Hematopathology I

Question 1

State of Maturity of Cells in Acute Hematopoietic Malignancies

Answer 1

Presence of very immature cells (blasts)

Question 2

State of Maturity of Cells in Chronic Hematopoietic Malignancies

Answer 2

Presence of differentiated cells (mature)

Question 3

What is leukemia?

Answer 3

The leukemias are malignant neoplasms of the hematopoietic cells characterized by diffuse replacement of the bone marrow by neoplastic cells

Question 4

What are the classifications of acute leukemia?

Answer 4

• Lymphoid

- Myeloid

Question 5

What is the difference in leukemia and lymphoma?

Answer 5

“Leukemia” is used for hematopoietic neoplasms that present with widespread involvement of the bone marrow and blood.

“Lymphoma” is used to describe proliferations arising as discrete tissue masses.

Question 6

What are some of the findings of ALL and AML?

Answer 6

Anemia, neutropenia, thrombocytopenia

Question 7

What is the onset of acute leukemia?

Answer 7

Abrupt stormy onset

Question 8

What are some of the symptoms of acute leukemia?

Answer 8

– fatigue, often caused by anemia
– fever, reflecting infection caused by neutropenia
– bleeding, secondary to thrombocytopenia

Question 9

What population does acute lymphoblastic leukemia (ALL) tend to affect?

Answer 9

Children. 80% of acute leukemias in children are ALLs

Question 10

What are the neoplastic cells in ALL?

Answer 10

Lymphoblasts (pre-B/pre-T)

Question 11

What are the most common types of ALLs?

Answer 11

pre-B cell ALLs - they make up around 85% of ALLs (B-ALLs)

Question 12

What are the typical patients of pre-T cell ALL (T-ALL)?

Answer 12

Tends to present in adolescent males often with thymic involvement manifesting as a mass in the mediastinum.

Question 13

What is unique about the presentation of T-ALL?

Answer 13

As it presents as a mass in the mediastinum, it presents as a “lymphoma” it is followed by a leukemic phase - involvement of the blood and bone marrow

Question 14

What is seen on microscopic evaluation of ALL?

Answer 14

Lymphoblasts usually show scant basophilic cytoplasm and fine nuclear chromatin (not clumpy), often nuclear convolutions

Question 15

Name the marker that is commonly expressed in pre-B and pre-T lymphoblasts in a large majority of ALL cases.

Answer 15

TdT - Terminal deoxynucleotidyl transferase

Question 16

What will TdT staining show?

Answer 16

Cells that stain brown are positive for TdT

Question 17

What is another method for ALL diagnosis outside of TdT markers?

Answer 17

Up to 90% of ALL patients have numerical or structural changes in the chromosomes of the leukemic cells, correlating with immunophenotype and sometimes prognosis

– hyperdiploidy (more than 50 chromosomes) is common – t(12;21) [TEL1-AML1 (ETV6-RUNX1)]
– t(9;22) [BCR-ABL; Philadelphia chromosome]
– t(4;11) [AF4-MLL]

Question 18

What are favorable prognostic indicators of ALL?

Answer 18

– Age 2 to 10 years
– hyperdiploidy
– t(12;21) [TEL1-AML1 (ETV6-RUNX1)]

Question 19

What are some unfavorable prognostic indicators of ALL?

Answer 19

– age under 2
– adolescent or adult presentation
– presence of t(9;22) [seen in 3% of childhood ALL, but up to 25% of adult cases]

Question 20

What is the mutation and significance of the Philadelphia chromosome?

Answer 20

t(9;22) - BCR-ABL -> 1st genetic abnormality found in cancer

Question 21

What population does acute myeloid leukemia (AML) tend to affect?

Answer 21

Mostly a disease of adults that peaks in incidence after 60 years of age

Question 22

What are the 4 WHO classifications of AML and what are the prognosis outcomes of each of them?

Answer 22

t(8;21) AML1-ETO good
t(15;17) PML/RARA good
Inv(16) CBFB/MYH11 good
t(11q23;v) MLL poor

Question 23

What are myelodysplastic syndromes (MDS)?

Answer 23

Pre-leukemic states - Clonal stem cell disorders showing defective and ineffective hematopoiesis with increased risk for transformation to AML.

They can be of primary idiopathy or secondary to chemoradiation therapy.

Question 24

What is the pathogenesis of MDS?

Answer 24

Hypercellular marrow with peripheral cytopenia due to ineffective hematopoiesis. MDS arises on a background of stem cell damage.

Question 25

What are the morphological findings in MDS?

Answer 25

Nuclear irregularity, nuclear budding, multinucleation, separated nuclear lobes in cells where the nucleus is segmented normally

Question 26

What is the prognosis of primary VS secondary MDS?

Answer 26

Secondary MDS will have a FAR worse prognosis

Question 27

What are some of the differences in the signs of AML VS ALL?

Answer 27

Signs and symptoms related to infiltration of tissues are usually less striking in AML than in ALL, although mild lymphadenopathy and organomegaly may be appreciated.

CNS spread is less common.

Question 28

What are the special findings in acute promyelocytic leukemia (APL)?

Answer 28

In acute promyelocytic leukemia [t(15;17)], particularly, procoagulants released by leukemic cells may produce DIC

Question 29

What is a morphological finding of APL?

Answer 29

Auer Rods are present within cells

Question 30

Name the characteristic translocation in acute promyelocytic leukemia and explain its pathogenetic importance.

Answer 30

t(15;17) PML/RARA

Fusion gene encodes an abnormal retinoic acid receptor that blocks myeloid cell differentiation

Question 31

What is the treatment for APL?

Answer 31

All-trans-retinoic acid overcomes the differentiation block

Question 32

What will stains of AML show?

Answer 32

Myeloperoxidase or alpha napthyl butyrate esterase

Question 33

What are some of the features in AML diagnosis?

Answer 33

• Myeloperoxidase or alpha napthyl butyrate esterase
• Auer Rods
• Flow cytometry: CD13, CD33, CD34, CD117 (myeloid)

Question 34

What is the general prognosis for AML?

Answer 34

• t(15;17), t(8;21) or inversion of chromosome 16 are associated with relatively good prognoses
• Translocations involving chromosome 11q23 (MLL) have a poor outcome

Question 35

What etiology of AMLs have particular poor prognoses?

Answer 35

AMLs arising out of MDS or after chemotherapy have particularly poor prognoses