Leukemia Lecture Part 2 - Pathology

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Leukemia Lecture Part 2 - Pathology

Lecture Contents

■ Basic features

■ Acute leukemias

■ Chronic leukemias

Chronic lymphocytic leukemia

Chronic myelogenous leukemia

■ Multiple myeloma

■ Summary


Chronic Lymphocytic Leukemia

■ Neoplastic proliferation of small matureappearing

lymphocytes

■ >99% are B-cell derived

■ Older patients (> 40)

■ Disease may be discovered incidentally

■ Fatigue, weakness, weight loss, anorexia,

and/or recurrent infections may occur

■ Variable splenomegaly and nontender

lymphadenopathy

■ Leukemic counterpart of small lymphocytic

lymphoma


CLL Physical Findings

From Hoffbrand and Pettit

Color Atlas of Clinical Hematology

2nd Edition, 1994


CLL - Physical

Findings

Hoffbrand and Pettit, 1994


Chronic Lymphocytic Leukemia

■ Absolute lymphocytosis (> 4000/mm 3 )

■ Smudge cells

■ Variable anemia, neutropenia, and

thrombocytopenia

■ Hypercellular bone marrow with

lymphocytic infiltrates

■ Hypogammaglobulinemia

■ Elevated serum LDH

■ Trisomy 12


CLL Course & Prognosis

■ Inappropriately termed “indolent”

■ Median survival of 4-6 years

■ No cure is available

■ Recurrent infection is clinical problem

■ Autoimmune hemolytic anemia or

idiopathic thrombocytopenic purpura

may occur

■ Transformation to prolymphocytic

leukemia, large cell lymphoma, or ALL

occurs in ~ 15%


Bone Marrow in CLL

■ Infiltration of

small mature

lymphocytes

■ Normal marrow

elements

crowded out


CLL with 1,000,000 WBC/uL


Bone Marrow in CLL


Immunology of CLL

■ B-cell lymphoproliferative disease

B-cell antigens (CD19+, etc.)

CD5+ (T-cell antigen)

■ Monoclonal light chains

Kappa or lambda


Immunology of CLL


Immunology of CLL


Lecture Contents

■ Basic features

■ Acute leukemias

■ Chronic leukemias

Chronic lymphocytic leukemia

Chronic myelogenous leukemia

■ Multiple myeloma

■ Summary


Chronic Myeloproliferative Disorders

■ Chronic Myelogenous Leukemia

(CML)

■ Polycythemia Vera

■ Essential Thrombocythemia

■ Agnogenic Myeloid Metaplasia

(Myelofibrosis)


Peripheral Blood in CML

■ 15-20% of all leukemias

■ Young or middle-aged patients

■ Asymptomatic, fatigue, abdominal fullness,

early satiety, weight loss, anorexia

■ Splenomegaly, bone pain, bone tenderness

■ Proliferation of myeloid cells in blood and

bone marrow (mostly myelocytes → polys)

■ Slow progression (3 yr survival without Rx)

■ Ph 1 chromosome in > 95%

■ All patients have chimeric bcr/abl mRNA


Peripheral Blood in CML

500x


Bone Marrow in CML

■ Hypercellular bone marrow

■ High Myeloid:Erythroid Ratio

Myeloid hyperplasia

Relatively few blast cells

Mostly mature neutrophils

Increased basophils and

eosinophils

■ Increased megakaryocytes


Bone Marrow in CML


Bone Marrow in CML


Molecular Biology of CML

■ Philadelphia (Ph 1 ) chromosome

■ Reciprocal translocation between

chromosomes 9 and 22

■ Juxtaposition of oncogene from

chromosome 9 with breakpoint

cluster gene on chromosome 22

■ Chimeric / mRNA has

increased tyrosine kinase activity


Philadelphia Chromosome


Clinical Course of CML

■ Chronic Phase

2- 22 years

■ Spent Phase

Myelofibrosis

■ Accelerated Phase

Increased blast count

Resistance to treatment

Additional chromosomal defects

■ Blast crisis


Differential Diagnosis of CML

■ Leukemoid Reaction

eukocyte lkaline hosphatase

(LAP) score

translocation

■ Other myeloproliferative diseases

■ AML

translocation

Morphology/blast cell count


Treatment of CML

■ Bone marrow transplantation

■ Chemotherapy

Alkylating agents

Hydroxyurea

■ Interferons


Myelofibrosis with Myeloid Metaplasia

■ Collagen deposition in bone

marrow

■ Hematopoietic cells are crowded

out

■ Stem cells go to spleen

Marked splenomegaly


Peripheral Blood in Myelofibrosis

■ Anemia

Tear drop cells

■ Leukoerythroblastosis

Early release of nucleated RBCs

and granulocytes


Tear Drop Cells


Bone Marrow in Myelofibrosis

■ Hypercellular bone marrow

■ Reticulin fibrosis


Lecture Contents

■ Basic features

■ Acute leukemias

■ Chronic leukemias

Chronic lymphocytic leukemia

Chronic myelogenous leukemia

■ Multiple myeloma

■ Summary


Multiple Myeloma

■ Cancer of plasma cells

■ Disease of older men and women (> 60

years)

■ Produce abundant useless monoclonal Ig

(paraprotein, M-protein)

■ Decreased normal Ig, infections occur

■ Lytic bone lesions , bone pain,

pathologic fractures, hypercalcemia

■ Tumorous masses of plasma cells (spine,

skull, ribs, pelvis)

■ Renal failure may develop


The Discovery

of Multiple

Myeloma

Dear Dr. Bence Jones,

Nov. 1, 1845

The tube contains urine of very

high specific gravity. When boiled

it becomes highly opaque. On the

addition of nitric acid it

effervesces, assumes a reddish

hue, and becomes quite clear; but

as it cools assumes the

consistence and appearance

which you see. Heat reliquefies it.

What is it?

Sincerely,

Dr. Thomas Watson


Hoffbrand and Pettit, 1994

Multiple Myeloma


Peripheral Blood in MM

■ Rouleaux

formation

■ Nonspecific

reaction to

blood proteins


Bone

Marrow in

Multple

Myeloma


Bone

Marrow in

Multple

Myeloma


Diagnosis of Multiple Myeloma

■ Demonstrate Monoclonal Protein

erum rotein Immun lectro horesis

(SPEP)

rine rotein Immun lectro horesis

(UPEP)

Immunofixation

■ IgG - 55%, IgA - 25%, light chains only - 20%,

IgD or IgE - 1%

■ Skeletal survey

Punched out lesions

■ Bone Marrow Aspirate

Plasma cells


Protein

Electrophoresis


Treatment of Multiple Myeloma

■ No treatment for indolent

disease

■ Good multispecialty care for

medical problems

■ Radiation for localized disease or

palliation

■ Chemotherapy

■ Bone Marrow transplantation


Lecture Contents

■ Basic features

■ Acute leukemias

■ Chronic leukemias

Chronic lymphocytic leukemia

Chronic myelogenous leukemia

■ Multiple myeloma

■ Summary


Leukemia Classification

Lymphoid

Myeloid

Acute Chronic

ALL CLL

AML

CML


Acute Lymphoblastic Leukemia

■ Proliferation of lymphoblasts

Anemia, thrombocytopenia,

increased WBC

Lymphadenopathy/splenomegaly

■ B- or T-cell

Flow cytometry

■ TdT+

■ Uric acid breakdown during

chemotherapy


Acute Myelogenous Leukemia

■ Proliferation of myeloblasts

Anemia, thrombocytopenia,

increased WBC

■ Myeloid, monocytic, RBC, or

megakaryocytic

Flow cytometry

Myeloperoxidase +, TdT-

■ Auer rod

■ APL with t(15;17), DIC; retinoic

acid


Chronic Myelogenous Leukemia

■ Myeloproliferative diseases (PV,

ET)

■ Proliferation of more mature

granulocytes

Normal to increased platelets

Anemia

■ Splenomegaly

■ t(9;22)(bcr-abl)(Ph chromosome)

■ LAP score


Chronic Myelogenous Leukemia

■ Long chronic phase

■ Blast crisis

■ Hydroxyurea, interferons

■ Bone marrow transplantation


Chronic Lymphocytic Leukemia

■ Proliferation of small mature Blymphocytes

Flow cytometry (monoclonal

Kappa or lambda)

■ Lymphadenopathy

Relationship to small lymphocytic

lymphoma

■ May have Ab production/AIHA

■ 50% 5-year survival


Multiple Myeloma

■ Neoplasm of plasma cells

Monoclonal protein in serum (SPEP)

Proteinuria (Bence-Jones) (UPEP)

■ Lytic lesions in bones

Fractures, hypercalcemia, pain

■ Anemia, increased globulin

Rouleaux formation

■ Renal failure/ amyloidosis

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