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Strom - Hematology > 3.25.14* Benign/Reactive Lymphadenopathies and Hematologic Malignancies III > Flashcards

3.25.14* Benign/Reactive Lymphadenopathies and Hematologic Malignancies III Flashcards

PPT 1* Lecture Notes 1* PPT 2* Lecture Notes 2* Pictures (go back and double check last few slides)

1
Q

anti-apoptotic signaling protein used by B cells?

A

BCL-2

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2
Q

T cell differentiation occurs in what region of the lymph nodes?

A

paracortex

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3
Q

B cell differentiation happens in what zone of the lymph nodes?

A

within follicles of the cortex (aka germinal centers with surrounding mantle zone)

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4
Q

What immunophenotypes are observed in lymph node biopsies to determine B cell and T cell zones?

A

B cells/ germinal centers: CD20 and CD10

T cells/ paracortex: CD5 or CD3

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5
Q

key clinical finding in reactive lymph nodes?

A

tender and mobile on palpation. Nodes involved by a malignancy are usually nontender and immobile.

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6
Q

Reactive follicular hyperplasia is associated with

A

bacterial infection (B cell proliferation)

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7
Q

Cause of paracortical expansion of lymph node?

A

infectious mononucleosis (viral infection) causing increased T cells and APCs in lymph node -> polymorphic cell population

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8
Q

What is seen in the PBS in patient with infectious mononucleosis?

A

huge reactive mononuclear cells that are actually activated T cells. These are polymorphic.

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9
Q

What is lupus lymphadenitis?

A

necrosis of the lymph node

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10
Q

What is seen in dermatopathic lymphadenopathy?

A

large pale areas in biopsy that are aggregates of histiocytes (tissue-based macrophages) in lymph nodes adjacent to skin lesions in patients with chronic skin diseases (eczema, psoriasis, pemphigus). Dark pigment in histocytes is melanin. This is due to lots of dead skin cells draining to lymph nodes, melanin accumulates in the histiocyte.

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11
Q

HIV lymphadenopathy appearance?

A

Germinal centers cannot form without CD4 cells. There are mantle zones without germinal centers, but sometimes with histiocytes in the center (which may can activate B cells.)

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12
Q

Immunophenotypes of B cell precursors within the bone marrow

A

TdT
CD10
(CD19 and CD20 late stage)

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13
Q

Immunophenotypes of B cells after class switching (plasma cells)

A

CD38
CD138
(CD20-)

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14
Q

Immunophenotypes of naive B cells within lymph nodes?

A

CD20

CD19

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15
Q

Immunophenotype of B cell undergoing follicular maturation (activated B cell)

A

CD10

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16
Q

Immunophenotypes of B cells (early to late expression)

A 
Bone marrow
a. TdT 
b. CD10
Naive (mantle and germinal)
a. CD20
b. CD19
Germinal center (activated)
a. CD10
Perifollicular area (mature plasma cell)
a. CD38
b. CD138
(CD20-)
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17
Q

What are the Ig promotors common in B cell malignancies?

A

IgH
Ig lamda
Ig kappa

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18
Q

Follicular lymphomas/ CLL involve what sites

A

peripheral blood
bone marrow
lymph nodes

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19
Q

Burkitt lymphoma involves what sites

A

bone marrow
lymph nodes
GI tract

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20
Q

What type of B cells mutate in CLL?

A

memory B cells, often found just outside the mantle zone in the lymph node.

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21
Q

Chronic Lymphocytic leukemia/lymphoma

CLL/SLL

A

a. clinical presentation: high familial incidence.
b. morphology: arise from memory B cells, Small lymphocytes with very little cytoplasm (smudge cells). Increasing presentation of immature lymphocytes

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22
Q

PBS of CLL

A

lymphocytes are small with scant cytoplasm and mature (dense) chromatin (smudge cells)

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23
Q

lymph node appearance in CLL

A

pseudofollicular appearance (larger follicular regions that are undergoing DNA synthesis and mitosis)

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24
Q

Genes involved in CLL/SLL

A

del(13q)
trisomy 12
del (17p) p53, bad prognosis

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25
Immunophenotype of CLL
``` CD 5 CD23 Light chain restricted (kappa or lambda) Zap70 (bad) CD38 (bad) CD20 (weak) ```
26
What are markers of somatic hypermutation status in CLL?
ZAP-70 | CD38
27
Mantle Cell Lymphoma (MCL)
a. clinical presentation- lymphadenopathy b. derived from mantle cell c. involved sites- lymph nodes, bone marrow, spleen, PB, GI d. morphology: smudge cells, lymphocytosis
28
What cells is mantel cell lymphoma derived from
mantle cells
29
What are the involved sites in MCL
Lymph nodes > bone marrow, spleen, peripheral blood, | GI tract
30
What is seen in the PBS of MCL
smudge cells, lymphocytosis
31
What is the appearance of the lymph nodes in MCL
Homogeneous effacement (*no germinal centers)
32
What is the immunophenotype of MCL
CD5 CD20 light chain restricted CD23-
33
what is the distinguishing immunophenotype between CLL and MCL?
strong CD20 | no CD23
34
genetic seen in all MCL (mantel cell lymphoma)
t(11,14) IgH;Cycin D Overexpression of cyclin D moves cell through G1-S checkpoint
35
What is the purpose of a Ki-67 immunostain?
reveals mitotic rate of cell population. Prognostic marker for mantle cell because most are rapidly replicating.
36
t(11,14)
IgH; Cyclin D1 | Seen in all cases of MCL (mantle cell lymphoma)
37
Plasma cell neoplasms
a. clinical presentation- older individuals. b. involved sites- bone marrow > peripheral blood c. immunophenotype: CD38+, CD138+
38
Mild plasma cell neoplasms
a. MGUS (monoclonal gammaopathy of uncertain significance) | b. increased total protein. Rouleaux noted on peripheral smear.
39
Severe plasma cell neoplasms
multiple lytic bone lesions (plasma cell myeloma), pain, fractures, renal failure
40
sites involved in plasma cell neoplasms
bone marrow >> peripheral blood
41
Lab findings in plasma cell neoplasms
increased total protein; Rouleaux noted on peripheral smear
42
Rouleaux
little "stacks" of red cells seen in PBS
43
test for increased serum protein
a. serum protein electrophoresis is standard | b. immunofixation elecrophoresis for abnormal protein species
44
Morphology seen in bone marrow biopsy of plasma cell neoplasm
plasma cells with eccentric nuclei with clumpy chromatin. Large collections tend to erode bone.
45
immunophenotype of plasma cell neoplasms
``` CD38+++ CD138+++ CD19- CD20- light chain restricted ```
46
plasma cell neoplasms progress to
multiple myeloma. survival 3-4 yrs
47
key negative clinical predictors for plasma cell neoplasms
del 17p (p53 region) Analyzed by FISH regions, which indicates more aggressive neoplasm (others: Serum beta 2 microglobulin t(4;14) FGFR3 t(14;16) C-MAF t(14;20) MAFB)
48
Follicular lymphoma pathogenesis
Failure of germinal center B-cells to apoptose (because they overexpress an anti-apoptotic protein, Bcl-2).
49
What is seen in follicular lymphoma
a. enlarged lymph node follicles (due to follicle proliferation by overexpressed Bcl-2). Follicles are normally degraded by macrophages, no macrophage digestion in follicular lymphoma. b. less mitotic figures (due to prevention of cell death rather than hyperproliferation)
50
Follicular lymphoma
a. clinical presentation: lymphadenopathy b. involvement: lymph nodes, bone marrow 40-70%, can have peripheral blood c. immunophenotype: CD19+, CD20+, BCL-2, BCL-6, CD10
51
Immunophenotype of follicular lymphoma
CD19+, CD20+. CD10+ (60%). BCL-2+ (90%). BCL-6+ (85%)
52
Follicular lymphoma can progress to
diffuse large B-cell lymphoma
53
Genetics of follicular lymphoma
t(14,18) in >85% | Ig promoter infront of Bcl-2 gene
54
t(14,18)
follicular b cell lymphoma | 20-30% of diffuse large B cell lymphomas
55
How is follicular lymphoma graded?
by increasing presence of centroblasts 1-3. Centroblasts are larger cells
56
Diffuse large B-cell lymphoma
a. clinical presentation- rapid adenopathy, elderly, 40% extranodal (GI, bone marrow) b. immunophenotype: CD19, CD20, CD10 (30-60%)
57
genetics of diffuse large B cell lymphoma
t(v, 3q27)(v, BCL-6) in 30% | t(14,18) BCL-2 in 30%
58
Immunophenotype of diffuse large B cell lymphoma
CD19 CD20 CD10 (30-60%)
59
Hodgkin lymphoma
a. clinical presentation- males 30-50, less common in children. localized or diffuse adenopathy b. involvment of lymph nodes and spleen c. morphology: reed-sternberg cells d. origin cell:
60
Morphology of Hodgkin lymphoma
a. reed/sternberg cells: large lymphoid cells with mono or bi-nucleate appearance, huge eosinophilic nucleoli, overall horseshoe shape b. diverse background cells: small lymphocytes, plasma cells, eosinophils, neutrophils, histiocytes c. collagenous bands in lymph nodes d. prognosis- curable with chemo, 10 year 97%
61
Nodular Lymphocyte Predominant Hodgkin lymphoma morphology
a. smaller reed-sternberg cells with less prominent nucleoli | b. nodular appearance
62
Reed/Sternberg cell
a. contain re-arranged Ig (V) genes with constituitive NFkB expression (anti-apoptotic) b. may have anti-apoptotic genes from EBV c. NO IG expression on surface d. survive germinal center; clonal proliferation after move into B cell follicle CD30 expression
63
Lymph node morphology of classical Hodgkin lymphoma
a. mostly lymphocytes b. large number of R/S cells c. fibrous bands (but very variable)
64
Immunophenotype of R/S cells
CD30 | others: CD15 Pax5 (weak CD20)
65
What is the main difference between HL and NLPHL S/L cells.
NLPHD do express Ig
66
Nodular lymphocyte predominant hodgkin lymphoma lympho node morphology
popcorn cells (lympho-histiocyte, L&H cells)
67
Immunophenotype of NLPHL
``` CD20+ CD15- Pax5+ (B cell transcription factor) CD30- * T cells surrounded the R/S cells ```
68
Nodular Lymphocyte Predominant Hodgkin lymphoma prognosis
80% 10 year survival | 3-5% progress to diffuse large B-cell lymphoma
69
trend of severity with B cell malignancies
the less differentiated are more severe, in T cells there is no correlation
70
immunophenotype of T cells in the bone marrow/thymus
TdT CD7 CD3 (CD4 and CD8)
71
naive and effector T cell immunophenotype
NK: CD3 cytoplasmic γδ: CD3+, surface CD4 or CD8
72
What lab method is used to demonstrate clonality in T cell lymphoma/leukemia
PCR of the T cell receptor gene
73
Angioimmunoblastic T-cell lymphoma
b. origin cell- follicular T-helper cells c. involved sites- lymph nodes, spleen/liver, bone marrow, skin d. immunophenotype: excess CD10 cells in paracortex e. medial survival less than 3 years
74
Lymph node morphology of AITL (angioimmunoblastic T-cell lymphoma)
increase of cells in the paracortex. Some are immunoblasts (large nuclei with prominent nucleoli. More eosinophilia due to thickening of paracortical vessels.
75
Angioimmunoblastic T-cell lymphoma
CD10+ (excess in paracortex**) CD4 CD10 CD21 (FDC marker showing ghosts of germinal centers)
76
Peripheral T-cell lymphoma NOS
a. (30% of TCLs) b. clinical presentation- diffuse lymphadenopathy. B symptoms (fever, night sweats, weight loss), paraneoplastic features (esosinophilia, pruitis, hemolytic anemia, esoinophilia) c. origin cell- unclear d. involved sites- anywhere except blood e. immunophenotype: CD3, 5, 7, and 4 OR 8 f. aggressive 5 year survival (20-30%)
77
Peripheral T-cell lymphoma NOS lymph node morphology
a. expanded paracortex b. distinct subset of uniform cells c. clusters of "epitheliod histiocytes" with abundant eosinophilic cytoplasm usually in paracortex near the capsule of the node.
78
immunophenotype of Peripheral T-cell lymphoma NOS
CD3 ,5, 7 and 4 or 8 | sometimes both cd4 and 8
79
CD20
b cell marker
80
CD56
macrophage/monocyte marker
81
CD30
R/S marker
82
Virus infections usually cause ________ hyperplasia and bacterial infections usually cause _____________ hyperplasia within the lymph node/
paracortical, follicular
83
What is not a feature of a reactive lymph node a. many germinal centers b. effacement of normal architecture c. paracortical expansion d. necrosis e. tingible body macrophages
necrosis and effacement of the normal architecture
84
What features would favor diagnosis of mantle cell lymphoma instead of CLL/SLL?
expression of cyclin D1 under control of IgH promoter.
85
What is seen in the patient with serum protein electrophoresis and immmunofixation electrophoresis in the slide set?
A monoclonal immunoglobulinn: IgG, kappa (light chain restricted).
86
what is the appearance of reactive vs. neoplastic germinal centers?
reactive- variable sizes neoplastic- all the same (not really but this is how it will look on the test)
87
immunostain for follicular lymphoma looks for
BCL-2 expression
88
What are the malignant cells in Hodgkin lymphoma?
Reed/Sternberg cell
89
big cells that don't express CD30 but do express CD20?
NLPHL, popcorn cells
90
Burkitt lymphoma (sporadic)
a. children or young adults, higher in HIV+ b. normal cell: Memory B-cells c. involved sites: ileo-cecal area/ovaries/kidneys d. morophology: medium sized cells with basophilic, vacuolated cytoplasm. Homogeneous lymph node/ e. immunophenotypes: typical B cell markers (CD10 CD19, CD20) f. genetics: promoter (igH, kappa, lambda) infront of MYC (chromosome 8) oncogene
91
Cytologic appearance of burkitt lymphoma
medium sized cells with basophilic, vacuolated cytoplasm
92
Burkitt lymphoma (endemic)
a. jaw/facial bone mass in childs (4-7) in malaria endemic area b. most are EBV positive (otherwise same as sporadic burkitt)
93
Mycosis fungoides
a. clinical presentation: patch flat red skin lesions that can progress to thick, psoriasis-like or ulcerated lesions; can involve bloodstream (Sezary Syndrome), usually in elderly b. normal cell: CD4 c. cytology: normal lymphocyte with indented nuclei. In PBS there are bland lymphocytes with cerebriform nuclei.
94
Morphology seen in mycosis fungoides
brain lymphocytes, lymphocytes invade epidermis

Strom - Hematology (6 decks)

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