Lymphomas Flashcards
1
Q
Lymphadenopathy (LAD)
A
- In young people most are not malignant, but rather a reactive hyperplasia (local or systemic) to an infection
- In DDx for lymphomas you should include: reactive hyperplasia, primary neoplasm (lymphoma) and neoplastic metastasis
- Chances that LAD is lymphoma increase w/ age
- LAD unlikely to be malignant if it lasts >2wks w/o other symptoms, or over 1 yr w/o growing
2
Q
Malignant lymphomas
A
- The malignant lymphocytes in lymphomas circulate in blood to a degree
- Lymphomas can also occur in spleen, GALT, MALT, skin, and BM
- When the neoplastic cells are also found in large amounts in blood the disease is a lymphocytic leukemia
- Lymphomas can be B cell (large or small, diffuse or follicular), and T cell (diffuse only) in origin
- Account for 10% of all cancer deaths
3
Q
Methods to analyze lymphomas
A
- Morphology in biopsy
- Immunohistochemistry
- Flow cytometry (FC) to see wham markers are expressed
- FISH to see what translocations present
- Molecular changes to identify mutations
4
Q
Incidence for various lymphomas
A
- Hodgkin’s lymphoma (HL): 15% in adults, rare in kids
- Non-hodkin’s lymphoma (NHL): many types
- Follicular B cell: 30% in adults, rare in kids
- Burkitt’s: 30-50% of child lymphomas
- DLBCL: 30% in adults, rare in kids
- T cell lymphoblastic (TCLL): 40% of child lymphomas
- Burkitt’s and T lymphoblastic resembles embryonic origin cell types, the rest are adult cell types
5
Q
Etiology of lymphomas
A
- Multiple hits occur, a sustained immune response increases the hit rates (most are translocation events)
- Translocations often involve chromosomes 2, 22 (both for Ig light chain), and chrom 14 (Ig heavy chain)
- Other agents include viruses such as HTLV1 (human T leukemia virus) causing TCLL and EBV causing Burkitt’s
- Autoimmune and immunodeficiency disease show increased incidence (abnormal sustained stimulation)
6
Q
Chromosomal markers for lymphoma
A
- Burkitt’s shows a t(8;14), which moves c-myc (8) next to Ig heavy chain (IgH, 14). This up regulates c-myc, converting it to an oncogene and and increasing cellular proliferation
- Follicular center B cell (FCC) shows a t(14;18) that moves the bcl2 (18) gene next to IgH (14). Leads to over expression of bcl2, which inhibits apoptosis. This prevents cell death and the cells accumulate
- Mantle cell lymphoma shows a t(11;14) w/ up regulation of bcl1 (coding for cyclin D, 11) by moving it next to IgH (14). The up regulation of cyclin D leads to increased proliferation
7
Q
Dx for lymphomas
A
- Almost all monoclonal lymphocytic proliferations are considered as malignant lymphomas or lymphocytic leukemias
- There is a difference in how aggressive they are
- The gold standard for Dx is to biopsy the lymph node by removing the entire thing (morphologic classification)
- Other methods include CD markers, monoclonality (based on K/L light chains or heavy chains, TCR rearrangement, translocations)
- Also the size of the cell: large, intermediate, small
8
Q
Morphology of lymphomas
A
- Loss of normal LN architecture (cortex-> paracortex-> medulla from out to in), w/ or w/o follicles, mantle, marginal zones
- Cell size as compared to RBC (normal sized lymphocyte is around 10um)
- Presence of reed-sturnberg cells (RSCs) to divide HL from NHL (HL has RSCs)
- Diffuse (B or T) or follicular pattern (B only)
- Small cells are more mature, slower growing (well-behaved, seen in CLLs, FCC, mantle, marginal)
- Intermediate cells (burkitt’s) are usually rapidly dividing cells
- Large cells (DLBCL) are rapidly dividing and aggressive
9
Q
Characteristic phenotyping
A
- Based on pattern of CD markers, determined by IHC on sections or FC on live cells
- B cell markers: 19,20,21,22,79 (most around 20)
- T cell markers (≥8): 2,3,4,8
10
Q
Monoclonality
A
- Can also be distinguished by FC and IHC
- Presence of monoclonal light or heavy Ig chain
- Clonal Ig gene rearrangement
- Clonal TCR gene rearrangement
- Translocations/other genetic markers
11
Q
Classification of precursor lymphomas
A
- Can be B cells (B lymphoblastic leukemia/lymphoma, BALL) or T cells (T lymphoblastic leukemia/lymphoma, TALL)
- Both subsets are TdT+, CD34+ (stem cell marker)
12
Q
Classification of HLs
A
- Only B cell (RSC is the malignant cell)
- Nodular sclerosis (CD20-, CD15/30+)
- Lymphocyte predominant (CD20+, CD15/30-)
- Mixed cellularity (CD20-, CD15/30+)
- Lymphocyte depleted (CD20-, CD15/30+)
13
Q
Classification of B cell NHLs
A
- Small cell (CLL)
- Lymphoplasmacytic (waldenstrom’s)
- Multiple myeloma (MM)
- Marginal zone
- Follicular center cell (FCC)
- Mantle cell
- DLBCL
- Burkitt
14
Q
Classification of T cell NHLs
A
- Adult T cell
- Mycosis fungoides (sezary)
- Peripheral T cell
- Anaplastic large cell
15
Q
Precursor B (acute lymphoblastic lk/lymphoma)
A
- A type of B cell ALL, some may merge w/ Burkitt’s
- Cells resemble lymphoblasts, particularly occurs in childhood
- Display early CD markers, CD19,20 and CD10, as well as TdT+
- All B cell lymphomas (mature and lymphoblastic) show Ig gene rearrangement
16
Q
Mature B cell types
A
- Constitute lymphomas in adults, cells resemble mature lymphocyte phenotypes
- All (except plasmacytic) display CD19, 20, and 79 as the common B cell phenotypic markers
- All are monoclonal, some produce monoclonal Ig (especially plasmacytic)
- All B and T cell lymphomas besides ALL are mature cell type lymphomas
17
Q
B small cell lymphocytic lymphoma
A
- The same as CLL
- Diffuse proliferation of uniform, small lymphocytes, no histeocytes (no cells are dying)
- Disease of accumulation; long survival even untreated, difficult to cure
- Lymphoma is the tissue involvement of CLL, involves multiple nodes, spleen
- Has polymorphocytic varieties; some are larger cells and may be more aggressive
- t(11;19) bcl3 upregulated-> more NFkB
- Bad prognosis: presence of ZAP70
- Prognosis also depends on IgH mutations and CD38 expression
18
Q
Lymphoplasmacytic lymphoma (waldenstrom’s)
A
- Similar to small lymphocytic lymphoma but shows plasmacytoid differentiation, slow growing
- IgM monoclonal Ab (spike) common in serum, may produce hyperviscosity
- May have t(9;14) of pax5 (9) to IgH, up regulating pax5
- Pax5 encodes B cell specific activating protein
19
Q
Mantle cell lymphoma
A
- Comprised of mantle zone cells (at periphery of follicles), small B cells
- Aggressive and requires different Rx from other small B cell lymphomas
- Associated w/ t(11;14) which moves bcl1 (encoding cyclin D1) on chrom 11 onto IgH (14) and up regulates it
- More cyclin D leads to increased proliferation (induces G1->S phase transition)
20
Q
Follicular center cell (FCC) lymphoma
A
- One of the most common forms of NHL, predominantly small FCC lymphocytes (centrocytes)
- Can also have subtype that has a higher proportion of larger dividing (transformed type) cells (centroblasts)
- The more centroblasts, the more aggressive
- Most are due to t(14;18), where blc2 (18) is moved next to IgH thus increasing bcl2
- Bcl2 inhibits apoptosis thus cells accumulate
- Display all usual B cell markers plus CD 10
- Can be grade 1, 2, or 3 based on how many large cells there are
- Can complicate by progressing to DLBCL (if a single LAD LN grows even more)
