B-Cell Neoplasms: Non-Hodgkin Lymphomas & Leukemias Flashcards

1
Q

What are the precursor lymphoid neoplasms ?

A

ALL / LBL
B, T & NK cell precursors

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2
Q

What are the CD markers seen in pro B cells? Are they antigen dependent or independent? Where is the location of their differentiation?

A

CD34
TDT
CD10
CD19

antigen independent
bone marrow

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3
Q

What are the CD markers seen in Germinal center B cells?
Are they antigen dependent or independent?
Where is the location of their differentiation?

A

CD10
Antigen dependent
peripheral lymphoid tissue

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4
Q

What is the first cell to express the CD20 marker?
Are they antigen dependent or independent?
Where is the location of their differentiation?

A

some immature B cells, all mature naive B cells
antigen independent
immature (bone marrow)
mature naive (peripheral lymphoid tissue)

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5
Q

What are the CD markers seen in cytoplasmic & secreted immunoglobulins?
Are they antigen dependent or independent?
Where is the location of their differentiation?

A

CD38
antigen dependent
peripheral lymphoid tissue

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6
Q

What is the difference in presumption between monoclonal populations & polyclonal populations?

A

Monoclonal populations → neoplastic

Polyclonal → non-neoplastic

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7
Q

Mature B-cell non-hodgkin lymphomas usually affect what populations?

Origination?

Spread?

A

middle aged & older adults

usually originate lymph nodes (maybe extranodal in chronic inflammatory process)

spread is usually to non-contiguous lymph nodes & tissues

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8
Q

Is staging more important for guiding therapy of hodgkin lymphoma or non-hodgkin?

A

Hodgkin

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9
Q

Many low-grade B-cell lymphomas may produce small amounts of what substance, similar to plasma cell neoplasms?

A

monoclonal immunoglobulin

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10
Q

What is the definition of Chronic Lymphocytic Leukemia?

A

sustained monoclonal B-cell lymphocytosis of >5x103 / microliter with the following immunophenotype:

  • weak monotypic surface immunoglobulin (only one type Ig)
  • Weak expression B-markers (CD19, CD20, CD22); moderate expression CD23
  • Co-expression CD5
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11
Q

What is the mechanism of cell accumulation in CLL/SLL?

A

low proliferation but prolonged survival

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12
Q

What is the most common leukemia in adults in Western countries?

A

CLL/SLL

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13
Q

What mutations are associated with CLL/SLL?

A

BCL-2 is upregulated - not specific to CLL/SLL

increased expression of anti-apoptotic proteins, which is the key oncogenic factor

Defects in B-cell receptor + chronic antigenic stimulation (infection?)

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14
Q

CLL/SLL is associated with what risk factors?

A

chemicals or radiation

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15
Q

What are the sites involved in CLL/SLL?

A

peripheral blood & bone marrow (CLL)

if bone marrow is NOT involved it is called SLL

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16
Q

What is the clinical picture of a patient with CLL/SLL?

A

>80% are asymptomatic at diagnosis

fatigue, cytopenia, infections, other neoplasms, lymphadenompathy & splenomegaly

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17
Q

What are the laboratory findings that are indicative of CLL/SLL?

A
  • absolute lymphocytosis
  • small amounts monoclonal immunoglobulin
  • peripheral blood cytopenias
    • anemia, neutropenia, thromboytopenia
  • increased LDH
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18
Q

What specific peripheral blood cell findings would you expect to see in a patient with CLL/SLL?

A

small, round, mature lymphocytes with coarse “soccer ball” appearance of nuclear chromatin + scant cytoplasm & smudge cells (disrupted remnant lymphocyte nuclei)

autoimmune hemolytic anemia, spherocytes, polychomasia & nucleated RBC

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19
Q

What condition is shown in the provided blood smear?

A

CLL/SLL

“soccer ball” & “smudge cell”

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20
Q

What condition is seen in the provided image?

A

CLL/SLL lymph node

lymph nodes are diffusely replaced by small, monotonous lymphocytes with “proliferation centers” (increased prolymphocytes & are paler than surrounding small lymphocytes)

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21
Q

What is the prognosis of CLL/SLL?

A

⅓ never need treatment

⅓ will eventually need therapy

⅓ will immediately need therapy

indolent - noncurable

  • prognosis related to:
    • staging
    • molecular/cytogenic features
    • performance status/age
    • presence/absence Richter transformation
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22
Q

What condition is seen in the provided images of bone marrow?

A

CLL/SLL

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23
Q

What type of CLL/SLL transformation is seen in the provided image?

Prognosis?

A

Prolymphocytic transformation

increased # prolymphocytes (larger than small lymphocytes & central nucleolus)

death in 2 yrs

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24
Q

What type of CLL/SLL transformation is seen in the provided image?

Prognosis?

A

Richter Transformation

transformation to diffuse large cell lymphoma with retention of CLL/SLL immunophenotype

usually extramedullary

Death usually within less than 1 yr

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25
What is the most common type of non-Hodgkins lymphoma in the US?
Diffuse large B-cell lymphoma
26
What is Diffuse Large B-Cell Lymphoma (DLBCL)?
lymphoma with a diffuse growth pattern large B-cells- larger than the nucleus of the histiocyte (arrow); ~3x size of small mature lymphocyte
27
DLBCL cells usually express what markers?
pan-B cell markers CD19, CD20, CD22, CD79a
28
What are the risk factors associated with DLBCI?
* **Infection** * H. pylori * HIV * EBV & HHV-8 * **Immunodeficiency** * **Autoimmune disease** (esp B activating ones) * **Transformation** low grade B-cell lymphoma
29
What demographics are most commonly affected by DLBCL? Treatment? Sites involved?
late middle age/older adults (can occur in children/adolescents) aggressive- requires chemotherapy lymph nodes (may involved extranodal sites)
30
What is the clinical presentation of a patient with DLBCL?
* rapidly enlarging nodal / extranodal masses * systemic B-symptoms (weight los, fever, night sweats) * bone marrow involvement * usually present late stage
31
What condition is seen on this gross picture of the spleen?
tan/white “fish-flesh” appearance most common lymphoma in the spleen
32
What is the prognosis of de novo DLBCL vs those arising from Richter transformation?
* De novo * potentially curable w/ R-CHOP * Richer transformation * aggressive & resistant to therapy * poor prognois
33
What is a follicular lymphoma? It is associated with what mutation?
lymphoma comprised of malignant germinal center B-cells translocations involving BCL2 (not specific)
34
What is the most common indolent non-Hodgkin lymphoma?
Follicular lymphoma It the _second_ most common non-Hodgkin lymphoma in US
35
What genetic mutation is seen in 90% of follicular lymphomas? This has what metabolic effect?
**t(14;18)** **BCL2** on chromosome 18 is juxtaposed with IGH on derivative chromosome 14 overexpression of **anti-apoptotic** protein Bcl-2 → survival neoplastic cells \*Other molecular changes are necessary for the development of FL
36
You can use a BCL-2 stain for what differentiation?
reactive follicles (-) low-grade B-cell lymphoma (+) does NOT differentiate one lymphoma from another
37
What complication can arise from follicular lymphoma?
can transform to more aggressive lymphoma (DLBCL)
38
What sites are commonly involved with FL?
lymph node, liver, spleen, bone marrow, peripheral blood - usually widespread late in disease (surprisingly asymptomatic)
39
What condition is seen in the provided images?
follicular lymphoma left: spleen w/ small nodules right: lymph node “fish flesh”, nodular
40
The provided histological samples are from what condtion?
Follicular Lymphoma * partial / complete effacement lymph node or other tissue with closely packed neoplastic nodules (loss of medulla) * variable mixture small, cleaved lymphocytes (centrocytes) & larger cells (centroblasts) * more centroblasts = higher grade
41
What would you expect to seen in the peripheral blood of a patient with follicular lymphoma?
lymphocytes with indented nuclei “buttock cells”
42
What special cells are shown in the provided image? They are characteristic of what pathology?
buttock cells (indented nuclei) follicular lymphoma
43
What is the prognosis of high grade & low grade follicular lymphoma?
* Low grade * indolent but incurable * high grade * more aggressive but potentially curable
44
What is lymphoplasmacytic lymphoma?
rare neoplasm of small B-lymphocytes, plasmacytoid lymphocytes, & plasma cells
45
What specific immunophenotypic/genetic abnormalities are associated with lymphopasmacytic lymphoma (LPL)?
none diagnosis may be difficult
46
What is the clinical picture of a patient with LPL?
* middle-age to elderly * **IgM monoclonal protein** * weakness, fatigue, anemia * **hyperviscosity syndrome** * bleeding, headache, vision changes * **cryoglobinemia** (results in raynauds) * **cold agglutinin** hemolytic anemia * antibody deposition * diarrhea, neuropathy, coagulopathy * **NO lytic bony lesions** * **NO renal failure**
47
What sites are commonly involved in LPL?
bone marrow may involve blood, lymph nodes, & spleen occasionally extranodal
48
What would you expect to see in a bone marrow aspirate from a patient with LPL?
infiltration by hetergeneous mixture of small & plasmacytoid lymphocytes and plasma cells mast cells increased (tissue version of a basophil)
49
What is the prognosis of LPL?
incurable, indolent survival 5 - 8 yrs
50
What is MALT lymphoma?
low-grade B-cell lymphomas arising at extranodal sites
51
What is the clinical picture of a patient with MALT-lymphoma?
* 60s * indolent course * symptoms related to organ involvement * GI most common * lymphoepithelial lesions are common in affected tissue * associated with infections & autoimmune * bone marrow involvement is _unusual_
52
MALT-lymphoma arises in what conditions?
chronic inflammatory states * Infectious agent: *Helicobacter pylori* * Autoimmune disease * Sjogren syndrome * Hashimoto thyroiditis
53
What is the most common site for MALT-lymphoma?
GI tract
54
What would you expect to seen in a microscopic sample of MALT-lymphoma?
heterogeneous mixture small, monoclonal B-cells with plasmacytoid lymphocytes and plasma cells diffuse or nodular growth pattern mast cells are NOT increased
55
The provided histological slides are characteristic of what condition?
**MALT-lymphoma** heterogeneous mixture small, monoclonal B-cells with plasmacytoid lymphocytes and plasma cells diffuse or nodular growth pattern mast cells are _NOT_ increased
56
What is the prognosis of MALT-lymphoma?
* GI MALT-lymphoma may regress after treatment H. pylori (good prognosis) * other sites have worse prognosis * may transform to DLBCL (any sites)
57
What is Mantle Cell lymphoma?
aggressive mature B-cell lymphoma of monomorphic small lymphocytes
58
What genetic/cytologic markers are indicative of Mantle Cell Lymphoma?
**strong** expression pan-B cell markers (**CD19, CD20**, etc) also expressing **CD5** express **cyclin D1**
59
How can you differentiate CLL from MCL using cytogenic markers?
both express CD5 CLL = _weak_ expression pan-B cell markers MCL = _STRONG_ expression pan-B cell markers
60
How can you differentiate MCL from other types of lymphomas?
MCL cells express cyclin D1
61
MCL is associated with what genetic mutation?
**t(11;14)** juxtaposes **CCND1** on chromosome 11 with **IGH** on chromosome 14 results in **overexpression of cyclin-D1**
62
What are the common sites of involvement in Mantle Cell Lymphoma?
**lymph node** most common GI, spleen, bone marrow are common maybe blood involvement
63
What demographics are most commonly affected by MCL?
middle-age to older adults male predominance
64
What is the prognosis of MCL?
most patients present in late stage **incurable** (3-5 yrs is medial survival)
65
What condition is depicted in the following two histological slides? (left = peripheral blood smear & right = tissue)
* Peripheral blood * similar to CLL * Tissue * diffuse or nodular proliferation of **monomorphic small lymphocytes**, _without_ proliferation centers or centroblasts (pale centers) * **No plasmacytoid lymphocytes or plasma cells**
66
What transformations are possible with MCL?
may transform into aggressive **blastoid variant** _DOES NOT_ transform to diffuse large B-cell lymphoma (DLBCL)
67
What is Burkitt Lymphoma?
aggressive B-cell one of most rapidly-growing tumors known
68
What are the most common sites of involvement for Burkitt Lymphoma?
typically extranodal sites rather than lymph nodes all types are increased risk CNS involvement
69
What are the 3 clinical variants of Burkitt Lymphoma?
Endemic BL Sporadic BL Immunodeficiency-associated BL
70
What sites are most commonly involved with Endemic BL? Most commonly affects individuals of what age? It is associated with what virus?
jaw, facial bones, gonads, viscera, GI children (in equatorial Africa) almost all are EBV positive
71
What condition is shown in the provided histologic slides?
Blastoid Mantle Cell Lymphoma
72
Briefly describe the proposed pathogenesis associated with Endemic BL
falciparum malaria induced B-cell expansion & reactivation EBV malaria causes a decrease EBV-specific T-cells → loss of control of proliferation EBV-infected B-cells → may increase change of MYC translocation
73
What demographics are most commonly affected by Sporadic BL? Sites of involvement?
children/young adults (worldwide) abdomen (esp GI), gonads, kidney & breast _RARELY_ jaw
74
What demographics are most commonly affected by Immunodeficiency-associated BL? Sites of involvement? Associated virus?
adults (HIV/AIDS), post transplant lymphoproliferative disorders & drugs used to treat autoimmune disorders lymph node & bone marrow variable EBV involvement
75
What genetic mutations are seen in BL?
**translocations involving MYC** protooncogene **t(8;14)** translocations juxtapose intact MYC gene with enhancer element of IGH genes → upregulation of MYC → proliferation, transcription and apoptosis not SPECIFIC to BL
76
What type of tumor is shown in the provided slides?
Burkitt Lymphoma * “starry sky” due to **diffuse infiltrate** (not just follicle) of blast-like cells w/ non-neoplastic tingible-body macrophages * malignant lymphocytes are * medium-sized, * deeply basophilic cytoplasm, cytoplasmic lipid vacuoles (may overlie nucleus) * round nuclei - dispersed chromatin & multiple nucleoli * numerous mitotic figures (proliferation rate is 100% by Ki-67 stain)
77
What Burkitt Lymphoma variant is seen in the provided image? What cytogenic markers would you expect to see from this sample?
leukemic involvement * malignant lymphocytes are * medium-sized, * deeply basophilic cytoplasm, cytoplasmic lipid vacuoles (may overlie nucleus) * round nuclei - dispersed chromatin & multiple nucleoli * numerous mitotic figures (proliferation rate is 100% by Ki-67 stain) in spite of blast-like appearance, cells are NOT blasts - express more mature B-cell markers (CD19, CD20, CD10, BCL6, CD38 & surface Ig) Negative for lymphoblast markers (**TdT & CD34)**
78
What is the prognosis of Burkitt Lymphoma?
highly aggressive - but potentially curable because very chemosensitive
79
What morphological features can help you differentiate Follicular Lymphoma from a Reactive Lymphoid follicles?
Reactive Lymphoid follicles are usually more variable in size and shape & will maintain the mantle zone around them ("dark blue cap" around germinal center)
80
What immunophenotype markers are seen in Burkitt Lymphoma?
_Positive_: CD19, CD20, CD10, BCL6, CD38 (mature B cell markers) & strong light chain immunoglobulin expression _Negative_: **CD34, TdT**