Lymphoma Flashcards
Immunophenotype of mature B-cell lymphomas
Burkitt: CD 10, 19, 20, 22, sIg+ (90%IgM), c-myc translocations
DLBCL: CD 19, 20, 22, 79a, PAX-5, sIg+ light chain restricted 2/3 BCL-6, 1/3c-myc
PMBCL: CD 19, 20, 22, 79a, PAX-5, CD30, negative for surface Ig but cytoplasm+ Gain in 9p
Burkitt’s translocations
t(8,14) - IgH (80%)
t(2,8) - Igkappa (15%)
t(8,22) - Iglambda (5%)
Types of Burkitt’s lympoma
Endemic - 95%
EBV related Sporadic - 15%
EBV related Immunodeficiency-associated - 40% EBV
Grouping of Mature B NHL for treatment
FAB:
Grp A - stage 1 resected or abdominal stage 2 resected EFS 98%
Grp B - not A or C - EFS 90%
Grp C - Leukemia (>25% blasts), CNS disease, non-responder to Grp B therapy. EFS 79%
PTLD subtypes
Early lesion Polymorphic Monomophic (i.e. looks like NHL) *90% are mature B-cell
Lymphoblastic lymphoma immunophenotype
B cell: Tdt positive, CD19, CD79a, or CD22 positive. HLA-DR +
T-cell: cytoplasmic or membrane CD3, TdT+, HLA-DR and CD34 negative
Histology of Hodgkin lymphoma
Nodular sclerosing Mixed cellularity Lymphocyte rich Lymphocyte depleted Nodular-lymphocyte predominant
Immunophenotype of classical vs nodular lymphocyte predominant Hodgkin’s
classical: CD 15+, CD 30+. CD 45- NLPHL: CD 15-, CD 30-, CD 45 +
Key points of NLPHL
5% of HL 10-20% in pre-pubertal 75% are males Localized No B symptoms not bulky EBV negative Surgery alone sufficient for Stage 1A 10% transform to DLBCL
Key pathway in Hodgkin
NFkappaB activation leading to increased BCL-2 (anti-apoptotic) - EBV activation of LMP1 - mutations in IkB (negative regulator of NFkB) - increased CD30 signalling
Classic presentation of HL
- painless cervical, supraclav LN - Mediastinal mass (2/3) - Constitutional symptoms (10% wt loss in 6m, night sweats, fever x 3d) - evidence of inflammation (ESR, CRP, anemia,ferritin) - Immune dysreg (AIHA, ITP, AIN, nephrotic syndrome)
Mediastinal mass differential
Malignant: - HL, - NHL: lymphoblastic, DLBCL, PMBCL, ALCL - GCT - Soft tissue sarcoma - mets Non-malignant: - thymus - infectious: mycobacterium, EBV, toxo, histo - lymphoproliferative d/o - PTGC
Role of PET in HL
- staging - response assessment
- NOT for surveillance post therapy.
Most relapse detected clinically < 12 m off therapy
Ann Arbor classification definition of extra letters and bulk
A - asymptomatic
B - B symptoms
E - extralymphatic organ
S - splenic involvement
X - bulky mediastinal disease
Bulk: >1/3 thoracic diameter on PA CXR, nodal aggregate > 6cm on longitudinal axis
Prognostic factors
- Stage
- B symptoms
- Bulk disease
- Extra-nodal extension
- Poor response to therapy
Most common secondary malignancy in HL
Breast cancer in women
- highest for girls <10
Greatest relative risk is for leukemia
Which tumors are CD 30 positive
- cHodgkin
- ALCL
- PMBCL
- embryonal carcinoma
Late effects of HL therapy
Which HL patients can avoid radiation?
- Low risk (1A, 2A) with CR post 2 cycles OEPA
- Intermediate risk getting ABVE-PC and rapid early responder on PET after 2 cycles, and CR after 4 cycles (AHOD0031)
What are the prognostic factors for relapsed HL?
- B symptoms
- Early relapse (3-12 months from end of therapy)
- Failure to respond to second-line therapy
What are the treatment options for relapsed HL?
- Chemo + auto HSCT *current SOC
- Myeloablative (BEAM or CBV most common), wide range of EFS/OS reported
- Chemo + allo HSCT
- Historically only used if failed auto or primary refractory
- Targeted therapy
- Brentuximab (against CD30)
- Ritux (if CD20 positive)
- PD-1 inhibitors - pembrolizumab, nivolumab - high response rate in multiply relapse/heavily treated adult patients
What is the Deaville 5-point scale for PET response?
1) No uptake.
2) Uptake ≤ mediastinal blood pool.
3) Uptake > mediastinal blood pool and ≤ normal liver.
4) Moderately increased uptake > normal liver.
5) Markedly increased uptake > normal liver.
PET positive if 3/4/5
Treatment for low risk HL
2 cycels of OEPA
rads can be omitted unless poor response
Treatment of intermediate risk HL
Based on AHOD0031
- 2 cycles ABVE-PC then PET
- If RER - 2 more cycles of ABVE-PC. Can avoid rads if PET negative and no bulk
- If SER and PET negative - 2 cycles ABVE-PC and IFRT
- If SER and PET positive - 2 cycles DECA then ABVE-PC
Treatment for HR HL
- 2 cycels OEPA then PET
- 4 cycles COPDAC
- Rads
Diffuse Large B-cell Lymphoma
- immunophenotype
- cytogenetics
- subtypes
- CD19, 20, 22, 79a, Pax-5, CD40
- 2/3 BCL-6, 1/3 have cMYC
- 90% germinal center B-cell like, 10% activated b-cell like t(14;18)
ALCL
- immunophenotype
- translocations
- immuno: CD15-CD30+ CD45+, Tcell marker: CD3, 43, TCR rearrangement
- 75% have t(2;5) translocation with NPM-ALK
Presentation of NHL
St. Jude Classification
