Pathoma Chapter 6 WBCs
Terms in this set (83)
How does cortisol affect leukocyte count?
Initially impairs leukocyte adhesion leading to release of the marginated pool - leukocytosis
Later induces apoptosis of lymphocytes - leukopenia
Monocytosis is commonly caused by what?
chronic inflammatory states (autoimmune and infectious) and malignancy
What are some causes of eosinophilia?
Allergic rxns (Type 1 hypersensitivity)
Basophilia is commonly seen in this leukemia/lymphoma
Why does bordatella pertussis cause a lymphocytic leukocytosis? (remember bacteria usually cause a neutrophilic leukocytosis)
They produce lymphocytosis-promoting factor, which prevents them from leaving the blood and entering lymph nodes
What is infectious mononucleosis?
EBV infection-> lymphocytic leukocytosis comprised of CD8+ T cells
CMV is a less common cause
EBV primarily infects (3)
The CD8+ response to EBV infection leads to hyperplasia of the __ in lymph nodes and __ in spleen
paracortex - generalized lymphadenopathy (LAD)
Periarterial lymphatic sheath (PALS) - Splenomegaly
What is the monospot test? What does a negative monospot test suggest
Detects heterophile IgMs that cross-react with horse or sheep RBCs - screen for EBV
- monospot = CMV
Dormancy of EBV/CMV virus in B cells can cause __, especially if immunodeficiency develops
What is the definition of acute leukemia?
>20% blasts (myeloblasts and lymphoblasts) in marrow
If you saw large, immature white cells with a punched out nucleus, what would you think?
What stain can you use for lymphoblasts?
Positive nuclear stain for TdT (DNA polymerase) - is absent in myeloid cells and mature lymphocytes
What leukemia/lymphoma is associated with Down's syndrome after age 5? Which one before age 5?
ALL; AML (megakaryoblastic)
If you had lymphoblasts expressing TdT+, CD10, CD19, and CD20, what would you think?
What are the translocations in B-ALL? What age group are they seen in and which has a better prognosis?
t(12;21) - children, good prognosis
t(9;22) - adults, bad prognosis (Phl chromosome)
If you had lymphoblasts expressing TdT+, and CD2-8, but not CD10, what would you think? What demographic does this present in?
Teenagers - mediastinal thymic mass (a lymphoma)
What are Auer rods?
Crystal aggregates of MPO in myeloblasts
What is the translocation for APL? What is translocated?
The retinoic acid receptor (RAR) on c17 moves to chromosome 15. RAR normally allows maturation of myeloblasts
How do you treat APL?
ATRA (all-trans retinoic acid), vit A derivative, will bind the altered receptor and allow the blasts to mature
Where does acute monocytic leukemia infiltrate?
What kinds of AMLs lack MPO?
Myelodysplastic syndrome can lead to what?
AML, especially with prior exposure to alkylating agents or radiotherapy
Myelodysplastic syndromes usually present how?
cytopenias, hypercellular bone marrow, abn maturation of cells, increased blasts
What kind of markers do you see in CLL?
Naive B cells that express both CD5 and CD20 (CD5 is normally on T cells)
What leukemia/lymphoma do you see smudge cells?
What are complications of CLL?
Hypogammaglobulinemia (don't make varied Abs, infection risk)
Autoimmune hem. anemia - make bad Igs
Transformation to diffuse large B cell lymphoma (Richter transformation)
Transformation of CLL to a large B cell lymphoma is known as what?
What is classically seen?
enlarging lymph node or spleen
Hairy cell leukemia
Where does the name come from?
What is the marker?
How do you treat?
Hairy cytoplasmic processes on mature B cells
marker: + for TRAP (tartrate resistant acid phosphatase)
Tx: 2-CDA (cladribine) - ADA inhibitor, leads to toxic accumulation of adenosine in in B cells
Clinical features of hairy cell leukemia
Splenomegaly (hairy cells accumulate in the red pulp) and "dry tap" marrow - marrow fibrosis
Usually no lymphadenopathy
ATLL (adult T cell leukemia/lymphoma is associated with __ virus. What regions is it seen in more?
Which blood cell disorders do you see lytic (punched out) bone lesions? How would you tell them apart?
ATLL, multiple myeloma
You see a rash with MM
Aggregates of neoplastic CD4+ cells in the epidermis are called __. The overall disease is ___.
Pautrier microabscesses; Mycosis fungoides (has nothing to do with fungus)
lymphocytes with cerebriform nuclei - spread of mycosis fungoides T cells to the blood
What characterizes myeloproliferative disorders?
what is characteristic about bone marrow?
proliferation of mature cells of myeloid lineage
results in high white blood cell count with hypercellular bone marrow
What are common complications of MPD?
inc risk for hyperuricemia and and gout bc of high turnover rates;
progression to marrow fibrosis of transformation to acute leukemia
proliferation of granulocytes and their precursors
-basophils are characteristically increased
The t(9;22) (Philadelphia chromosome) is seen in AML, ALL, and CML collectively because __. The translocation generates a __ fusion product which has increased __ production.
How would you treat it?
The mutation is a pleuripotent stem cell
BCR:ABL; tyrosine kinase
Imanitib, a tyrosine kinase inhibitor
Which 3 ways would you distinguish CML from a leukemoid reaction (response to infection)?
CML is LAP (-), leukemoid reaction are LAP (+)
CML has inc. basophils
Presence of t(9;22)
P. vera is associated with this mutation __, so are these (2)
JAK2 kinase; essential thrombocythemia, myelofibrosis
This is the most common cause of Budd-Chiari
Symptoms of Polycythemia vera?
due to hyperviscosity of blood
-blurry vision and headache, inc risk of thrombosis, flushed face due to congestion, itching, esp after bathing
What is the initial tx for p. vera? What is the 2nd line?
How do you distinguish p. vera from reactive polycythemia, or ectopic production from RCC?
Reactive polycythemia due to altitude or lung disease, SaO2 will be low and EPO will be inc.
RCC - SaO2 normal and EPO inc.
p. vera - SaO2 normal and EPO dec.
Essential thrombocythemia (ET) has no increased risk for hyperuricemia or gout. Why?
Platelets don't have nuclei so there's no excess nuclear material being produced
In what disease do you see teardrop RBCs and why?
Myelofibrosis - stretched as they try to leave
Myelofibrosis vs ET
Megakaryocytes vs. platelets
Pathophysiology of myelofibrosis
Megakaryocytes produce excess PDGF causing marrow fibrosis
Extramedullary hematopoiesis takes place
Immature granulocytes because there aren't reticulin gates in the spleen to keep them in until they are small and mature enough
When do you seen follicular hyperplasia?
B cell region-Rheumatoid Arthritis and early HIV
T cells - viral infections (ie infectious mono)
A lymph node that is draining a cancer (these are deep in the medulla)
What types of lymphomas are small B cells?
Follicular, mantle cell, marginal, small lymphocytic (CLL that involves tissue)
Diffuse large B cell lymphoma
What is Follicular lymphoma
-clinically presents as?
painless lymphadenopathy in late adulthood
progression to diffuse large B cell lymphoma
Translocation in follicular lymphoma
t(14;18) - bcl-2 (ch 18) moves to the Ig heavy chain locus (18)
-results in over expression of bcl-2 which inhibits apoptosis
Treatment for follicular lymphoma
Rituzimab (anti CD-20 Ab
-usually reserved for symptomatic pts
How to distinguish follicular lymphoma from normal follicular hyperplasia?
Lymphoma will disrupt the normal architecture
Lymphoma lacks tingible body macrophages (they come to clean up the debris after normal apoptosis)
Lymphoma has Bcl-2 expression
Monoclonality (not the normal 3:1)
What is the translocation in mantle cell lymphoma?
t(11;14) Cyclin D1 (11) to Ig heavy chain (14)
What is important about cyclin D?
- promotes transition from G1-S phase***
What is a marginal zone lymphoma associated with?
Chronic inflammatory states - Hashimoto's, Sjogrens, H. pylori
(remember Sjogrens can progress to lymphoma - unilateral)
What is a MALToma?
a marginal zone lymphoma in mucosal sites
Burkitt lymphoma is associated with this virus, this B cell size, and this translocation
t(8;14) - c-myc (8) to the Ig heavy chain (14) - promotes growth
African form of Burkitt lymphoma involves __
Sporadic form involves __
Where do you see "starry sky" on microscopy?
What is the most common NHL? What does it look like?
Diffuse large B cell
Grows diffusely in sheets, large B cells, very aggressive
Can be from a transformation of a low-grade lymphoma or sporadically
Reed-Sternberg cells are seen in
Basic pathophysiology of Hodgkin lymphoma
What markers are seen?
R-S cells secrete cytokines which draw in other cells.
Causes "B symptoms" - fever, chills, night sweats.
Is classified based on the types of cells that make the bulk of tumor
What is the most common subtype of HL? What is the presentation, and where are the R-S cells?
Young female with cervical or mediastinal lymph node
R-S cells found in lacunar spaces
Which subtype of HL has the best prognosis? Which has the worst?
Lymphocyte-rich; lymphocyte-depleted (associated with immunosuppression)
Which subtype of HL is associate with abundant eosinophils? This would mean that the R-S cells are producing this cytokine __
IL-5, which draws in eosinophils
The most common primary malignancy of bone is __, however, the most common malignancy of bone overall is __
Which cytokine can be elevated in multiple myeloma?
IL-6 - stimulates plasma cell growth and Ig production
What causes the bone destruction in multiple myeloma?
neoplastic plasma cells active RANK receptor on osteoclasts (osteoclast activating factor), leading to bone destruction
An M-spike on SPEP can be seen in
Multiple myeloma - means monoclonal Ig (of any kind- but often due to IgG or IgA).
The monoclonal Abs lack diversity and inc risk for infection
Multiple myeloma causes this type of amyloidosis
Primary AL amyloidosis - free light chains circulate and deposit in tissues (light chain is overproduced relative to heavy chain)
What is a myeloma kidney? What is the proteinuria called?
Free light chain is excreted in urine as Bence-Jones protein. Can deposit in renal tubules and lead to kidney failure
What is Rouleaux formation and where do you see it?
RBCs on blood smear are stacked like poker chips - the inc serum protein decreases the charge btw RBCs so they stick together
Seen in Multiple Myeloma
What is an MGUS?
Monoclonal gammopathy of undertermined significance
M spike without clinical features/symptoms of MM (1% develop MM each year)
B cell lymphoma with monoclonal IgM
-M spike but no bone lesions
Visual and neuro deficits (retinal hemorrhage, stroke) due to hyperviscosity of blood (IgM is biggest Ig)
Hyperviscosity also leads to dec platelet aggregation - bleeding
Why does MM cause bone lesions?
Neoplastic plasma cells activate RANK receptor on osteoclasts - punched-out lesions with hypercalcemia
What are the markers for Langerhans cells? How do they appear on electron microscopy?
CD1a+ and S100+ (melanoma marker)
Birbeck granules (tennis rackets)
What are the 3 types of Langerhans cell histiocytoses? What is the mnemonic?
If it is named after someone it is malignant with a skin rash, if it has 2 names it is children <2, if it has 3 names it is children >3
Malignant proliferation of Langerhans cells
Skin rash and cystic skeletal defects in an infant <2
Benign proliferation of Langerhans cells in bone
Pathological fractures, skin not involved
Describe Hand-Schuller-Christian disease
Malignant proliferation of Langerhans cells
Scalp rash, lytic skull lesions, diabetes insipidus, and exopthalmos