count belo. 1788"9! in adults or belo. /888"9! in children
b. Etiology
i. Human immunodeficiency *irus (H5A+
ii. 5mmunodeficiency
DiBeorge syndrome (?-cell deficiency+
2e*ere combined immunodeficiency ($- and ?-cell deficiency+
iii. 5mmune destruction (e.g.) 2!E+
i*. Corticosteroids
*. <adiation
!ymphocytes are the most sensiti*e cells to destruction by radiation.
c. Pathogenesis
i. 5ncreased destruction
Examples-lysis of CD1 helper ? cells by the *irus@ apoptosis by
corticosteroids@ immune destruction
ii. Decreased production
Example-radiation
iii. Decreased release from lymph nodes
Example-corticosteroids
Disorders in*ol*ing monocytes@ monocytosis
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1. 6bsolute monocyte count o*er #88"9!
. Etiology
a. Chronic infection (e.g.) tuberculosis+
b. 6utoimmune disease (e.g.) rheumatoid arthritis+
c. &alignancy (e.g.) carcinoma) malignant lymphoma+
/. Pathogenesis
o <esponse to chronic inflammation or malignancy
Leukemias (Acute and Chronic)
Epidemiology
1. &alignant diseases of bone marro. stem cells that may in*ol*e all cell lines
. <isk factors
a. Chromosomal abnormalities
Examples-Do.n syndrome) chromosome instability syndromes
b. 5oni4ing radiation
c. Chemicals (e.g.) ben4ene+
d. 6lkylating agents (particularly busulfan+
/. 6ge ranges for common leukemias
a. ;e.born to 11 years old
6cute lymphoblastic leukemia (6!!+
b. Persons 17 to /= years old
6cute myelogenous leukemia (6&!+
c. Persons 18 to D8 years old
ii 6&! (ED8C of cases+
iii Chronic myelogenous leukemia (18C of cases+
b. Persons o*er D8 years of age
Chronic lymphocytic leukemia (C!!+
Epidemiology
1. &alignant diseases of bone marro. stem cells that may in*ol*e all cell lines
. <isk factors
a. Chromosomal abnormalities
Examples-Do.n syndrome) chromosome instability syndromes
b. 5oni4ing radiation
c. Chemicals (e.g.) ben4ene+
d. 6lkylating agents (particularly busulfan+
/. 6ge ranges for common leukemias
a. ;e.born to 11 years old
6cute lymphoblastic leukemia (6!!+
b. Persons 17 to /= years old
6cute myelogenous leukemia (6&!+
c. Persons 18 to D8 years old
ii 6&! (ED8C of cases+
iii Chronic myelogenous leukemia (18C of cases+
b. Persons o*er D8 years of age
Chronic lymphocytic leukemia (C!!+
Pathogenesis
1. $lock in stem cell differentiation
o &onoclonal proliferation of neoplastic leukocytes behind the block
. !eukemic cells
a. <eplace the bone marro.
<eplace normal hematopoietic cells
b. Enter the peripheral blood
c. &etastasi4e throughout the body
Clinical findings in acute leukemia
1. 6brupt onset of signs and symptoms
. ,e*er (infection+) bleeding (thrombocytopenia+) fatigue (anemia+
/. &etastatic disease
a. Hepatosplenomegaly
b. Benerali4ed lymphadenopathy
c. Central ner*ous system (C;2+ in*ol*ement (especially in 6!!+
d. 2kin in*ol*ement (especially ?-cell leukemias+
1. $one pain and tenderness
o Due to bone marro. expansion by leukemic cells
!aboratory findings in acute leukemia
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1. Peripheral :$C count
a. $elo. 18)888"9! (normal+ to more than 188)888"9!
b. $last cells usually more than 8C (e.g.) myeloblasts) lymphoblasts+.
. ;ormocytic to macrocytic anemia
o &acrocytic if folate is depleted in production of leukemic cells
2. ?hrombocytopenia (usually F188)888"9!+
3. $one marro. findings
o Hypercellular .ith more than 8C blasts (e.g.) myeloblasts) lymphoblasts+
Clinical findings in chronic leukemia
a. 5nsidious onset
b. Hepatosplenomegaly and generali4ed lymphadenopathy
!aboratory findings in chronic leukemia
a. Peripheral :$C count
i. 2imilar to that of acute leukemia
ii. $last cells usually less than 18C
iii. E*idence of maturation of cells
b. ;ormocytic to macrocytic anemia
o &acrocytic if folate is depleted in production of leukemic cells
b. ?hrombocytopenia (usually F188)888"9!+
o Exception in C&!) in .hich thrombocytosis occurs in 18C of cases
c. $one marro. findings
o Hypercellular .ith less than 18C blasts
eoplastic Meloid Disorders
G*er*ie.
1. &yeloid disorders are neoplastic stem cell disorders.
o &ay in*ol*e one or more stem cell lines
. Classification
a. Chronic myeloproliferati*e disorders
b. &yelodysplastic syndrome
c. 6cute myeloblastic leukemia
G*er*ie.
1. &yeloid disorders are neoplastic stem cell disorders.
o &ay in*ol*e one or more stem cell lines
. Classification
a. Chronic myeloproliferati*e disorders
b. &yelodysplastic syndrome
c. 6cute myeloblastic leukemia
Chronic myeloproliferati*e disorders
!a"le 12#1$ La"orator %indings in &olcthemias
&olcthemia 'BC &lasma (a)2 *&)
Mass +olume
Polycythemia *era ;ormal
6ppropriate polycythemia (e.g.) CGPD) cyanotic congenital heart
disease+
;ormal
5nappropriate polycythemiaH ectopic EPG (e.g.) renal disease+ ;ormal ;ormal
<elati*e polycythemia (e.g.) *olume depletion+ ;ormal ;ormal ;ormal
CGPD) chronic obstructi*e pulmonary disease@ EPG) erythropoietin@ 2aG) oxygen saturation.
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1. Classification
a. Polycythemia *era
b. Chronic myelogenous leukemia
c. &yeloid metaplasia .ith myelofibrosis
d. Essential thrombocythemia
. Beneral characteristics
a. 2plenomegaly
b. Propensity for reacti*e bone marro. fibrosis (0spent phase0+
c. Propensity for transformation to acute leukemia
/. Polycythemia
a. 5ncreased hemoglobin (Hb+) hematocrit (Hct+) and <$C count
b. Plasma *olume (PA+ *aries .ith the type of polycythemia.
c. <$C count *ersus <$C mass
i. <$C count is the number of <$Cs per 9! of blood.
ii. <$C mass is the total number of <$Cs in the body in m!"kg.
iii. <$C count is the ratio of <$C mass to plasma *olume (PA+.
sho.s the normal relationship bet.een <$C count) <$C mass) PA)
erythropoietin (EPG+) and G saturation (2ao+.
d. <elati*e polycythemia
i. 5ncreased <$C count due to a decrease in PA
Example-*olume depletion from s.eating
ii. <$C mass is normal.
No increase in bone marro. production of <$Cs
iii. Erythropoietin (EPG+ and 2ao are normal.
e. 6bsolute polycythemia
i. 5ncrease in bone marro. production of <$Cs
5ncreased <$C count and <$C mass
ii. 6ppropriate absolute polycythemia if there is a hypoxic stimulus for EPG release
Examples-primary lung disease) cyanotic congenital heart disease) li*ing
at high altitude
Decreased G saturation (2ao+
5ncreased <$C count) <$C mass) EPG
;ormal PA
iii. 5nappropriate absolute polycythemia if there is no hypoxic stimulus for EPG
release
Polycythemia *era (see belo.+
Ectopic secretion of EPG (e.g.) renal cell carcinoma+
5ncreased <$C count) <$C mass) EPG@ normal PA and 2ao
1. Polycythemia *era
a. Pathogenesis
i. Clonal expansion of the trilineage myeloid stem cell
ii. 5ncrease in <$Cs) granulocytes (neutrophils) eosinophils) basophils+) mast cells)
and platelets
b. Clinical findings
i. 2plenomegaly
ii. ?hrombotic e*ents due to hyper*iscosity (e.g.) hepatic *ein thrombosis+
iii. 2igns of increased histamine (released from mast cells in the skin+
<uddy face
Pruritus after bathing
Peptic ulcer disease (histamine stimulates production of gastric acid+
i*. Bout
Due to increased breakdo.n of nucleated cells .ith release of purines
(con*erted to uric acid+
c. !aboratory findings in polycythemia *era
i. 5ncreased <$C mass and PA
Gnly type of polycythemia .ith an increase in PA
ii. 6bsolute leukocytosis (leukocytes E1)888"9!+
iii. ?hrombocytosis (platelets E188)888"9!+
i*. Decreased EPG
5ncreased G content inhibits EPG release.
Gnly type of polycythemia .ith decreased EPG
*. ;ormal 2ao
*i. Hypercellular bone marro. .ith fibrosis in later stages
d. 2ummary table of the polycythemias
7. Chronic myelogenous leukemia (C&!+
a. Epidemiology
i. 'sually occurs bet.een 18 and D8 years of age
ii. <isk factors
Exposure to ioni4ing radiation and ben4ene
b. Pathogenesis
i. ;eoplastic clonal expansion of the pluripotential stem cell
?his stem cell has the capacity to differentiate into a lymphoid or
trilineage myeloid stem cell.
ii. t=@ translocation of ABL proto-oncogene
Proto-oncogene fuses .ith the break cluster region ($C<+ on
chromosome (BCR-ABL fusion gene+.
c. Clinical findings
i. Hepatosplenomegaly and generali4ed lymphadenopathy
Due to metastasis
ii. $last crisis
'sually occurs in 7 years
5ncrease in numbers of myeloblasts or lymphoblasts
&yeloblasts do not contain 6uer rods (see belo.+
d. !aboratory findings
i. Peripheral :$C count 78)888 to 88)888 cells"9!
&yeloid series in all stages of de*elopment
ii. ;ormocytic to macrocytic anemia
&acrocytic if folate is depleted in the production of leukemic cells.
iii. Platelet count
?hrombocytosis (18-78C+) thrombocytopenia in the remainder of cases
i*. $one marro. findings
&yeloblasts less than 18C
Hypercellular
*. Positi*e Philadelphia chromosome (=7C of cases+
5t is not specific for C&! and is present in other leukemias.
5t is not lost during therapy unless I-interferon is used.
*i. BCR-ABL fusion gene (188C of cases+
,usion gene is the most sensiti*e and specific test for C&!
*ii. Decreased leukocyte alkaline phosphatase (!6P+
!6P is absent in neoplastic granulocytes and present in benign
granulocytes.
D. &yelofibrosis and myeloid metaplasia
a. Pathogenesis
i. &arro. fibrosis occurs earlier than in other types of myeloproliferati*e disease.
ii. ;eoplastic cells are produced in the spleen and other sites (extramedullary
hematopoiesis) E&H+.
b. Clinical findings
i. &assi*e splenomegaly .ith portal hypertension
ii. 2plenic infarcts .ith left-sided pleural effusions
c. !aboratory findings
i. $one marro. fibrosis due to stimulation of fibroblasts
ii. Peripheral :$C count 18)888 to 78)888 cells"9!
iii. ;ormocytic anemia
?ear-drop cells (damaged <$Cs+
!eukoerythroblastic reaction
i*. Platelet count is *ariable (increased or decreased+.
>. Essential thrombocythemia
a. Pathogenesis
i. ;eoplastic stem cell disorder .ith proliferation of megakaryocytes
ii. Platelets are increased@ ho.e*er) they are nonfunctional.
b. Clinical findings
i. $leeding (usually gastrointestinal .ith concomitant iron deficiency+
ii. 2plenomegaly
c. !aboratory findings
i. ?hrombocytosis (platelets ED88)888"9!+
Platelet morphology is abnormal.
ii. &ild neutrophilic leukocytosis
iii. Hypercellular bone marro. .ith abnormal megakaryocytes
&yelodysplastic syndrome
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1. Epidemiology
o 'sually occurs in men bet.een 78 and #8 years old
. Pathogenesis
a. Broup of neoplastic stem cell disorders
Chromosomal abnormalities in 78C of cases (e.g.) 7-
-
) trisomy #+
b. ,re-uently progresses to acute myelogenous leukemia (6&!@ /8C of cases+
0Preleukemia0
. !aboratory findings
a. 2e*ere pancytopenia
ii ;ormocytic to macrocytic anemia
Dimorphic <$C population (microcytic and macrocytic+
iii !eukoerythroblastic reaction
b. $one marro. findings
ii <inged sideroblasts (nucleated <$Cs .ith excess iron+
iii &yeloblasts less than 8C (if E8C) disease is progressing to 6&!+
6cute myelogenous leukemia
!a"le 12#2$ %rench#American#British Classi,ication o, Acute Melogenous Leukemia
(AML)
Class Comments
&8H &inimally differentiated 6&! ;o 6uer rods
&1H 6&! .ithout differentiationH
8C
<are 6uer rods
&H 6&! .ith maturation &ost common type (/8-18C of cases+.
6uer rods present
17-7=-year-old age bracket
&/H 6cute promyelocytic ;umerous 6uer rods
D5C is in*ariably present
t(17@1>+ translocation
6bnormal retinoic acid metabolismH high doses of *itamin 6 may induce remission by
maturing cells
&1H 6cute myelomonocytic 6uer rods uncommon
&7H 6cute monocytic ;o 6uer rods
Bum infiltration
&DH 6cute erythroleukemia $i4arre) multinucleated erythroblasts
&yeloblasts present
&>H 6cute megakaryocytic &yelofibrosis in bone marro.
5ncreased incidence in Do.n syndrome in children F/ years old
D5C) disseminated intra*ascular coagulation.
1. Epidemiology
a. 'sually occurs bet.een 17 and 7= years of age
b. ,rench-6merican-$ritish (,6$+ classification is used
. Cytogenetic abnormalities are common.
o Example-t(17@1>+ in acute promyelocytic leukemia (&/+
2. Clinical findings
i. Disseminated intra*ascular coagulation (D5C+ is common.
5n*ariable in acute promyelocytic leukemia
ii. Bum infiltration is common in acute monocytic leukemia (&7+.
. 6uer rods
i. 2plinter-shaped to rod-shaped structures in the cytosol of myeloblasts
6uer rods are fused a4urophilic granules
ii. Gnly present in acute myelogenous leukemia (& and &/+
?hey are not present in myeloblasts in chronic myelogenous leukemia.
Lmphoid Leukemias
6cute lymphoblastic leukemia (6!!+
1. Epidemiology
a. &ost common leukemia in children (ne.born to 11 years of age+
b. 2ubtypes
i. Early pre-$-cell 6!! (#8C+
ii. Pre-$-) $-) and ?-cell 6!!
. Pathogenesis
o Clonal lymphoid stem cell disease
2. Early pre-$-cell 6!!
a. Positi*e marker studies for common 6!! antigen (C6!!6) CD18+
b. Positi*e marker studies for terminal deoxynucleotidyl transferase (?d?+
c. t(1@1+ translocation offers a fa*orable prognosis.
d. Breater than =8C achie*e complete remission.
6t least t.o thirds of patients can be considered cured.
. ?-cell 6!!
o CD18 negati*e and ?d? positi*e
. Clinical findings
o &etastatic sites similar to those of 6&!
o $-cell types
Commonly metastasi4e to the C;2 and testicles
o ?-cell type
Presents as anterior mediastinal mass or acute leukemia
/. !aboratory findings
o Peripheral :$C count 18)888 to 188)888"9!
G*er 8C lymphoblasts in peripheral blood
o ;ormocytic anemia .ith thrombocytopenia
o $one marro. findings
$one marro. often totally replaced by lymphoblasts
6cute lymphoblastic leukemia (6!!+
1. Epidemiology
a. &ost common leukemia in children (ne.born to 11 years of age+
b. 2ubtypes
i. Early pre-$-cell 6!! (#8C+
ii. Pre-$-) $-) and ?-cell 6!!
. Pathogenesis
o Clonal lymphoid stem cell disease
2. Early pre-$-cell 6!!
a. Positi*e marker studies for common 6!! antigen (C6!!6) CD18+
b. Positi*e marker studies for terminal deoxynucleotidyl transferase (?d?+
c. t(1@1+ translocation offers a fa*orable prognosis.
d. Breater than =8C achie*e complete remission.
6t least t.o thirds of patients can be considered cured.
. ?-cell 6!!
o CD18 negati*e and ?d? positi*e
. Clinical findings
o &etastatic sites similar to those of 6&!
o $-cell types
Commonly metastasi4e to the C;2 and testicles
o ?-cell type
Presents as anterior mediastinal mass or acute leukemia
/. !aboratory findings
o Peripheral :$C count 18)888 to 188)888"9!
G*er 8C lymphoblasts in peripheral blood
o ;ormocytic anemia .ith thrombocytopenia
o $one marro. findings
$one marro. often totally replaced by lymphoblasts
6dult ?-cell leukemia
1. Epidemiology
a. &alignant leukemia associated .ith human ?-cell leukemia *irus (H?!A-1+
b. &ay present as a malignant lymphoma
. Pathogenesis
a. 6cti*ation of TAX gene) .hich inhibits the TP! suppressor gene
b. !eads to monoclonal proliferation of neoplastic CD1 helper ? cells
/. Clinical findings
a. Hepatosplenomegaly and generali4ed lymphadenopathy
b. 2kin infiltration
Common finding in all ?-cell malignancies
c. !ytic bone lesions
ii Due to lymphoblast release of osteoclast-acti*ating factor
iii 6ssociated .ith hypercalcemia
. !aboratory findings
a. Peripheral :$C count 18)888 to 78)888"9!
ii G*er 8C lymphoblasts
iii Positi*e CD1 marker study
iiii ;egati*e for ?d?
b. ;ormocytic anemia and thrombocytopenia
c. $one marro. findings
<eplaced by CD1 lymphoblasts
Chronic lymphocytic leukemia (C!!+
1. Epidemiology
a. Gccurs in indi*iduals o*er D8 years old
b. &ost common o*erall leukemia
c. &ost common cause of generali4ed lymphadenopathy in the same age bracket
. Pathogenesis
o ;eoplastic disorder of *irgin $ cells ($ cells that cannot differentiate into plasma cells+
2. Clinical findings
a. Benerali4ed lymphadenopathy
b. &etastatic sites similar to those of 6&!
c. 5ncreased incidence of immune hemolytic anemia
$oth .arm (5gB+ and cold (5g&+ types
/. !aboratory findings
d. Peripheral :$C count 17)888 to 88)888"9!
ii !ymphoblasts less than 18C
iii ;eutropenia
iiii ;umerous 0smudge0 cells (fragile leukemic cells+
b. ;ormocytic anemia (78C of cases+ and thrombocytopenia (18C of cases+
c. $one marro. findingsH usually replaced by neoplastic $ cells
d. Hypogammaglobulinemia is common.
Hairy cell leukemia
1. ?ype of $-cell leukemia
o &ost common in middle-aged men
. Clinical findings
a. 2plenomegaly (=8C of cases+
b. 6bsence of lymphadenopathy
Gnly leukemia "ithout lymphadenopathy
c. Hepatomegaly (8C of cases+
d. 6utoimmune *asculitis and arthritis
. !aboratory findings
a. Pancytopenia
!eukemic cells ha*e hair-like proJections
b. Positi*e tartrate-resistant acid phosphatase stain (?<6P+
2ummary table of the lymphoid leukemias
!a"le 12#-$ (ummar o, Acute and Chronic Lmphoid Leukemias
Leukemia Description
6cute lymphoblastic &ost common leukemia in children
(Early pre-$ type+ ;e.born to 11 years old
C6!!6 (CD18+ and ?d? positi*e
t(1@1+ offers a good prognosis
Chronic lymphocytic Airgin $ cell leukemia
Patients E D8 years old
&ost common cause of generali4ed lymphadenopathy in same age bracket
Hypogammaglobulinemia
6dult ? cell H?!A-1 association
!eukemic cells CD1 positi*e and ?d? negati*e
2kin infiltration
!ytic bone lesions .ith hypercalcemia
Hairy cell $ cell leukemia
Cytoplasmic proJections
?<6P stain positi*e
2plenomegaly
6bsence of lymphadenopathy
Pancytopenia
Dramatic response to purine nucleosides
C6!!6) common acute lymphoblastic leukemia antigen@ H?!A) human ?-cell leukemia@ ?d?) terminal deoxynucleotidyl transferase@
?<6P) tartrate resistant acid phosphatase.