Leukemias and lymphomas 20 study document

I. Hematologic Malignancies Overview

Hematologic malignancies are cancers that affect the blood, bone marrow, and lymphatic system.

They include:

1. Leukemias

2. Lymphomas

3. Plasma cell disorders (e.g., multiple myeloma)

Key Diagnostic Tools:

• Clinical presentation

• Morphology

• Immunophenotyping

• Molecular studies

• Cytogenetics

• Bone marrow biopsy and aspiration

II. Leukemias

1. Definition:

• Malignancy of hematopoietic cells starting in the bone marrow

• Can spread to blood, lymph nodes, and organs

• Types by lineage:

o Myeloid

o Lymphoid

• Types by course:

o Acute

o Chronic

2. Acute vs. Chronic Leukemia A. Pathophysiology

III. Acute Leukemias

A. Pathophysiology

• Malignant clonal proliferation of immature myeloid or lymphoid cells

• Mechanisms:

o Clonal expansion

o Maturation arrest

• Consequences:

o Crowds out normal hematopoiesis

o Organ infiltration

III. Acute Leukemias B. Clinical Features

A. Pathophysiology

• Malignant clonal proliferation of immature myeloid or lymphoid cells

• Mechanisms:

o Clonal expansion

o Maturation arrest

• Consequences:

o Crowds out normal hematopoiesis

o Organ infiltration

III. Acute Leukemias C. Acute Myeloid Leukemia (AML)

• ≥ 20% blasts in marrow/blood for diagnosis

• Presence of Auer rods in cytoplasm of myeloblasts

• Multiple subtypes: M0-M7 (FAB classification)

Important Subtype:

• AML-M3 (Acute Promyelocytic Leukemia):

o Characterized by Faggot cells

o Associated with DIC

o Treated with ATRA (All-trans retinoic acid)

III. Acute Leukemias D. Acute Lymphoblastic Leukemia (ALL)

D. Acute Lymphoblastic Leukemia (ALL)

• Malignancy of lymphoid blasts

• More common in children

• Good prognosis in many pediatric cases

Classification by Immunophenotype:

• B-lineage (Better prognosis)

• T-lineage (Worse prognosis)

Prognostic Factors:

• Better:

o Age 1–10 years

o WBC < 10,000

o Hyperdiploidy

• Worse:

o T-cell origin

o Very high WBC

o <1 or >10 years of age

III. Acute Leukemias E. Treatment of Acute Leukemias

• Chemotherapy

• Bone marrow transplantation

• Prognosis varies:

o Worse in therapy-related AML

o Better in pediatric ALL with favorable cytogenetics

IV. Myelodysplastic Syndromes (MDS)

• Clonal stem cell disorders with ineffective hematopoiesis

• Dysplasia in one or more myeloid lineages

• Risk of progression to AML

• Common in elderly

• Blood findings: Macrocytic anemia, cytopenias

• Bone marrow: Hypercellular with dysplastic features

V. Chronic Leukemias A. Chronic Myeloid Leukemia (CML)

• Age: Adults (25–60 years)

• Genetics: t(9;22) Philadelphia chromosome → BCR-ABL fusion

• Peripheral blood:

o Very high TLC (>100,000/mm³)

o Myelocytes, basophilia, thrombocytosis

• Bone marrow: Hypercellular with granulocytic precursors

Clinical Course:

1. Chronic phase

2. Accelerated phase

3. Blast crisis → resembles acute leukemia

B. Chronic Lymphocytic Leukemia (CLL)

• Most common leukemia in adults in the West

• B-cell origin (CD19+, CD20+, CD23+)

• Smudge cells in peripheral smear

• Often asymptomatic; may present with:

o Fatigue, weight loss

o Recurrent infections

o Autoimmune phenomena: AIHA, ITP

• May transform into:

o Prolymphocytic leukemia

o Richter syndrome → Diffuse large B-cell lymphoma (DLBCL)

VI. Lymphomas A. General Features

VI. Lymphomas

A. General Features

• Malignancy of lymphoid cells, originating in lymph nodes

• May spread to blood, bone marrow, and extranodal sites

• Two broad categories:

1. Hodgkin Lymphoma (HL)

2. Non-Hodgkin Lymphoma (NHL)

VII. Hodgkin Lymphoma (HL)

A. Definition and Features

• Characterized by presence of Reed-Sternberg (RS) cells in a reactive inflammatory

background

• Arises in a single lymph node region, spreads contiguously

• Less commonly involves extranodal sites

• Associated with EBV in some subtypes

B. Subtypes (WHO Classification)

B. Subtypes (WHO Classification)

1. Nodular sclerosis (65–75%)

o Most common

o Features Lacunar cells

o Frequent in young adults, especially females

o Involves cervical, supraclavicular, and mediastinal nodes

o Excellent prognosis

2. Mixed cellularity (25%)

o Numerous classic RS cells, abundant inflammatory background

o More common in older males

o Often presents with B symptoms

o Intermediate prognosis

3. Lymphocyte-rich

o Many lymphocytes, few RS cells

o Good prognosis

4. Lymphocyte-depleted

o Few lymphocytes, many RS cells

o Worst prognosis

5. Lymphocyte-predominant (non-classical)

o "Popcorn" cells (L&H variants)

o Often in young males

o Indolent, good prognosis

C. Reed-Sternberg Cells

C. Reed-Sternberg Cells

• Classic RS: large (15–45 microns), binucleated or bilobed, "owl’s eye" nucleoli

• Variants:

o Mononuclear RS cell

o Lacunar RS cell (Nodular sclerosis)

o L&H cell (Lymphocyte predominant)

o Mummified RS cell (degenerative)

D. Spread and Staging

D. Spread and Staging

• Predictable spread pattern: lymph nodes → spleen → liver → marrow → extranodal sites

Ann Arbor Staging:

• I: One LN region or single extranodal site

• II: Two or more LN regions on same side of diaphragm

• III: LN regions on both sides of diaphragm ± spleen

• IV: Disseminated involvement (e.g., liver, marrow)

VIII. Non-Hodgkin Lymphoma (NHL)

VIII. Non-Hodgkin Lymphoma (NHL)

A. General Characteristics

• More heterogeneous than HL

• Often presents with multiple peripheral nodes, extranodal involvement

• Non-contiguous spread

• Higher association with immunodeficiency (e.g., AIDS)

VIII. Non-Hodgkin Lymphoma (NHL) B. Classification

B. Classification

• Origin:

o ~85% are B-cell lymphomas

o ~15% are T-cell/NK-cell lymphomas

• Based on:

o Cell of origin

o Morphology

o Immunophenotype

o Genetic abnormalities

C. Common B-cell NHL Subtypes:

C. Common B-cell NHL Subtypes:

1. Follicular lymphoma

o Most common indolent NHL in the U.S.

o Originates from germinal center B-cells

o t(14;18) → BCL2 overexpression

o Slow-growing; may transform to DLBCL

2. Diffuse large B-cell lymphoma (DLBCL)

o Most common aggressive NHL

o Rapidly enlarging mass

o Treatable with chemo (R-CHOP)

3. Mantle cell lymphoma

o Older males

o t(11;14) → Cyclin D1 overexpression

4. Marginal zone lymphoma

o Associated with chronic inflammation

▪ e.g., H. pylori (MALT lymphoma)

5. Burkitt lymphoma

o Highly aggressive

o t(8;14) → c-MYC activation

o Associated with EBV

o “Starry-sky” appearance

6. Small lymphocytic lymphoma (SLL)/CLL

o Same disease as CLL, but with low peripheral lymphocytosis

D. T-cell and NK-cell Lymphomas:

D. T-cell and NK-cell Lymphomas:

• Less common, often aggressive

• Examples:

o Adult T-cell leukemia/lymphoma (HTLV-1)

o Mycosis fungoides/Sezary syndrome

o Anaplastic large cell lymphoma

IX. Immunophenotyping (CD Markers)

X. Plasma Cell Neoplasms

X. Plasma Cell Neoplasms

A. Multiple Myeloma

• Malignancy of plasma cells in bone marrow

• Produces monoclonal immunoglobulin (M protein)

• Bone destruction → lytic lesions

Clinical Features: CRAB

• Calcium elevation (hypercalcemia)

• Renal insufficiency

• Anemia

• Bone pain, lytic lesions

XI. Summary Table – Comparison of leukemias and lymphomas