Flashcards in White Blood cell disorders Deck (214):
What is the marker for hematopoietic stem cells? (CD(__))?
What are the two divisions of the lymphoid route of stem cell maturation?
B cells (to plasma cells)
T cells to CD4 or CD8 cells
What are the four myeloid cells that stem cells can differentiate into?
What are the three cells that myeloblasts give rise to?
What are the two major causes of neutropenia?
What is the treatment for neutropenia? (2)
What are the four major causes of lymphopenia? (3)
-High cortisol state
-Autoimmune disease (e.g. SLE)
-Whole body radiation
What are the most sensitive cells to radiation?
When does neutrophil leukocytosis occur? (3)
-High cortisol state
What is a left shift?
Increased band cells
What does premature neutrophils lack as compared to normal neutrophils? What is the marker that identifies this?
Decreased CD16 indicates what?
Proliferation of immature neutrophils and a lack of Fc receptors
What is the MOA of neutrophilic leukocytosis with high cortisol states?
Causes PMN detachment from endothelial cells of the blood vessels (loss of marginated pool)
What are the two causes of monocytosis?
-Chronic inflammatory states
What are the three causes of eosinophilia?
In what malignancy is there a high amount of eosinophils present? What causes this?
-Increased IL-5 production
Basophilia is seen in what malignancy?
What general type of infectious diseases cause a lymphocytic leukocytosis? Which bacteria can cause this, and why?
-Bordetella pertussis, which produces a lymphocyte promoting factor, preventing leukocytes from leaving the blood
What are the two viral causes of mononucleosis?
-EBV infection predominate
-CMV less common cause
What is the T cell type that predominates in infectious mononucleosis? What does this result in (3)?
CD8 + T cells
-High white count
Which are of the lymph node will be enlarged in a viral infection?
Where are B cells found in a lymph node?
What is in the white pulp part of the spleen? Red pulp?
Red pulp = blood
White pulp = cells
What part of the white pulp of the spleen is enlarged in viral infections?
Periarterial lymphatic sheath (PALS)
Where are the T cells present in the spleen?
Around the blood vessels
What does the monospot test assess for?
-IgM to heterophile antibodies
A negative monospot usually indicates that what virus is usually causing the mono-like symptoms?
What is the definitive test for mono?
EBV viral capsid antigen
A rash can develop if a patient with Mono is given what abx?
**How long do patients with mono have to avoid contact sports d/t the chance of splenic rupture?**
What is the basis for acute leukemia?
Accumulation of blast cells d/t cell inability to mature properly
Acute leukemia is defined as when there is more than what percent of blasts in the bone marrow?
When there is >20% of blasts in the bone marrow
What is the cause of the ssx of acute leukemia? Why?
Loss of a type or many types of cell lines, d/t blast cells crowding out normal cells/not producing normal cells (so anemia, neutropenia, leukopenia etc)
Why is there a high WBC count if there are not any mature cells being produced in leukemia?
Tons of blasts
What are the histological findings of acute leukemia?
Large, immature cells with punched out nucleoli
What is the marker for ALL? AML?
ALL = tdt
tdt in the nucleus of an immature WBC = what disease? What is tdt?
DNA pol for lymphoid cells
Auer rod = what disease? What is an auer rod?
Down syndrome is associated with what hematological malignancy? What age does this appear after?
After age of 5 yo
What age group usually gets ALL?
What are the two divisions of ALL?
B-ALL surface markers = which three?
What is the prognosis for B-ALL?
Good with chemo
What parts of the body need to be given prophylaxis of chemo for B-ALL?
scrotum and CSF
What are the two translocations associated with B-ALL? Which is associated with children and has a good prognosis, and which with adults and has a bad prognosis?
-t(12;21) = kids
-t(9;22) = adults (philadelphia chromosome)
What are the cell markers for T-ALL? Which CD marker is not expressed on T cells, but is on B cells for ALL?
CD2 through CD8
What is the usual presentation of T-ALL that distinguishes it from B-ALL?
Thymic mass in a teenager
What are auer rods?
Crystallized myeloperoxidase--an enzyme only found in myeloblasts, hence why these are pathognomonic for AML
Punched out nucleolus = what type of cell?
What is the age range that usually gets AML?
Old people (50-60)
What are the three types of classification in AML?
-Lineage of myeloblasts
What is the chromosomal translocation found in acute promyelocytic leukemia?
What disease is caused by a t(15;17)? how? What is the treatment and prognosis?
-Acute promyelocytic leukemia
-Retinoic acid receptor disrupted, inhibiting promyelocyte maturation
-Treat with ATRA (great prognosis)
Promyelocytes that contain numerous Auer rods, as seen in acute promyelocytic leukemia, poses a risk for what emergent complication?
What is the treatment for acute promyelocytic leukemia?
ATRA (all trans-retinoic acid)--very good prognosis
What is the cause of acute monocytic leukemia? What is the telltale sign of this?
-Proliferation of monoblasts that lack MPO
-Infiltration of the gums = gingival hypertrophy
What is the cause of acute megakaryoblastic leukemia? What disease is associated with this?
Proliferation of megakaryocytes that lack MPO
Down syndrome BEFORE age 5)
What is the CA that appears before the age of 5 for down syndrome pts? After?
-Before = acute megakaryoblastic leukemia
-After = ALL
What chemotherapeutic agent can lead to AML?
What is myelodysplastic syndrome? What can this progress to?
Cytopenia with *hyper*cellular bone marrow from blasts, but less than 20% blasts
**Most patients who have myelodysplastic syndrome die from what complication?**
**Infection or bleeding**
What, generally, are chronic leukemias?
Neoplastic proliferation of *mature* circulating lymphocytes
Is the WBC high or low in chronic leukemia?
Who usually gets chronic leukemia? What is the course?
-Slow onset and slow progression
CLL is caused by what? What are the cell markers that distinguish this from other proliferations?
Neoplastic proliferation of naive B cells
CD5 and CD20
Increased lymphocytes and smudge cells = ?
How does CLL progress to small lymphocytic lymphoma?
When bad B cells go to lymph nodes, will cause "lymphoma"
What are the classical hematological findings with CLL? (2)
-Autoimmune hemolytic anemia
What is the cause of the autoimmune hemolytic anemia seen in CLL?
Bad B cells producing crappy Igs that attack RBCs
CLL can progress to what? What is the classic presentation of this?
Large B cell lymphoma (enlarging spleen/lymph node)
What, generally, is hairy cell leukemia?
Neoplastic proliferation of mature B cells that have hairy cytoplasmic processes
What are the two findings for hairy cell leukemia? (histological, and protein)
Hairy cytoplasmic processes
Cells are TRAP +
What are the three clinical features of hair cell leukemia (bone tap, LAD, splenomegaly)?
1. Splenomegaly (red pulp)
2. Dry bone marrow aspiration
3. Lymphadenopathy is absent
What is odd about the splenomegaly in hairy cell leukemia, as opposed to other leukemias?
Enlargement is found in the red pulp
What is the best way to remember the clinical features of hairy cell leukemia?
-Tartrate-resistant acid phosphatase (TRAP) +
-B cells Trapped in the red pulp
-B cells trapped in the bone marrow
-B cells trapped so no lymphadenopathy
What is the drug that is used to treat hair cell leukemia? MOA? Prognosis?
-Adenosine deaminase, which is used in the purine degradation pathway, and results in the death of neoplastic cells
What is ATLL caused by? What infection is this associated with? Where in the world is this usually seen?
Neoplastic proliferation of CD4+ T cells
HTLV-1 (Japan and the caribbean)
What are the clinical features of ATLL? (3)
-Generalized LAD with HSM
-Lytic bone lesions w/ hypercalcemia
Lytic bone lesions = what two diseases in your ddx? What can help differentiate these?
Multiple myeloma OR
ATLL will have a rash
What is mycosis fungoides?
Neoplastic proliferation of mature CD4+ T cells
What are the clinical features of mycosis fungoides?
Pautrier microabscesses = ?
skin abscesses of Mycosis fungoides (CD4+)
What is Sezary syndrome? What are the histological characteristics of the cells that are found in this?
-Neoplastic CD4+ T cells proliferating in the skin (advanced mycosis fungoides)
-lymphocytes with cerebriform nuclei
**lymphocytes with cerebriform nuclei = ?**
Chronic myelogenous leukemia is what?
Overproduction of mature myeloblasts (PMNs, basophils, eosinophils)
Chronic overproduction of RBCs is what? Is this the only cell line that is overproduced in this?
Polycythemia vera, not the only cell line
Chronic overproduction of megakaryocytes is what?
Who usually gets myelodysplastic syndromes?
What are the WBC and bone marrow findings in myelodysplastic syndrome?
-Hypercellular bone marrow
True or false: in any myelodysplastic syndrome, all cells of myeloid lineage are increased
Why is there an increased risk for hyperuricemia and gout in myelodysplastic syndrome?
Increased production/turnover of all myeloid cells
What causes the "burnt out" phase of myelodysplastic syndromes?
Bone marrow fibrosis
What can myelodysplastic syndromes lead to?
What is chronic myeloid leukemia?
Neoplastic proliferation of mature myeloid cells, especially granulocytes
What cell type is classically increased in CML?
CA with Basophilia =?
What is the genetic translocation and mutation in CML? Medication for this? MOA?
-t(9;22) causing an increase in tyrosine kinase
-Imatinib--blocks Y-kinase activity
True or false: splenomegaly is uncommon in CML
False--common, and may indicate the transition from chronic to accelerated phase
How can you tell if CML is progressing or not?
Increasing spleen size
CML can lead to which neoplastic diseases? Why?
Acute leukemia (AML or ALL)
Genetic cause is in the HSC, and is predisposed to forming other neoplastic processes
What are the three ways to differentiate leukocytosis due to CML vs infection?
1.Granulocytes that are Leukaline phosphatase (LAP) -
What is polycythemia vera? What is the mutation that leads to this?
Proliferation of mature myeloid cells, especially RBCs
JAK2 kinase mutation
What are the clinical symptoms of polycythemia vera? (4)
-Itching after bathing
What is Budd-Chiari syndrome, and how does it relate to polycythemia vera?
a condition caused by occlusion of the hepatic veins that drain the liver. It presents with the classical triad of abdominal pain, ascites, and liver enlargement.
Why does polycythemia vera present with itching following bathing?
Increased production of mast cells that can be activated by heat
What is the treatment for polycythemia vera? (2)
What is reactive polycythemia?
some disease causing increased RBC (hypoxemia, EPO producing tumor etc)
How do you distinguish polycythemia vera from reactive polycythemia?
Decreased EPO in polycythemia vera, whereas there is an increased production of EPO if reactive
What is the cause of essential thrombocythemia? Genetic mutation?
Neoplastic proliferation of mature myeloid cells, especially platelets
What must essential thrombocythemia be differentiated from? Why?
-Fe deficiency anemia
-Looks very similar
What other cells are overproduced in essential thrombocythemia?
RBC and granulocytes
What are the symptoms of essential thrombocythemia? Why?
Crappy platelets = increased bleeding, or lots of okay platelets and thrombosis
Is there a risk for hyperuricemia or gout with essential thrombocythemia? Why or why not?
No, because platelets do not have nuclei or DNA
How often does essential thrombocythemia progress to acute leukemia?
What is primary myelofibrosis? Which cell in particular is overproduced? Mutation that causes it?
Increased proliferation of mature myeloid cells, especially megakaryocytes
JAK2 Kinase mutation
What is the pathophysiology of the marrow fibrosis in primary myelofibrosis?
Neoplastic megakaryocytes cause increased PDGF, causing fibroblasts proliferation in the bone marrow
What is the cause of Splenomegaly in primary myelofibrosis?
Extramedullary hematopoiesis occurs due to a loss of marrow
What is the leukoerythroblastic smear in primary myelofibrosis, and what causes it?
Normally, Reticulin in the bone inhibits reticulocytes from leaving early, but this is not found in the spleen. Thus, when there is extramedullary hematopoiesis, immature cells have nothing stopping them from escaping, allowing large, immature cells from leaving the spleen prematurely
What is the cause of the increase in thrombosis, infx, and bleeding in primary myelofibrosis?
not enough cell produced from the spleen, relative to the entirety of the bone marrow
**Tear drop cells = ?**
**Primary myelofibrosis due to a lack of reticulin in the spleen, where RBC production shifts**
What is the ddx of *painless* LAD? (3)
Expansion of the follicles of lymph nodes is usually found in what two diseases?
Expansion of the paracortex in lymph nodes is usually due to what type of infections? Why?
T cell proliferation
Where do T cells live in lymph nodes? B cells?
T cells = paracortex
B cells = cortex
Where do histiocytes live in lymph nodes?
Sinuses of the medulla
What are the three major types of lymphomas that arise from lymph nodes?
Where do lymphoma generally arise?
LN or extranodal tissues
What are the two general categories of lymphoma? Which is more common?
What is the dark area that immediately surrounds the follicle of a lymph node?
What is the area immediately around the mantle of a LN?
What is follicular lymphoma? When and how does it usually present?
t(14;18) causing Neoplastic proliferation of small B cells in the follicles of lymph nodes
Presents in late adulthood with generalized, painless LAD
What is the cell marker for follicular lymphoma?
What are the histological findings of follicular lymphoma?
Proliferation of follicles of lymph nodes
What is the chromosomal translocation for follicular lymphoma? What is the protein that is coded for in these chromosomal regions? What does this result in?
BCL-2 on chr 18 translocates to a heavy chain Ig locus on 14
Results in overexpression of Bcl-2, which inhibits apoptosis of B cells
What is the treatment for follicular lymphoma? What are the criteria for treatment?
Low dose CTX or rituximab, i.f.f. symptomatic
What may follicular lymphoma progress to? How will this present?
Progression to diffuse large B cell lymphoma, which presents as an enlarging lymph node
What is the monoclonal antibody that is used to treat follicular lymphoma, and how does it work?
Rituximab--Anti CD20 antibody
How do you distinguish follicular lymphoma from follicular hyperplasia? (4)
Follicular lymphoma has:
- disrupted LN architecture
-Lack of tingible macrophages in the LN
-Expression of BCL-2 in follicles
What is the importance of tingible body macrophages in LNs?
Macrophages in LNs eat up apoptotic cells or bacteria, and are normally found in lymph nodes.
This can help distinguish between follicular lymphoma, and follicular hyperplasia secondary to infection
BCL-2 within LNs is diagnostic of what?
How can you tell if the cells in follicular lymphoma is a normal reaction to infection, or the result of monoclonal expansion?
Expressing only one ab is characteristic of tumors, whereas polyclonal is suggestive of infection
What is mantle cell lymphoma?
Neoplastic proliferation of small B-cells that expand the mantle zone of a lymph node follicle
What is the marker for B cells?
What are the ssx of mantle cell lymphoma?
Painless LAD in late adulthood
Neoplastic proliferation of cells that expands the region immediately adjacent to the LN follicle = ?
Mantle cell lymphoma
What is the translocation involved in mantle cell lymphoma? What is the protein that is overexpressed here?
-Cyclin D1 on chr 11 translocates to Ig heavy chain on chr 14
Overexpression of what protein is the cause of mantle cell lymphoma? What does this protein do?
Cyclin D1--promotes G1/S transition in cell cycle
What is marginal zone lymphoma?
Neoplastic Proliferation of B cells in the marginal zone of a LN.
What chronic inflammatory states is marginal zone lymphoma associated with? (three, 2 autoimmune, and 1 infx)
When are marginal zones present within lymph nodes normally? How does this relate to marginal zone lymphoma?
During infection to expand the B cell population.
Thus certain infectious/inflammatory conditions can lead to marginal zone expansion
What is a MALToma?
Marginal zone lymphoma in mucosal sites
What is the usual cause of MALToma? What is the treatment?
-Treat the H.pylori infection
What is Burkitt's lymphoma?
Neoplastic proliferation of *intermediate sized* B cells, that is associated with EBV infections
What is the infectious agent that is associated with Burkitt's lymphoma?
What is the usual presentation of Burkitt's lymphoma?
Extranodal mass in children or young adults, usually in african children's jaw
The sporadic form of Burkitt's lymphoma usually presents how?
What is the translocation that drives Burkitt's lymphoma? What are the oncogenes involved?
-t(8;14) resulting in
-overexpression of c-myc
Starry-sky appearance on histology = ?
What is responsible for the starry sky appearance of Burkitt's lymphoma on histology?
"Blue sky" = over proliferating B cells
"Stars" = tingible body macrophages eating up bad B cells
What is diffuse large B cell lymphoma? How does it grow?
Neoplastic proliferation of *large B cells* that grow diffusely in sheets
Proliferation of large B cells in diffuse sheets = ?
Diffuse large B cell lymphoma (DLBCL)
What is the most common form of NHL?
Is DLBCL aggressive or indolent? What CA lead to progress from?
-May be a transformation of follicular lymphoma
What is a typical presentation of DLBCL (age, s/sx)?
Late adulthood as an enlarging LN or extranodal mass
What is the key difference between Hodgkin's lymphoma and NHL?
Hodgkin's lymphoma is caused by a single type of cell that proliferates amongst other, normal cells to form a mass, and draws in other inflammatory cells
What is the key cell responsible for HL? What are this cell's histological characteristics?
Large B cell with multilobed nuclei ("owl eyes")
What are the two CD markers on Reed-Sternberg cells?
CD15 and CD30
What is the cause of B symptoms in HL?
Reed-sternberg cells secreting cytokines
Why can HL lead to fibrosis?
Reed-sternberg cells secreting cytokines
Unlike NHL, HL tumor are made up mostly of what?
Non-cancerous cells (e.g. lymphocytes)
What are the four common subtypes of HL?
1. Nodular sclerosis
2. Lymphocyte rich
3. Mixed cellularity
4. Lymphocyte depleted
What is the usual presentation of nodular sclerosis? Who usually gets this? Is this HL or NHL?
Enlarging cervical or mediastinal LN in young, female adult
What is the classic histology of nodular sclerosis?
Broad bands of fibrosis cut into lymph into nodules, with lacunar areas of RS cells
What subtype of HL has the best prognosis (nodular sclerosing, lymphocyte rich, mixed cellularity, or lymphocyte poor)? Which has the worst?
Best = Lymphocyte rich
Worst = lymphocyte depleted
Mixed cellularity HL is associated with which granulocyte cell? What is the cytokine produced here?
**What subtype of HL has the worst prognosis? Who usually gets this?**
Elderly and HIV+**
What is multiple myeloma?
Malignant proliferation of plasma cells in the bone marrow
What is the most common primary malignancy of bone?
What is the cytokine that can be elevated in multiple myeloma? Why?
-Growth factor for plasma cells
Neoplastic plasma cells activate what receptor on osteoclasts? What is the consequence of this?
causes "punched out" lytic bone lesions
What bones usually have lytic bone lesions with multiple myeloma?
Vertebrae and skull
What is the major issue with the lytic bone lesions seen with multiple myeloma?
Increased risk of fracture
What is the cause of the ostalgia and hypercalcemia seen with multiple myeloma?
Activation of osteoclasts by neoplastic plasma cells
What is the "M-spike" seen in multiple myeloma?
Increased monoclonal antibody seen in S-PEP (serum protein electrophoresis) of some type of Ig
What is the M protein seen in multiple myeloma?
Monoclonal Ig class of some type (IgA, IgG, IgE etc), but usually IgG or IgA
What are the two subclasses of abs that are usually elevated in multiple myeloma?
What is the major complication of producing only one type of ab, as is found in multiple myeloma?
Loss of antigenic diversity, thus increases the chance of infection
Why are patients with multiple myeloma susceptible to infection?
Only one class of Ig produced, thus lower antigenic diversity
What is the most common cause of death in pts with multiple myeloma?
Rouleaux formation on blood smear = ?
What is the cause of the rouleaux formation seen in multiple myeloma?
Increased serum protein decreases charge between RBCs
What is the cause of amyloidosis in multiple myeloma?
Increased production of free *light chain* in serum deposits in
What are bence jones proteins?
Free *light chain* ab excreted in urine of pts with multiple myeloma
What is the cause of renal failure in multiple myeloma?
Deposition of light chain antibodies in the tubules
What is MGUS? Why is this concerning?
Increased serum protein with M spike on SPEP, but without any symptoms of multiple myeloma
May progress to multiple myeloma
What is Waldenstrom's macroglobulinemia?
B cell lymphoma with monoclonal IgM production
What are the clinical features of Waldenstrom's macroglobulinemia? (3)
-Generalized LAD, withOUT lytic bone lesions
-Visual and neurological defects
What is the cause of bleeding and visual/neurological defects in Waldenstrom's macroglobulinemia?
Hyperviscosity secondary to increased pentamer of IgM
What is the treatment for Waldenstrom's?
What is Langerhans cell histiocytosis?
Neoplastic proliferation of Langerhans cells
What are Langerhans cells?
APCs in the epidermis, derived from bone marrow monocytes
Tennis racket (birbeck) granules on EM = ?
Langerhans cell histiocytosis
What are the cell markers for Langerhans cells? (2)
CD1a and S100
There are three subtypes of Langerhans cell histiocytosis. If the disease is named after someone, what does this indicate?
It is malignant and involves the skin
There are three subtypes of Langerhans cell histiocytosis. If there are two names in the disease, what does this indicate?
Occurs in children
There are three subtypes of Langerhans cell histiocytosis. If there are three names in the disease, what does this indicate?
Occurs in children >3 yo
What is Letterer-Siwe disease?
Malignant subtype of Langerhans cell histiocytosis with skin rash, and multiple organ failure. Occurs in children
What is eosinophilic granuloma? S/sx?
Benign proliferation of Langerhans cells in bone
Pathological fractures in adolescent, without skin involvement
Biopsy of Eosinophilic granuloma will show what?
Langerhans cells with mixed inflammatory cells, including eosinophils
What is Hand-Schuller-christian disease? Presentation? Age?
--Malignant proliferation of Langerhans cells.
-Scalp rash, lytic skull defects, DI, exophthalmos
-Usually >3 yo
What is the effect of cortisol on lymphocytes?
What are the histological characteristics of mononucleosis?
Atypical lymphocytes with a large, odd shaped nucleus
Where does the EBV virus remain dormant?