Incidence Etiology Pathoph.

Symptoms
Myeloid Leukemias
Acute M>F Heredity
Median age at dx: 67 (Trisomy 21, Fanconi,
Peak at 60s Bloom, ataxia-telangiectasia)
Radiation
Chemicals
(Benzene, smoking,
petroleum, paint,
embalming fluids, ethylene
oxide, herbicides, pesticides)
Abnormal proliferation of Abrupt/gradual
myeloid precursor cells. Non-specific
Decreased apoptosis rate. Anemia
Arrest in cellular differentiation. (normochr, normocyt):
fatigue, weakness.
Leukocytosis/leukopenia
Leukocyte dysfx.
Thrombocytopenia
Anorexia, weight loss
Fever of unknown origin

Drugs Abnormal hemostasis

(Anticancer drugs, (Bleeding, bruising)
chloramphenicol,
phenylbutazone, Bone pain
chloroquine, Lymphadenopathy
methoxypsoralen) Non-spec cough,
headache, diaphoresis.
Chronic M>F Genetic Philadelphia chromosome Chronic phase (2-5yrs):
Median age: >45 High-dose radiation t(9;22) BCR-ABL1 May be asymptomatic
(Atomic bomb, etc.)
Long-lastic hematopoietic sc in Accelerated phase
chronic phase (6-18mos):
Abdominal pain
Accelareted phase: excessive (splenomegaly)
proliferation and accumulation Abdominal fullness
of malignant cells (Hepatosplenomegaly)
Infections, fever,
weight loss.
Gouty arthritis
(hyperuricemia)
 Terminal (blast) phase
(3-6mos):
Painful splenomegaly
Abdominal fullness
(Hepatosplenomegaly)
Lymphadenopathy
Gouty arthritis
Infections, fever,
weight loss.
Lymphoid Leukemias Incidence Etiology Pathoph. Symptoms
Acute
B-ALL 85% ALL cases Genetic Lymphoblast proliferation in Several weeks of fatigue
Peak: 3-4 years marrow replaces production of Easy bruising
(peak BM prod of B other cells, causing pancytopenia. Bleeding (gums, GI,etc.)
cells) Fever, infection
Mutated transcription factor Bone pain
genes TEL1, AML1, E2A, PAX5, Skin involvement
EBF. CNS involvement
Ovary/testis involvement
Abdominal fullness/pain

Loss of appetite
Weight loss
Hypogeusia (sweet,sour)
Muscle atrophy
Dysphagia
T-ALL Peak: 15 years Genetic NOTCH1 mutation Abrupt and stormy onset
15-20years Chromosomal errors leading Fatigue
(thymus reaches its to overexpression of Fever
greatest size) transcription factors TAL1, Bleeding
M>F LMO1, LMO2. Bone pain/tenderness
These dysregulated factors Generalized
interfere with E2A activity lymphadenopathy,
 a transcription factor req splenomegaly,
for proper B- and T-cell dev. hepatomegaly.
CNS involvement
More often presents as (headache, vomiting,
"lymphomas" (thymus mass) palsies)
that progresses rapidly to
leukemic phase.
Chronic Median age: 70yrs. Genetic Deletions of chr 11, 13, 14, 17 Asymptomatic
(Lymphoma version: Trisomy 12
SLL) Fatigue
Chr13 deletion loss of genes that Weight loss
encode several microRNA Anorexia
that negatively regulates
expression of other genes.
Unable to repress expression of
genes that promote cell growth.

Chr17 deletion contribute to

inactivation of p53.

High levels of BCL2 (apoptosis

inhibitor) -> survival

Immune dysregulation;
B cell function suppresion
resulting in
hypogammaglobulinemia.
Signs Lab Periph. Smear Marrow Smear

Fever Reticulocyte count: > RBC morph: >20% blast cellularity

Splenomegaly Anisocytosis Myeloblasts or promyelocytes:
Hepatomegaly Leukocyte count: Poikilocytosis (mild) Delicate nuclear chromatin
Lymphadenopathy Mostly 15 000/L Nucleated (sometimes) 3-5 nucleoli
Sternal tenderness 25-40% <5000/L Stippled Fine, azurophillic, cytoplasmic
Evidence of infection, 20% >100 000/L granules.
hemorrhage Neutropenia Platelets:
Giant platelets Auer rods:
Platelet count: Poorly granulated
~75% <100 000/L
25% <25 000/L Neutrophil:
Hypersegmented,
50% Hyperuricemia hyposegmented,
Serum LDH < hypogranular mature
neutrophils.
Blood blast count:
>100 000/mm3 Myeloblasts
(Hyperleukocytosis)

Splenomegaly Leukocytosis Basophilia Increased marrow cellularity

Hepatomegaly (immature and mature Eosinophilia M/E ratio increase
Fever granulocytes) Monocytosis Blast percentage: n / elevated
Hyperuricemia Thrombocytosis Basophilia
Lymphadenopathy Anemia Accelerated phase: Eosinophilia
(normochr, normocyt) Blast 10-20% Monocytosis
Basophils 20% Fibrosis (reticulin-stain)
Leukocyte AP: > Platelet count <100 000/L
Accelerated phase:
Basophilia -> histamine Blast crisis: Blast 10-20%
(diarrhea, pruritus, Blast 20% Basophils 20%
flushing) (Myeloid, lymphoid,
erythroid, undiff.) Blast crisis:
 Hyposegmented Blast 20%
neutrophils (Pelger-Huet)

Signs Lab Periph. Smear Marrow Smear

Anemia Immunophenotyping: Lymphoblasts: Lymphoblasts: 25% cellularity

Thrombocytopenia TdT expression Fine chromatin
Neutropenia CD19 expression Small nucleoli
Scant agranular cytoplasm
Splenomegaly
Hepatomegaly Anemia
Lymphadenopathy Thrombocytopenia
Granulocytopenia
Petechiae/ecchymosis
Skin discoloration
Gum bleed
Hematuria
Midcycle/heavy menses

Anemia Immunophenotyping: Lymphoblasts ALL blasts >25% cellularity

Neutropenia TdT expression No blast (aleukemic Lymphoblast: coarse, clumped
Thrombocytopenia CD3 expression leukemia) chromatin, 1-2 nucleoli, scant
(Petechiae/ecchymosis agranular cytoplasm.
Epistaxis Anemia
Gum bleed) Thrombocytopenia
(<100 000/L)
 Neutropenia
WBC count variable:
50% >100 000/L
50% <10 000/L

Lymphadenopathy Lymphocytosis Increased number of Contains aggregates, clusters,

Hepatosplenomegaly small, round lymphocytes, sheets of similar cells as in
Lymph node biopsy: which are fragile and peripheral smear.
Autoimmune hemolytic Diffuse infiltration of often breaks during
anemia small lymphocytes smear (smudge cells)
Autoimmune and patchy collections
thrombocytopenia of larger, mitotically Lymphocyte count:
active cells (prolif ctrs) >4000/L
Frequent bacterial infx
Immunohistochemis: Leukocyte count:
Low lvls of Ig expression may be >200 000/L
(usually IgM)
Pan-B-cell markers
(CD19, CD20, CD23)
Mature T cell marker
(CD5)