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

B-cell neoplasms Flashcards

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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
DLBCL - sites of involvement
* lymph nodes & others * NOT IN THE BONE
26
DLBCL - pathogenesis
* **transformation from low-grade B-cell lymphomas**, ex: CLL (Richter) * de novo * **infections** * h. pylori * HIV (esp CNS), HHV-8, EBV * immunodeficiency /autoimmune
27
DLBCL - clinical presentation
* more acute than other NHLs * rapidly enlarging lymphadenopathy * _systemic B-cell sx common_: fever + night sweats + weight loss
28
DLBCL - morphology overall
* 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
identify picture, note important features
DLBCL B-cells w/ nucleus the size of histiocyte nucleus or 3x normal B-lymphocyte nucleus
30
DLBCL - prognosis/therapy
* **is very aggressive & requires chemotherapy: CHOP-R** * prognosis depends on pathogenesis * **de novo -** potentially curable * **from Richter transformation (CLL)** - resistant to therapy. prognosis
31
“fish flesh” mass on spleen. seen with * DLBCL * follicular lymphoma
32
follicular lymphoma (FL) - definition
lymphoma comprised of **malignant germinal B-cell centers** & strong associated with **blc-2 overexpression**
33
FL - epidemiology
* most common indolent NHL * second most common NHL (1st = DLBCL)
34
FL - pathogenesis
* **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
FL-clinical presentation
most commonly asymptomatic with indolent presentation
36
FL - overall morphology
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
what is the importance of blc-2 in FL?
* 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
discuss the staging of FL
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
FL - prognosis / therapy
generally indolent and incurable. * low grade: tho more indolent, i**s incurable** * high grade: tho more aggressive, is **potentially curable**
40
FL - sequelae
can transform to DLBCL
41
identify picture, note important features
FL - lymph node microscopic: * **closely packed nodules** make of: * **centrocytes** _(small, cleaved cells_) * **centroblasts** _(large, un-cleaved cells_)
42
FL - lymph node microscopic loss of lymph node structure. **no mantles** (areas of dark, small lymph nodes) arund germinal center
43
identify picture, note important features
FL - lymph node, microscopic * bcl-2 negative germinal center (white) * blc-2 positive germinal center (red) due to a lymphoma
44
identify picture, note important features
* FL - _blood_ microscopic * **buttock cells:** lymphocytes with **nuclear indentation**, seen where the is a **leukemic aspect of FL**
45
lymphoplasmacytic lymphoma (LPL)
definition: rare neoplasm of 1. small B-lymphocytes + 2. plasmacytoid lymphocytes + 3. plasma cells + 4. inc mast cells (usually)
46
LPL - pathogenesis
* not associated with any specific genetics / immunophenotypes * possibly d/t hep C
47
LPL - immunophenotype
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
LPL - clinical presentation
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
LPL - morphology
* microscopic - bone marrow: presence of * small lymphocytes * plasma cells * plasmacytoid lymphocytes * mast cells
50
LPL prognosis
incurable, indolent
51
extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- _definition_
* B-cell lymphoma arising from **extra-nodal sites,** often in the context of **chronic inflammation**
52
extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma) - _pathogenesis_
* arises in the context of **chronic inflammatory states:** * **infectious - H. pylori** * **autoimmune - sjogren's, hashimotos**
53
extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- _epidemiology_
nothing distinct, seen in adults in their 60s
54
extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- _clinical features_
* indolent course, sx related to the organ involved * m/c, stomach: anemia, weight loss, pain
55
extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- sites of _involvement_
**GI tract is the most common location**
56
extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- _microscopic morphology_
* similar to lymphocytic lymphoma. presence of * small, monoclonal B-lymphocytes * plasmacytoid lymphocytes * plasma cells * **but no mast cells** * **+ presence of lymphoepithelial lesions**
57
extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- _prognosis / therapy_
**may regress after _treatment of H. pylori_ with antibiotics or PPIs** (90% 5 year survival)
58
extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- _sequelae_
may transform to DLCBL
59
mantle cell lymphoma - immunophenotype
* **strong expression** **of pan-B cell markers:** CD19, CD20, CD22 * **expression of CD5** (typically only seen in T-cells) * **presence of cyclin D**
60
mantle cell lymphoma phenotype
* NHL characterized by p**ersistent 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
mantle cell lymphoma- pathogenesis
* **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
mantle cell lymphoma - morphology
* morphology microscopic: * blood (like CLL) - **smudge cells + basketball cells** * lymph tissue (unlike CLL) * **presence of lymphomatous polyposis** * _no_ proliferation centers * _no_ centroblasts
63
mantle cell lymphoma - prognosis
incurable
64
mantle cell lymphoma - sequelae
can aggress to a **blastoid variant** - aggressive
65
which NHLs can transform into DLBCL?
* follicular lymphoma * Extranodal marginal (MALT lymphoma)
66
which B-cell NHLs are associated with genetic mutations? list each one with the corresponding mutation
* 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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