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Fundamentals 3- Heme > Lymphocytic Neoplasia > Flashcards

Lymphocytic Neoplasia Flashcards

1
Q

What three cells make up lymphocytes?

A

B cells ,T cells NK cells

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2
Q

What is the difference between leukemia and lymphoma?

A

Leukemia is when the lymphocyte neoplasm is primarily in the blood or bone marrow
Lymphoma is when the primary lymphocyte neoplasm is in the lymph node or solid tissue like the spleen

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3
Q

How are leukemias and lymphomas classified?

A

Genetically, phenotypically and morphologically

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4
Q

What is an immunophenotype?

What two things can it help you infer?

A

an antigenic “fingerprint” of cells determined by the types of molecules they express.
It can infer:
1. cell lineage
2. documentation of abherrant expression

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5
Q

What are the normal B cell markers?

A

CD19, 20, 22
CD79a
Pax 5
k and l Ig light chains

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6
Q

What are the typical T cell markers?

A

CD1a, 2, 3, 4, 5, 7, 8

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7
Q

What are the typical NK cell markers?

A

CD 2, 7, 8 (same as T)

CD 16, 56

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8
Q

What is CD45?

A

Leukocyte common antigen. It is seen on all normal leukocyte populations (except plasma cells)

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9
Q

What are the markers from Hodgkin’s lymphoma?

What can the markers allow you to do?

A 
CD 45
CD 30 
CD 15
CD 20
CD 3 
The markers can help you differentiate between classic hodgkins and nodular lymphocyte predominant Hodgkins
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10
Q

What are CD34 and TdT markers for?

What other marker has the same principle role, but is more specific?

A

They are a sign of immaturity in lymphoid populations so can tell you if the leukemia/lymphoma is blastic.
CD1a is also an immaturity marker but only for T cells

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11
Q

What are the CD10 and CD5 marker useful for?

A

They help subcategorize B-lineage lymphomas and leukemias.
Certain B-cell lymphomas have neither of these markers.
Other B-cell lymphomas have ONE of these markers.
NO B-cell lymphoma have both.

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12
Q

What is Ki67 a marker for?

A

Cell proliferation which can help us determine the number/percentage of neoplastic cells that are actively proliferating.

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13
Q

What are the techniques used for cytogenetic investigation used to categorize leukemia/lymphoma and aid in prognosis and therapeutic planning?

A

FISH and karyotyping (because a lot of the lymphocytic neoplasms are translocations)

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14
Q

Tumors compose of immature lymphocytes are designated with what 4 titles?
Tumors of mature lymphocytes are designated by what 2 titles?

A

Immature:

  1. blastic
  2. acute
  3. precursor
  4. central

Mature:

  1. chronic
  2. peripheral
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15
Q

What “blast” is not really an immature lymphocyte?

A

Immunoblast- is a transformed, reactive, mature lymphocyte that has a few features that appear immature (dispersed chromatin, large nucleoli)

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16
Q

What is lymphocytosis? What are 4 potential causes?

A

It is too many lymphocytes in the periphery.

  1. Chronic immunologic stimulation (TB)
  2. Viral infection
  3. Bordetella pertussis
  4. Stress (car accident, cerebral vascular accident)
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17
Q

Neoplasms of immature lymphoid cells arise from:

A
  1. defects in stem cells that lead to clonal expansion of leukemic blasts
  2. secondary suppression of normal hematopoiesis`
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18
Q

What are the two major types of acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL) ?
Which are 85% of the cases in the US?

A
  1. B-ALL/LBL- immature B cells “hematogones”
  2. T-ALL/LBL- immature T cells “thymocytes”

B-ALL/LBL accounts for 85% of cases in US

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19
Q

What is a hematogone? What cancer is it associated with?

What are the markers?

A

It is an immature B cell in B-ALL/LBL
CD19, 22, CD79a (sometimes CD20)
CD10
CD34 and Tdt

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20
Q

What is a thymocyte? What cancer is it associated with?

What are the markers?

A

It is an immature T-cell associated with T-ALL/LBL.
CD1a, 2, 3, 4, 5, 7, 8
CD34, TdT

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21
Q

Benign counterparts of hematogones and thymocytes express the same markers. How do you differentiate benign from neoplastic?

A

The intensity and pattern of the expression

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22
Q

What is the age distribution for ALL/LBL?

A

Bimodal with a peak in early childhood and the elderly (over 65)

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23
Q

What are common symptoms of ALL/LBL?

A
  1. bone/joint pain (due to overproduction of precursor WBC in the marrow)
  2. Lymphadenopathy
  3. skin lesion
  4. organomegaly
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24
Q

What mass is associated with T-ALL/LBL?

A

anterior mediastinal mass with or without vena caval syndrome

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25
Is ALL/LBL aggressive or indolent? | Is it curable or incurable?
Both B an T forms are highly aggressive and require intense chemo. Cure rate is high in children with continued therapy (3 years after undetectable) Cure rate is bad in elderly (less than 10% make it 3 years)
26
Speaking generally, what is the difference in cure rate between indolent and aggressive cancers?
Indolent are not that bad and people can live with them for a long time, but there is no cure. Aggressive need to be caught early because they can be devastating, but if caught early, they can be cured.
27
What are the two broad categories of mature lymphoma?
1. Non-Hodgkin's lymphoma | 2. Hodgkin's lymphoma
28
Non-Hodgkins lymphomas (NHL) are roughly _____% B cell lineage and ___% T cell lineage.
80% B cell 20% T cell NK are categorized as T cell lymphomas because of the similar clinical behavior
29
Where do the majority of NHLs manifest predominantly? | Where do the remaining cases occur?
60-70% are in the lymph nodes. | The rest are in extra-nodal locations
30
What are the 3 ways a NHL can arise?
1. polyclonal lymphoid proliferation with a second mutation allowing for a monoclonal outgrowth (MALT with chronic gastritis) 2. Translocation of an oncogene into an antigen receptor locus (Ig or TCR) to overexpress the oncogene 3. genetic rearrangement to make a novel hybrid protein with uncontrolled cell growth
31
What are the characteristics of an indolent (low grade) lymphoma? 1. cell size 2. rate of proliferation 3. location
1. small lymphoid cells 2. low rate of proliferation 3. disseminated at presentation Basically, because the cells are so small and grow so slowly, it was disseminated before the person even noticed
32
What are the characteristics of aggressive lymphomas? 1. cell size 2. rate of proliferation 3. location
1. larger cells 2. high rate of proliferation (high expression of Ki67) 3. localized at presentation
33
What are the indolent forms of B-NHL? (7)
1. Follicular lymphoma 2. B-cell small lymphocytic leukemia CLL/SLL 3. Mantle cell lymphoma 4. MALT lymphoma (mucosa-associated lymphoma tissue) 5. splenic marginal zone lymphoma 6. nodal marginal zone lymphoma 7. lymphoplasmacytic lymphoma
34
What are the aggressive forms of B-NHL?
1. Diffuse large B-cell lymphoma (DLBCL) | 2. Burkitt lymphoma
35
What are T cell NHL known as? Are they indolent or aggressive?
Peripheral T-cell lymphoma (PTCL) and are usually aggressive
36
Is follicular lymphoma indolent or aggressive? What is the mean age of presentation? Is it curable? What is the survival time?
Indolent 60 years Incurable 8-10 years
37
How do patients present with follicular lymphoma? Clinical staging can show involvement of what 3 organs?
Progressive, painless lymphadenopathy Only 20% have B symptoms (night sweat, fever, weight loss) Spleen (40%) Liver (50%) Bone Marrow (60%)
38
Follicular lymphoma presents in a similar way to reactive lymphoid hyperplasia. How can you identify it as a neoplasm and not an inflammatory hyperplasia?
Hyperplasia would be polyclonal expansion and follicular lymphoma would be monoclonal. Tough to diagnose except if you do cytogenetic analysis and see t(14,18) involving BCL-2 and IGH.
39
What cells are in the follicle of a follicular lymphoma?
1. centrocytes- cells with nuclear grooves | 2. centroblasts- round cells
40
How are follicular lymphomas graded?
on a scale of 1-3 based on the number of large centroblasts present (higher blasts=higher grade)
41
What is the translocation associated with follicular lymphoma?
t(14,18) where BCL2 is placed next to the IGH on chromosome 14 which inhibits apoptosis
42
What is the mechanism for why there are more follicles and more packed follicles in follicular lymphoma?
BCL2 is placed next to IGH (t14,18). The overproduction of BCL2 inhibits apoptosis so the cells pack the follicles
43
What are the common sites for extranodal marginal zone B-cell lymphomas of mucousal-associated lymphoid tissue (MALT)?
stomach, thyroid, lungs,orbits, salivary glands, skin
44
Are MALT lymphomas indolent or aggressive? Who are they seen in? Are they curable or incurable?
Indolent (but typically remain localized) mean age of 60 These lymphomas are the exception to "indolent=incurable" They ARE curable with local therapy, radiation/excision and for H. pylori-->antibiotics
45
What 4 conditions were noted to be associated with MALT lymphomas?
conditions with chronic immune stimulation like: 1. Helicobacter pylori gastritis in stomach 2. Sjogren's syndrome sialadenitis (salivary) 3. Hashimotos thyroiditis 4. Borrelia burdorferi in the skin
46
Do follicular lymphomas express CD10 or CD5 or both or neither?
CD10
47
Do MALT lymphomas express CD10 or CD5 or both or neither?
neither
48
What are the 3 translocations and genes associated with MALT lymphomas?
1. t(11,18) with AP12 and MALT1 2. t(14,18) with IGH and MALT 1 3. t (1,14) with BCL10 and IGH
49
Are DLBCL aggressive or indolent? Who does it affect? Is it curable?
It is aggressive composed of large lymphoid cells arranged in diffuse architecture It affects median age of 60 but can occur in any age group. If untreated it is rapidly fatal, but with anthracycline-containing chemo plus rituxamib can cure 50%
50
What is the most common NHL in the US?
Diffuse large B-cell lymphoma (DLBCL)
51
How do patients present with DLBCL?
with a rapidly growing mass that may involve lymph node or extranodal tissue
52
Do DLBCL present with CD10, CD5, neither? | What other antigen is present in 20-100% of cases?
CD10 is in 25-50% of cases | Ki67 are seen in the rapidly proliferating cells
53
What 2 genetic abnormalities are associated with DLBCL?
1. t (14.18) same as follicular | 2. 3q27 abnormality of BCL-6
54
What are the three clinical variants of Burkitt lymphoma? Which age group does each infect? Which are associated with EBV?
1. Endemic- equatorial Africa, children, EBV 2. Sporadic- children/YA 3. Immunodeficiency-related- HIV, young age, CD4>200, half EBV
55
Is Burkitt lymphoma aggressive or indolent? | Is it curable?
VERY aggressive, but complete remission is possible with intense chemo
56
What is seen on microscopic examination of Burkitt's lymphoma?
"Starry-sky" appearance where the sheets of blue are the lymphoma cells and the "stars" are histiocytes with abundant cytoplasm that are clearing apoptotic debris.
57
Describe the lymphoma cells of Burkitts.
uniform, medium size with round nuclei, serveral peripheral small nucleoli, deeply basophilic cytoplasm with lipid-containing vacuoles. Multiple mitotic figures.
58
Do Burkitt lymphoma cells express CD10 CD5 or neither? | What other antigen do they have nearly 100% positive staining for?
CD10. | 100% for Ki67
59
What is the translocation associated with Burkitt's lymphoma?
1. t (8,14) where c-MYC is placed next to IGH | 2. t (8.22) or t(2,8) where c-MYC is placed next to light chains
60
What are the four subcategories of classic Hodgkin's lymphoma?
1. nodular sclerosis 2. mixed cellularity 3. lymphocyte-rich 4. lymphocyte-depleted
61
What is the age distribution of Hodgkin's lymphoma? What do patients present with? Is it curable?
Two peaks: 1. 15-35 2. 50 Lymphoma arises in the lymph nodes of the cervical region or mediastinum. Half present with B-symptoms. It disseminates in a contiguous manner to adjacent lymph node groups or lymphoid structures and can be aggressive and cause death but is cured 90% of the time
62
How are therapeutic regimens determined for classic Hodgkin's lymphoma?
1. Ann Arbor Staging Classification | 2. presence or absence of B-symptoms
63
What is the age distribution of nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL)? Is it indolent or aggressive?
unimodal with a peak between 30 and 50 (though it can be seen in children) It is indolent and rarely fatal although it can progress to high-grade cancer in 2% of patients Treat with excision, radiation and rituxamib
64
What structures are involved in NLPHL?
a single lymph node in cervical, axillary or inguinal regions. NO mediastinal involvement and RARE B-symptoms
65
What causes tissue enlargement in Hodgkin's lymphoma?
Reed-Sternberg cells release cytokines that bring in infiltration of benign, reactive inflammatory cells. The lymphoma cells are in small number.
66
What are the 3 types of lymphoma cells associated with Hodgkin's lymphoma? What are the reactive cells they bring in?
1. RS cells- bilobed nuclei 2. popcorn cells -bizarre nuclei 3. Hodgkins cells- monolobated nuclei B, T, plasma, eosinophils, neutrophils, histiocytes
67
The immunophenotype of the neoplastic cells in NLPHL clearly indicate _________ lineage. Classic Hodgkin's lymphoma is of _________ immunophenotype.
NLPHL= B cell lineage CHL = undetermined lineage (99% are B)
68
What is the immunophenotype of NLPHL?
``` 45 + 30 - 15 - 20 + 3 - ```
69
What is the immunophenotype of CHL?
``` 45 - 30 + 15 + 20 - 3 - ```
70
What are pure leukemias?
Disease state when blood and bone marrow are the primary sites of involvement
71
What are the B-cell "pure" leukemias?
1. B-cell chronic lymphocytic leukemia (CLL) 2. B-cell prolymphocytic leukemia 3. Hairy cell leukemia
72
What are the T/NK "pure" leukemias?
1. large granular lymphocytic leukemia 2. Adult T cell leukemia 3. T-cell prolymphocytic leukemia 4. Aggressive NK cell leukemia
73
What is "sezary syndrome"?
leukemic phase of peripheral T cell lymphoma (PTCL) known as mycoses fungiodes with diffuse dermal erythema and diffuse lymphadenopathy
74
What is the most common form of leukemia in the US? | What age does it normally affect?
Chronic lymphocytic leukemia/ small lymphocytic leukemia (CLL/SLL) Affects people over 40 and incidence increases with age
75
How do patients present with CLL/SLL?
Asymptomatic or if they are symptomatic they have; fatigue due to anemia bleeding due to thrombocytopenia swollen glands due to lymphadenopathy
76
Is CLL/SLL indolent or aggressive? | Is it curable or incurable?
It is indolent and is incurable but the course of disease is over 15 years
77
What is it called if CLL/SLL progresses to a higher grade leukemia/lymphoma?
Richter's syndrome- large cell lymphoma
78
What is the highest risk category for CLL/SLL?
lymphocytosis and thrombocytopenia is stage IV
79
CLL/SLL cells come from what lineage? | Do they express CD10, CD5 or neither?
They are B-cell lineage but express the T cell marker CD5
80
What two B cell lymphomas/leukemia express CD5 (a T cell antigen)?
1. CLL/SLL | 2. Mantle cell lymphoma
81
Plasma cell tumors will show a __________ because they are monoclonal and only make one Ig.
M-spike

Fundamentals 3- Heme (19 decks)

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