K. Neoplastic Hematology Intro (L11, L12 & Hematopoesis SS) Flashcards
What is leukemia? What are the main classifications of leukemia?
= neoplastic proliferation of WBCs in the blood
• Acute vs. chronic
• Mylogenous vs. lymphoid –> AML, CML, ALL & CLL
What is lymphoma? What are the main classifications of lymphoma?
= neoplastic proliferation of WBCs in the lymph nodes that forms mass
• Hodgkins vs. non-hodgkins
What are the 3 main areas within a lymph node and what are the main cells that live there?
- Follicle = B
- Parafollicular = T
- Medulla = Sinus Histiocytes
What cell is the “starting point” of all hematopoiesis?
• Hematopoetic stem cell
What can a hematopoetic stem cell directly turn into? (Next step(s))
- Myeloid Progenitor
* Lymphoid Progenitor
What can the lymphoid progenitor turn into?
- B lymphoblast –> Naïve B –> plasma cell
* T lymphoblast –> Naïve T –> mature CD4 or CD8 T
What lives in a primary follicle?
• Naïve B cells that have not yet seen antigen
What 2 things can the myeloid progenitor directly turn into?
- Granulocyte/Macrophage Progenitor
* Megakaryocyte/Erythrocyte Progenitor
Ultimately what does the myeloid progenitor turn into?
- Erythroblast –> RBC
- Myelobast –> Granulocytes (Nuetrophils, eosinophils, basophils)
- Monoblast –> monocyte (macrophage)
- Megakaryoblast –> megakaryocyte –> platelets
If nucleated RBCs are seen in blood what is it mostly likely?
Orthochromatic Erythroblast
What is the normal ration of myeloid to erythroid cells in the bone marrow?
3:1 (not intuitive)
Are undifferentiated/precursor cancers more or less aggressive than differentiated/peripheral cancers?
• Undifferentiated = more aggressive
Do B or T cells cause more lymphomas?
• B = 85%
Where are Tingible Body Macrophages found? What is their function?
- Germinal Center
- Remove the naive B cells that are not presented with antigen
In follicular hyperplasia, not follicular lymphoma
What are the 3 main zones of a follicle (most easily differentiated during follicular hyperplasia)?
- Germinal Center
- Mantel
- Marginal Zone (prominent during follicular hyperplasia)
Where on the body are bone marrow aspirates & biopsy most often performed?
• Superior iliac crest
What will be the main difference in appearance of a lymph node during reactive lymphadenopathy and lymphoid proliferation?
- During reactive hyperplasia the normal architecture is preserved (can see open medulla and follicles with heterogenous cells)
- During lymphoid proliferation normal architecture is replaced by proliferating lymphoid cells (monomorphic cells)
Can lymphoid proliferation always be seen morphologically?
• No, sometimes heterogenous proliferation with relatively intact architecture –> need immunophenotypic and genetic studies
What are the 2 main types of immunophenotyping when diagnosing hematological cancers? Why are they useful?
- Immunohistochemistry
- Flow cytometry
- Cells retain the markers of the normal cells which they are mimicking –> can determine where in the cycle things went wrong
When you find enlarged lymph nodes what are the 2 main things you should keep in mind for possible causes?
- Reactive hyperplasia
* Neoplastic disorder
What are the 2 main types of neoplastic disorders that cause enlarged lymph nodes?
- Neoplastic metastasis from somewhere else in the body
* Lymphoma (HL & NHL)
What causes reactive lymphadenopathy?
- Infections (bacterial, viral or fungal)
- Autoimmune diseases
- Drugs
- Foreign Matter
What regions of the lymph node can be enlarged in reactive lymphadenopathy?
• Can have enlargement of all areas or selective enlargement of individual areas such as follicular hyperplasia, Interfollicular Hyperplasia or Sinus histiocytosis
If lymph nodes are tender that generally points to what sort of cause?
• Reactive hyperplasia, not neoplasm
What does BCL-2 staining signify?
- BCL-2 is an anti-apoptotic protein
- Presence in follicle (Rather than around it) signifies follicular lymphoma
BCL-2 keeps Bax gate closed –> no Cyt C leaks out –> no apoptosis –> cells build up
If lymph nodes are enlarging is a reactive or neoplastic disorder most likely?
Neoplastic
How does likelihood of lymphadenopathy being related to neoplasm change with age?
• Chances of neoplastic cause increase dramatically after the age of 50 (very low for people under 30)
What does Ki67 staining signify? Is it seen in reactive hyperplasia or lymphoma?
- Cell proliferation
- Hyperplasia, not lymphoma (In lymphoma cells stay around for a long time, don’t undergo apoptosis & don’t get replaced)
Is flow cytometry performed on a fresh sample or a paraffin embedded sample? What about immunohistochemistry?
- Fresh
* Paraffin embedded
How does immunohistochemistry work?
- Have specific Ab to the surface marker you are testing
- Then have general Ab to the specific Ab that has an enzyme attached
- Enzymatic reaction causes a brown color in tissues where the enzyme is concentrated
How does flow cytometry work?
- Use Ab to specific surface markers that fluoresce a certain color which is detected
- Also use side scatter (granularity) & forward scatter (size) to differentiate cells
If a monoclonal Ab population is found, what cell type is neoplastically affected?
B cells
What serological test is used most often to screen for suspected mononucleosis? What is it testing for?
- Monospot
* Heterophile Ab which can coagulate horse blood
What morphological finding is suggestive of Mono?
Atypical lymphocytes
In a healthy adult what is the ratio of RBCs to WBCs?
- 1000:1
* 5 million RBCs per micro liter verse 5k for WBCs
Normal Platelet count?
• 150-400 thousand per mm^3
Are reactive/atypical lymphocytes unique to mono?
- No, a small number of these are normally found in healthy person
- But a large percentage of them is relatively unique to mono
What type of antibody causes a positive monospot test?
IgM heterophile
If monospot test is normal, what more specific test can be performed for mono?
• Serologic tests for IgM against EBV viral capsid
What type of infection is most likely for patients that present with mono, but are negative for specific EBV serologic tests?
CMV
Why do lymph nodes enlarge in reactive lymphadenopathy?
Body is producing more WBCs to fight infection (or whatever else triggered it)
Why do lymph nodes hurt when reactive lymphadenopathy is present?
Pain signifies inflammation
Lymph node enlargement in somebody that is younger than 30 y.o. is most likely benign or neoplastic?
benign
What is the most likely cause of local reactive lymphadenopathy? What about systemic lymphadenopathy?
Infection
Systemic disease like autoimmune Lupus
What are the most likely cause of painless local lymphadenopathy?
Mets to lymph node draining area of cancer
Hodgkins Lymphoma
What is the most likely cause of painless systemic lymphadenopathy?
Mets of leumkemia
Follicular B cell lymphoma
What region of the lymph node undergoes hyperplasia in response to viral infections? What cell type increases in number?
Paracortex
T cells
Is NHL treatment based mainly on morphology or classification?
Classification
What type of reactive hyperplasia results in expansion of the sinus histiocytes?
metastatic tumors
What type of reactive hyperplasia results in expansion of the follicle?
Autoimmune
Toxoplasmosis
Syphilis
What is effacement of a lymph node?
When the normal architecture is lost & proliferative cells replace normal cells
Are the abnormal proliferative cells in the lymph node always monomeric?
No sometimes they are polymorphic
