Hematopathology I Flashcards
State of Maturity of Cells in Acute Hematopoietic Malignancies
Presence of very immature cells (blasts)
State of Maturity of Cells in Chronic Hematopoietic Malignancies
Presence of differentiated cells (mature)
What is leukemia?
The leukemias are malignant neoplasms of the hematopoietic cells characterized by diffuse replacement of the bone marrow by neoplastic cells
What are the classifications of acute leukemia?
- Lymphoid
- Myeloid
What is the difference in leukemia and lymphoma?
“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.
What are some of the findings of ALL and AML?
Anemia, neutropenia, thrombocytopenia
What is the onset of acute leukemia?
Abrupt stormy onset
What are some of the symptoms of acute leukemia?
– fatigue, often caused by anemia
– fever, reflecting infection caused by neutropenia
– bleeding, secondary to thrombocytopenia
What population does acute lymphoblastic leukemia (ALL) tend to affect?
Children. 80% of acute leukemias in children are ALLs
What are the neoplastic cells in ALL?
Lymphoblasts (pre-B/pre-T)
What are the most common types of ALLs?
pre-B cell ALLs - they make up around 85% of ALLs (B-ALLs)
What are the typical patients of pre-T cell ALL (T-ALL)?
Tends to present in adolescent males often with thymic involvement manifesting as a mass in the mediastinum.
What is unique about the presentation of T-ALL?
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
What is seen on microscopic evaluation of ALL?
Lymphoblasts usually show scant basophilic cytoplasm and fine nuclear chromatin (not clumpy), often nuclear convolutions
Name the marker that is commonly expressed in pre-B and pre-T lymphoblasts in a large majority of ALL cases.
TdT - Terminal deoxynucleotidyl transferase
What will TdT staining show?
Cells that stain brown are positive for TdT
What is another method for ALL diagnosis outside of TdT markers?
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]
What are favorable prognostic indicators of ALL?
– Age 2 to 10 years
– hyperdiploidy
– t(12;21) [TEL1-AML1 (ETV6-RUNX1)]
What are some unfavorable prognostic indicators of ALL?
– 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]
What is the mutation and significance of the Philadelphia chromosome?
t(9;22) - BCR-ABL -> 1st genetic abnormality found in cancer
What population does acute myeloid leukemia (AML) tend to affect?
Mostly a disease of adults that peaks in incidence after 60 years of age
What are the 4 WHO classifications of AML and what are the prognosis outcomes of each of them?
t(8;21) AML1-ETO good
t(15;17) PML/RARA good
Inv(16) CBFB/MYH11 good
t(11q23;v) MLL poor
What are myelodysplastic syndromes (MDS)?
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.
What is the pathogenesis of MDS?
Hypercellular marrow with peripheral cytopenia due to ineffective hematopoiesis. MDS arises on a background of stem cell damage.
What are the morphological findings in MDS?
Nuclear irregularity, nuclear budding, multinucleation, separated nuclear lobes in cells where the nucleus is segmented normally
What is the prognosis of primary VS secondary MDS?
Secondary MDS will have a FAR worse prognosis
What are some of the differences in the signs of AML VS ALL?
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.
What are the special findings in acute promyelocytic leukemia (APL)?
In acute promyelocytic leukemia [t(15;17)], particularly, procoagulants released by leukemic cells may produce DIC
What is a morphological finding of APL?
Auer Rods are present within cells
Name the characteristic translocation in acute promyelocytic leukemia and explain its pathogenetic importance.
t(15;17) PML/RARA
Fusion gene encodes an abnormal retinoic acid receptor that blocks myeloid cell differentiation
What is the treatment for APL?
All-trans-retinoic acid overcomes the differentiation block
What will stains of AML show?
Myeloperoxidase or alpha napthyl butyrate esterase
What are some of the features in AML diagnosis?
- Myeloperoxidase or alpha napthyl butyrate esterase
- Auer Rods
- Flow cytometry: CD13, CD33, CD34, CD117 (myeloid)
What is the general prognosis for AML?
- 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
What etiology of AMLs have particular poor prognoses?
AMLs arising out of MDS or after chemotherapy have particularly poor prognoses
