Pathoma Chapter 6: Part 1 Flashcards
Myeloid stem cells give rise to what?
- Erythroblasts (RBCs)
- Myeloblasts (neutrophils, basophils, eosinophils)
- Monoblasts (monocytes)
- Megakaryoblasts (Megakaryocytes)
What is a normal white cell count?
4.4-11.3 K/ul
What are some causes of neutropenia?
- drug toxicity (chemo with alkylating agents)
- severe infection (gram- species)
How do chemo alkylating agents cause neutropenia?
they damage stem cells resulting in decreased production
How do severe infections cause neutropenia?
increased movement of neutrophils into tissue results in decreased circulating neutrophils
What are some causes of lymphopenia?
- immunodeficiency (DiGeorge or HIV)
- High cortisol state (Cushing’s of exogenous corticosteroids)
- Autoimmune destruction (SLE)
- Whole body radiation
How does a high cortisol state cause lymphopenia?
it induces apoptosis of lymphocytes
What are some causes of eosinophilia?
- type I hypersensitivity
- parasitic infections
- Hodgkin lymphoma
What are some causes of basophilia?
- acute myeloid leukemia
What are some causes of lymphocytosis?
- viral infections
- Bordetella pertussis infection (via lymphocytosis promoting factor secreted by the bacteria which prevents them from leaving blood to enter lymph)
What is acute leukemia?
neoplastic proliferation of blasts; defined as an accumulation of 20+% of blasts in the bone marrow or peripheral blood
Why is it called “acute” leukemia?
increased blasts crowd-out normal hematopoiesis, resulting in an acute presentation
Clinical presentation of acute leukemia?
- anemia (fatigue)
- thrombocytopenia (bleeding)
- possible neutropenia (infection)
T or F. WBC is usually elevated in acute leukemia
T. due to blasts entering the blood stream
What is acute lymphoblastic leukemia defined as?
accumulation of 20+ % of lymphocytes in the bone marrow
How are lymphoblasts identified?
via positive nuclear staining for TdT, a DNA polymerase
TdT is absent in myeloid blasts and mature lymphocytes
ALL is common in what patient population?
usually kids (associated with down syndrome) presents after 5 y/o typically
Subclasses of ALL?
B-ALL (most common) and T-ALL based on surface markers
How is B-ALL identified?
usually characterized by lymphoblasts (TdT) that express CD10, CD19, and CD20.
Clinical course for B-ALL?
requires prophylaxis to scrotum and CSF- great response
Prognosis of B-ALL?
based on cytogenetic abnormalities
i. t(12,21)-kids- has a good prognosis
ii. t(9,22)-adults- has a poor prognosis (philadelphia)
What is T-ALL characterized by?
lymphoblasts (TdT+) that express markers ranging from CD2 to CD8 (e.g. CD3/4/7).
don’t express CD10
What patient population is common for T-ALL?
usually presents in teenagers as a mediastinal (thymic) mass (called acute lymphoblastic lymphoma because the malignant cells form a mass)
What is acute myeloid leukemia defined as?
20+% of immature myeloid precursors (myeloblasts) in the bone marrow
How are myeloblasts identified?
positive cytoplasmic staining for MPO (crystals of MPO commonly seen as Auer rods)
Patient population for AMLs?
older adults (avg 50-60 y/o)
High-yield subtypes of AML (based on cytogenetics, lineage of immature myeloid cells, and surface markers):
- Acute promyelocytic leukemia (APL)
- Acute monocytic leukemia
- Acute megakaryoblastic leukemia
What causes APL?
t(15,17) PML-RARa. The fusion protein causes enhancement of RARa function, which is to disrupt myeloid differentiation, but proliferation is unaffected so promyeloblasts accumulate
What is a common risk associated with APL?
DIC
What is the treatment for APL?
ATRA (vitamin A derivative) which binds the receptor and causes the blasts to mature (and eventually die)
What causes acute monocytic leukemia?
- proliferation of mono blasts that usually lack MPO
- these blasts characteristically infiltrate gums
What causes acute megakaryocytic leukemia?
-proliferation of megakaryoblasts that usually lack MPO
What is acute megakaryocytic leukemia associated with? When does it present?
Down syndrome (usually arise BEFORE age 5)
What else can AML arise from?
-pre-existing dysplasia (myelodysplastic syndromes)
How does myelodysplastic syndromes usually present?
- cytopenias
- hyper cellular bone marrow
- increased blasts (but less than 20%)
Outcome of myelodysplastic syndrome patients?
most die from infection or bleeding, though some progress to acute leukemia
What causes chronic leukemia?
neoplastic proliferation of mature circulating lymphocytes (high WBC count)
Patient population for chronic leukemia?
insidious onset in older adults
What causes chronic lymphocytic leukemia (CLL)?
neoplastic proliferation of naive B cells that co-express CD5 and CD20 (most common leukemia overall)
What are some complications with CLL?
- hypogammaglobinemia
- autoimmune hemolytic anemia
- Transformation to diffuse large B-cell lymphoma (Richter transformation)
Hairy cell leukemia (HCL) patients are positive for what?
TRAP (tartrate-resistant acid phosphatase)
Clinical features of HCL?
- splenomegaly due to accumulation of hairy cells in red pulp
- dry tap on bone marrow aspiration (due to marrow fibrosis)
- no lymphadenopathy
How is HCL treated?
excellent response to 2-CDA (Cladribine), an adenosine deaminase inhibitor
What is adult T-cell leukemia/lymphoma (ATLL) caused by?
neoplastic proliferation of mature CD4+ T cells
associated with HTLV-1
Clinical presentation of ATLL?
- rash (skin infiltration)
- generalized lymphadenopathy with hepatosplenomegaly
- lytic (punched out) bone lesions with hypercalcemia
Normal counterpart in mycosis fungicides (chronic leukemia type)?
mature CD4 T cells
When MF spreads to include peripheral blood it is called _____.
Sezary syndrome
