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STEP 6: HemeOnc PATHOMA > WBC Disorder Associations > Flashcards

WBC Disorder Associations Flashcards

1
Q

What are the two driving forces for acute inflammation?

A

1) Bacterial infection

2) Tissue necrosis

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2
Q

Which leukopenia/leukocytosis is associated with bacterial infections? What is one exception of bacterial species?

A

NEUTROPHIL LEUKOCYTOSIS - Increased neutrophils (left-shift)
Exception = BORDATELLA PERTUSSIS - Results in lymphocyte leukocytosis

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3
Q

Which leukopenia/leukocytosis is associated with chronic myeloid leukemia (CML)?

A

BASOPHILIA

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4
Q

Which leukocytosis is Hodgkin lymphoma associated with?

A

EOSINOPHILIA

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5
Q

What marker is decreased in neutrophil leukocytosis?

A

CD16 (i.e. Decreased Fc receptor expression from LEFT SHIFT - Increase in release of immature neutrophils from the bone marrow as a response to bacterial infection or tissue necrosis)

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6
Q

High cortisol state (e.g. exogenous cortisol or Cushing’s Syndrome) is associated with which 2 leukopenia/leukocytosis?

A

1) LYMPHOPENIA - Due to induction of lymphocyte apoptosis by cortisol
2) NEUTROPHIL LEUKOCYTOSIS - Due to cortisol-mediated impairment of neutrophil adhesion to the endothelial lining of vasculature (i.e. marginated pool) -> Release of marginated neutrophils into the serum

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7
Q

Which leukopenia/leukocytosis is associated with infectious mononucleosis (mono)? What is the most common viral agent of mono, what is the less common viral agent?

A 
LYMPHOCYTE LEUKOCYTOSIS (reactive CD8+ CTL) 
Most common = EBV
Less common = CMV
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8
Q

EBV infection increases the risk of which neoplastic condition? Particularly in which pt population?

A

B CELL LYMPHOMA, particularly in IMMUNOCOMPROMISED pt population (e.g. HIV pts)

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9
Q

What is the main difference between ACUTE leukemia and CHRONIC leukemia?

A

ACUTE Leukemia - Neoplastic proliferation of IMMATURE BLASTS in the BONE MARROW
CHRONIC Leukemia - Neoplastic proliferation of MATURE, CIRCULATING lymphocytes in the BLOOD

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10
Q

What is the most common type of acute lymphoblastic leukemia (ALL)?

A

B-ALL: B-lymphoblast acute lymphoblastic leukemia

Accumulation of >20% B-lymphoblasts in the bone marrow

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11
Q

What are the surface markers of B-ALL(leukemia)?

A

CD34+ (HSC)/ tDt+ (Lymphoblast)/ CD10,CD19,CD20 (B-lymphoblast)

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12
Q

What are the surface markers of T-ALL(lymphoma)? Which surface marker do these T-lymphoblasts NOT express?

A

CD34 (HSC)/ tDt (Lymphoblast)/ CD2-CD8 (T-Lymphoblast)

Do NOT express CD10

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13
Q

Which age population is acute lymphoblastic leukemia most prevalent in?

A

Children, associated with Down’s syndrome AFTER age 5

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14
Q

What is the prognosis of B-ALL based on? What are the two important prognoses (1 good, 1 bad) based on?

A

Cytogenetic abnormalities -
1) GOOD PROGNOSIS - t(12;21) in children
2) BAD PROGNOSIS - t(9;22) in adults - Philadelphia chromosome
(Ph+ ALL)

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15
Q

What is the difference between lymphoma and leukemia? Which ALL is associated with which?

A

LYMPHOMA - Malignant cells form a MASS = T-ALL (T-lymphobast acute lymphoma)
LEUKEMIA - Malignant cells float around in BLOOD = B-ALL (B-lymphoblast acute leukemia)

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16
Q

Which pt population is acute myeloid leukemia most prevalent in?

A

Older age pt population - avg age 55yo

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17
Q

What are the 4 main sub-classes of acute myeloblastic leukemia (AML)

A

1) ACUTE PROMYELOCYTIC LEUKEMIA (APL)
2) ACUTE MONOBLASTIC LEUKEMIA
3) ACUTE MEGAKARYOBLASTIC LEUKEMIA
4) AML that has arisen from a background of pre-existing dysplasia (MYELODYSPLASTIC SYNDROME)

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18
Q

Why is APL considered a medical emergency? What is the treatment of APL?

A

Risk of DIC

Translocation t(15;17) -> Disrupted retinoic acid receptor expression -> Inhibits maturation of promyelocytes -> HIGH [promyelocytes] -> HIGH [Auer rods inside promyelocytes] -> Activation of coagulation cascade -> DIC

Tx = ATRA (all-trans-retinoic acid)

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19
Q

Which leukemia is associated with infiltration and swelling of the gums?

A

ACUTE MONOCYTIC/MONOBLASTIC LEUKEMIA

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20
Q

Which pt population does chronic leukemia affect the most?

A

Older adults

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21
Q

Which leukemia can transform to diffuse large B-cell lymphoma (called RICHTER TRANSFORMATION - marked as enlarging lymph node or spleen)?

A

CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) - Neoplastic proliferation of NAIVE B cells in the blood -> Migrates to lymph nodes -> SMALL LYMPHOCYTIC LYMPHOMA

Lymphoma cells pick up additional mutations -> RICHTER Transformation -> Rapid growth/hypertrophy of lymph node/spleen = DIFFUSE LARGE B CELL LYMPHOMA

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22
Q

Which chronic leukemia is an exception of the general rule that LAD and splenomegaly generally result after a neoplastic proliferation of mature circulating lymphocytes?

A

HAIRY CELL LEUKEMIA (HCL) - TRAP pneumonic

TRAP+, Trapped in splenic RED pulp and bone marrow so can not distribute into lymph nodes (Absent LAD)

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23
Q

Which virus is ACUTE T-CELL LEUKEMIA LYMPHOMA strongly associated with? Where is this virus most commonly found?

A

HTLV1

Japan + Caribbean

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24
Q

Which cancer is associated with LYTIC BONE LESIONS + HYPERCALCEMIA?

A

MULTIPLE MYELOMA

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25
Which cancer is associated with LYTIC BONE LESIONS + HYPERCALCEMIA + **RASH**?
ADULT T-CELL LEUKEMIA LYMPHOMA (ATLL) | *Remember that T-cell leukemias like to migrate to the epidermis and skin
26
Which chronic leukemia is associated with Pautrier microabscesses (aggregates of neoplastic CD4+ T cells in the skin)? What syndrome is it now called if these neoplastic cells migrate into the blood?
``` MYCOSIS FUNGOIDES SEZARY SYNDROME (Contains **cerebriform nuclei**) ```
27
What are the surface markers of chronic lymphocytic leukemia (CLL) naive B cells?
CD5 and CD20 | *Aberrant expression of CD5 because it's NORMALLY expressed on T cell surfaces NOT B cells
28
What is the most common leukemia overall?
Chronic lymphocytic leukemia (CLL)
29
What is the most common cause of death in chronic lymphocytic leukemia?
INFECTION due to the complication of HYPOGAMMAGLOBULINEMIA (Low Ig production) due to neoplastic naive B cells "crowding out" normal Ab production
30
What are the 3 general complications of myeloproliferative disorders with the exception of ESSENTIAL THROMBOCYTHEMIA?
1. Increased risk of HYPERURICEMIA/GOUT - Due to high turnover of nuclei -> Hyper-activation of purine degradation pathway -> INCREASED URIC ACID 2. Progression to MARROW FIBROSIS 3. Transformation to ACUTE LEUKEMIA (AML 2/3 or ALL 1/3)
31
What needs to be ruled out when looking at a blood smear of CML? How do you rule that disease process out?
REACTIVE LEUKEMOID REACTION (High WBC count reactive/secondary to an acute infection/inflammatory process) 1. CML - LAP NEGATIVE (leukocyte alkaline phosphatase) 2. CML - t(9;22) 3. CML - BASOPHILIA
32
Which myeloproliferative disorders are driven by a Jak2 kinase mutation? Which one is driven by a Tyr kinase mutation in the HSC?
JAK2 MUT- Polycythemia vera, Essential thrombocythemia, Myelofibrosis TYR K. MUT - Chronic myeloid leukemia (CML)
33
What is the classic example of venous thrombosis related to hepatic infarction? What is the MOST COMMON CAUSE of this syndrome?
BUDD-CHIARI SYNDROME: Hepatic vein thrombosis -> Hepatic infarction Most common cause = POLYCYTHEMIA VERA
34
What condition needs to be differentiated from POLYCYTHEMIA VERA? How do you rule it out?
REACTIVE POLYCYTHEMIA due to 1. Lung disease -> Hypoxia (Low SaO2, Increased EPO) 2. Renal cell carcinoma -> Ectopic EPO production (Normal SaO2, Increased EPO PV: DECREASED EPO (due to negative feedback), NORMAL SaO2
35
Which tumor is most commonly associated with ECTOPIC ERYTHROPOIETIN (EPO) production?
RENAL CELL CARCINOMA
36
Which two conditions need to be on my differential if I see INCREASED PLATELETS in a blood smear?
ESSENTIAL THROMBOCYTHEMIA | Fe-DEFICIENY ANEMIA
37
Which myeloproliferative disorder is associated with tear-drop RBC production?
MYELOFIBROSIS - Tear-shaped due to RBC-production within a fibrotic bone marrow and "squeezed" exit out to the blood
38
t(9;22) cytogenetic abnormality is a defining feature of which neoplastic leukemia? Which leukemia constitutes a small subset of this translocation pt pool?
CHRONIC MYELOID LEUKEMIA | Small subset - Acute lymphoblastic leukemia (mostly B-ALL)
39
Ddx of INCREASED granulocytes and their pre-cursors on blood smear
1. LEUKEMOID REACTION (Increased WBC secondary/reactive to a primary inflammatory/infectious process) 2. CML (Chronic myeloid leukemia) - Especially BASOPHILIA
40
Ddx of INCREASED platelets on blood smear
1. ESSENTIAL THROMBOCYTHEMIA | 2. Secondary Reactive Thrombocytosis: FE-DEFICIENCY ANEMIA + SPLENECTOMY/AUTOSPLENECTOMY
41
Ddx of PAINLESS LAD (3)
1. CHRONIC INFLAMMATION (e.g. autoimmune diseases) 2. METASTATIC CARCINOMA (e.g. axillary lymph node enlargement from breast cancer metastasis) 3. LYMPHOMA (eg. Follicular Lymphoma)
42
Which region of the lymph node is expanded (resulting in reactive LAD) for rheumatoid arthritis and early HIV?
CORTEX - specifically follicular dendritic cells of the cortex
43
Which region of the lymph node is expanded (resulting in reactive LAD) with a viral infection (e.g. EBV causing infectious mononucleosis)?
PARACORTEX
44
Which region of the lymph node is expanded (resulting in reactive LAD) with lymph node drainage of an area of cancer?
MEDULLA - Specifically the sinus histiocytes of the medulla (HISTIOCYTOSIS)
45
Are NON-HODGKIN LYMPHOMA neoplastic cells mostly B cells or T cells?
B CELLS
46
Which lymphomas (4) constitute a neoplastic proliferation of SMALL B Cells?
1. FOLLICULAR LYMPHOMA 2. MANTLE CELL LYMPHOMA 3. MARGINAL ZONE LYMPHOMA 4. SMALL LYMPHOCYTIC LYMPHOMA - CLL cells that spread to the lymph node
47
Which lymphoma is a neoplastic proliferation of INTERMEDIATE B cells?
BURKITT LYMPHOMA
48
Which lymphoma is a neoplastic proliferation of LARGE B cells?
DIFFUSE LARGE B CELL LYMPHOMA
49
Diffuse large B-cell lymphoma can be a complication of which original lymphomas?
SMALL LYMPHOCYTIC LYMPHOMA - CLL Naive B cells FOLLICULAR LYMPHOMA - Small B cells Generalized LAD -> These cells acquire additional mutations -> 1 of the lymph nodes FURTHER ENLARGES -> DIFFUSE LARGE B CELL LYMPHOMA
50
Which cytogenetic abnormality constitutes FOLLICULAR LYMPHOMA?
t(14;18) - BCL2 on Chrom 18 translocates to IgH on Chrom 14 OVEREXPRESSION of BCL2 -> EXCESSIVE ANTI-APOPTOSIS post-somatic hypermutation (B cells that SHOULD be apoptosed after SH do NOT die) -> LYMPHOMA
51
Which lymphomas present in LATE ADULTHOOD + manifest with PAINLESS LAD?
1. FOLLICULAR LYMPHOMA (SMALL B CELL) | 2. MANTLE CELL LYMPHOMA (SMALL B CELL)
52
MANTLE CELL LYMPHOMA is driven by which chromosomal translocation? And what is the end result in terms of expression?
t(11;14) - Cyclin D1 overexpression by its translocation from Chrom 11 to IgH locus on Chrom 14
53
MARGINAL ZONE LYMPHOMA is associated with which general conditions?
CHRONIC INFLAMMATORY CONDITIONS (Eg. autoimmune) 1. HASHIMOTO THYROIDITIS 2. SJOGREN SYNDROME 3. H.PYLORI GASTRITIS
54
BURKITT LYMPHOMA is driven by which chromosomal translocation? What does it result in with regard to expression?
t(8;14) - C-myc overexpression due to its translocation from Chrom 8 to the IgH locus on Chrom 14
55
Starry sky appearance histological appearance is associated with which lymphoma?
BURKITT LYMPHOMA - Due to very high mitotic index (lots of blue tumor nuclei in "sky" and tingible body macrophages present due to dying cells from rapid overgrowth "starry")
56
What is the MOST COMMON form of Non-Hodgkins Lymphoma?
DIFFUSE LARGE B CELL LYMPHOMA
57
What is the main difference between Hodgkins lymphoma and Non-Hodgkins lymphoma?
NHL - ENTIRE mass is made up of malignant cells HL - Mass = Rare neoplastic Reed Sternberg cells (Large B cells) + Reactive inflammatory cells (lymphocytes, eosinophils, plasma cells, macrophages - **Bulk of the mass)
58
What are the cell surface markers of neoplastic Reed Sternberg cells of HODGKINS LYMPHOMA?
CD15+ and CD30+
59
Which form of HL has the BEST prognosis and which form of HL has the WORST prognosis?
BEST - Lymphocyte-rich HL | WORST - Lymphocyte-depleted HL
60
What is the most common malignancy of bone? What is the most common PRIMARY malignancy of bone?
MOST COMMON - Metastatic carcionma | MOST COMMON PRIMARY MALIGNANCY - Multiple myeloma
61
What is the most common mAb overproduced resulting in the SPEP M-Spike by neoplastic plasma cells in MULTIPLE MYELOMA?
IgG or IGA
62
What is the most common cause of death in multiple myeloma pts? Why?
INFECTION Due to LOSS of antigenic diversity - neoplastic plasma cell resulting in a MONOCLONAL proliferation of ONLY either IgG or IgA
63
Which serum cytokine is elevated in the serum that drives the overproduction of plasma cells in MULTIPLE MYELOMA?
IL-6
64
What are two diagnostic findings of MULTIPLE MYELOMA?
1. SPEP - M SPIKE 2. BLOOD SMEAR - Rouleaux formation of RBC Increased serum protein -> Decrease in charge between RBC -> RBC no longer equally distributed -> RBC pile on top of each other like poker chips
65
What are the 4 complications of MULTIPLE MYELOMA?
1. Increased risk of infection - Due to monoclonal proliferation and loss of Ag diversity **Most common cause of death 2. PRIMARY AMYLOIDOSIS - Due to overproduction of light chain and deposits in the blood as amyloid protein 3. PROTEINURIA (specifically bence jone proteins) - Excretion of light chain in the urine 4. MYELOMA KIDNEY (renal failure) - Deposits of light chain in kidney tubules
66
Differential diagnosis of M-SPIKE shown on SPEP:
1. MULTIPLE MYELOMA (IgG or IgA) 2. MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE (MGUS - IgG or IgA) 3. WALDENSTROM MACROGLOBULINEMIA (IgM
67
BIRBECK (Tennis racket) Granules associated with ___?
LANGERHANS CELL HISTIOCYTOSIS
68
What are the immunohistochemistry markers seen in LANGERHANS CELL HISTIOCYTOSIS?
LANGERHANS CELLS - CD1a+ and S100+
69
Which lymphoma is associated with EBV?
BURKITT LYMPHOMA
70
Ddx of an adolescent having a pathologic fracture
1. OSTEOSARCOMA (tumor of the bone) | 2. EOSINOPHILIC GRANULOMA (Langerhans cell histiocytosis)
71
Down's syndrome increases the risk of leukemia. Which leukemia BEFORE age 5 and which one AFTER age 5?
AFTER age 5: B-ALL - B-lymphoblastic acute leukemia | BEFORE age 5: ACUTE MEGAKARYOBLASTIC LEUKEMIA
72
Which chromosomal translocation is DIFFUSE LARGE B CELL LYMPHOMA associated with?
3;14 - BCL-6 (3) translocation onto IgH (14)
73
Which leukemia is B-RAF mutation associated with?
HAIRY CELL LEUKEMIA
74
RUDDY COMPLEXION of the face (flushed face) + ERYTHROMELALGIA (burning in palms/soles of feet) + ITCHING after hot bath are pathognomonic for ___
POLYCYTHEMIA VERA
75
ELEVATED HCT + MICROCYTIC ANEMIA are lab values pathognomonic of ___?
POLYCYTHEMIA VERA
76
What are 4 physical findings of secondary neoplastic proliferation more prevalent in ACUTE MYELOID LEUKEMIA versus ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)?
1. HEPATOSPLENOMEGALY, SPLENOMEGALY - Actually see this in ALL as well 2. GUMS - ACUTE MONOCYTIC/MONOBLASTIC LEUKEMIA 3. INFILTRATION TO SKIN - Although more common in T cell leukemias 4. ALTERED MENTAL STATUS - Due to EXTREMELY HIGH WBC
77
What clinical physical Sx (2) is most specific to ACUTE LYMPHOBLASTIC LEUKEMIA?
1. BONE PAIN due to Bone marrow expansion (>20% blasts in the bone marrow) 2. TESTICULAR ENLARGEMENT
78
What clinical Sx is most specific to ACUTE MYELOID LEUKEMIA?
Gum swelling + Altered mental status changes (high WBC and vascular sludging in the CNS)
79
Which staining detects MONOCYTES?
Non-specific ESTERASE
80
What is the most common INDOLENT form of NON HODGKINS LYMPHOMA? What is the most common form of NON HODGKINS LYMPHOMA?
Most common indolent = FOLLICULAR LYMPHOMA | Most common = DIFFUSE LARGE B CELL LYMPHOMA
81
What is the most CONSISTENT structural/numerical/chromosomal change seen ACUTE LYMPHOBLASTIC LEUKEMIA?
HYPERPLOIDY
82
What are good prognosis factors for ACUTE LYMPHOBLASTIC LEUKEMIA? What are bad prognosis factors?
GOOD: t(12;21) - CHILDREN (age: 2-10), LOW WBC, HYPERDIPLOIDY BAD: t(9;22) - ADULTS or INFANTS (
83
Which staining detects MYELOBLASTS?
MPO
84
Which leukemia is associated with STAT3 signaling mutations?
CHRONIC MYELOID LEUKEMIA (CML) STAT3 dysregulation associated with BCR-ABL fusion protein
85
What is the most appropriate course of action for a pt with ACUTE MYELOID LEUKEMIA presenting thrombocytopenia and bleeding everywhere?
Bring pt to ER! | Especially if pt has APL, pt is at risk of DIC
86
What are the two biggest risk factors (BAD PROGNOSIS factors) for ACUTE MYELOID LEUKEMIA?
1. Prior CHEMO therapy (alkylating agents) or radiotherapy: Pre-existing dysplasia - Cells don't form properly, can't exit the bone marrow or enter the blood -> Accumulate blasts 2. Previous lymphoma (MYELODYSPLASTIC SYNDROME) with subsequent irradiation therapy
87
What are good prognosis factors of ACUTE MYELOID LEUKEMIA?
1. Age
88
What is a general important distinction in terms of overall CBC count with chronic conditions - CHRONIC LEUKEMIA vs MYELOPROLIFERATIVE DISORDERS?
1. CHRONIC LEUKEMIA (e.g. HAIRY CELL LEUKEMIA) - will have ELEVATED WBC, but pancytopenia elsewise (like Acute leukemia) 2. MYELOPROLIFERATIVE DISORDERS (e.g. CHRONIC MYELOID LEUKEMIA) - Will have PREDOMINANTLY ELEVATED WBC, and an elevated count across all cells in the myeloid lineage
89
What cell markers are expressed in NORMAL Follicular cells? Which marker is additionally expressed in neoplastic follicular cells in FOLLICULAR LYMPHOMA?
NORMAL: CD19, CD20, IgM, BCL6 | FOLLICULAR LYMPHOMA: BCL2 in addition to CD19, CD20, IgM, BCL6
90
What is the normal bone marrow cellularity of a growing child? What is the normal bone marrow cellularity of an adult?
CHILD: 60-70% ADULT: 40-50%
91
Nearly all cells show proliferation Ag Ki-67 + starry sky appearance. What lymphoma am I?
BURKITT LYMPHOMA
92
Is BURKITT LYMPHOMA responsive or unresponsive to chemotherapy?
RESPONSIVE
93
Which virus is most commonly associated with ENDEMIC BURKITT LYMPHOMA? Which virus is commonly associated with SPONTANEOUS BURKITT and DIFFUSE LARGE B CELL LYMPHOMA?
Endemic Burkitt - EBV | Spontaneous Burkitt and DLBCL - HIV but need to be very deficient in T cells, generally more EBV as well now
94
Which type of HODGKIN LYMPHOMAS contains EBV viral DNA?
1. LYMPHOCYTE-DEPLETED: Most aggressive, >90% RS cells + EBV viral DNA 2. MIXED CELLULARITY: 70% of RS cells + EBV viral DNA
95
Which type of HODGKINS LYMPHOMA has the best prognosis?
LYMPHOCYTE RICH HL - Contains atypical REED STERNBERG CELLS - Do express B cell markers (CD20 and BCL-6) + No association with EBV at all
96
CHEMOTHERAPY is most associated with which leukopenia OR leukocytosis?
NEUTROPENIA - chemotherapy with alklylating agents -> Damage to stem cells -> Decreased WBC production
97
SEVERE Gm- SEPSIS is most likely associated with which leukopenia or leukocytosis?
Mild/moderate Gm-sepsis: Associated with INCREASED NEUTROPHILS But SEVERE Gm- sepsis: Associated with NEUTROPENIA as circulating neutrophils are out of blood (decreased) and in tissue
98
What is the Tx of NEUTROPENIA associated with chemotherapy and severe Gm- bacteria sepsis?
GM-CSF, G-CSF GM-CSF (Granulocyte/Monocyte colony stimulating factor) G-CSF (Granulocyte colony stimulating factor)
99
What immune cell is most sensitive to whole body radiation? Thus, what is the earliest change?
LYMPHOCYTES | Earliest change = LYMPHOPENIA
100
What other pathologies are associated with LYMPHOPENIA? [Hint: Think 1 congenital, 1 acquired, 1 endocrine, 1 autoimmune, 1 iatrogenic]
IMMUNODEFICIENCY (DiGeorge, HIV) HIGH CORTISOL STATE (e.g. Cushing's or exogenous corticosteroids) SLE = Type II HSR against WBC (as well as RBC, PLT) Whole body radiation
101
What is the Tx of HAIRY CELL LEUKEMIA? What is its mechanism?
2-CDA (CLADRIBINE) = ADENOSINE DEAMINASE INHIBITOR Adenosine deaminase = Purine degradation enzyme Hairy cell leukemia -> Neoplastic proliferation of MATURE B CELLS -> Cladribine ACCUMULATES ADENOSINE -> Toxic to cells -> Kills of mature B cells

STEP 6: HemeOnc PATHOMA (8 decks)

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