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Wk 4 Lymphoid and Leukemia Flashcards

1
Q

What are categorized as lymphoid neoplasms?

A
  1. lymphomas
  2. lymphocytic leukemias
  3. plasma cell neoplasms
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2
Q

What type of cell dominates in lymphoid neoplasms?

A

B-cells (~90%)
T-cells (KN/T-cell) (~10%)

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3
Q

What are 4 characteristics of leukemia?

A
  1. clonal expansion of hematopoietic cells
  2. predominantly in blood and/or BM
  3. can be lymphoid or myeloid
  4. can be immature (acute) or mature (chronic)
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4
Q

What are 4 characteristics of lymphoma?

A
  1. clonal expansion of hematpoietic cells
  2. predominantly in lymph nodes or other tissues
  3. lymphoid lineage
  4. cells are MATURE
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5
Q

What are 5 categories of lymphoid neoplasms?

A

1.
Precursor B-cell neoplasms
Immature B-cell (lymphoblast)
2.
Peripheral B-cell neoplasms
Mature B-cell
3.
Precursor T-cell neoplasms
Immature T-cell (lymphoblast)
4.
Peripheral T-cell and NK-cell neoplasms
Mature T- or NK-cell
5.
Hodgkin lymphoma

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6
Q

What are 5 categories of lymphoid neoplasms?

A

1.
Precursor B-cell neoplasms
Immature B-cell (lymphoblast)
2.
Peripheral B-cell neoplasms
Mature B-cell
3.
Precursor T-cell neoplasms
Immature T-cell (lymphoblast)
4.
Peripheral T-cell and NK-cell neoplasms
Mature T- or NK-cell
5.
Hodgkin lymphoma

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7
Q

What does clonal expansion occur secondary to?

A
  1. antigen exposure
  2. chromosomal rearrangements
  3. genetic mutations
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8
Q

What technique is used to determine whether B cells are clonal?

A

flow cytometry or PCR can measure unique immunoglobulins

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9
Q

How are B-cell leukemias/lymphomas classified?

A

By cell of origin

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10
Q

Know this

A
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11
Q

What CD antigens do I need to know?

A
  1. CD3 – T-cell lineage marker
  2. CD19 – B-cell lineage marker
  3. CD20 – mature B cell marker
  4. CD34 – immaturity marker
  5. Kappa & Lambda light chains – assessment of B-cell clonality
  6. MPO – myeloid lineage marker
  7. TdT – immature lymphocyte marker
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12
Q

How are lymphomas classified?

A
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13
Q

What are the stages of lymphoma?

A

Stage I – one lymph node region or single non-lymphoid organ
Stage II – two or more lymph node regions on same side of diaphragm
Stage III – two or more lymph node regions above and below diaphragm, may include spleen
Stage IV – widespread involvement of non- lymphoid organs and/or bone marrow

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14
Q

What are 6 B-cell lymphomas?

A
  • Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
  • Mantle cell lymphoma
  • Follicular lymphoma
  • Diffuse large B-cell lymphoma
  • Burkitt lymphoma
  • Hodgkin lymphoma
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15
Q

CLL

A
  1. ~70 yo
  2. Usually presents in leukemic phase (CLL in lymph nodes is SLL) and asymptomatic
  3. increased WBC w/ absolute lymhocytosis
  4. blood smear - small mature lymphocytes, clumped chromatin, scant cytoplasm
  5. Tx - Rituximab (anti-CD20) or Ibrutinib (kinase inhibitor) often only when WBC rapidly increase or evidence of disease progression or symptomatic
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16
Q

Follicular lymphoma

A
  1. common, 50-60 yo, Caucasians
  2. dx w/ lymphadenopathy
  3. chromosomal translocation t(14;18) IGH-BCL2 (-> overexpression of BCL2 (anti-apoptotic protein)
  4. Tx:
    - low-grade (good px) - radiation or Rituximab
    - high-grade (worse px) - R-CHOP
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17
Q

Mantle cell lymphoma

A
  1. 60 yo
  2. dx w/ lymphadenopathy & hepatosplenomegaly
  3. monomorphic small lymphocytes in lymph nodes
  4. chromosomal translocation t(11;14) CCND1-IGH (-> overexpression of Cyclin D1)
  5. aggressive, incurable Tx w/ chemotherapy then stem cell transplant
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18
Q

Diffuse Large B-cell Lymphoma

A
  1. 70 yo
  2. rapidly enlarging tumor mass at single or multiple sites (lymph nodes or other tissues)
  3. B symptoms (fever, night sweats, weight loss) may be present
  4. lymph node architecture diffusely effaced by large atypical cells
  5. can have translocation w/ MYC, BCL2 or BCL6 gene loci
  6. worse px
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19
Q

Burkitt Lymphoma

A
  1. Common in peds
  2. 3 forms: endemic, sporadic, immunodeficiency-associated
  3. lymph node w/ “starry sky” appearance
  4. chromosomal translocation t(8;14) MYC-IGH -> overexpression of MYC oncogene
  5. tx chemotherapy (diff regimens for adults and peds)
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20
Q

What are the 3 forms of Burkitt Lymphoma?

A
  1. Endemic - equatorial Africa, children, jaw mass, EBV+
  2. Sporadic - worldwide, peds, young adults, elderly, abdominal mass, EBV-
  3. immunodeficiency-associated - HIV+ patients, LM involvement
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21
Q

Hodgkin Lymphoma

A
  1. bimodal age dist: young adults and elderly
  2. bulky lymphadenopathy and/or mediastinal mass (B symptoms common)
  3. Lymph node w/ large atypical cells w/ eosinophilic nuclei (Hodgkin cells) or large atypical binucleate cells (Reed-Sternberg cells)
  4. Tx chemotherapy +/- localized radiation therapy
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22
Q

Lymphoma comparison chart

A
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23
Q

What is leukemia?

A

A hematologic neoplasm
-clonal expansion of immature cells (lymphoid or myeloid)
-clone resides in the BM
-malignant cells spill out to peripheral blood

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24
Q

What are the terms when clone of hematologic neoplasm is found outside the BM?

A
  1. lymphoma - when clone is lymphoid
  2. myeloid sarcoma - when clone is myeloid
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25
Subdivisions of leukemia
1. acute - neoplastic cells are immature precurors 2. chronic - comprised of mature lymphoid/myeloid cells
26
Lymphoma classification
27
What are most non-Hodgkin lymphomas?
B-cell makes up 80% -can be indolent or aggressive/high-grade
28
What is the primary classification of lymphomas?
1. Hodgkin 2. Non-Hodgkin
29
What are 6 B-cell non-Hodgkin lymphomas?
1. Follicular 2. Diffuse large B-cell lymphoma -aggressive 3. CLL/SLL 4. Mantle cell 5. Burkitt 6. Lymphoblastic leukemia/lymphoma - B or T cell
30
4 Classic lymphoma histology examples
1. DLBCL 2. Hodgkin - owl eye = Reed Sternberg 3. Burkitt - starry sky 4. Follicular - back to back follicles
30
4 Classic lymphoma histology examples
1. DLBCL 2. Hodgkin - owl eye = Reed Sternberg 3. Burkitt - starry sky 4. Follicular - back to back follicles
31
Tumor staging
Stage II - >1 region (noncontiguous) Stage III - above and below diaphragm Stage IV - marrow or liver or extranodal -describe spread of disease A: absence of B symptoms B: fever, night sweats, >10% weight loss
32
Leukemia categories
33
What defines acute leukemia?
>20% blasts in blood or marrow
34
Dx of AML
MPO + Auer Rods Adults
35
Signs of Myeloid Neoplasms
1. failed hematopoiesis 2. cell underproduction
36
Translocations to know
1. t(8;14) most common in Burkitt lymphoma due to overexpression c-myc 2. t(9;22) CML, misregulation of a tyrosine kinase (Bcr-Abl) - tx = Imatinib 3. t(14;18) - follicular lymphoma - overexpression Bcl-2 (anti-apoptotic) 4. t(15;17) - acute promyleocytic leukemia - fusion of retinoic acid receptor (RAR alpha) to PML (a tumor suppressor), TX = tretinoin, ATRA, all-trans retinoic acid)
37
Key differences b/w pediatric and adult tumors
38
What is a decrease in CD16 indicate?
Left shift - immature cells have decreased Fc receptors, like CD16
39
What is CD34 a marker for?
Expressed by HSCs
40
What cell type might be in excess w/ Hodgkin's Lymphoma?
Eosinophils, which is increased by Il-5 production
41
When is basophilia seen?
CML
42
What does TdT+ tell us?
There are lymphoblasts in the blood which is characteristic of B-ALL (most common) and T-ALL -is a DNA polymerase, so present in nucleus -absent in myeloid blasts and mature lymphocytes
43
What does MPO+ indicate in blood?
=myeloperoxidase -indicative of AML -in structure called Auer rods
44
ALL
TdT+ -most common in kids -assoc w/ Down Syndrome after 5 yo -can be B-ALL (more common, express CD10, CD19, CD20) or T-ALL (don't need to know)
45
B-ALL markers and genetic abnormalities
TdT+ CD10, CD19, CD20 t(12;21) - more common, good px, in 25% B-ALL t(9;22)- more common in adults, poor px (BCL-ABL = Philadelphia chromosome)
46
T-ALL markers and genetics
TdT+ CD2-CD8 (blasts do not express CD10) -presents at Thymic mass (mediastinal) -presents in Teenager -call it acute lymphoblastic lymphoma b/c it's a mass
47
APL
=acute promyelocytic leukemia, a type of AML t(15;17) -> PML/RARalpha (retinoic acid) receptor is disrupted -> promyelocytes accumulate, which have Auer rods and are a risk for DIC -give ATRA to cause blasts to mature
48
What is ATRA?
=all trans retinoic acid (derivative of vitamin A) cause blasts to mature and alleviate leukemic burden in pt
49
Acute monocytic leukemia
=proliferation of monoblasts that infiltrate the gums and lack MPO
50
Acute megakaryoblastic leukemia
=proliferation of megakaryolbasts - lack MPO -assoc w/ Down syndrome (before age 5) (compare w/ associated after age 5 w/ ALL)
51
What are characteristics of myelodysplastic syndromes?
Cytopenias w/ hypercellular bone marrow -abnorm maturation w/ increased blasts (<20%) -most pts die from infection or bleeding -may progress to acute leukemia (>20% blasts)
52
Chronic leukemia characteristics
=neoplastic proliferation of mature circulating lymphocytes -high WBC -older adults, asymptomatic -smudge cells -immunoglobulinemia
53
CLL
=neoplastic proliferation of naive B-cells -cells co-express CD5 and CD20 -increased lymphocytes and smudge cells (splattered-looking cell) -> generalized lymphadenopathy which is called small lymphocytic lymphoma
54
3 Complications of CLL
1. hypogammaglobulinemia (low Ig) -> primary cause of death is infection 2. autoimmune hemolytic anemia 3. transformation to diffuse large B-cell lymphoma
55
Hairy Cell Leukemia
=neoplastic proliferation of mature B cells -characterized by hairy cytoplasmic processes -cells are TRAP+ (enzyme) -splenomegaly (red pulp) -absent lymphoadenopathy dry tap w/ BM aspiration *TRAP: TRAP+, trapped in red pulp, trapped in BM, b/c they're trapped, cannot go to expected place, a lymphnode
56
TX for Hairy Cell Leukemia
Drug = 2-CDA -adenosine deaminase inhibitor adenosine accumulates to toxic levels in neoplastic B cells, killing them
57
ATLL
=Adult T-cell leukemia =neoplastic proliferation of mature DC4+ T-cells -assoc w/ HTLV-1 (human T cell leukemia virus 1) - more often seen in Japan and Caribbean
58
ATLL Clinical Features
1. Rash - T-cells like to go to skin, can differentiate from multple myeloma 2. Generalized LAD (lymphadenopathy) w/ HSM (hepatosplenomegaly) 3. lytic bone lesions w/ hypercalcemia (seen in multiple myeloma too)
59
What is Sezary syndrome?
Seen when mycosis fungoides (neoplastic prolif of mature CD4+ T cells) spreads from skin to blood -> characteristic lymphocytes w/ cerebriform nuclei (Sezary cells)

MCC (44 decks)

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