Malignant Hematology

Question 1

Hematopoietic Stem Cells

Answer 1

• Initiates hematopoiesis
• Rare cells
• Differentiates into committed progenitor cells
• Self-renewal capacity ⇒ differentiates a stem cell from any other cell

Question 2

Hematopoiesis

Functions

Answer 2

• Proliferation:
  
  • Replacement of normal blood cell loss
  • Amplification of the number of mature blood cells during times of stress
• Differentiation resulting in:
  
  • Oxygen carrying capacity: red blood cells/hemoglobin
  • Hemostasis: platelets
  • Innate Immunity: neutrophils and NK cells
  • Adaptive Immunity: T- and B- lymphocytes

Question 3

Hematopoiesis

Location

Answer 3

• Adults ⇒ blood cells produced in red marrow
  
  • Restricted to the bones of the axial skeleton
• Fetal life ⇒ the major hematopoietic tissues are:
  
  • < 6 weeks → yolk sak
  • 6 weeks-6-7 months → liver and spleen
• In hematopoietic diseases, the liver and/or spleen can become hematopoietic centers ⇒ extramedullary hematopoiesis

Question 4

B-lymphocyte

Development

Answer 4

• Pro-B-cells re-arrange germline Ig genes
  
  • Heavy chain first then light chain
• Forms a unique Ig that is expressed on cell surface ⇒ immature B-cell
• Immature B-cells migrate from the mantle zone (lymph node) to the germinal center
• Undergo somatic hypermutation of the variable region genes
• B-cells stimulated by Ag + APC ± T-cell help ⇒ plasma cells
• Plasma cells move to bone marrow and produce highly specific immunoglobulin
• No longer express immunoglobulin on their cell surface

Question 5

T-lymphocyte

Development

Answer 5

• Pre-T-cells undergo TCR gene re-arrangement in the thymic cortex
• T-cells that express high-affinity receptors for self-Ag undergo negative selection (aka clonal deletion) by apoptosis
• In the thymic medulla, cells undergo further maturation ⇒ either CD4⁺ T helper cells or CD8⁺ cytotoxic T-cells
• Stimulation of TCRs requires Ag presentation by APC as peptides held on an HLA molecule (HLA restricted)
  
  • CD4+ T-cells recognize class II HLA molecules
  • CD8+ T-cells recognize class I HLA molecules
• With co-stimulatory signal ⇒ T-cell activation
• Without co-stimulatory molecules ⇒ T-cells anergy

Question 6

Leukocyte

Classes

Answer 6

Question 7

Leukocytosis

Causes

Answer 7

Question 8

Normocellular Bone Marrow

Histology

Answer 8

Question 9

Aplastic Anemia

Answer 9

• Bone marrow failure syndrome
• Characterized by peripheral pancytopenia and marrow hypoplasia

Question 10

Leukemia

Characteristics

Answer 10

• Group of hematologic malignancies
• Characterized by proliferation of immature hematopoietic cells (blasts) and maturation arrest
• Leukemia initiating cell has self-renewal properties (leukemic stem cell)
• Can be myeloid, lymphoid, or (rarely) biphenotypic

Question 11

Acute Lymphoblastic Leukemia

(ALL)

Answer 11

• Lymphoblasts are positive for:
  
  • TdT – terminal deoxytransferase
  • CD10 – common ALL Ag
  • Acid phosphatase
  • PAS
• Symptoms are secondary to marrow failure:
  
  • Anemia ⇒ fatigue, exertional dyspnea
  • Leukopenia ⇒ risk for infection
  • Thrombocytopenia ⇒ risk for bleeding/bruising

Question 12

Acute Myeloid Leukemia

(AML)

Answer 12

• Most common acute leukemia in adults (~70%)
• Auer rods are specific for myeloid lineage
• Symptoms are secondary to marrow failure:
  
  • Anemia ⇒ fatigue, exertional dyspnea
  • Leukopenia ⇒ risk for infection
  • Thrombocytopenia ⇒ risk for bleeding/bruising

Question 13

Benign Reactive

Lymphadenopathy

Answer 13

Question 14

Lymphoma

Characteristics

Answer 14

• Tumors of malignant lymphoid cells
• Nodal ⇒ Lymph nodes
  
  • Present as enlarged non-tender lymph nodes (>2 cm)
• Extra-nodal ⇒ Non-lymphoid organs including bone marrow
  
  • Present w/ symptoms related to the site of involvement

Question 15

Hodgkin Lymphoma

Answer 15

Question 16

Non-Hodgkin Lymphoma

Diffuse Large B-cell Lymphoma

Answer 16

Question 17

Hodgkin Lymphoma

vs

Non-Hodgkin Lymphoma

Answer 17

Question 18

Myeloid Neoplasms

Answer 18

• MDS ⇒ mostly a problem of abnormal differentiation (qualitative)
• MPN ⇒ excessive proliferation w/ normal differentiation (quantitative)
• AML ⇒ excessive proliferation and maturation arrest (qualitative and quantitative)

Question 19

Myeloproliferative Neoplasms

(MPN)

Answer 19

• Group of (mostly) clonal hematologic disorders
• Characterized by accumulation of mature cells
  
  • Accumulation can involve one or more cell lines
• No age, sex or race predilection
• Rare disorders w/ collective annual incidence of 5/100,000

Question 20

MPN

WHO Classification

Answer 20

• Chronic Myelogenous Leukemia (CML), BCR-ABL1 ⊕
• Chronic Neutrophilic Leukemia
• Chronic Eosinophilic Leukemia
• Polycythemia Vera (PV)
• Essential Thrombocythemia (ET)
• Primary Myelofibrosis (PMF)
• Mastocytosis
• Chronic Myeloproliferative Neoplasm, unclassifiable

Note: Know the ones in bold.

Question 21

Myelodysplasic Syndromes

(MDS)

Answer 21

• Group of hematological disorders characterized by:
  
  • Clonal myelopoiesis ⇒ frequent cytogenetic abnormalities
  • Ineffective hematopoiesis ⇒ hypercellular bone marrow in the setting of peripheral blood cytopenia(s)
  • Abnormal differentiation ⇒ dysplastic changes and tendency to develop acute leukemia
• Syndromes are preleukemic

Question 22

Dysplastic Changes

Answer 22

Question 23

Plasma Cell Dyscrasias

Answer 23