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S3B5 Pathology > B-Cell Neoplasms: Non-Hodgkin Lymphomas & Leukemias > Flashcards

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
Q

What is the most common type of non-Hodgkins lymphoma in the US?

A

Diffuse large B-cell lymphoma

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26
Q

What is Diffuse Large B-Cell Lymphoma (DLBCL)?

A

lymphoma with a diffuse growth pattern

large B-cells- larger than the nucleus of the histiocyte (arrow); ~3x size of small mature lymphocyte

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27
Q

DLBCL cells usually express what markers?

A

pan-B cell markers

CD19, CD20, CD22, CD79a

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28
Q

What are the risk factors associated with DLBCI?

A
  • Infection
    • H. pylori
    • HIV
    • EBV & HHV-8
  • Immunodeficiency
  • Autoimmune disease (esp B activating ones)
  • Transformation low grade B-cell lymphoma
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29
Q

What demographics are most commonly affected by DLBCL?

Treatment?

Sites involved?

A

late middle age/older adults (can occur in children/adolescents)

aggressive- requires chemotherapy

lymph nodes (may involved extranodal sites)

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30
Q

What is the clinical presentation of a patient with DLBCL?

A
  • rapidly enlarging nodal / extranodal masses
  • systemic B-symptoms (weight los, fever, night sweats)
  • bone marrow involvement
  • usually present late stage
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31
Q

What condition is seen on this gross picture of the spleen?

A

tan/white “fish-flesh” appearance

most common lymphoma in the spleen

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32
Q

What is the prognosis of de novo DLBCL vs those arising from Richter transformation?

A
  • De novo
    • potentially curable w/ R-CHOP
  • Richer transformation
    • aggressive & resistant to therapy
    • poor prognois
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33
Q

What is a follicular lymphoma?

It is associated with what mutation?

A

lymphoma comprised of malignant germinal center B-cells

translocations involving BCL2 (not specific)

34
Q

What is the most common indolent non-Hodgkin lymphoma?

A

Follicular lymphoma

It the second most common non-Hodgkin lymphoma in US

35
Q

What genetic mutation is seen in 90% of follicular lymphomas? This has what metabolic effect?

A

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
Q

You can use a BCL-2 stain for what differentiation?

A

reactive follicles (-)

low-grade B-cell lymphoma (+)

does NOT differentiate one lymphoma from another

37
Q

What complication can arise from follicular lymphoma?

A

can transform to more aggressive lymphoma (DLBCL)

38
Q

What sites are commonly involved with FL?

A

lymph node, liver, spleen, bone marrow, peripheral blood - usually widespread late in disease (surprisingly asymptomatic)

39
Q

What condition is seen in the provided images?

A

follicular lymphoma

left: spleen w/ small nodules
right: lymph node “fish flesh”, nodular

40
Q

The provided histological samples are from what condtion?

A

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
Q

What would you expect to seen in the peripheral blood of a patient with follicular lymphoma?

A

lymphocytes with indented nuclei

“buttock cells”

42
Q

What special cells are shown in the provided image?

They are characteristic of what pathology?

A

buttock cells (indented nuclei)

follicular lymphoma

43
Q

What is the prognosis of high grade & low grade follicular lymphoma?

A
  • Low grade
    • indolent but incurable
  • high grade
    • more aggressive but potentially curable
44
Q

What is lymphoplasmacytic lymphoma?

A

rare neoplasm of small B-lymphocytes, plasmacytoid lymphocytes, & plasma cells

45
Q

What specific immunophenotypic/genetic abnormalities are associated with lymphopasmacytic lymphoma (LPL)?

A

none

diagnosis may be difficult

46
Q

What is the clinical picture of a patient with LPL?

A
  • 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
Q

What sites are commonly involved in LPL?

A

bone marrow

may involve blood, lymph nodes, & spleen

occasionally extranodal

48
Q

What would you expect to see in a bone marrow aspirate from a patient with LPL?

A

infiltration by hetergeneous mixture of small & plasmacytoid lymphocytes and plasma cells

mast cells increased (tissue version of a basophil)

49
Q

What is the prognosis of LPL?

A

incurable, indolent

survival 5 - 8 yrs

50
Q

What is MALT lymphoma?

A

low-grade B-cell lymphomas arising at extranodal sites

51
Q

What is the clinical picture of a patient with MALT-lymphoma?

A
  • 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
Q

MALT-lymphoma arises in what conditions?

A

chronic inflammatory states

  • Infectious agent: Helicobacter pylori
  • Autoimmune disease
    • Sjogren syndrome
    • Hashimoto thyroiditis
53
Q

What is the most common site for MALT-lymphoma?

A

GI tract

54
Q

What would you expect to seen in a microscopic sample of MALT-lymphoma?

A

heterogeneous mixture small, monoclonal B-cells with plasmacytoid lymphocytes and plasma cells

diffuse or nodular growth pattern

mast cells are NOT increased

55
Q

The provided histological slides are characteristic of what condition?

A

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
Q

What is the prognosis of MALT-lymphoma?

A
  • GI MALT-lymphoma may regress after treatment H. pylori (good prognosis)
  • other sites have worse prognosis
  • may transform to DLBCL (any sites)
57
Q

What is Mantle Cell lymphoma?

A

aggressive mature B-cell lymphoma of monomorphic small lymphocytes

58
Q

What genetic/cytologic markers are indicative of Mantle Cell Lymphoma?

A

strong expression pan-B cell markers (CD19, CD20, etc)

also expressing CD5

express cyclin D1

59
Q

How can you differentiate CLL from MCL using cytogenic markers?

A

both express CD5

CLL = weak expression pan-B cell markers

MCL = STRONG expression pan-B cell markers

60
Q

How can you differentiate MCL from other types of lymphomas?

A

MCL cells express cyclin D1

61
Q

MCL is associated with what genetic mutation?

A

t(11;14)

juxtaposes CCND1 on chromosome 11 with IGH on chromosome 14

results in overexpression of cyclin-D1

62
Q

What are the common sites of involvement in Mantle Cell Lymphoma?

A

lymph node most common

GI, spleen, bone marrow are common

maybe blood involvement

63
Q

What demographics are most commonly affected by MCL?

A

middle-age to older adults

male predominance

64
Q

What is the prognosis of MCL?

A

most patients present in late stage

incurable (3-5 yrs is medial survival)

65
Q

What condition is depicted in the following two histological slides? (left = peripheral blood smear & right = tissue)

A
  • 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
Q

What transformations are possible with MCL?

A

may transform into aggressive blastoid variant

DOES NOT transform to diffuse large B-cell lymphoma (DLBCL)

67
Q

What is Burkitt Lymphoma?

A

aggressive B-cell

one of most rapidly-growing tumors known

68
Q

What are the most common sites of involvement for Burkitt Lymphoma?

A

typically extranodal sites rather than lymph nodes

all types are increased risk CNS involvement

69
Q

What are the 3 clinical variants of Burkitt Lymphoma?

A

Endemic BL

Sporadic BL

Immunodeficiency-associated BL

70
Q

What sites are most commonly involved with Endemic BL? Most commonly affects individuals of what age? It is associated with what virus?

A

jaw, facial bones, gonads, viscera, GI

children (in equatorial Africa)

almost all are EBV positive

71
Q

What condition is shown in the provided histologic slides?

A

Blastoid Mantle Cell Lymphoma

72
Q

Briefly describe the proposed pathogenesis associated with Endemic BL

A

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
Q

What demographics are most commonly affected by Sporadic BL? Sites of involvement?

A

children/young adults (worldwide)

abdomen (esp GI), gonads, kidney & breast

RARELY jaw

74
Q

What demographics are most commonly affected by Immunodeficiency-associated BL? Sites of involvement? Associated virus?

A

adults (HIV/AIDS), post transplant lymphoproliferative disorders & drugs used to treat autoimmune disorders

lymph node & bone marrow

variable EBV involvement

75
Q

What genetic mutations are seen in BL?

A

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
Q

What type of tumor is shown in the provided slides?

A

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
Q

What Burkitt Lymphoma variant is seen in the provided image? What cytogenic markers would you expect to see from this sample?

A

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
Q

What is the prognosis of Burkitt Lymphoma?

A

highly aggressive - but potentially curable because very chemosensitive

79
Q

What morphological features can help you differentiate Follicular Lymphoma from a Reactive Lymphoid follicles?

A

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
Q

What immunophenotype markers are seen in Burkitt Lymphoma?

A

Positive: CD19, CD20, CD10, BCL6, CD38 (mature B cell markers) & strong light chain immunoglobulin expression

Negative: CD34, TdT

S3B5 Pathology (13 decks)

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