Non-Hodgkins Lymphoma, ASPHO Flashcards
1
Q
2 ways to divide up NHL?
A
T vs B cell derived, mature vs immature
2
Q
give an immature t-cell derived NHL
A
t-lymphoblastic
3
Q
give an immature b-cell dervied NHL
A
b-lymphoblastic
4
Q
give a t-cell derived mature NHL
A
anaplastic large cell
5
Q
give 3 b cell derived mature NHLs
A
burkitts, diffuse large B, primary mediastinal b cel
6
Q
give 4 rare NHLs
A
marginal zone, follicular, peripheral T cell, NK cell, gamma delta T cell, primary CNS lymphoma, primary lymphoma of the bone
7
Q
what is the realtive prevalence of the various NHLs?
A
Burkitts 40%…and then 20% for each: ALCL, T-LLy, DLBL
8
Q
most NHLs (60%) are what stage at dx?
A
3-4
9
Q
what % of NHLs are secndary maligs?
A
<1%
10
Q
approximate realtive % of B cell lymphoblastic lymphoma and primary mediastinal b cell lymphoma within NHLs?
A
B-LLy 3%; PMBCL 1.5%
11
Q
peds NHLs are more common with what demographcis?
A
males, younger children, caucasians
12
Q
incidence of NHLs in people <20?
A
4 per million; 800 cases/year in US
13
Q
Burkitts has a gender preference?
A
yes, 5x more common in males than females
14
Q
discuss NHLs with relation to age
A
incidence increases with age, except for lymphoblastic lymphoma
15
Q
etiology fo lymphoma?
A
EBV infection (burkitt), immunodef/immunosuppression, pesticides
16
Q
immunodeficiences increase the risk of what?
A
NHL
17
Q
give 5 primary immunodefs that increase risk fo NHL
A
WAS, IgA def, CVID, SCID, hyper-IgM syndrome….also chediak-higashi, x-link agammaglobuolinemia
18
Q
give 3 acquired immunodefs that increase risk of NHL
A
following chemo for HL, immunosupprsesion after SOT, HIV
19
Q
give 4 immunodefs from chrom instab that increase risk fo NHL
A
Ataxia telangiectasia, bloom syndrome, Nijegen breakage syndrome, werner syndrome
20
Q
___ cell defs predipose you to ___ ___ lymphoma, often with ___ disease that is ___ ___
A
t-cell; b-cell; extra-nodal; EBV positive
21
Q
describe the histo for burkitts
A
homogenous medium sized cells, high mitotic index, “starry sky”…KI67/MIB1>99% of cells are positive
22
Q
burkitts: highly aggressive ___ ___ mature b cell lymphoma
A
germinal centre
23
Q
epi for burkitts: gender, age, sporadic vs endemic?
A
males>females; 5-10 yrs, both
24
Q
immunophenotype for burkitts? (6)
A
CD10,19,20,22,sIg+ (>90% IgM), low BCL-2 (anti-apoptotic)
25
burkitts: % that is Ki-67+
99%
26
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
```
27
burkitts is the first human tumour to what? (3)
be associated with a virus (EBV), be known to have recurrent translocations, associated with HIV
28
have do you treat burkitt leukemia?
like burkitt lymphoma
29
decribe burkitts with relation to geography (sporadic vs endemic)
sporadic in north america, europe; endemic in equatorial africa, brazil, turkey, new guinea
30
incidence of burkitt if sporadic vs endemic?
0.2 per 100k vs 10 per 100 k
31
age for burkitt if sporadic vs endemic?
6-12 vs 4-7
32
EBV prev in burkitts if sporadic vs endemic?
15% vs 95%
33
presentation for burkitts if sporadic vs endemic?
sporadic: abdo, nodes, marrow, cns, csf...endemic: jaw, orbit, mesentery, CNS in 1/3
34
both endemic and sporadic burkitts express what?
ebv latency proteins
35
do translocations in burkitts differ if sporadic vs endemic?
no, they're the same
36
what makes the starry sky apperance in burkitts?
reactive macropahges engulfing apoptoic debris from rapidly dividing cells
37
other than in burkitts, where else can you see c-myc expression adn b-cell markers? (2)
DLBCL, PMBCL
38
describe histo for DLBCL
large cells, abundant cytoplasm
39
immunophenoytpe for DLBCL? 7
sIg+, CD19, 20, 22, 79a, PAX5, occasional CD30+.
40
cytogenetics for DLBCL?
2/3 express BCL-6; 1/3 express cMYC
41
% of Ki-67+ cells in DLBCL?
<90%
42
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
43
how does DLBCL present?
more diverse (LN, liver, spleen, marrow, mediastinum), extranodal abdo (bowel, mesentery, retroperitoneum), may present with intussusception, often adv stage
44
primary mediastinal b cell lymphoma= rare thymic b cell lymphoma...% of DLBCL?
20%...but overall 1% of NHL
45
PMBCL: gene profile overaps with waht?
classic HL
46
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
47
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
48
how does PMBCL present?
SVC syndrome in 50%
49
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
50
in lymphoblastic lymphoma, get sheets fo ___ + lymphoblasts
Tdt+
51
what's the difference between lymphoblastic lymphoma and leukemia?
lymphoma: <25% in marrow; leukemia: >25% blasts in marrow
52
frequency of T lineage LL vs B?
75% T, 25% B
53
lymphoblastic lymphoma: what % of T are stage 3-4?
>90%
54
lymphoblastic lymphoma: what % of B are stage 3-4?
10%
55
sites of T lineage LL?
mediastimum>marrow>CNS rare
56
sites of B lineage LL?
isolated nodes>bone, skin
57
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
58
what types of translocations do you see in T lineage LL vs B?
T: TCR promoter onto trx factors...less characterized in B
59
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
60
immunophenotype: CD15 neg, CD30+, CD45+, t cell marekrs in 60%= CD3, CD43, CD45RO, TCR genes rearranged...which cancer?
anaplastic large cell lymphoma
61
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
62
presentation of anaplastic large cell?
progressive systemic sx, or highly aggressive robust inflamm state, HLH...may have cutaneous invovleent of ALK+ ALCL
63
cutaenous ALCL: describe
CD30+, ALK neg, requires less therapy...can wax and wane....NOTE: this = different from SYSTEMIC ALCL with cutaneous INVOLVEMENT
64
describe presenattion of endemic burkitts
jaw swelling, abdo/orbital swelling, paraspinal mass, CNS, marrow, intussusception
65
describe sporadic burkitt presenation
rapidly expanding abdo mass/spont tumour lysis, marrow, CNS, non-specfic GI sx, intuss
66
describe presentation fo DLCBL
more diverse (LN, liver, spleen, marrow, mediastinum), extranodal abdo (bowel, mesentery, retropetioneum), often advanced stage
67
describe presentation of primary mediastinal
medastinal mass, lcoal invasion, rsep sx, svc sydnrome in 50%
68
describe presentation fo lymphoblastic lymphoma
mediastinal mass, pleural/pericardial effusions, pain, dysphagia, dyspnea
69
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
70
intuss occurs in which 2 lymphomas?
abdo burkitts, DLBCL
71
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)
72
why can you NOT intubate pts with mediastinal mass for airway protection?
obstruction can occur distal to ETT
73
if must to steroids, radiation emergently: biopsy may become uninterpretable after how long?
48 hours
74
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
75
name for staging for NHL?
st jude (murphy) classication
76
descirbe stage 1 in murphy classification
1: single nodal or extranodal tumour (EXCLUDING mediastinum adn abod)
77
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)
78
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
79
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
80
what are the 2 ways to risk stratify in mature b cell lymphoma?
FAB/LMB and BFM
81
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
82
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
```
83
in lymphoma, who doesn't need chemo? (2)
pediatric follicular (completely resected), stage 1 nodular lymph predom HL
84
in NHL, who doesn't need CNS ppx?
resected abdo burkitt, dlbcl
85
in NHL, who does NOT have short duration/intense tx?
lymphblastic lymphoma
86
in NHL, who DOES need rads?
CNS + lymphoblastic lymphoma
87
structure of lymphoblastic lymphoma tx?
induction, consolidation, mainteance...duration fo therapy at least 2 yrs
88
surival in burkitt?
95%
89
survival in DLBCL?
95%
90
survival in lymphoblastic lympohma?
92%
91
survival in ALCL?
90%
92
survival in PMBCL?
80%
93
in NHL, higher stages--> what for tx?
more cycles...so based # cycles based on stage and response
94
in burkitt and DLCBL what improves outcomes and when?
rituximab improves otucomes for high stage diseae (3 with high LDH, all stage 4)
95
in pmbcl tx, includes ___ and may benefit from ___ ___
ritux; checkpoint inhibitor
96
for ALCL, ___ monotherapy with ___, ___, or ___ can result in durable remission in relapsed ALCL
prolonged, brentuximab, crizotinib, vinblastine
97
in T-LLy: what reduces CNS relapses of T-ALL
nelarabine
98
in B-LLy, relapsed B-LLy has a ___ ___prognosis
very poor (unlike B ALL)...CD19 directed therapy may be an option
99
indication for SCT in burkitt/DLCBL?
auto: 1st relapse (CR2)
100
indication for SCT in t-lly?
allo: 1st relapse (CR2)
101
indication for SCT in B-LLy?
Allo: 1st relapse CR2
102
indication for SCT in PMBCL?
auto/all: 1st relapse, CR2...no standard of care
103
indication for ST in ALCL?
allo: no starndard of care...maybe CR3...crizotinib, ritux, vbl monotherapy can all induce prolonged remission
104
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
105
diff between HL and NHL in age?
HL >10, bimodal...NHL<10
106
diff in spread between HL and NHL?
HL= continguous nodes; NHL= systemic disease
107
diff in b symptoms between HL and NHL
HL: prog...NHL: not prog
108
diff in bulk disease between HL and NHL?
HL: prog...NHL: not
109
diff in marrow eval between HL and NHL
HL: yes (PET)...NHL yes (biopsy)
110
diff in flow order between HL and NHL
HL: nO...NHL: yes
111
CSF eval in HL vs NHL?
HL: no...NHL: yes
112
CSF ppx in HL vs NHL?
HL: no...NHL: yes
113
staging in HL vs NHL?
HL: Ann arbor
NHL: st jude (murphy)
114
radiation in HL vs NHL?
YES in HL (esp slow response)...NO in NHL (soem CNS+ T-LL)
115
basic diff betwen stage 1 ann arbor vs murphy?
ann arbor: singel node/site...mruphy: single/site but not GIT or intrathoracic
116
basic diff betwen stage 2 ann arbor vs murphy?
ann arobor: >2 nodes/sites...mruphy: >2 nodes/sites or pirmary GI if >95% rsesected
117
basic diff between stage 3 in ann arbor vs murphY?
AA: crosses diaphragm...M: crosses diaphragm/extensive GI involvemnt/ANY intrathoracic/paraspinal/epidural
118
basic diff in stage 4 bewtwen aa and murphY?
aa: disseminated (>1 extarnodal site)...m: marrow or CNS
119
substage in HL vs NHL
HL: b symptoms, bulk...non in NHL
120
rituximab: target and diseases?
anti-CD20, burkitt, DLBCL, NLPHL
121
nelarabine: mech and diseases? 2
purine analogue, T ALL, T-LLy
122
bretuximab vedotin: mech and potential diseases?
anti-CD30 conjugated to MMAE...classic HL and ALCL
123
crizotinib: mech and diseases?
ALK inhibitor; ALCL, Neuroblastoma
124
nivolumab, pembrolizumab: mech adn diseases?
checkpoint inhbitor; reverses inactivation fo anti-tumor t cells..classic HL, NLPHL, ALCL, PMBCL
125
T cell therapy: mech adn disease?
CTL specific for EBV LMP..EBV+ classic HL, PTLD
126
bortezomib: mech and diseases?
proteasome inhibitor, blocks degradation of IkappaB...T-LL, T ALL, cHL
