LEUKEMIALEUKEMIA

Masatoshi Kida, M.D.Dept. of Pathology

University of Vermont

““leukoproliferative disorders”leukoproliferative disorders”

lymphoid lymphoid neoplasms acute

chronic

myeloidmyeloid neoplasms acute

chronic

Lymphoid NeoplasmsLymphoid Neoplasms

general aspects of lymphoid neoplasms1. histologic examination is required for diagnosis

2. wide range of behavior

3. majority are of B-cell origin (80-85%)

4. disruption of normal immune regulatory mechanisms

5. deriving from a single transformed cell (monoclonal)

6. homing to and growing in the areas of origin

7. tends to spread through lymphatics and peripheral blood to distant lymphoid tissue

Acute LeukemiaAcute Leukemia

• monoclonal proliferation of immature “blast” cells that fail to participate in the normal maturation process

• as the cells accumulate, they spill over into the peripheral blood

• morbidity and death are rarely caused by leukemic cells

Acute LeukemiaAcute Leukemia

general overview• abrupt stormy onset• depression of marrow function

– fatigue anemia– fever, infection WBC– bleeding platelet

• bone pain and tenderness marrow expansion

Acute LeukemiaAcute Leukemia

- generalized lymphadenopathysplenomegaly ALL > AMLhepatomegaly

- testicular involvement ALL > AML

- CNS involvement ALL > AMLheadachevomitingnerve palsie

Acute Lymphocytic Acute Lymphocytic Leukemia/Lymphoma (ALL)Leukemia/Lymphoma (ALL)

• 40% of acute leukemia• children, young adults• most frequent malignancy of childhood• 80% of childhood acute leukemia• 50% of cancer deaths in children <15 y/o• white : non-white = 2 : 1• male > female

Acute Lymphocytic Acute Lymphocytic Leukemia/Lymphoma (ALL)Leukemia/Lymphoma (ALL)

pre B-cell

pre T-cellNull cell

80-85%

15% <5%

child ALL: almost curable

adult ALL: recent improvement in prognosis, but still with significant mortality

Acute Lymphocytic Acute Lymphocytic Leukemia/Lymphoma (ALL)Leukemia/Lymphoma (ALL)

• BM failure (pallor, lethargy, abnormal bleeding)• bone & joint pain• peripheral lymphadenopathy• splenomegaly• CNS involvement

CSF : increased pressure and cellularity

decreased glucose

normal protein

Acute Lymphocytic Acute Lymphocytic Leukemia/Lymphoma (ALL)Leukemia/Lymphoma (ALL)

• Peroxidase-granule negative ( AML)• terminal deoxynucleotidyl transferase (TdT)• common acute lymphoblastic leukemia antigen (CALLA)• T-cell antigen (T) --- mostly negative• surface Ig (sIg) --- mostly negative• cytoplasmic Ig (cIg)• PAS-pos cytoplasmic aggregate

ALL ALL peripheral blood smearperipheral blood smear

• normocytic, normochromic anemia• thrombocytopenia• WBC may be low, normal, or high

acid phosphatase PAS ++

peripheral B-cell

pre B-cellpre T-cell

ALL ALL clinical courseclinical course

• Remission in the majority of children• 5 yrs disease free period in 50% of cases• complete cures possible• significant recent improvement in survival rate for T-cell type

ALL ALL prognostic factorsprognostic factors

good bad

age 2-10 y/o <1 y/o; adult

sex female male

WBC >50,000 blast/L

phenotype early precursor B-cell mature B-cell, null cell

cytogenetics high hyperploidy pseudo-diploid

t(9;22) 3% of pediatric ALL 25% of adult ALL

t(8;14)

““leukoproliferative disorders”leukoproliferative disorders”

lymphoid lymphoid neoplasms acute

chronic

myeloidmyeloid neoplasms acute

chronic

[Lymphoproliferative Disorders][Lymphoproliferative Disorders]

• clonal expansions of antigen stimulated lymphocytes• maturation arrest due to molecular derangements• primarily B cell origin• may be induced by chromosomal translocations, retrovirus,

or oncogene activation

1. chronic lymphocytic leukemia (CLL)

2. hairy cell leukemia

Chronic Lymphocytic Leukemia (CLL)Chronic Lymphocytic Leukemia (CLL)

• most common form of leukemia in North America and Northern Europe• essentially identical to small lymphocytic lymphoma (SLL)• M > F (2 : 1)• elderly (>60 y/o)• considered incurable• mostly asymptomatic• hepatosplenomegaly may be present• peripheral lymphocytosis (>200,000)• increased susceptibility to bacterial infection (most frequent cause of

death)• may associated with autoimmune hemolytic anemia

Chronic Lymphocytic Leukemia (CLL)Chronic Lymphocytic Leukemia (CLL)

• Indolent clinical course• median survival : 4-6 yrs• occasional transformation to large non-Hodgkin’s lymphoma (Richter’s

syndrome) --- 3 to 5 %

Hairy Cell LeukemiaHairy Cell Leukemia

uncommon variant of peripheral B-cell neoplasmclinically middle age to elderly (younger than CLL)

splenic red pulp involvement

histologically lymphocyte with finger-like projections

phenotypically TRAP (Tartrate Resistant Acid Phosphatase)

CD19, CD20

Hairy Cell Leukemia Hairy Cell Leukemia clinicalclinical

• M > F (3-5 : 1)• splenic red pulp involvement red pulp “lake”• tends to follow an indolent course

• pancytopenia - most prominent feature

- granulocytopenia recurrent bacterial infection

- anemia fatigue

- thrombocytopenia bleeding• good response to some chemotherapy regimen