B-cell neoplasms Flashcards
monoclonal vs polyclonal populations
which are neoplastic?
- monoclonal - neoplastic
- polyclonal - non-neoplastic
discuss the general, defining features of NL (non-hodgekins) lymphomas
- affects: middle aged/older adults
- originates: usually in lymph nodes, but can have extra-nodal origin
- can spread: to non-contiguous lymph nodes
what is generally true of low grade B-cell lymphomas
they produce small amounts of monoclonal Ig
at which B-cell maturation stages are the following markers seen:
- CD10
- CD20
- CD38
- TDT
- 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
chronic lymphocytic leukemia - definition
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
what immunophenotype constitutes CLL/SLL?
- weak monotopic surface Ig, &
- specific marker expression:
- CD19, 20, 22 - weak
- CD23 - moderate
- CD5 - co-expression
CLL/SLL - epidemiology
is the most common leukemia of adults in western countries
CLL/SLL - pathogenesis
- multifactorial
- inc expression of Bcl-2 (non-specific)
- defects in BCR
- +/- association w/ chemicals/radiation
CLL/SLL - sites of involvement?
it depends on weather CLL or SLL
- CLL (chronic lymphocytic leukemia)
- blood
- bone marrow
- SLL (small cell lymphoma)
- blood
- NO BLOOD MARROW
CLL/SLL - clinical presentation
- m/c: asymptomatic adenopathy - so indolent they can grow very large w/out pt noticing
- if sx: d/t cytopenia
CLL/SLL - peripheral blood findings
- 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
CLL/SLL - morphology overall
- blood: smudge cells (disrupted lymphocyte remnants) + “soccer” cells (small, round, coarse)
- lymph nodes: proliferation centers
CLL/SLL - blood morphology
- soccer-ball cells: small, round mature course lymphocytes
- smudge cells: disrupted segments of lymphocyte nuclei
CLL/SLL - lymph node morphology
diffuse replacement of node by proliferation centers: small, monotonous B-lymphocytes
identify picture, note important features
CLL/SLL
- soccer-ball cells: small, round mature course lymphocytes
- smudge cells: disrupted segments of lymphocyte nuclei
identify picture, note important features
diffuse replacement of node by proliferation centers: small, monotonous B-lymphocytes
CLL/SLL - prognosis/therapy requirements
- ⅓ need tx soon after dx
- ⅓ need tx long after dx
- ⅓ _dont eve_r need tx
CLL/SLL - sequelae
- 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
-
CLL-promyelocyte transformation
CLL-promyelocyte
- can arise from what kind of transformation?
- immunophenotype?
- pertinent morphology?
- prognosis?
- 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
diffuse large B-cell lymphoma (DLBCL)
- can arise from what kind of transformation?
- immunophenotype
- pertinent morphology?
- prognosis?
- 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
identify picture, note important features
left: lymphocytes 3-5x normal size & bizare
right: higher # of promyelocytes compared to CLL
DLBCL - definition
- 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
-
contain nuclei that are:
DLBCL - phenotype
- pan b-cell marker (mature B-cell marker) expression
- CD19, CD20, CD22
- CD79a
(unless from CLL, then has CLL phenotype?)
DLBCL - epidemiology
most common NHL in the US
DLBCL - sites of involvement
- lymph nodes & others
- NOT IN THE BONE
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
-
infections
DLBCL - clinical presentation
- more acute than other NHLs
- rapidly enlarging lymphadenopathy
- systemic B-cell sx common: fever + night sweats + weight loss
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
identify picture, note important features
DLBCL
B-cells w/ nucleus the size of histiocyte nucleus or 3x normal B-lymphocyte nucleus
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
- prognosis depends on pathogenesis
“fish flesh” mass on spleen. seen with
- DLBCL
- follicular lymphoma
follicular lymphoma (FL) - definition
lymphoma comprised of malignant germinal B-cell centers & strong associated with blc-2 overexpression
FL - epidemiology
- most common indolent NHL
- second most common NHL (1st = DLBCL)
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
FL-clinical presentation
most commonly asymptomatic with indolent presentation
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
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)
- presence in germinal center can be used to differentiate normal vs FL follicles:
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
FL - prognosis / therapy
generally indolent and incurable.
- low grade: tho more indolent, is incurable
- high grade: tho more aggressive, is potentially curable
FL - sequelae
can transform to DLBCL
identify picture, note important features
FL - lymph node microscopic:
-
closely packed nodules make of:
- centrocytes (small, cleaved cells)
- centroblasts (large, un-cleaved cells)
FL - lymph node microscopic
loss of lymph node structure. no mantles (areas of dark, small lymph nodes) arund germinal center
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
identify picture, note important features
- FL - blood microscopic
- buttock cells: lymphocytes with nuclear indentation, seen where the is a leukemic aspect of FL
lymphoplasmacytic lymphoma (LPL)
definition: rare neoplasm of 1. small B-lymphocytes + 2. plasmacytoid lymphocytes + 3. plasma cells + 4. inc mast cells (usually)
LPL - pathogenesis
- not associated with any specific genetics / immunophenotypes
- possibly d/t hep C
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
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
LPL - morphology
- microscopic - bone marrow: presence of
- small lymphocytes
- plasma cells
- plasmacytoid lymphocytes
- mast cells
LPL prognosis
incurable, indolent
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
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
extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- epidemiology
nothing distinct, seen in adults in their 60s
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
extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- sites of involvement
GI tract is the most common location
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
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)
extra-nodal marginal zone lymphoma of MALT type (MALT lymphoma)- sequelae
may transform to DLCBL
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
mantle cell lymphoma phenotype
- 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
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
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
mantle cell lymphoma - prognosis
incurable
mantle cell lymphoma - sequelae
can aggress to a blastoid variant - aggressive
which NHLs can transform into DLBCL?
- follicular lymphoma
- Extranodal marginal (MALT lymphoma)
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