B-Cell Neoplasms: Non-Hodgkin Lymphomas & Leukemias Flashcards
What are the precursor lymphoid neoplasms ?
ALL / LBL
B, T & NK cell precursors
What are the CD markers seen in pro B cells? Are they antigen dependent or independent? Where is the location of their differentiation?
CD34
TDT
CD10
CD19
antigen independent
bone marrow
What are the CD markers seen in Germinal center B cells?
Are they antigen dependent or independent?
Where is the location of their differentiation?
CD10
Antigen dependent
peripheral lymphoid tissue
What is the first cell to express the CD20 marker?
Are they antigen dependent or independent?
Where is the location of their differentiation?
some immature B cells, all mature naive B cells
antigen independent
immature (bone marrow)
mature naive (peripheral lymphoid tissue)
What are the CD markers seen in cytoplasmic & secreted immunoglobulins?
Are they antigen dependent or independent?
Where is the location of their differentiation?
CD38
antigen dependent
peripheral lymphoid tissue
What is the difference in presumption between monoclonal populations & polyclonal populations?
Monoclonal populations → neoplastic
Polyclonal → non-neoplastic
Mature B-cell non-hodgkin lymphomas usually affect what populations?
Origination?
Spread?
middle aged & older adults
usually originate lymph nodes (maybe extranodal in chronic inflammatory process)
spread is usually to non-contiguous lymph nodes & tissues
Is staging more important for guiding therapy of hodgkin lymphoma or non-hodgkin?
Hodgkin
Many low-grade B-cell lymphomas may produce small amounts of what substance, similar to plasma cell neoplasms?
monoclonal immunoglobulin
What is the definition of Chronic Lymphocytic Leukemia?
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
What is the mechanism of cell accumulation in CLL/SLL?
low proliferation but prolonged survival
What is the most common leukemia in adults in Western countries?
CLL/SLL
What mutations are associated with CLL/SLL?
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?)
CLL/SLL is associated with what risk factors?
chemicals or radiation
What are the sites involved in CLL/SLL?
peripheral blood & bone marrow (CLL)
if bone marrow is NOT involved it is called SLL
What is the clinical picture of a patient with CLL/SLL?
>80% are asymptomatic at diagnosis
fatigue, cytopenia, infections, other neoplasms, lymphadenompathy & splenomegaly
What are the laboratory findings that are indicative of CLL/SLL?
- absolute lymphocytosis
- small amounts monoclonal immunoglobulin
- peripheral blood cytopenias
- anemia, neutropenia, thromboytopenia
- increased LDH
What specific peripheral blood cell findings would you expect to see in a patient with CLL/SLL?
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
What condition is shown in the provided blood smear?
CLL/SLL
“soccer ball” & “smudge cell”
What condition is seen in the provided image?
CLL/SLL lymph node
lymph nodes are diffusely replaced by small, monotonous lymphocytes with “proliferation centers” (increased prolymphocytes & are paler than surrounding small lymphocytes)
What is the prognosis of CLL/SLL?
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
What condition is seen in the provided images of bone marrow?
CLL/SLL
What type of CLL/SLL transformation is seen in the provided image?
Prognosis?
Prolymphocytic transformation
increased # prolymphocytes (larger than small lymphocytes & central nucleolus)
death in 2 yrs
What type of CLL/SLL transformation is seen in the provided image?
Prognosis?
Richter Transformation
transformation to diffuse large cell lymphoma with retention of CLL/SLL immunophenotype
usually extramedullary
Death usually within less than 1 yr
What is the most common type of non-Hodgkins lymphoma in the US?
Diffuse large B-cell lymphoma
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
DLBCL cells usually express what markers?
pan-B cell markers
CD19, CD20, CD22, CD79a
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
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)
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
What condition is seen on this gross picture of the spleen?
tan/white “fish-flesh” appearance
most common lymphoma in the spleen
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
What is a follicular lymphoma?
It is associated with what mutation?
lymphoma comprised of malignant germinal center B-cells
translocations involving BCL2 (not specific)
What is the most common indolent non-Hodgkin lymphoma?
Follicular lymphoma
It the second most common non-Hodgkin lymphoma in US
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
You can use a BCL-2 stain for what differentiation?
reactive follicles (-)
low-grade B-cell lymphoma (+)
does NOT differentiate one lymphoma from another
What complication can arise from follicular lymphoma?
can transform to more aggressive lymphoma (DLBCL)
What sites are commonly involved with FL?
lymph node, liver, spleen, bone marrow, peripheral blood - usually widespread late in disease (surprisingly asymptomatic)
What condition is seen in the provided images?
follicular lymphoma
left: spleen w/ small nodules
right: lymph node “fish flesh”, nodular
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
What would you expect to seen in the peripheral blood of a patient with follicular lymphoma?
lymphocytes with indented nuclei
“buttock cells”
What special cells are shown in the provided image?
They are characteristic of what pathology?
buttock cells (indented nuclei)
follicular lymphoma
What is the prognosis of high grade & low grade follicular lymphoma?
- Low grade
- indolent but incurable
- high grade
- more aggressive but potentially curable
What is lymphoplasmacytic lymphoma?
rare neoplasm of small B-lymphocytes, plasmacytoid lymphocytes, & plasma cells
What specific immunophenotypic/genetic abnormalities are associated with lymphopasmacytic lymphoma (LPL)?
none
diagnosis may be difficult
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
What sites are commonly involved in LPL?
bone marrow
may involve blood, lymph nodes, & spleen
occasionally extranodal
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)
What is the prognosis of LPL?
incurable, indolent
survival 5 - 8 yrs
What is MALT lymphoma?
low-grade B-cell lymphomas arising at extranodal sites
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
- symptoms related to organ involvement
- associated with infections & autoimmune
- bone marrow involvement is unusual
MALT-lymphoma arises in what conditions?
chronic inflammatory states
- Infectious agent: Helicobacter pylori
- Autoimmune disease
- Sjogren syndrome
- Hashimoto thyroiditis
What is the most common site for MALT-lymphoma?
GI tract
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
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
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)
What is Mantle Cell lymphoma?
aggressive mature B-cell lymphoma of monomorphic small lymphocytes
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
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
How can you differentiate MCL from other types of lymphomas?
MCL cells express cyclin D1
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
What are the common sites of involvement in Mantle Cell Lymphoma?
lymph node most common
GI, spleen, bone marrow are common
maybe blood involvement
What demographics are most commonly affected by MCL?
middle-age to older adults
male predominance
What is the prognosis of MCL?
most patients present in late stage
incurable (3-5 yrs is medial survival)
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
What transformations are possible with MCL?
may transform into aggressive blastoid variant
DOES NOT transform to diffuse large B-cell lymphoma (DLBCL)
What is Burkitt Lymphoma?
aggressive B-cell
one of most rapidly-growing tumors known
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
What are the 3 clinical variants of Burkitt Lymphoma?
Endemic BL
Sporadic BL
Immunodeficiency-associated BL
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
What condition is shown in the provided histologic slides?
Blastoid Mantle Cell Lymphoma
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
What demographics are most commonly affected by Sporadic BL? Sites of involvement?
children/young adults (worldwide)
abdomen (esp GI), gonads, kidney & breast
RARELY jaw
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
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
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)
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)
What is the prognosis of Burkitt Lymphoma?
highly aggressive - but potentially curable because very chemosensitive
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)
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
