General Principles of B cell neoplasia Flashcards
B cell development and markers
Neoplasms arising from precursor B cells
B-acute lymphoblastic lymphoma
Pre-germinal center B cell neoplasms
Mantle cell lymphoma
Germinal center B cell neoplasms
Follicular lymphoma
Burkitt’s lymphoma
DLBCL, GCB type
Hodgkin’s lymphoma
Post-germinal center B cell neoplasms
Marginal zone lymphoma
Mucosal-associated lymphoid tissue lymphoma
CLL/SLL
DLBCL, Non-GCB type
Centroblast
Larger GC cell with open chromatin, high N:C ratio.
Centroblasts reside in the dark zone of the GC.
They express low levels of surface immunoglobulins and switch off BCL-2, making them susceptible to apoptosis.
They are CD10 positive, BCL6 positive, LMO2 positive, HGAL positive, and BCL2 negative.
Centrocyte
Smaller GC cells with angulated to twisted nuclei and a lower N:C ratio than centroblasts. Some just look like normal mature lymphocytes.
Reside in the light zone of the GC.
Express higher levels of surface immunoglobulins and have undergone somatic hypermutation and heavy chain class switching.
IRF4 (MUM1) downregulates BCL6 expression
BCL6 negative, IRF4/MUM1 positive.
Follicular dendritic cell
Larger cell with relatively round nucleus and a prominent central nucleolus. The chromatin is slightly finer and paler than surrounding lymphocytes in a germinal center.
Unlike many other DCs, follicular DCs are of mesenchymal origin, not hematopoietic origin.
Stain for CD21/CD23.
Marginal zone cells
Post-GC memory B cells.
Cytologically, MZ cells have small to medium size, pale-to-clear cytoplasm, irregular nuclei with dispersed chromatin, and inconspicuous nucleoli.
Reside in marginal zones of lymph nodes, spleen, and MALT. Marginal zones are often hard or impossible to see on H&E outside of the spleen.
Express pan-B antigens and surface IgM, sometimes low level IgD. CD5 and CD10 negative, BCL2 and HLA-DR positive.
What are the cells in the area highlighted by the yellow arrows?
Mantle cells
Present in all secondary follicles, immediately surrounding the germinal center.
Mantle cells are pre-germinal center and are thus IgD or IgM positive.
Wild-type mantle cells are TCL1 positive.
Plasma cell markers
CD138, BLIMP1, Cyclin D1
Loss of PAX5
Pan-B cell markers
CD19, CD79a
PAX5 and CD20 (except plasma cells)
WHO definition of CLL
WHO definition of SLL
WHO definition of monoclonal B-cell lymphocytosis
“CLL-type” monoclonal B-cell lymphocytosis
Low-count MBL
vs
High-count MBL
Atypical or Non-CLL-type MBL
Richter transformation
Transformation of an SLL into a DLBCL (or a Hodgkin lymphoma).
Occurs in 2-10% of patients with CLL/SLL.
The resultant DLBCL often loses CD5 expression and is typically of non-GCB type, but may occasionally be of GCB type.
Richter transformation to Hodgkin lymphoma
“Subtypes” of Mantle cell lymphoma presentation
Classic MCL: nodal or extra-nodal
Leukemic MCL: JUST circluating MCL cells
The “lymphomatous polyposis” presentation of lymphoma in the GI tract is most commonly caused by. . .
Mantle cell lymphoma
Blastoid MCL
Leukemic MCL phenotype
Often CD5-, SOX11-
Can be tricky to diagnose, but you always can rely on the t(11;14) translocation to demonstrate Cyclin D1 is rearranged.
Leukemic MCL has a better overall survival than classical MCL.
Reporting of follicular lymphoma pattern
“Diffuse” pattern follicular lymphoma
Can be called ONLY if the lymphoma is low-rade (a grade 3A or 3B diffuse pattern would be DLBCL)
No follicular structures present, but follicular lymphoma by IHC and molecular features, with centrocytes +/- centroblasts.
Follicular lymphoma grading in the WHO4R
Follicular lymphoma grading in the WHO5
Follicular lymphoma grading in the ICC
How to decide between FL3A/cFL and FL3B/FLBCL
I think it’s follicular lymphoma, but my BCL2 stain is negative.
What next?
Juxtratrabecular
vs
Paratrabecular
Juxtatrabecular: Adjacent to, but not immediately abutting, the bony trabeculae. Seen in lymphoplasmacytic lymphoma.
Paratrabecular: Immediately abutting the bony trabeculae. Seen in follicular lymphoma.
2nd most common mutation in LPL
CXCR4
30% of cases
Other neoplasms with MYD88 L265P
IgM MGUS (but not IgG/IgA)
Nodal MZL
Splenic MZL
MALT lymphoma
CLL
Non-GC-type DLBCL
Over 50% of primary cutaneous DLBCL, leg type
DLBCL at immune privileged sites (testes, CNS)
The variable LPL immunophenotype
What are molecular features that can help distinguish LPL from IgM myeloma?
IgM myeloma usually has t(11;14) IgH::CyclinD1, and never has MYD88 L265P
The many faces of nodal MZL
Weirdly, hairy cell leukemia affects ____ the most
Monocytes
Hairy cell leukemia patients have basically no monocytes, so much so that if your patient DOES you should hesitate to diagnose hairy cell outright.
The most specific markers for Hairy cell
BRAFV600E
CD103
Annexin A1
CD25+ and CD11c bright are good screening tools
EBF1
Pioneer transcription factor that drives early chromatin remodeling to initiate the B cell program.
Recruits Brg1 and FUS via a prion-like C-terminal domain
