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PATH Heme-Onc II > B-cell neoplasms > Flashcards

B-cell neoplasms Flashcards

1
Q

monoclonal vs polyclonal populations

which are neoplastic?

A
  • monoclonal - neoplastic
  • polyclonal - non-neoplastic
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2
Q

discuss the general, defining features of NL (non-hodgekins) lymphomas

A
  • affects: middle aged/older adults
  • originates: usually in lymph nodes, but can have extra-nodal origin
  • can spread: to non-contiguous lymph nodes
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3
Q

what is generally true of low grade B-cell lymphomas

A

they produce small amounts of monoclonal Ig

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4
Q

at which B-cell maturation stages are the following markers seen:

  • CD10
  • CD20
  • CD38
  • TDT
A
  • TDT markers: only on immature B-cells (lymphoblast)
  • CD20: first seen in mature or nearly mature B-cells
  • CD10: often seen in B-cells in germinal centers - antigen dependent
  • CD38: expressed by plasma cells (Ig secreting B-cells) - antigen dependent
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5
Q

chronic lymphocytic leukemia - definition

A

aka CLL/SLL

  • an NHL characterized by sustained monoclonal B-cell lymphocytosis (> 5 x 103 / uL) of B-cells of a certain immunophenotype:
    • weak monotopic surface Ig, &
    • specific marker expression:
      • CD19, 20, 22 - weak
      • CD23 - moderate
      • CD5 - co-expression
        • CD25 typically only a T-cell marker
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6
Q

what immunophenotype constitutes CLL/SLL?

A
  • weak monotopic surface Ig, &
  • specific marker expression:
    • CD19, 20, 22 - weak
    • CD23 - moderate
    • CD5 - co-expression
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7
Q

CLL/SLL - epidemiology

A

is the most common leukemia of adults in western countries

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8
Q

CLL/SLL - pathogenesis

A
  • multifactorial
    • inc expression of Bcl-2 (non-specific)
    • defects in BCR
    • +/- association w/ chemicals/radiation
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9
Q

CLL/SLL - sites of involvement?

A

it depends on weather CLL or SLL

  • CLL (chronic lymphocytic leukemia)
    • blood
    • bone marrow
  • SLL (small cell lymphoma)
    • blood
    • NO BLOOD MARROW
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10
Q

CLL/SLL - clinical presentation

A
  • m/c: asymptomatic adenopathy - so indolent they can grow very large w/out pt noticing
  • if sx: d/t cytopenia
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11
Q

CLL/SLL - peripheral blood findings

A
  • laboratory:
    • CBC: absolute lymphocytosis (monoclonal B-cells)
    • cytopenia of myeloid cells - neutropenia, anemia, thrombocytopenia
    • small amounts of monoclonal Ig
    • increased LDH - seen in many NHL, not specific for CLL/SLL
  • smear:
    • soccer-ball cells: small, round mature course lymphocytes
    • smudge cells: disrupted segments of lymphocyte nuclei
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12
Q

CLL/SLL - morphology overall

A
  • blood: smudge cells (disrupted lymphocyte remnants) + “soccer” cells (small, round, coarse)
  • lymph nodes: proliferation centers
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13
Q

CLL/SLL - blood morphology

A
  • soccer-ball cells: small, round mature course lymphocytes
  • smudge cells: disrupted segments of lymphocyte nuclei
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14
Q

CLL/SLL - lymph node morphology

A

diffuse replacement of node by proliferation centers: small, monotonous B-lymphocytes

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15
Q

identify picture, note important features

A

CLL/SLL

  • soccer-ball cells: small, round mature course lymphocytes
  • smudge cells: disrupted segments of lymphocyte nuclei
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16
Q

identify picture, note important features

A

diffuse replacement of node by proliferation centers: small, monotonous B-lymphocytes

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17
Q

CLL/SLL - prognosis/therapy requirements

A
  • ⅓ need tx soon after dx
  • ⅓ need tx long after dx
  • ⅓ _dont eve_r need tx
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18
Q

CLL/SLL - sequelae

A
  • can progress (“transform”) to other cancers while retaining CLL phenotype:
    • CLL-promyelocyte transformation
      • morphology: greater # of pro-myelocytes than typical CLL
      • prognosis: death within 2 yrs
    • diffuse large B-cell lymphoma (DLBCL)
      • morphology: cells 3-5x larger & more bizarre than CLL
      • prognosis: death within 1 year
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19
Q

CLL-promyelocyte

  • can arise from what kind of transformation?
  • immunophenotype?
  • pertinent morphology?
  • prognosis?
A
  • promyelocytic transformation
  • immunophenotype = that of CLL: monotypic Ig + weak CD19,20,22, moderate CD23 + CD-5
  • morphology: greater # of pro-myelocytes than typical CLL
  • prognosis: death within 2 yrs
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20
Q

diffuse large B-cell lymphoma (DLBCL)

  • can arise from what kind of transformation?
  • immunophenotype
  • pertinent morphology?
  • prognosis?
A
  • Richter transformation - occurs in extramedullary tissue
  • monotypic Ig + weak CD19,20,22, moderate CD23 + CD-5
  • morphology: cells 3-5x larger & more bizarre than CLL
  • prognosis: death within 1 year
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21
Q

identify picture, note important features

A

left: lymphocytes 3-5x normal size & bizare
right: higher # of promyelocytes compared to CLL

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22
Q

DLBCL - definition

A
  • NHL involving large-b-cells that:
    • contain nuclei that are:
      • the size of a histiocyte nucleus, or
      • 3x normal B-lymphocyte nucleus
    • express pan mature C-bell markers
      • CD19, CD20, CD22
      • CD79a
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23
Q

DLBCL - phenotype

A
  • pan b-cell marker (mature B-cell marker) expression
    • CD19, CD20, CD22
    • CD79a

(unless from CLL, then has CLL phenotype?)

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24
Q

DLBCL - epidemiology

A

most common NHL in the US

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25
Q

DLBCL - sites of involvement

A
  • lymph nodes & others
  • NOT IN THE BONE
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26
Q

DLBCL - pathogenesis

A
  • transformation from low-grade B-cell lymphomas, ex: CLL (Richter)
  • de novo
    • infections
      • h. pylori
      • HIV (esp CNS), HHV-8, EBV
    • immunodeficiency /autoimmune
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27
Q

DLBCL - clinical presentation

A
  • more acute than other NHLs
    • rapidly enlarging lymphadenopathy
    • systemic B-cell sx common: fever + night sweats + weight loss
28
Q

DLBCL - morphology overall

A
  • blood - large B-cells with nucleus that are
    • size of histiocyte nucleus
    • 3x normal B-lymphocyte nucleus
  • spleen - large mass with “fish-flesh” appearance
29
Q

identify picture, note important features

A

DLBCL

B-cells w/ nucleus the size of histiocyte nucleus or 3x normal B-lymphocyte nucleus

30
Q

DLBCL - prognosis/therapy

A
  • is very aggressive & requires chemotherapy: CHOP-R
    • prognosis depends on pathogenesis
      • de novo - potentially curable
      • from Richter transformation (CLL) - resistant to therapy. prognosis
31
Q
A

“fish flesh” mass on spleen. seen with

  • DLBCL
  • follicular lymphoma
32
Q

follicular lymphoma (FL) - definition

A

lymphoma comprised of malignant germinal B-cell centers & strong associated with blc-2 overexpression

33
Q

FL - epidemiology

A
  • most common indolent NHL
  • second most common NHL (1st = DLBCL)
34
Q

FL - pathogenesis

A
  • t(14,18) mutation → over-expression of Blc-2 (anti-apoptotic)
    • IGH on chromosome 14 is juxtaposed with BCL-2 on chromosome 18 → Bcl-2 overexpression
35
Q

FL-clinical presentation

A

most commonly asymptomatic with indolent presentation

36
Q

FL - overall morphology

A

microscopic

  • lymph node:
    • closely packed nodules make of centrocytes (small, cleaved cells) and centroblasts (large, un-cleaved cells)
    • germinal centers lack of a mantle
  • blood:
    • buttock cells - lymphocytes w/ indented nuclei (if leukemic involvement)
  • gross - “fish flesh mass” on spleen
37
Q

what is the importance of blc-2 in FL?

A
  • overexpression d/t t14:t18 juxtaposition seen in 90% of cases
    • presence in germinal center can be used to differentiate normal vs FL follicles:
      • Blc-2 negative germinal centers are reactive → normal follicles (white)
      • Blc-2 positive germinal centers → FL follicles (red)
38
Q

discuss the staging of FL

A

based on lymph node microscopic morphology:

  • low grade: many centrocytes (small, cleaved), few centroblasts (large, un-cleaved)
  • high grade: many centroblasts: 15 centroblasts / hpf
39
Q

FL - prognosis / therapy

A

generally indolent and incurable.

  • low grade: tho more indolent, is incurable
  • high grade: tho more aggressive, is potentially curable
40
Q

FL - sequelae

A

can transform to DLBCL

41
Q

identify picture, note important features

A

FL - lymph node microscopic:

  • closely packed nodules make of:
    • centrocytes (small, cleaved cells)
    • centroblasts (large, un-cleaved cells)
42
Q
A

FL - lymph node microscopic

loss of lymph node structure. no mantles (areas of dark, small lymph nodes) arund germinal center

43
Q

identify picture, note important features

A

FL - lymph node, microscopic

  • bcl-2 negative germinal center (white)
  • blc-2 positive germinal center (red) due to a lymphoma
44
Q

identify picture, note important features

A
  • FL - blood microscopic
    • buttock cells: lymphocytes with nuclear indentation, seen where the is a leukemic aspect of FL
45
Q

lymphoplasmacytic lymphoma (LPL)

A

definition: rare neoplasm of 1. small B-lymphocytes + 2. plasmacytoid lymphocytes + 3. plasma cells + 4. inc mast cells (usually)

46
Q

LPL - pathogenesis

A
  • not associated with any specific genetics / immunophenotypes
  • possibly d/t hep C
47
Q

LPL - immunophenotype

A

not associated with any specific immunophenotype, however tends to cause a monoclonal IgM rise (called Waldenstrom macro-globinemia) that is responsible for a lot of the clinical presentation

48
Q

LPL - clinical presentation

A

largely d/t igM monoclonal protein:

  • hyper-viscosity syndrome = neural issues
    • oronasal bleeding
    • vision changes
    • HA
  • cryoglobulinemia → small vessel impairment (reynauds)
  • cold agglutinin → hemolytic anemia
  • IgM deposits lead to
    • diarrhea
    • neuropathy
    • coagulopathy
49
Q

LPL - morphology

A
  • microscopic - bone marrow: presence of
    • small lymphocytes
    • plasma cells
    • plasmacytoid lymphocytes
    • mast cells
50
Q

LPL prognosis

A

incurable, indolent

51
Q

extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- definition

A
  • B-cell lymphoma arising from extra-nodal sites, often in the context of chronic inflammation
52
Q

extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma) - pathogenesis

A
  • arises in the context of chronic inflammatory states:
    • infectious - H. pylori
    • autoimmune - sjogren’s, hashimotos
53
Q

extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- epidemiology

A

nothing distinct, seen in adults in their 60s

54
Q

extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- clinical features

A
  • indolent course, sx related to the organ involved
    • m/c, stomach: anemia, weight loss, pain
55
Q

extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- sites of involvement

A

GI tract is the most common location

56
Q

extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- microscopic morphology

A
  • similar to lymphocytic lymphoma. presence of
    • small, monoclonal B-lymphocytes
    • plasmacytoid lymphocytes
    • plasma cells
    • but no mast cells
  • + presence of lymphoepithelial lesions
57
Q

extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- prognosis / therapy

A

may regress after treatment of H. pylori with antibiotics or PPIs (90% 5 year survival)

58
Q

extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- sequelae

A

may transform to DLCBL

59
Q

mantle cell lymphoma - immunophenotype

A
  • strong expression of pan-B cell markers: CD19, CD20, CD22
  • expression of CD5 (typically only seen in T-cells)
  • presence of cyclin D
60
Q

mantle cell lymphoma phenotype

A
  • NHL characterized by persistent B-cell lymphocytosis (small, monomorphic - similar to CLL) with specific immunophenotype:
    • strong expression of pan-B cell markers: CD19, CD20, CD22
    • expression of CD5 (typically only seen in T-cells)
    • presence of cyclin D
61
Q

mantle cell lymphoma- pathogenesis

A
  • t(11:14) mutation → overexpression of cyclin-D1
    • juxtaposes CCND1 at chromosome 11 with IGH with chromosome 14 leads to overexpresion of cyclin-D1
62
Q

mantle cell lymphoma - morphology

A
  • morphology microscopic:
    • blood (like CLL) - smudge cells + basketball cells
    • lymph tissue (unlike CLL)
      • presence of lymphomatous polyposis
      • no proliferation centers
      • no centroblasts
63
Q

mantle cell lymphoma - prognosis

A

incurable

64
Q

mantle cell lymphoma - sequelae

A

can aggress to a blastoid variant - aggressive

65
Q

which NHLs can transform into DLBCL?

A
  • follicular lymphoma
  • Extranodal marginal (MALT lymphoma)
66
Q

which B-cell NHLs are associated with genetic mutations? list each one with the corresponding mutation

A
  • CLL/SLL: associated with inc Bcl-2, but not specific
  • follicular lymphoma: t(14:18) → overexpression of Bcl-2
  • Mantle cell lymphoma: t(11:14) → over-expression of cyclin-D1 (CCND1)
  • Burkitt’s: t(8:14) → Myc protooncogene

PATH Heme-Onc II (6 decks)

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