B Cell Lymphomas Part I (LPL and Large Cells) Flashcards
What sites must be involved by
Lymphoplasmacytic lymphoma
to fit criteria?
- must involve the bone marrow
- can be seen in LN, blood and extranodal sites
- original cell:
- Memory B cell
What spectrum of morphology cacn be
observed in Waldenstrom Macroglobulinemia
(LPL)?
- can have small lymphoid cells
- lymphoplasmacytoid cells
- plasma cells
- Dutcher bodies may be seen
- Lymph node architecture
- can be preserved with cells in sinuses
- or effaced
- PAS + material in sinuses, dutcher bodies
IMP: mast cell infiltrates accompany LPL in bone marrow, also amyloid
What are some clinical associations
of Lymphoplasmacytic lymphoma?
- Hepatitis C
- Cryoglobulinemia
IMP: these will respond to antiviral therapy
What is Waldenstroms Macroglobulinemia?
- lymphoplasmacytic lymphoma with an IgM monoclonal gammopathy
- marrow is also involved
What is the immunophenotype of
Lymphoplasmacytic lymphoma?
- Positive:
- CD19, CD20, CD38
- surface Ig bright
- cytoplasmic Ig in plasma cells
- Negative (or sometimes dim)
- CD5, CD23
- CD43 and CD10
What are the genetics of
Lymphoplasmacytic Lymphoma?
- MYD88 L265P gene mutations in >90% of LPL
- CXCR4 mutations are associated with poor prognosis and resistance to therapy
What is heavy chain disease and what is the most
common cause of it?
- rare, LPD that only forms immunoglobulin heavy chains
- Most common:
- alpha H chain disease
- also known as Mediterranean lymphoma
- stimulated by C. jejuni
- associated with immunoproliferative small intestine disease
What is Franklin H chain disease?
- form of heavy chain disease
- gamma heavy chain
- history of rheumatoid arthritis
- in 1/3 of patients
What is the most frequent clinical presentation
of DLBCL, NOS?
- rapidly enlarging nodal or extranodal mass (often in the GI tract)
- usually localized at presentation
- bone marrow involvement seen in 10% of patients
- 1/3 of patients have B symptoms
- 1/3 have elevated LDH at presentation
What is the frequent morphology seen in
DLBCL, NOS?
- diffuse proliferation of large lymphoid cells
- nuclei are at least as large as that of a macrophage or twice the size of a lymphocyte
- morphology can be:
- centroblastic
- immunoblastic
- anaplastic
What is the typical immunohistochemistry
of DLBCL, NOS?
- Positive:
- CD19, CD20, CD22, and CD45
- usually BCL2
- variable: CD10, CD5, and BCL6
Note: CD5 + DLBCL distinguished from blastoid MCL
- lack of BCL1 expression or CCND1
In DLBCL what does expression
of CD10 and BCL6 correlate with?
- germinal center phenotype
- more favorable prognosis
Note: expression of MUM1 in the absence of CD10 indicates an activated B cell type (worse prognosis)
What morphological features point towards
GCB vs. ABC?
- GCB:
- more centroblastic morphology
- BCL2 t(14;18) more common
- ABC:
- more immunoblastic morphology
- BCL6 t(3;x)
What is the definition of
Primary DLBCL of the CNS?
- specifically excludes dural lymphoma, intravascular lymphoma, secondary involvement by systemic lymphoma, and lymphoma associated with immunodeficiency
- median age is 60
What is the clinical presentation of
a Primary DLBCL of the CNS?
- supratentorial mass within the frontal, temporal or parietal lobes
- solitary or multifocal lesions with radiographic features that mimic glioblastoma
- tendency to spread along the white matter tracts
- cross the midline
- may present or recur as intraocular lymphoma
What is the histology and immunohistochemical
findings for Primary DLBCL of the CNS?
- neoplastic cells are typically perivascular in cuffs
- express pan B cell antigens
- most express MUM1
- negative for CD10
- BCL6 rearrangment is common and they express BCL6
- Bcl2 rearrangement is rare
What is the clinical presentation and
microscopic findings of TCRBCL?
- usually late stage with a poor prognosis
- mean age, 40 years
- Microscopic
- diffuse proliferation
- neoplastic cells are large B cells
- < 10% are B cells
- cant form aggregates
- look like immunoblasts, centroblasts, RS
- scattered within background of reactive lymphocytes
How is TCRBCL differentiated from
NLPHL?
- TCRBCL lacks the nodular architecture
- CD57 T cell rosettes are absent
- Small B cells are essentially absent
- No CD21/CD23 FDC network
What are the IHC findings for
TCRBCL?
- pan B cell markers positive
- BCL6 positive
- some positive for BCL2 and EMA
- Negative
- CD15, CD30 and EBV
- Background lymphocytes: CD8 positive
What is the pattern of bone marrow
involvement of TCRBCL?
- involves the marrow in a paratrabecular pattern
- similar to Follicular lymphoma
What is the classic clinical presentation of
Primary Mediastinal (thymic) Large B cell
Lymphoma?
- affects young adult women (20-40 yrs)
- presents as a medistinal mass
- superior vena cava syndrome
- sclerosing process that diffusely infiltrates the mediastinum
What is the morphology often seen in
Primary mediastinal large B cell lymphoma?
- large centroblast like cells
- entrapped/compartmentalized within bands of hyalinized stroma
- cells have somewhat clear cytoplasm
What are the immunohistochemical findings
of Primary mediastinal large B cell lymphoma?
- CD45, CD19 and CD20 (+)
- MUM1 and CD30 (+)
- MAL1 (+) - good marker
- BCL2 and BCL6 may be positive
- Negative for:
- CD10 and CD5
What genetic alterations can be seen in
Primary Mediastinal Large B cell Lymphoma?
- MAL gene, gains in 9p
- location of JAK2
- Lacks rearrangement of BCL2 and BCL6
What is the differential in a
primary mediastinal mass?
- Nodular sclerosing Hodgkin Lymphoma
- T cell lymphoblastic lymphoma
- Primary mediastinal (thymic) Large B cell lymphoma
- Castleman’s disease
What is key to diagnosing ALK (+)
Large B cell Lymphoma?
- ALK (+)
- EMA
- CD138
- cytoplasmic Ig –> usually IgA
- Negative
- CD30
- tumor composed of immunoblastic/plasmablastic cells
