Compare thalassemia minor and thalassemia major.
Thalassemia minor = 1 deletion, mild anemia (trait)
microcytic, hypochromic
*note: looks like iron deficiency!!
Thalassemia major = hemolysis accompanied by splenomegaly, hemosiderosis, hepatomegaly, BM compensatory hyperplasia
Why are RBCs round in hereditary spherocytosis?
There are mutations in the genes encoding that proteins that make up the membrane skeleton.
What is immune hemolytic anemia?
Recall: four blood groups = A, B, AB, O
Autoimmune hemolytic anemias develop as a consequence of an immune reaction to RBC autoantigens or neoantigens formed between the body's own proteins and hapten.
Explain the pathogenesis of immune hemolytic anemia.
Hemolytic anemias:
1. Autoantigens present on RBCs are normally not recognized as foreign by the body. In some persons the body produces antibodies to its own antigens on RBCs. This occurs for no obvious reasons.
2. Alloantigens are foreign antigens. For example, blood group B RBCs are recognized as foreign by group A persons.
3. Neoantigens are from from the body's own protein's linked to a non-immunologic hapten. IgG, immunoglobulin G.
Compare primary and secondary polycythemia.
Primary = clonal proliferation of hematopoietic stem cells and increased total RBC mass (neoplastic)
Secondary = increased RBC volume as a result of erythroid bone marrow hyperplasia caused by erythropoietin
What is leukopenia, and what are its causes?
leukopenia = reduction in the WBC count
Can be caused by:
drugs
chemicals
radiation
aplastic anemia
What is leukocytosis, and what are its causes?
leukocytosis = increased WBCs (>10,000)
Causes:
reactive luekocytosis (splenomegaly in response to bacterial infection)
lymphoma
leukemia
What are the possible causes of lymph node enlargement?
- common in children with URI
- with EBV
- early stages of AIDs
- most common presenting symptom of lymphoma
What is the difference between lymphoma and leukemia?
Lymphoma = lymphoid cell malignant disease prodominantly involving the lymph nodes
Leukemia = increased number of malignant WBC in the peripheral blood due to WBC precursors in the BM
What causes lymphomas and leukemias?
Most causes are unknown.
viruses = HTLV-1, EBV
oncogenes = translocation (Burkitts), philadelphia chromosome (CML), hybrid BCR, ABL
What are the common features of all leukemias?
- BM is infiltrated with malignant cells
- Peripheral blood contains increased immature cells
- Chromosomal and genetic changes specific for each disease
- Complications: anemia, recurrent infections, uncontrollable bleeding
**INFECTION = most common cause of death in all forms of leukemia
What distinguishes acute from chronic leukemia and lymphocytic from myelogenous leukemia?
List the most important features of acute lymphoblastic leukemia and correlate the pathologic findings with the clinical features of this disease.
-
massive BM infiltration with immature lymphoid cells (blasts = T and B precursors)
-
most common form of leukemia in children, and most common malignant disease in children <5yrs
-
rapid course, marked recurrent infections, generalized weakness, bleeding into the skin and internal organs
- remission can be induced, 2/3 are CURED
List the most important features of acute myelogenous leukemia.
Clonal proliferation of myeloblasts in the bone marrow. Must find 20% in the BM biopsy!
- Most common form of acute leukemia in adults.
- Treatment: high dose radiation and chemo.
List the most important features of chronic myelogenous leukemia.
Malignant disease of pluripotent stem cells capable of differentiating into neutrophilic leukocytes.
- Mostly affects ADULTS
- SLOW onset; anemia, SM, thrombosis
- Tx: radiation + chemo = 70% 3 yr survival
3 phases of CML
-
chronic phase: marked leukocytosis, increased eosinophils and basophils. BM <10 % blasts
-
accelerated phase: BM >10% blasts, >20% basophils in peripheral blood.
-
blast crisis: BM >20% blasts
90% of patients have the Philadelphia chromosome with BCR-ABL gene arrangement . . . for which leukemia???
CML
Do you have worse or better prognosis when you have the Philadelphia chromosome?
BETTER!!!
List the most important features of chronic lymphocytic leukemia.
Malignant disease of lymphoid cells.
- Disease of OLDER age (>50)
- SLOW course
- Sx = lymphadenopathy and peripheral leukocytosis
- Tx: cells do not grow rapidly, therefore NO CHEMO
- can TRANSFORM into more aggressive form
How do you diagnose CLL?
CLL cells look NORMAL on a smear!! Suspect if lymphocytes >5000 (Nl = <4000). BM Biopsy confirms diagnosis.
How are non-Hodgkin’s lymphomas classified?
Two categories:
- B-cell
- T-cell and NK cell
True or False:
All lymphomas are malignant
True
True or False:
Most lymphomas have a B-cell phenotype
TRUE
Extranodal sites for lymphomas are . . .
can be outside of the lymph nodes, like eyes, brain, skin.
Most common is the GI system!
Immunohistochemistry
Uses antibodies to analyze tissues for tumor cells.
Can help determine B and T cell and zones of the lymph node (cortical, mantle, germinal center)
What method is used to determine maturation and phenotype of lymphocytes?
flow cytometry
List the most common symptoms and clinical findings of non-Hodgkin’s lymphomas.
- painless lymphadenopathy
- systemic constitutional symptoms
- extranodal spread
What are systemic constitutional symptoms?
- fatigue
- malaise
- fever
- weight loss
- pruritis
- sweating
What is the most common form of lymphoma in the UNited states?
Follicular lymphoma
Follicular Lymphoma
The follicular structure of lymph nodes is preserved.
- SLOW growing
- Sx: long term lymphadenopathy, mild constitutional sx
- Tx: does not response well to chemo
