Non-Hodgkins Lymphoma, ASPHO Flashcards
2 ways to divide up NHL?
T vs B cell derived, mature vs immature
give an immature t-cell derived NHL
t-lymphoblastic
give an immature b-cell dervied NHL
b-lymphoblastic
give a t-cell derived mature NHL
anaplastic large cell
give 3 b cell derived mature NHLs
burkitts, diffuse large B, primary mediastinal b cel
give 4 rare NHLs
marginal zone, follicular, peripheral T cell, NK cell, gamma delta T cell, primary CNS lymphoma, primary lymphoma of the bone
what is the realtive prevalence of the various NHLs?
Burkitts 40%…and then 20% for each: ALCL, T-LLy, DLBL
most NHLs (60%) are what stage at dx?
3-4
what % of NHLs are secndary maligs?
<1%
approximate realtive % of B cell lymphoblastic lymphoma and primary mediastinal b cell lymphoma within NHLs?
B-LLy 3%; PMBCL 1.5%
peds NHLs are more common with what demographcis?
males, younger children, caucasians
incidence of NHLs in people <20?
4 per million; 800 cases/year in US
Burkitts has a gender preference?
yes, 5x more common in males than females
discuss NHLs with relation to age
incidence increases with age, except for lymphoblastic lymphoma
etiology fo lymphoma?
EBV infection (burkitt), immunodef/immunosuppression, pesticides
immunodeficiences increase the risk of what?
NHL
give 5 primary immunodefs that increase risk fo NHL
WAS, IgA def, CVID, SCID, hyper-IgM syndrome….also chediak-higashi, x-link agammaglobuolinemia
give 3 acquired immunodefs that increase risk of NHL
following chemo for HL, immunosupprsesion after SOT, HIV
give 4 immunodefs from chrom instab that increase risk fo NHL
Ataxia telangiectasia, bloom syndrome, Nijegen breakage syndrome, werner syndrome
___ cell defs predipose you to ___ ___ lymphoma, often with ___ disease that is ___ ___
t-cell; b-cell; extra-nodal; EBV positive
describe the histo for burkitts
homogenous medium sized cells, high mitotic index, “starry sky”…KI67/MIB1>99% of cells are positive
burkitts: highly aggressive ___ ___ mature b cell lymphoma
germinal centre
epi for burkitts: gender, age, sporadic vs endemic?
males>females; 5-10 yrs, both
immunophenotype for burkitts? (6)
CD10,19,20,22,sIg+ (>90% IgM), low BCL-2 (anti-apoptotic)
burkitts: % that is Ki-67+
99%
3 translocations in burkitts? and 3 other changes in >50%?
IgH-cMYC= t(8;14)(q24;q32)> Igkappa-cMYC= t(2;8)(p11;q24)> Iglamda-cMYC= t(8;22)(q24;q11)....-13q, +1q, -6q
burkitts is the first human tumour to what? (3)
be associated with a virus (EBV), be known to have recurrent translocations, associated with HIV
have do you treat burkitt leukemia?
like burkitt lymphoma
decribe burkitts with relation to geography (sporadic vs endemic)
sporadic in north america, europe; endemic in equatorial africa, brazil, turkey, new guinea
incidence of burkitt if sporadic vs endemic?
0.2 per 100k vs 10 per 100 k
age for burkitt if sporadic vs endemic?
6-12 vs 4-7
EBV prev in burkitts if sporadic vs endemic?
15% vs 95%
presentation for burkitts if sporadic vs endemic?
sporadic: abdo, nodes, marrow, cns, csf…endemic: jaw, orbit, mesentery, CNS in 1/3
both endemic and sporadic burkitts express what?
ebv latency proteins
do translocations in burkitts differ if sporadic vs endemic?
no, they’re the same
what makes the starry sky apperance in burkitts?
reactive macropahges engulfing apoptoic debris from rapidly dividing cells
other than in burkitts, where else can you see c-myc expression adn b-cell markers? (2)
DLBCL, PMBCL
describe histo for DLBCL
large cells, abundant cytoplasm
immunophenoytpe for DLBCL? 7
sIg+, CD19, 20, 22, 79a, PAX5, occasional CD30+.
cytogenetics for DLBCL?
2/3 express BCL-6; 1/3 express cMYC
% of Ki-67+ cells in DLBCL?
<90%
what are the subsets fo DLBCL and their %s?
90% germinal centre b-cell like= GCL DLBCL….10%: activated b-cell like (ABC DLBCL…t14;18…ABC more in adutls and worse prog
how does DLBCL present?
more diverse (LN, liver, spleen, marrow, mediastinum), extranodal abdo (bowel, mesentery, retroperitoneum), may present with intussusception, often adv stage
primary mediastinal b cell lymphoma= rare thymic b cell lymphoma…% of DLBCL?
20%…but overall 1% of NHL
PMBCL: gene profile overaps with waht?
classic HL
immunophenotype…this is for what cancer? CD19,20,22,79a,PAX5, no SIgG, CD30=80%, PD-L1, PD-L2 (70%), low MHC II
primary mediastinal b cell lymphoma
describe the genetics of PMBCL
9p24.1 amplifcation–> increased PD-L1, PD-L2 expression….CIITA alterations–> decreased MHCII expression…9p gains/amplification (encodes JAK2)…SOCS1 mutations = negative regulatory of JAK-STAT, IL-4 receptor activating mutations
how does PMBCL present?
SVC syndrome in 50%
in lymphoblastic luekemia/lymphoma, LN architecture is ___ ___
completely effaced…just see sheets of small round blue cells (no follicles)…get small to med sized cells with open chromatin, minute nucleoli, lymphoblasts of LL and AL are cytologically identical
in lymphoblastic lymphoma, get sheets fo ___ + lymphoblasts
Tdt+
what’s the difference between lymphoblastic lymphoma and leukemia?
lymphoma: <25% in marrow; leukemia: >25% blasts in marrow
frequency of T lineage LL vs B?
75% T, 25% B
lymphoblastic lymphoma: what % of T are stage 3-4?
> 90%
lymphoblastic lymphoma: what % of B are stage 3-4?
10%
sites of T lineage LL?
mediastimum>marrow>CNS rare
sites of B lineage LL?
isolated nodes>bone, skin
immunophenotype in T linerage LL vs B?
Both have Tdt
In T, see CD1a, 2, 3, 5, 7, +/-4 and 8…whereas B has CD10,19,22,79a, HLA-DR
what types of translocations do you see in T lineage LL vs B?
T: TCR promoter onto trx factors…less characterized in B
anaplastic large cell lymphoma: describe histo
large, pleomorphic cells, nuc can be horseshoe like “hallmark” or may be multinucleated…sometimes see perinuclear hof= perinuclear clearing
immunophenotype: CD15 neg, CD30+, CD45+, t cell marekrs in 60%= CD3, CD43, CD45RO, TCR genes rearranged…which cancer?
anaplastic large cell lymphoma
what translocation do you see in anaplastic large cell lymphoma?
75% have t (2;5)= NPM-ALK fusion–> overexpression of ALK…triggers PI-3K, AKT pathway
presentation of anaplastic large cell?
progressive systemic sx, or highly aggressive robust inflamm state, HLH…may have cutaneous invovleent of ALK+ ALCL
cutaenous ALCL: describe
CD30+, ALK neg, requires less therapy…can wax and wane….NOTE: this = different from SYSTEMIC ALCL with cutaneous INVOLVEMENT
describe presenattion of endemic burkitts
jaw swelling, abdo/orbital swelling, paraspinal mass, CNS, marrow, intussusception
describe sporadic burkitt presenation
rapidly expanding abdo mass/spont tumour lysis, marrow, CNS, non-specfic GI sx, intuss
describe presentation fo DLCBL
more diverse (LN, liver, spleen, marrow, mediastinum), extranodal abdo (bowel, mesentery, retropetioneum), often advanced stage
describe presentation of primary mediastinal
medastinal mass, lcoal invasion, rsep sx, svc sydnrome in 50%
describe presentation fo lymphoblastic lymphoma
mediastinal mass, pleural/pericardial effusions, pain, dysphagia, dyspnea
describe presentation of ALCL
slowly progressive, systemic sx, organs and skin, nodal, extranodal, can be very aggressive with inflammatory response adn HLH…adv disease in 2/3 but CNS and marrow are rare
intuss occurs in which 2 lymphomas?
abdo burkitts, DLBCL
onc emergeis you can see in lymphoma
airway compression (mediastinal mass), breathing (pulmonary eff), circ= SVC syndrome/tamponade/arrhythmia, disability = paraspinal/epidural –> pain, paralysis, electrolysis (TLS), failing organ (kidneys (ureter compression, increased uric acid), GI (obstruction, intuss, bleeding, perf, jaudncie, pancreatitis), hematological (cytopenias from marrow infiltr)
why can you NOT intubate pts with mediastinal mass for airway protection?
obstruction can occur distal to ETT
if must to steroids, radiation emergently: biopsy may become uninterpretable after how long?
48 hours
how to eval NHL
hx, resp adn constituional sympoms (b symptoms not prog)
phys exam (LAD, signs infection, airway)
labs: cbc, inflamm markers, biochem, TSL labs
CXR
no empiric steroids….
later: CT neck and chest, CT or MRI of abdo and pelvis…most will get FDG-PET…exisional or incisional LN bx (histo, flow, cytogen, molec), bilateral BMA and bx, cerebal spinal fluid cytology
name for staging for NHL?
st jude (murphy) classication
descirbe stage 1 in murphy classification
1: single nodal or extranodal tumour (EXCLUDING mediastinum adn abod)
describe stage 2 in murphy
a) single exranodal tumour with regional LN involvement or b) two or more nodal areas on the same side of the diaphragm, or c) two extranodal tumours on teh same side of the diphragm (with or without regional node involvement) or d) primary GI tract tumour that is resectable (without ascites…usually ileocecal with or without reginal node involvement)
describe stage 3 in murphy
a) 2 extranodal tumors on opp sides of diaphram
b) 2 or more nodal areas above and below the diaphragm
c) any intrathoracic disease (lung, pleura, mediastinum, thymic)
d) all extensive primary intraabdo disease
e) all paraspinal or epidural disease
describe stage 4 in murphy
BM involvement >5%, CNS involvement (other than facial nerve palsy or paraspinal disease), CSF blasts, CNS mass, CN palsy, cord comp, parameningeal disease
what are the 2 ways to risk stratify in mature b cell lymphoma?
FAB/LMB and BFM
describe FAB/LMB risk stratification for mature b cell lymphoma
stratum a= completely resected stage I/abdo stage II
stratum b= non-resected I-4
stratum C: CNS + or >25% blasts in marrow
describe BFM risk strat for mature b cell lymphoma
R1= completely resected stage 1 or abdo stage 2 R2= Stage 3 with LDH<500 or nonresected stage 1/2 R3= stage 3 with LDH 500-999 or stage 4 with marrow>25% blasts adn LDH<1000 R4= stage 3 with LDH at least 1000 or stage 4 wtih marrow >25% blasts and LDH at least 1000 or stage 4 with any CNS disease
in lymphoma, who doesn’t need chemo? (2)
pediatric follicular (completely resected), stage 1 nodular lymph predom HL
in NHL, who doesn’t need CNS ppx?
resected abdo burkitt, dlbcl
in NHL, who does NOT have short duration/intense tx?
lymphblastic lymphoma
in NHL, who DOES need rads?
CNS + lymphoblastic lymphoma
structure of lymphoblastic lymphoma tx?
induction, consolidation, mainteance…duration fo therapy at least 2 yrs
surival in burkitt?
95%
survival in DLBCL?
95%
survival in lymphoblastic lympohma?
92%
survival in ALCL?
90%
survival in PMBCL?
80%
in NHL, higher stages–> what for tx?
more cycles…so based # cycles based on stage and response
in burkitt and DLCBL what improves outcomes and when?
rituximab improves otucomes for high stage diseae (3 with high LDH, all stage 4)
in pmbcl tx, includes ___ and may benefit from ___ ___
ritux; checkpoint inhibitor
for ALCL, ___ monotherapy with ___, ___, or ___ can result in durable remission in relapsed ALCL
prolonged, brentuximab, crizotinib, vinblastine
in T-LLy: what reduces CNS relapses of T-ALL
nelarabine
in B-LLy, relapsed B-LLy has a ___ ___prognosis
very poor (unlike B ALL)…CD19 directed therapy may be an option
indication for SCT in burkitt/DLCBL?
auto: 1st relapse (CR2)
indication for SCT in t-lly?
allo: 1st relapse (CR2)
indication for SCT in B-LLy?
Allo: 1st relapse CR2
indication for SCT in PMBCL?
auto/all: 1st relapse, CR2…no standard of care
indication for ST in ALCL?
allo: no starndard of care…maybe CR3…crizotinib, ritux, vbl monotherapy can all induce prolonged remission
give 5 late effects of NHL therapy
skeletal: decreased bone grwoth/AVN due to steroids
cardiac: cardiomyoapthy, effusion, pericarditis, CHF, CAD, AMI due to anthracyclines, alkylating agents
neuro: neurocog due to IT meds, hgih dose MTX
endo: infert due to alkylating agents
malig: AML/MDS due to alkylating aents, epipodophyllotoxins…and solid tumours due to alkylating agents
diff between HL and NHL in age?
HL >10, bimodal…NHL<10
diff in spread between HL and NHL?
HL= continguous nodes; NHL= systemic disease
diff in b symptoms between HL and NHL
HL: prog…NHL: not prog
diff in bulk disease between HL and NHL?
HL: prog…NHL: not
diff in marrow eval between HL and NHL
HL: yes (PET)…NHL yes (biopsy)
diff in flow order between HL and NHL
HL: nO…NHL: yes
CSF eval in HL vs NHL?
HL: no…NHL: yes
CSF ppx in HL vs NHL?
HL: no…NHL: yes
staging in HL vs NHL?
HL: Ann arbor
NHL: st jude (murphy)
radiation in HL vs NHL?
YES in HL (esp slow response)…NO in NHL (soem CNS+ T-LL)
basic diff betwen stage 1 ann arbor vs murphy?
ann arbor: singel node/site…mruphy: single/site but not GIT or intrathoracic
basic diff betwen stage 2 ann arbor vs murphy?
ann arobor: >2 nodes/sites…mruphy: >2 nodes/sites or pirmary GI if >95% rsesected
basic diff between stage 3 in ann arbor vs murphY?
AA: crosses diaphragm…M: crosses diaphragm/extensive GI involvemnt/ANY intrathoracic/paraspinal/epidural
basic diff in stage 4 bewtwen aa and murphY?
aa: disseminated (>1 extarnodal site)…m: marrow or CNS
substage in HL vs NHL
HL: b symptoms, bulk…non in NHL
rituximab: target and diseases?
anti-CD20, burkitt, DLBCL, NLPHL
nelarabine: mech and diseases? 2
purine analogue, T ALL, T-LLy
bretuximab vedotin: mech and potential diseases?
anti-CD30 conjugated to MMAE…classic HL and ALCL
crizotinib: mech and diseases?
ALK inhibitor; ALCL, Neuroblastoma
nivolumab, pembrolizumab: mech adn diseases?
checkpoint inhbitor; reverses inactivation fo anti-tumor t cells..classic HL, NLPHL, ALCL, PMBCL
T cell therapy: mech adn disease?
CTL specific for EBV LMP..EBV+ classic HL, PTLD
bortezomib: mech and diseases?
proteasome inhibitor, blocks degradation of IkappaB…T-LL, T ALL, cHL
