Quiz 2 Flashcards
What is Gout?
The deposition of MSU crystals in tissues (joints especially) due to hyperuricemia
What is the function of CD antigens?
They are the primay cell surface molecules used to determine cell lineage
What is the immunophenotype expressed by lymphocytes?
The pattern of expressed CD antigens
What is the T-cell lineage marker?
CD3
What is the B-cell lineage marker?
CD19
What is the mature B cell marker?
CD20
What is the immaturity marker of a cell?
CD34
What antigens are responsible for assessment of B-cell clonality?
Kappa and Lambda light chains
What antigen acts as a myeloid lineage marker?
MPO
What antigen acts as an immature lymphocyte marker?
TdT
What type of lymphoma is most likely indicated by a t(14;18) IGH-BCL2 translocation?
a follicular lymphoma
What type of lymphoma is most likely indicated by a t(11;14) CCND1-IGH translocation?
a mantle cell lymphoma
What type of lymphoma is most likely indicated by a t(8;14) MYC-IGH translocation?
Burkitt lymphoma
What test could be run for more information on the granulation status of neutrophils?
morphologic WBC analysis
In RNA/DNA catabolism, loss of Adenosine Deaminase (ADA) leads to shutting down of what enzyme?
Ribonucleotide Reductase (RNR)
Ribonucleotide Reductase (RNR) is required for synthesis of which DNA precursors?
All dNTP synthesis requires RNR
DNA catalysis requires stable free radicals scavenged by which molecule?
hydroxyurea
What is the role of an E1 ubiquitin ligase?
To activate multiple E2 ubiquitin ligases
What is the role of E2 ubiquitin ligases?
To hold ubiquitin (bullet) for the target protein
What is the role of E3 ubiquitin ligases?
To form a complex with E2 and identify the target protein for ubiquitination
What is the difference between monoubiquitylation and polyubiquitylation of a target protein?
M- changes target protein activity
P- leads to degradation through proteasome
What are dohle bodies a sign of in PMNs?
activation in response to inflammation
What are aquired causes of neutrophilia?
What are the 5 main causes of neutrophilia?
Infection
Medications (corticosteroids)
Stress/trauma w/ necrosis
Chron. inflam. or autoimmune (rh. arthritis)
neoplasms
Would reactive neutrophilia or CML be more likely in a patient with an LAP score of over 115?
Reactive neutrophilia
Would a CBC revealing elevated eosinophils and basophils with absolute basophilia be more indicative of reactive neutrophilia or CML?
CML
Which translocation would be expected in diagnosis of CML?
t(9;22) BCR/ABL
What are the 5 main causes of lymphocytosis?
Infection (viral most common)
autoimmune disease
smoking (polyclonal B-cell lymphocytosis)
Chronic lymphocytic leukemia (CLL)
Other non-Hodgkin lymphomas
What treatment is preferred for CML?
tyrosine kinase inhibitors
What lab testing would be preferred for reactive lymphocytosis?
infectious serology
What lab testing would be preferred for mononucleosis?
EBV, monospot, serology, PCR
What signs in the peripheral blood smear might indicate infectious mononucleosis?
Downey cells, or variant lymphocytes
What clinical signs might suggest mononucleosis?
fever, pharyngitis, cervical lympadenopathy (LAD)
What is the most likely clinical presenation for a pt with undiagnosed CML or CLL?
asymptomatic
An elderly patient with an elevated WBC count of 40,000 with monomorphous mature lymphocytes, atypical monoclonal B-cells, and + B-cell clonality is most likely to have reactive lymphocytosis or CLL?
CLL
What are the 5 most common causes of Eosinophilia?
Infection (parasitic or fungal most likely)
Allergic diseases
rheumatologic diseases
Drug rxns
neoplasm
Prolonged elevations of eosinophil counts above what level are usually injurious, and can lead to cardiac fibrosis?
5000u/L
Patients with hypereosinophilia of uncertain cause can be treated with what medication?
hydroxyurea
What are the most common causes of neutropenia?
Genetic: Kostmann syndrome, idiopathic
Acquired: Infection, antivirals or antipsychotics, autoimmune disorders, aplastic anemia, neoplasms
What are possible causes of neutrophil hyposegmentation?
Pelger-Huet anomaly, MDS, medications (tacrolimus)
What are possible causes of neutrophil hypersegmentation?
Vit B12/Folate deficiency, MDS, medications
What pathology would be indicated by a FISH finding of a t(9;22) BCR-ABL fusion?
Chronic myeloid leukemia
What is the pathology of Pelger-Huet anomaly?
It is a benign manifestation of hyposegmented neutrophils
T/F: A lymphoma can include immature lymphoid cells
False
T/F: A leukemia can be lymphoid or myeloid
True
What type of neoplasms are clonal disorders?
Lymphoid neoplasms
How are immunoglobulins expressed by B-cells measured?
flow cytometry or PCR
What are the most notable B-cell lymphomas?
CLL/SLL
Mantle cell lymphoma
Follicular lymphoma
DLBC lymphoma
Burkitt lymphoma
Hodgkin lymphoma
Which of the common B-cell lymphomas are considered high-grade, aggressive? What characterizes them?
Mantle cell lymphoma, DLBCL, Burkitt lymphoma
They affect adults, children, immunocompromised pts, usually present in stage Ib/IIb, grow rapidly and need immediate treatment, but generally curable
Which of the common B-cell lymphomas are considered low-grade, indolent? What characterizes them?
CLL/SLL, follicular lymphoma (can also be high-grade)
Pts commonly present in stage III/IV, usually in elderly (50-70 median age), generally incurable, but slow growth and long survival
Which B-cell lymphoma can have translocations involving MYC, BCL2, or BCL6
DLBCL
Which lymphoma is characterized by a “starry sky” appearance of lymph node histology?
Burkitt lymphoma
In cases of HIT, what medication may be indicated for a pt to switch to?
Argatroban is the IIa inhibitor indicated in cases of HIT
What are the symptoms of multiple myeloma?
CRAB symptoms:
hyper C alcemia
Renal failure (elevated creatinine)
Anemia
Bone pain
What is the Rouleaux formation as seen on a blood smear?
“Coin stacks” of RBCs
What do Auer rods indicate on a blood smear?
a cell of myeloid lineage
What pathology is associated with a t(15;17) PML-RARA translocation?
acute promyelocytic leukemia
Which leukemia is most associated with DIC and considered an acute hematological emergency?
AML t(15;17) PML-RARA (acute promyelocytic leukemia)
What treatments are used for acute promyelocytic leukemia?
ATRA (all-transretinoic acid) and arsenic trioxide
What is the significant finding on the bone marrow aspirate smear?
numerous promyelocytes
What 4 findings are most consistant with DIC?
elevated PT
elevated aPTT
decreased fibrinogen
elevated D- dimer
What is the biggest risk with DIC?
hemorrhage
What two types of AML are referred to as “CBF leukemias”?
AML t(8;21) RUNX1-RUNX1T1
AML t(16;16) CBFB-MYH11
What is a common presentation of acute B-lymphoblastic leukemia (B-ALL) with hyperdiploidy?
A high number of triploid or quadriploid chromsomes
Often presents with cytopenias and bone pain
What are the four Ts for ddx for a mediastinal mass?
“Terrible” lymphoma or leukemia
Thymic tumor
“Teratoma” or GC tumor
Thyroid tumor
Which type of cancer often presents as a mediastinal mass with/without BM involvement, more commonly in adolescents?
T-ALL (leukemia/ or lymphoma)
Which neoplasms fall into the group of acute myeloid neoplasms?
Which neoplasms fall into the group of acute lymphoid neoplasms
Which neoplasms fall int othe group of MPN-MDS?
Which neoplasms fall in to the group of mature lymphoid neoplasms?
What does a blast quantity of over 20% in peripheral blood indicate?
an acute leukemia
How can gene fusion be detected?
Chromosome analysis (karyotype), FISH, or molecular testing
What is considered a major molecular response in treatment of CML?
1,000 fold or a 3 log reduction in BCR-ABL1 transcripts
What chiefly characterizes Polycythemia vera?
-Exclusion of secondary causes of increased RBC mass
-Low serum EPO
-usually a JAK2V617F mutation
-usually hyperceullar BM with panmyelosis
What are three principal treatments of PV?
Phlebotomy, JAK inhibitors, hydroxyurea
Which conditions have a bimodal distribution in average age at dx?
Hodgkin’s lymphoma, ET,…
What characterizes essential thrombocythemia?
-Platelets >450K/uL
-atypical megakaryocyte hyperplasia in BM
-JAK2, CALR or MPL mutation
-must exclude secondary thrombocytosis
What is notable about this blood smear?
thrombocytosis
What are characteristics of myelofibrosis?
-Increased megakaryocytes and granulocytes in BM
-Fibrous CT in BM
-Leukoerythroblastic smear- teardrop cells, nucleated RBCs, left shift
-JAK2, CALR, MPL mutation
-extramedullary hematopoeisis
What are treatments for primary myelofibrosis?
JAK inhibitors, hydroxyurea, spenectomy (if massive), and SC transplant if progressed
Of PV, ET, and PMF, which has the poorest prognosis?
PMF
What are major similarities between PV, ET, and PMF?
-Peripheral blood thrombocytes
-Gene mutations in JAK2, MPL, or CALR
- BM abnormalities
What characertizes MDS?
-Ineffective hematopoeisis
-High risk of developing AML
-Abnormal cells remain in BM, causing peripheral cytopenias
What three features are required for a dx of MDS?
- Cytopenia
- Morphologic dysplasia (under microscope)
- Abnormal cytogenetic/chromsome studies
What treatments are used for MDS?
Limited options; but in younger patients, allogeneic SC transplant, maybe DNA methyltransferaseinhibitors (Azacitidine)
In what category do MGUS, smoldering myeloma and multiple myeloma fall?
Plasma cell neoplasms
Which anticoagulants are contraindicated in pregnancy?
Warfarin and DOACs
Where is DVT most likely to occur?
in the legs, usually the calves
What are the current treatments for DVT?
Direct Xa inhibitor
LMWH
Thrombin inhibitor (LMWH bridging)
Warfarin (LMWH briding)
How long is DVT usually treated?
3 months, but could be more depending on situation
What is a good treatment for DVT if bleeding is a problem? Why?
Unfractionated heparin; it is quickly/completely reversible with protamine
How is PE treated differently than DVR?
It is currently treated the same
Which is the pathology of heparin-induced thrombocytopenia?
Antibodies in the pt. bind to the heparin-PF4 complex
In the event of HIT after heparin administration, what would be the best course of action?
STOP heparin treatment, and administer a thrombin inhibitor (argatroban is preferred for HIT)
Which anticoagulants have been used most consistantly in cancer patients? Are there any other types that are becoming more commonly used?
LMWHs (dalteparin, enoxaparin, tinzaparin); DOACs (rivaroxaban, apixaban, edoxaban, dibigatran)
Of the following reversal protocols for Warfarin administration, which has the longest time of action?: PT complex concentrate, FFP, Vit K
Vit K
What are the most common B-cell neoplasms in adults?
Follicular lymphoma and DLBCL
What is the most common leukemia in adults in the Western hemisphere?
SLL/CLL
What is the main difference between CLL and SLL?
CLL: leukemic form
SLL: in node form
What are the approximate ratios of B-cell NHL, Hodgkin lymphoma, and T-cell NHL in the population?
B-cell NHL: 80%
Hodgkin lymphoma: 11%
T-cell NHL: 9%
What are the main differences between low grade/indolent and high grade/aggressive lymphomas?
LG/I: older pt, not curable, high stage
HG/A: younger pt, curable, low stage, B symptoms
What type of lymphoma is indicated by this biopsy? Why?
DLBCL; the lymphocytes are atypical and large (1.5-2x normal lymphocyte)
What type of lymphoma is indicated by this biopsy? why?
Hodgkin lymphoma; the classic “owl eye” cells are Reed Sternberg cells
What type of lymphoma is indicated by this biopsy? Why?
Burkitt lymphoma; the classic “starrry sky” appearance of the lymph node (increase in tingible body macrophages)
What type of lymphoma is indicated by this biopsy? Why?
Follicular lymphoma; low power view of back-to-back follicles
What translocation is associated with Burkitt lymphoma? What are other notable features?
t(8;14)
What translocation is associated with CML (required for CML dx, but also possible in ALL or AML)? What are other notable features
t(9;22)
What translocation is associated with Follicular lymphoma? What are other notable features?
t(14;18)
What translocation is associated with Acute promyelocytic leukemia? What are other notable features?
t(15;17)
What featuers are likely in CML, but NOT in reactive neutrophilia?
Absent toxic changes in neuotrphils, absolute basophilia, splenomegaly, low LAP score, BCR-ABL1 fusion t(9;22)
What is the difference between average age at dx for AML and ALL?
AML: mostly adults
ALL: mostly kids
What is the liklihood of splenomegaly in leukemia? In MDS? In aplastic anemia?
Leukemia: Common
MDS: less common
aplastic anemia: not common
What is a major differentiator between MDS and aplastic anemia?
MDS will have a hyper-cellular marrow
What is the criteria for monoclonal gammopathy of undetermined significance (MGUS)?
What is the criteria for multiple myeloma?
What is the criteria for smoldering myeloma?
A small, round, blue cell tumor is representative of what specific kind?
a pediatric tumor
What is the clinical use of Rituximab?
Immunotherapy; a monoclonal antibody used to treat CLL
What does the American Society for Hematology recommend in work-up for a plasma cell neoplasm?
1- CBC w/ diff, Ca, Cr, UA
2- SPEP for M-spike
3- Immunofixation to confirm Ig
4- Imaging and BM biopsy
What does an M-protein or M-spike look like on SPEP compared to normal?
What is another name for multiple myeloma?
plasma cell myeloma
In what type of of plasma cell myelomas is rouleax seen?
neoplasms with monoclonal proteins
In what age range would you expect to see ALL and AML respectively?
ALL: mostly in children and young adults
AML: ages 15-39
In what age range would you expect to see CML and CLL respectively?
CML: between 30-60 yo
CLL: over 50 yo
What type of test is a monospot test?
A serologic test for mononucleosis
What is the clinical indication of imatinib?
It is a popular tyrosine kinase inhibitor
What are two advantages of using FISH over PCR?
FISH is quicker
Allows detection in an intact cycle
Lack of HGPRTase is responsible for what disorder?
Lesch-Nyhan syndrome
What is the action of HGPRTase?
To salvage hypoxanthine, or guanine by attaching it to PRPP
What is a key symptom of Lesch Nyhan syndrome?
Uncontrollable lip/tongue biting, finger biting, or head banging
What is inhibited by allopurinol? What is the target molecule’s function?
Xanthine oxidase; it is a purine oxidizing enzyme that makes urate
On what kinds of cells is Ki-67 expressed?
cells actively cycling (NOT in G0)
Is PRPP used in the de novo or salvage pathways for purine biosynthesis?
It is required for both
ATM is a cell cycle “checkpoint” protein that is specific to what stage?
It is S-phase specific (blocks entry to S-phase
The improvements from around a 90% mortality rate to less than 10% of ALL in children is mostly due to what?
Optimal combinations and timing of chemotherapy
How would a Hodgkin lymphoma in stage Ia or IIa be treated?
chemotherapy plus radiation therapy
What is the therapeutic INR for most patients on warfarin?
2.0-3.0
What test was done to produce these results?
a gene expression microarray
What useful information about cancer can be provided by a gene expression microarray?
A GE microarray reveals abundance of RNA transcripts in cells tested; this can be correllated with expression/activity of proteins, and can provide information on the class or subtype of cancer present
What is the first step after finding lymphocytosis in a CBC?
Determining if the lymphocytes are derived from a single clone (leukemia/lymphoma) or have many variants (leukemoid reaction)
What is the result of a t(14;18) BCL-2 translocation?
Follicular lymphoma, more specifically, a mutation causing overexpression of BCL-2, an oncogene that inhibits apoptosis
Why is a protein electrophoresis of blood and urine an appropriate test to dx multiple myeloma?
In MM, an expanded clonal population of plasma cells secretes large amounts of intact (found in blood) Ig, or Ig light chains (Bence-Jones proteins) found in the urine
What type of leukemia is princibly treated with a tyrosine kinase inhibitor (iminitab)?
CML
When should a bone marrow biopsy be performed?
When the etiology of an abnormal peripheral blood count is uncertain or if a hematologic malignancy is expected
What is indicated by a high or low INR, respectively?
High- slow forming clots
Low- fast forming clots
What is a clinical sign that warrants inclusion of Follicular lymphoma on the ddx?
Painless lympoh nodes that wax and wane (usually in adults)
What are bone pain, proteinurea, and Rouleaux formation all signs of?
Multiple Myeloma (plasma cell myeloma)
What is the first step in treating a patient with an embolism causing an acute MI?
Dissolve the clot
What are major signs of TTP?
Pupura in extremities, schistocytes, low platelets, and elevated fibrinogen. Testing will reveal levels <10 of ADAMTS13
How does a COX1/2 inhibitor like aspirin impair platelet aggregation?
Inhibition of COX 1 and 2 results in decreased TxA2 production, causing platelets to not express GPIIb/IIa and fail to aggregate
What is the primary characterization of MDS vs PMF?
MDS: ineffective hematiopoiesis -> pancytopenia
PMF: deposition of megakaryocytes and granulocytes in BM -> marrow fibrosis
When is adjuvant chemotherapy given?
After surgery to reduce local and distant recurrence
When is neoadjuvant chemotherapy given?
Before surgery to improve outcomes
When is inducion chemotherapy given?
to achieve remission of cancer
When is consolidation chemotherapy given?
After induction to treat microscopic disease
When is maintenance chemotherapy given?
Over long-term to maintain remission
When is salvage chemotherapy given?
After relapse or refractory to previous therapy
What is the most common B-cell neoplasm in adults?
follicular lymphoma
t(14;18) IGH/BCL-2
What is the most common leukemia in adults in the Western hemisphere?
SLL/CLL
What is a likely cause of severe combined immunodeficiency (SCID)?
lack of Adenosine Deaminase (ADA)
