Lecture 46 - Hematophathology 1 - Leukemias, Myelomas

Question 1

What are the 4 families of neoplasms?

Answer 1

Leukemia, lymphomas (neoplasms of wbc),

carcinomas, sarcomas

Question 2

What is a leukemia?

Answer 2

Typical Leukemias are malignancies that typically involve marrow and (usually) blood (leukos haima ~ ‘white blood’) — spread out nomadic throughout the blood supply and bone marrow

Question 3

What is a lymphoma

Answer 3

○ Typical Lymphomas are malignancies that typically form discrete masses in tissue, often lymph nodes (‘oma’)

Question 4

what are some critical diagnostic techniques of leukemias

Answer 4

§ Immuno stains – CD45 is expressed by all WBCs

Flow Cytometry

Cytogenetics: FISH

Question 5

What are the two dichotomies of classifying leukemia ?

Answer 5

1) myeloid vs Lymphoid

2) Acute vs Chronic

Question 6

What is a myeloid leukemia?

what is a lymphoid leukemia?

Answer 6

marrow elements (i.e., neutrophils, eosinophils, basophils, rbcs, megakaryocytes), but may also involve the spleen and liver

B&T lymphocytes & plasma cell; may often behave like Lymphomas (leukemia/lymphomas)

Question 7

Acute Myeloid Luekemia (AML)
- what is it?
-

Answer 7

Accumulation of immature myeloid cells in the bone marrow and blood
Failure of normal hematopoiesis — patients are acutely ill

Dx - at least 20% blasts in marrow or blood

Question 8

what are the 4 categories of AML?

Answer 8

1) AML with genetic aberrations: defining the AML by the molecular abnormality; mostly translocations
2) AML with MDS-like features* – failure to develop in multiple/all of the lineages of the bone marrow
3) AML, therapy-related — AML that follows chemo-radiation therapy; poor prognosis
4) AML, not otherwise specified == vague categories of types (eg Erythroid AML, Megagarocytic AML, Monocytic AML)

Question 9

What is an imporatnt subtype of AML with genetic aberration?

• what is the genetic aberration?
• describe the morphology?
• what is a characteristic finding (although not specific)
• what can it be treated with?

Answer 9

APL – Acute Promyelocytic Leukemia (M3 Subtype of AML)

Genetic aberration: t(15;17)(q22;11-12) Translocation: Retinoic Acid Receptor/PML

PML is normally a tumor suppressor, but when translocated, loses its function

RAR is important for treatment mechanism
-Treated with All Trans Retinoic Acid

Morphology: Large, Bi-lobed nuclei, Granules, Auer Rods

Auer rods – not specific for APL, but characteristi

Question 10

Chronic Myeloid Proliferative Leukemia (CML)
- what is it?
what is the genetic aberration ?
- describe the progression

Answer 10

Governs growth, not differentiation; Lots of normally differentiated myeloid cells in the marrow and the blood

Genetic aberration: t(9;22) – BCR-ABL (Philadelphia chromosome)
Constituively active Tyrosine Kinase

Latent Phase – but may progress to AML or ALL (blast crisis)

• Accelerated Phase : 10-19% blasts
• Blasts Crisis - > 20% Blasts

Question 11

What is Lymhpoid Leukemia?
what are they?
describe their cell profiles

Answer 11

B&T lymphocytes & plasma cell; may often behave like Lymphomas (leukemia/lymphomas)

Acute Lymphoblastic Leukemia: Immature lymphoid cells – either B or T; Peripheral blood with lots of lymphoblasts

Chronic Lymphocytic Leukemia – neoplasm of mature lymphocytes; very indolent; very slow progression

Question 12

ALL – Acute Lymphoblastic Leukemia

• who gets this disease?
• Morphology
• specific stain for AML
• what causes it?

Answer 12

85% are B cell ALL; most cases in children

§ Morphology: Large Nuclei (high N:C ratio); High Mitotic Rate

TdT Stain — characterizes as ALL, not AML

ALL Chromosomal Changes: 90% of ALLs have Chromosomal Changes (a small portion have the BCR-ABL translocation)

Question 13

Chronic Lymphocytic Leukemia (CLL)

• who gets this ?
• Describe the progression –
• Specific morphology

Answer 13

Most common adult leukemia
very indolent disease/slow progression; may last in latent stages for years

Small Lymphocyte –
Pathognomonic — Proliferation Centers (Pseudofollicles)
“Smudge Cells”

Question 14

Myelodysplastic Syndromes (MDS)
what is it?
describe the progression?
Morphology?

Answer 14

Abnormal maturation of All lineages

High rate of progression to AML

	○ Morphology: All lineages are involved 
		§ Hypercellulary; Dysplastic morphologies in all lineages; abnormal erythrocytes, granulocytes, abnormal megakaryocytes 
		§ None of the cells look normal

Question 15

Myeloproliferative Disorders (neoplasms) –

• what is it?
• what are the 4 types?

Answer 15

increased numbers of mature/maturing blood cells; but not of all lineages

CML – Myeloid Lineage – BCR/ABL

Polycythemia Vera – High Erythrocytes

Essential Thrombocythemia – high platelets

Primary Myelofibrosis - Fibrotic bone marrow, leaidng to cytopenias

Question 16

Polycythemia Vera

• what is the mutation ?
• what is the result?
• progression?

Answer 16

Hypercellular marrow; predominatly erythrocytes

JAK 2 tyrosine kinase

			□ 20% progress to Spent Phase (fibrosis marrow; severe splenomegaly as it takes over hematopoiesis)

Question 17

Essential Thrombocythemia
- what is it ?
mutations?
morphology

Answer 17

Elevated Platelet Counts

JAK 2, MPL

Rarely progress to AML or the Spent Phase

Megkaryocytes are large; Large and increased Number of Platelets

Question 18

Primary Myelofibrosis

• what is it?
• mutations?

Answer 18

JAK2, MPL

marrow becomes fibrotic

□ Most cases present with progressive marrow fibrosis and loss of marrow elements;
Immature forms released into the blood bc marrow is being overtaken by fibrosis
Cytopenias
Bone marrow scars over and may ossify