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294 terms

hema lymph pathologies

RBC, WBC disorders
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thalassemia
microcytic anemia (Cooley = homozygous)
etio: congen vHb a/B chain synth rate
-a = insuff a chain -> B4 tetramers
-B = insuff B chain -> a4 tetramers
normal Hb synthesis: chains
y = most active in infancy -> HbF
B = most active in adult -> HbA
d = made by infants + adults -> HbA2
B-thalassemia
vB chain -> a4 tetramers accum:
-heterozygote: mild anemia, HbA2>3.5%
-homozyote: Cooley anemia, intramedullary hemolysis, crew cut sign, splenomeg, 2o hemochromatosis, HbF>30%
B-thalassemia Hb electrophoresis: heterozyogote (HbA2>3.5%)
B-thalassemia crew cut
B-thalassemia blood smears
a-thalassemia: genetics
1 gene mut -> silent carrier: no anemia
2 gene mut -> a-thal trait: mild anemia
3 gene mut -> Hb H dx (B4): mod anemia
4 gene mut -> Hb Barts dx (y4): severe anemia
microcytic anemia: common etio
Fe2+ deficiency
anemia of chronic dx: impaired Fe2+ release
thalassemia: B type > a type
macrocytic anemia: common etio
Vit B12 (cobalamin) >> FA (Vit B9) def
--| thymidine synth delay/--| erythroblast div
Vit B12 (cobalamin) def
etio: vIntake, vAbs -pernicious anemia, ^use
takes 3-6y for onset of Sx
Px: --| thymidine synth
-> delay/no erythroblast div, v myelin synth
Sx: macrocytic anemia, neuro Sx
Vit B12 deficiency: serum
v VitB12 (50% will be normal)
^methylmalonic acid
^homocysteine
macro-ovalocytes, hyperseg PMN
Vit B12 deficiency: imaging
Vit B12 deficiency: histo
macro-ovalocyte
hypersegmented PMN: 6+
megaloblastic erythroblasts in BM
pernicious anemia
autoi2 Ab *gastric parietal cells
-> lower IF -> no IF-Vit B12 complex
-> no Vit B12 abs
-> macrocytic anemia

etio: tapeworm i2
FA (Vit B9) deficiency
etio: v intake, abs @jej, phenytoin, ^use
takes 1-6mo to see Sx
Sx: VitB12 def-like, NO NEURO Sx, NT defect
serum: vFA serum + RBC, ^homocysteine
hemolysis: lab pathway
hemolysis: 2 basic signatures
1: BM compensation: reticulocytosis
2: ^LDH1, 2 + Hb (and ^bili) in serum
what is intravascular hemolysis?
occurs in circulation
how: free Hb binds +Haptoglobin -> clear *liver
dx: vHaptoglobin, Hb in serum + urine
what is extravascular hemolysis?
occurs in spleen
how: Hb phagocytosed *resident MF
-> unconj bili +Alb ->liver: conj bili ->biliary exc
dx: normal Haptoglobin, no Hb in serum or urine
how to distinguish between intravascular and extravascular hemolysis by labs?
intravascular: vHaptoglobin, free Hb *serum, UA
extravascular: ok Haptoglobin, no free Hb
hemolysis: intrinsic causes
mut Hb: SCD, thalassemia
mut RBC memb: hered spherocytosis, HPN
mut enz: G6PDH deficiency
SCD: sickle cell disease
etio: 6Glu->Val on Hb B chain -> HbS 85-90%
crisis: HbS precip (when de-O2)
Sx: splenic trapping, microvascular occlusion, abd/extremity pain, hemolysis
trait: hetero HbA + HbS
hereditary spherocytosis
mut RBC memb: ankyrin >spectrin, band 3
AD 75%
Sx: spherocytes, splenomegaly, cholelithiasis, extravasc hemolysis, macrocytic anemia, ^osmotic fragility to low ionic strength
Tx: splenectomy
hereditary spherocytosis: proteins
transmemb prot: band 3
x-linking prot: ankyrin (of spectrin + band 3)
intracellular prot: spectrin
hereditary spherocytosis: smear
spherocytes
PNH: paroxysmal nocturnal hemoglobinuria
etio: acq mut GPI-link glycoprot: PI glycan A
-> no CD55/DAF, CD59/ C3 convertase inhib
-> depo MAC + C3b
-> HSC derivatives opsonized + phagocytosed
= complement-mediated hemolytic anemia
PNH: labs + Sx
RBC: no CD55, CD59 - none on flow cytometry
normocytic anemia
vFe2+, hemosiderinuria
hematuria 25% intermittent
VTE 50% fatal: cerebral, portal
may tx -> AML
normocytic anemia: etio
aplastic anemia
pure RBC anemia
paroxysmal nocturnal hemoglobinuria
G6PDH deficiency: enzymes
part of PPP
G6PDH deficiency: epidemiology
X-linked recessive
Kurdish Jews, West Africans
^ risk oxidative stress-> precip Hb: Heinz body
rf: oxidizers (dapsone, chloroquine), fava beans
-> intravascular hemolysis
G6PDH deficiency: histo
what is a Heinz body?
precipitated Hb
-due to oxidative damage of Hb in G6PDH def
warm autoi2 hemolytic anemia
extravasc hemolysis
IgG *RBC Ag (ie Rh) -> spleen MF FcR
labs: + direct Coombs a-IgG, a-C3b 70%
smear: spherocytes
tx: prednisone 2/3, splenectomy 1/3
warm autoi2 hemolytic anemia: smear
spherocytes (like hereditary spherocytosis)
what causes RBC spherocytes?
1 warm autoi2 hemolytic anemia: IgG *RBC Ag
2 heredit spherocytosis: ankyrin mut...
cold autoi2 hemolytic anemia
intravasc + extravasc hemolysis
etio:idio, nHL, mycoplasma, EBV
IgM *RBC Ag -> spleen MF C3bR, RBC agg
bind @0-4C
labs: direct Coombs +Cb3-RBC, agg titer
what are schistocytes and what causes them?
fragmented RBC
etio: hemolytic trama = macro/microangioPx
-DIC, TTP
trauma: macroangioPx - hemolytic anemia
#1 cause traumatic hemolytic anemia
Px: RBC fragmentation in capillaries
smear: schistocytes
etio: DIC: fibrin strands, TTP: vWF strands, malig HTN, vasculitis, meta Ca
trauma: microangioPx - hemolytic anemia
causes: traumatic hemolytic anemia
etio: defective heart valves
smear: schistocytes
blood loss anemia
acute: fluid shift slow -> no immediate ΔHb, hypovolemic shock, slow RBC mass recov

chronic: anemia if v[Fe2+] -> Fe2+ def anemia
erythrocytosis/polycythemia
^RBC mass: M: Hct >54%, F: Hct >47%
hyperviscosity synd: vBF when Hct >60%
relative etio (common): vH2O, tobacco smoke
absolute etio: ^RBC mass, PV, v/^Epo
hyperviscosity syndrome
vBF when Hct>60%
Sx: visual, neuro
dx: PCV, Waldenstrom macroGbemia
neutropenia
ANC <1.8K/uL
suppressed HSC/ committed precursors
Rx: alkylating agent, antimetab, aminopyrine, sulfonamides, chlorpromazine, chloramphenicol, phenylbutazone, thiouracil
neoplasia: large granular lymphocytic leukemia
congenital
ineffective hematopoiesis/MDS
^destruction/use: i2, splenic seq, ^margination
agranulocytopenia
ANC <500/uL
#1 etio: Rx
-dose dept: alkylating agents, antimetabolites
-idiosyncratic: chloramphenicol, aminopyrine, sulfonamides, chlorpromazine, phenylbutazone, thiouracil
neutrophilia
ANC >7K/uL
^granulopoiesis: i2, neoplasia, drugs (G-CSF)
^release from BM: i2, hypoxia
v margination: exercise, catecholamines
^ extravasation: GC, i2
neutrophilia: smear
congenital neutrophil disorders
LAD1, LAD2, CGD (x-linked, AR), MPO def, Chediak-Higashi syndrom
LAD1
defect: B-chain of Cd11/18 integrins
-> no ^aff binding of PMN @site i2
LAD2
defect: fucosyl transferase -> mut selectin ligand
-> no rolling adhesion @site i2: selectin + ligand
CGD
v Oxidative burst: NADPH oxidase
-memb (X-linked)
-cyto (AR)
MPO deficiency
defective MPO-H2O2 system: v microbicide
Chediak-Higashi syndrome
mut LYST: lysosomal mt polymerization
-> no phagocytosis by WBC
acquired neutrophil disorders
DM, malignancy, sepsis, dialysis: adh/chemotax
leukemia, anemia, sepsis, DM, malnut: phag
eosinophlia
allergy
parasite
peripheral T-cell lymphoma
basophilia
CML
allergy
monocytosis
chronic i2, ie IBD
collagen vasc dx: SLE
lymphocytosis
>4K/uL adults
>7K/uL ped
>9K/uL infants

etio: viral, acute/chronic bacterial, proliferative
atypical lymphocytes
viral i2, CD8+ T cells, skirting cytoplasm
seen in i2 mononucleosis +EBV
lymphocyte: blast v atypical
lymphocytopenia
ANC<1.5K/uL adults
<3K/uL ped

v pdt: congen/acq, HL
^ destruction: chemo/rad, steroids, ACTH, AIDS
^loss: lymph dx, prot losing enteroPx, Whipple dx, ^central venous P
LN hyperplasia: patterns
1 follicular
2 paracortical/interfollicular
3 sinus histiocytosis
4 mixed pattern
follicular hyperplasia
2o follicles:^# + size
etio: i2, RA, Rx, AIDS
ddx: follicular lymphoma
follicular hyperplasia: biopsy
compare follicular hyperplasia v follicular lymphoma
follicular hyperplasia: no Bcl2
follicular lymphoma: ^Bcl2 due to t(8;14)
paracortical/interfollicular hyperplasia
Px: paracortex expands by heterogenous pop
etio: viral i2, SLE, Rx ADR
paracortical/interfollicular hyperplasia: biopsy
sinus histiocytosis
^MF in sinuses
LN: neck, axillay
etio: i2, cancer drainage
mixed cell hyperplasia
toxoplasmosis: follicular hyperplasia +
granuloma + sinusoidal dilation
neoplasia: all myeloid + lymphoid
neoplasia: division of myleoid v lymphoid
myeloproliferative neoplasms
CML: chronic myeloid leukemia
PCV: polycythemia vera
PMF: 1o myelofibrosis
ET: essential thrombocytosis
mastocytosis
myeloproliferative neoplasia: histo
myeloproliferative: compare
CML
Bcr-Abl: t(9;22)(q34;q11) 90% Philadelphia prot
-> Ras, Jak/STAT, Akt constit ON
20% all leukemia; mid-elderly
tx: Imatinib/Gleevec
CML: histo
what 2 myeloproliferative diseases are definitively diagnosed by cytogenetics?
CML: Bcr-Abl
PCV: JAK2
BCR-Abl rearrangement: Philadelphia protein = P210 fusion prot
BCR-Abl = tyrosine kinase
inhibited by Imatinib/Gleevec
WBC >20K/uL
CML presentation
hepatosplenomegaly - LUQ pain
insiduous
thrombosis/bleeding
CML pathology
leukocytosis >> 20K/uL: all stages maturation
BM <10% blasts, hypercellular, mild fibrosis
spleen: extramedullary hematopoiesis
basophilia
CML natural history
chronic: 2-8y
accelerated: blasts 10-19%; karyotype evo
blast crisis: <1YS, >20% blasts
-70% AML, 30% ALL - this is unique to CML!!
PCV: polycythemia vera
^RBC mass
etio: Jak2: chrom9p 1849 G->T 97% ->
-> loss autoinhib ->STAT5 -> ^Epo, IL-3 sens
epid: mid-elderly, rare
tx: Ruxolitinib --| Jak2
PCV Sx
^RBC mass: hyperviscosity syndrome
splenomealy
thrombosis/bleeding
PCV: labs
^RBC, Hb, HCT: normocytic unless Fe2+ def
thrombocytosis/eosinophilia/basophilia
Epo: low/normal (high sens)
BM: hypercellular: ^RBC, vFe2+, ^megakaryo
spleen: extramedullary hematopoiesis
PCV histo
PCV natural history
prolif phase: 10y avg; RBC prolif
spent phase: stable RBC mass, Fe2+ depletion
post-PCV myelofibrosis: 15-20%; anemia
AML 2%
PM: 1o myelofibrosis
HSC neoplasia + reactive fibrosis
leukoerythroblastosis +extramed hematopoiesis
tear drop anisopoikilocytes
JAK2 mut: 50%, MTL mut 1-5%
-Ruxolitinib *JAK2
5-20% -> AML
PM: histo
ET: essential thrombocytosis
^platelets + abnorm fcn: plt >1M/uL
circulating megakaryocyte fragments
mid-elderly
JAK2 mut 50%, MPL mut 5-10%
indolent
ET: histo
mastocytosis
^mast cells + abnorm fcn
etio: c-Kit RTK mut (CD117), tryptase +
urticaria pigmentosa 50% ped, systemic 10%
mastocytosis histo
AML
>20% blasts in BM
20% leuk, 85% adult leuk; ^incid post-mid age
AML etiology
100% untreated CML->AML
benzene
ionizing rad/chemo
alkylating agents
trisomy 21
chromosomal instability
hema dx: MDS, MPN, PNH, aplastic anemia
AML classification
WHO: +genetic aberrations, MDS-like, tx-related, not otherwise specified

FAB: 0-7
-3: promyelocytic t(15;17)
-4: inv(16)/t(16;16)
AML: labs
blasts - blood + BM
-Sudan black B+, myeloperoxidase +
-CD13, 33, 34, 117, Tdt(-)
-Auer rods - confirm myeloid lineage

BM: hypercellular
AML: histo
AML genetic aberrations
t(15;17) - M3, PML-RARα
FLT3 - bad prognosis -> high risk
NPM1; CEBPA - good prog -> low risk
AML: systemic Px
leukostasis
granulocytic Sa
AML: acute promyelocytic leukemia
AML-M3
t(15;17) PML-RARa --| RAR-a gene
promyelocytes: granulocytes + Auer rods
Sx: DIC
Tx: ATRA + good prog
AML: acute promyelocytic leukemia
promyelocyte: butterfly nuc
lots Auer rods
AML natural history
rapidly fatal
+chemo: 60% remission, 15-30% 5YS
good prog: t(15;17), t(8;21), inv(16)
poor prog: >60yo, MDS, 5q-, 7q-, LC>100K/uL
MDS: myelodysplasic syndromes
clonal SC dx -> ineffective hematopoiesis
Px: pancytopenia, hypercell BM, macro anemia
etio: benzene, rad, alk chemo Rx, TopoII inhib, chrom 5 deletion
course: smoldering -BMT dept; 10-40% ->AML
MDS: histo
mickey mouse cells
bi-lobe PMN
ringed sideroblast: Fe2+ locked in
MDS: Sx
cytopenia, macrocytic anemia, abnorm granulo
BM: hypercellular, ^blasts, cytogen weird
Langerhans cell histiocytosis
uncommon
mixed eos, plasma, PMN
cells: coffee-bean nuc, Birbeck granules
Langerhans cell histiocytosis: histo
coffee-bean nuclei
Langerhans cell histiocytosos: types
Letterer-Siwe dx: <2yo - most severe; 50% 5YS
Hand-Schuller-Christian dx: 2-5yo
eosinophilic granuloma: 5-30yo
pulmonary histiocytosis: smokers
Letterer-Siwe dx
most severe Langerhans cell histiocytosis
leukemia v lymphoma
leukemia: 1o BM + blood, myeloid/lymphoid origin, 2o LN + solid

lymphoma: 1o LN + solid, lymphoid origin, 2o BM + blood

CLL/SLL (leuk/lymph)
ALL/LL
LBL: lymphoblastic lymphoma
solid
<25% blasts in BM
rare
ALL: acute lymphoblastic leukemia/
LBL: lymphoblastic lymphoma
ALL: blood + BM, >25% blasts in BM, common
LBL: LN, <25% blasts in BM, rare
ALL: B v T - determines Tx
ped: 85% B cell; adult: B>T
favorable: 85% cure +chemo
ALL: histo
no: Auer rods, granules (v myeloblasts)
express Tdt
ALL: epidemiology
#1 malig ped (75% of cases), also >50yo
-ped 85% B-ALL, adult: B>T
etio: rad, i2 state, trisomy 21
ALL:Sx
very acute onset + progress (weeks)
anemia + thrombocytopenia - severe
fever
bone pain: LC blasts highjack BM + divide!
hepatosplenomegaly
lymphadenoPx
ALL Px
blood: leukocytosis + blasts (50/50%), anemia,
thrombocytopenia
BM: hypercellular, ^mitosis, blast sheets
ALL: B v T markers
both: Sudan black -, myeloperoxidase -, Tdt+
ALL genetics
favorable: hyperdiploidy, t(12;21), B-ALL, 4-10yo
WBC <10K/uL, no organ involved

unfav: t(4;11), t(9;22), T-ALL, <2y, >10y

+chemo -> 95% remission ped; lower for adults
75-86% cure if favorable
CLL/SLL: chronic lymphocytic leuk/small lymphocytic lymphoma
mature B-LC
65yo avg: no ped
#1 leukemia in US
CLL/SLL Sx
most: aSx
ser: lymphocytosis, anemia, thrombocytopenia
BM: small LC infiltrate, diffuse, nodular
i2: autoi2 hemolysis, hypo-yGb, paraprotein
LN: diffuse small, round, dense LC
CLL/SLL histo
CLL/SLL dx
CD5*, 19, 20, sIg (monoclonal K or λ)
(-) CD10

*CD5 normally only expressed by T cells
CLL/SLL flow cytometry
CLL/SLL grade
low: mutated/ M-CLL/SS
mut Ig +IgVh somatic hypermut; >50%
>7YS - don't treat + BMT if aSx

high: unmutated/U-CLL/SLL
mut Ig + unmut IgVh; <50%
3YS
CLL/SLL poor prognosis
U-CLL/SLL: 3YS avg
-prolymphocytic tx: 15-30% splenomegaly <2YS
-Richter tx: 5-10% large cell lymphoma <1YS
Richter tranformation
CLL/SLL 5-10%
large cell lymphoma
^lymphadenoPX
<1YS
hairy cell leukemia
mature B LC + villous cytoplasmic projection
mid-elderly, M>F
Sx: indolent course
blood: hairy cells, absolute monocytopenia
BM: reticulin fibrosis
spleen: red pulp involved
hairy cell leukemia: histo
hairy cell leukemia: markers
CD19, 20, 11c, 25, 103, sIg
TARP: tartare restistant acid Ptase +
(-) CD5, 10
Which pathology is associated with TARP?
hairy cell leukemia
What pathology is associated with B-cell markers and CD5?
CLL/SLL
mantle cell lymphoma
follicular lymphoma
common lymphoma in US
indolent 7-9YS
hepatosplenomegaly + lymphadenoPx
LN: nodular infiltrate; no mantle zones, no MF
large cells: poor prognosis
follicular lymphoma: histo
make sure to rule out follicular hyperplasia
LN: small, cleaved LC
follicular lymphoma: markers
CD10, 19, 20, sIg
(-) CD5
gen: t(14;18) -> Bcl2 overexp --| apoptosis
Bcl2 is a marker of which condition?
follicular lymphoma; hyperplasia will be (-)
DLBCL: diffuse large B cell lymphoma
#1 lymphoma in US
extranodular Sx
cleaved cells
DLBCL: histo
germinal center blasts + extranodal blasts
non-cleaved large B LC
DLBCL: markers
large, non-cleaved LC
CD19, 20, sIg, may have CD10
(-) CD5
assoc + EBV, KSHV/HHV8
which pathology is associated with viral pathogens?
DLBCL - assoc + EBV, HHV8/KSHV (HIV pt)
Burkitt: EBV, t(8;14) c-myc
HL: EBV
Adult T-cell leuk/lymph: HTLV-1
what is the ratio of B/T lymphoid neoplasms?
B 80%, T20%
plasma cell neoplasms
MM
smoldering myeloma
MGUS
all: paraproteins (M component), mid-elderly

other: solitary extra/osseous plasmacytoma,
Waldenstrom's macroglobulinemia, light chain
depo dx, heavy chain dx, 1o amyloidosis
what are Bence-Jones proteins?
paraproteins in urine
what is a paraprotein?
immunoglobulin (Ig) or fragment
M component (monoclonal)
secreted by plasma cell
found in serum - electrophoresis, urine, depo
MGUS
BM <10% plasma cells
1%/y tx -> MM
Waldenstrom macroglobulinemia
hyperviscosity syndrome
^IgM paraprotein: underlying LL or B-CLL/SLL
MM: diagnosis
BM >10% plasma cells
serum, UA: paraprotein Ig-k/λ, BJ prots
imaging: bone lesions
smear: Rouleaux formation
MM: Sx features (CRAB)
C: ^Ca2+
R: renal dx
A: anemia
B: bone lysis: ^RANK-L -> osteoclast act

avg 4-6YS
MM histo
Burkitt lymphoma/leukemia
endemic: equit Afria; ped; 95% EBV, extranodal
sporadic: US, ped/adult, extranodal - abdomen
HIV-assoc: EBV 25%

90% cure in ped
Burkitt lymphoma: markers
CD10, 19, 20, sIg
(-) CD5, Tdt
t(8;14), t(2;8), t(8;22), c-myc @Ig locus
^mitotic rate: fastest growing + best response
LN: non-cleaved LC, 'starry sky' MF
BM: blast LC + blue cytoplasm
Burkitt lymphoma: histo
starry sky MF
mantle cell lymphoma
60yo, M>F 2:1
LN, spleen, BM, blood, Waldeyer ring
poor prognosis, despite small cell size
Cyclin D1 mut, CD5
mantle cell lymphoma: histo
mantle cell lymphoma: markers
CD5+ (despite being B-cell, like CLL/SLL)
-small cell size (unlike CLL/SLL)

CD19, 20, sIg, Cyclin D1
t(11;14)(q13;q32) 75% pt
how to distinguish mantle cell lymphoma from CLL/SLL?
both: CD5+
mantle cell lymphoma: small cell, Cyclin D1
CLL/SLL: CD23, leukemia before SLL; large cell
extranodal marginal zone B-cell lymphoma or MALT = MALT lymphoma
5-10% B-cell NHL, 50% 1o gastric lymphoma
assoc: H pylori, autoi2 - Sjogren, Hashimoto
-early i2 suppression = curative Tx
20% early BM involved
MALT lymphoma
common T-cell neoplasms
mycosis fungoides/Sezary syndrome
adult T-cell leuk/lymphoma
anaplastic large cell lymphoma
peripheral T-cell lymphoma, unspecified
Hodgkin lymphoma
mycosis fungoides/Sezary synd
CD4+ T cells
elderly
epidermotropism, Pautrier microabscesses
Sezary synd: leukemic phase, erythroderma
indolent 90% 5YS
extracutaneous = poor prog, unresponsive Tx
mycosis fungoides: histo
Pautrier microabscess, epidermotropism
convoluted nuc
mycosis fungoides: markers
CLA, CCR4, CCR10; CD4+ home->skin
Sezary syndrome: leukemic phase
adult T-cell leukemia/lymphoma
etio: HTLV-1
endemic: Japan, Caribbean, W Africa
Sx: skin dx, ^Ca2+
poor prognosis, especially leukemic phase
adult T cell leuk/lymphoma: histo
flower-shape nuc
anaplastic large cell lymphoma
t(2;5): Alk gene rearrangement - good prog
no Alk rearrangement - poor prog - 20% 5YS

tx marker: CD30 (normal exp in act B, T LC)
-treated with ADC Brentuximab --| CD30
anaplastic large cell lymphoma
hallmark cells: horseshoe cells
peripheral T-cell lymphoma, unspecified
mature T cells
poor prog: 20% 5YS
eosinophilia (T cells sec IL-5)
LN: architecture effacement, angiogenesis
markers: CD2, 3, 5,TCR-αβ/γδ (monoclonal)
HL: Hodgkin lymphoma
mature B-cell: Reed-Sternberg cell +reactive bg
bimodal: 15-35y, >50y; #1 malig 10-30yo
etio: EBV
nodal spread contiguous
2 types: classical +nodular
HL: histo
HL v nHL
HL: RS cells, heterogenous pop, nodal spread
young + elderly; good prognosis

nHL: homo cells, 1o extranodal, Waldeyer ring;
any age; variable prognosis
HL Sx
lymphadenoPx, splenomegaly, i2 dysfcn
B Sx: fever, night sweats, wt loss
prognosis: 90% cure
risk 2o malig, esp in youth
classical HL
Reed-Sternberg cells + heterogenous bg cells
CD15, 20+/-, 30
(-) for most T/B cell markers: no Ig
Reed Sternberg cells
origin: germinal center B cell - 2 nuc/lobes
large nucleoli
classical HL: 4 forms
nodular sclerosis: RS cells + fibrous bands
mixed cellularity: RS cell in mixed bf
lymphocyte depletion: RS cells, few LC
lymphocyte rich: rare
nodular sclerosis classical HL
CD19, 20
(-) CD15, 30
lacunar cells
good prognosis
mixed cellularity classical HL
lymphocyte depletion classical HL
lymphoma staging
I: 1 LN
II: 2+ LN or same side diaphragm
III: opp side diaphragm
IV: disseminated LN

A: aSx
B: fever, night sweats, -wt 10%
E: extranodal site
what pathologies have neoplastic blasts?
B-ALL, T-ALL
AML: Auer rods M3
what leukocytic neoplasias have characteristic genetic associations?
B-ALL: hyperdiploidy
Burkitt lymphoma: t(8;14), c-myc, EBV
AML: t(15;17), ATRA, M3
CML: t(9;22), BCR-Abl, Imatinib/Gleevec
what are the genetic associations of myeloproliferative neoplasms?
CML: t(9;22), BCR-Abl, Imatinib/Gleevec
PCV: JAK2
PM, ET: JAK2 50%
what are the markers of AML, CML, ALL, and CLL?
AML: t(15;17), CD13, 33/34; Tdt-, Auer rods
CML: t(9;22) BCR-Abl
ALL: 85% B-ALL: CD10/Tdt; 15% T-ALL
CLL: CD5, 19 (B cell); no tx -> ALL
what are the markers for other lymphocytic neoplasia?
CLL/SLL: CD5, CD20, CD23, sIg
Hairy cell: CD20, 11c, 25, 103
MALT: CD20
follicular: CD10 ,20, Bcl-2 -t(14;18)
mantle cell, CD5, 20, Cyclin D1
Burkitt: CD10, 19, 20
which neoplasia is characterized by Cyclin D1 overexpression?
mantle cell lymphoma
which neoplasia is characterized by Bcl-2 overexpression?
follicular lymphoma
which neoplasias are characterized by aberrant CD5 expression?
CLL/SLL: B cells
mantle cell lymphoma: also Cyclin D1
what is leukoerythroblastosis?
L-shift + ^RBC (esp nucleated)
etio: PM (1o myelofibrosis)
leukemoid reaction
^WBC, esp PMN + bands
toxic granulation
Dohle bodies
which neoplasia is characterized by 'starry sky' MF and t(8;14)?
Burkitt lymphoma
t(8;14) = C-myc
what is polycythemia?
= erythrocytosis (^RBC mass)

etio: PCV = JAK2 mut; assoc +hyperviscosity,
hypoxia, smoking, altitude, ^epo, paraproteinemia
what pathology can be diagnosed by flow cytometry?
PNH: RBC lack CD55, CD59
CD markers for leukemia, lymphoma
what pathologies can be diagnosed by a direct Coombs test?
warm autoi2 hemolytic anemia: a-IgG, C3b
cold" : a-C3b
what pathologies can be diagnosed using electrophoresis?
hemoglobinoPx
-a/B thalassemia: B: HbA2, HbF
-SCD, trait: have HbS
lymphoma classification
low-grade lymphoma: types
follicular lymphoma: CD10, Bcl-2
CLL/SLL: better if IgH mut
aggressive lymphoma: types
DLBCL: EBV, HHV8
mantle cell lymphoma: CD5, cyclin 1D
highly aggressive lymphoma: types
Burkitt's: t(8;14), c-myc, starry sky MF
lymphoblastic lymphoma
vWF disease
deficient vWF (1/1K incid)
-platelets can't bind EC (adhesion)
-> no soft platelet plug formation

also: no transport of FVIII -> hemophilia A-like dx
TTP
mut ADAMTS-13
-> no cleavage ultra multimeric vWF
-> spontaneous plt aggregation
What complaints signal possible serious lymphadenoPx?
night sweats, wt loss, fatigue, fever, abnormal fever/bruising
what size of LN is abnormal?
>1cm: abnormal
>2.25cm: 38% chance malignant
what are abnormal LN signatures on PE?
>1cm, esp painless
fixed/matted
shotty
rubbery or hard
Virchow's node
L supraclavicular LN
-indicates abdominal malignancy
epitrochlear LNoPx is a predictor of what disease under which conditions?
HIV: SubSaharan Africa
LN: drainage + Ddx
splenomegaly
i2: mono, malaria, typhoid, leishmania, SLE
congestive: portal HTN, thrombosis
infiltrative: ITP, neoplasia, hemolytic anemia
hypersplenism
splenomegaly + cytopenia (variable)
tx: splenectomy
thymoma
>40yo, M=F
etio: MG, pure RBC aplasia
pure RBC aplasia
thymoma, pancytopenia
anemia
M: Hb <14g/dL, HCT <42%
F: Hb <12g/dL, HCT <36%

types: micro/normo/macrocytic
prolif: hypo/hyper
anemia: chart
anemia: Sx
fatigue, dypsnea, angina, syncope
tachycardia, pallor, ^JVP, pitting edema
anemia: MCHC
mean cell Hb conc: 32-36 g/dL normal
-hypo/normo/hyperchromic
anemia: RDW
RBC distribution width: 12-15% normal
high RDW = anisocytosis
aplastic anemia
pancytopenia, normo/macrocytic anemia
BM: hypocellular <25% cellularity
Px: telomere mut, CD8, chloramphenicol
aplastic anemia: histo
BM: hypocellular <25% cellularity
aplastic anemia: tx/prog
inimmuosupp, allogeneic SCT, androgens
anti-thymocyte globulin: 50-70% respond
prog: poor - median 1YS
pure RBC aplasia
Px: thymoma, parvovirus B12 -intranuc incl
normocytic anemia
pure RBC aplasia
normocytic anemia
BM: few erythroblasts
intranuclear inclusions -parvovirus B19
pure RBC aplasia: tx/prog
thymectomy, anti-thymocyte globulin
good prognosis - 50% remission
Fe2+ deficiency anemia: etio
macrocytic anemia
vFe2+ total body stores -> less Hb
-less intake
-less abs: duodenal/prox jejunal injury
^ loss: GI bleeding - always ID etio in elderly!
^ use: pregnancy
Fe2+ def anemia: Sx
pica: ice craving
atrophic glossitis, koilonychia (nails)
Plummer-Vinson syndrome: esoph webs
Fe2+ deficiency anemia: labs
low: Fe2+, Ferritin, Transferrin sat
high: Transferrin, sol transferrin rec
Fe2+ deficiency anemia v Chronic dx anemia: labs
Fe2+ def anemia: vFerritin, ^TF, vTF sat
chronic dx: ^Ferritin, vTF, ok TF sat
what are the labs used to indicate Fe2+ status?
ferritin: total store of Fe2+ <12ng/mL
transferrin: Fe2+ scavenger in blood <40ug/dL
transferrin sat: % transferrin occupied <10%
soluble transferrin rec: Fe2+ scavenger
TIBC: tot bind cap of transferrin >400ug/dL
Fe2+ def anemia: histo
Plummer-Vinson syndrome
etio: Fe2+ deficiency anemia
glossitis, esoph webs
anemia chronic dx
normo/microcytic anemia
Px: hepcidin --| MF release of Fe2+
etio: cancer, i2, autoi2
total body stores ok
--Ferritin normal/high
--normal Transferrin, normal TF sat
HbA2 (a2d2) is >3.5% total Hb in what pathology?
heterozygous B-thalassemia
HbF (a2y2) is >30% total Hb in what pathology?
homozygous B-thalassemia (Cooley anemia)
what 2 forms of hemolysis does thalasemmia cause?
intramedullary + intravascular hemolysis
what is Cooley anemia?
severe anemia as infant
etio: B-thalassemia, homozygous
B-thalassemia: histo
basophilic stippling and target cells are characteristic of what pathology?
B-thalassemia
B-thalassemia: signatures
microcytic anemia
target cells, basophilic stippling
HbA2 >3.5% in heterozygote
HbF >30% in homozygote
how to distinguish Vit B12 from B9 (folic acid) deficiency?
Vit B12: ^methylmalonic acid, neuro Sx
Vit B9/FA: phenytoin Rx, vFA
what labs are used to diagnose extravascular/intravascular hemolysis?
^ in both: LDH, reticulocytes, unconj bili
Haptoglobin: v in intravascular
free Hb in serum + UA: (+) in intravascular
SCD: tx
Hydroxyurea: ^HbF
RBC transfusion
BMT
SCD: histo
PNH: GPI-linked glycoprotein
what pathology causes complement-mediated hemolysis?
PNH: RBC lack CD55, 59
paroxysmal cold Hburia: IgG*P-group on RBC
how is PNH diagnosed?
flow cytometry: RBC lack CD55, 59
labs: intravascular hemolysis
UA: Hb, hemosiderin
autoi2 hemolytic anemias
warm: IgG ->splen MF FcR, +Coombs IgG, C3b
cold: IgM, +Coombs *a-C3b
paroxysmal cold Hburia: IgG*P-group; L-D test
warm autoi2 hemolytic anemia
1o: idioPx 50%
2o hematopoietic neoplasia: CLL, nHL, HL,
autoi2, penicillin, cephalosporin, quinidine
cold autoi2 hemolytic anemia: smear
cold autoi2 hemolytic anemia: Tx
avoid cold
Rituximab
paroxysmal cold Hemoglobinuria
autoi2 hemolytic anemia
etio: idioPx, syphilis, measles, mumps, VZV
IgG *P group on RBC -> comp-med hemolysis
dx: Donath-Landsteiner test
Donath-Landsteiner test
if + hemolysis when returned -> 37C
(+) for paroxysmal cold Hburia
1o absolute erythrocytosis
PCV: vEpo levels
2o absolute erythrocytosis
^Epo levels - approp + inapprop
-approp: systemic hypoxia
-inapprop: local kidney hypoxia, paraneoplastic
which tumors secrete Epo and cause 2o absolute erythrocytosis?
RCC
HCC
cerebellar hemangioblastoma
uterine leiomyoma
absolute erythrocytosis: algorithm
DIC
Px: excess TF -> thrombophilia
what would change absorption of Fe2+?
vAbs: chelator, antacid, fluoroquinolone, tetracycline, gastric resection, duod/jej injury

^Abs: HCl, ascorbic acid: ^Ferrous (Fe2+)
what are Fe2+ storage sites?
10-20% intestinal EC, MF, HC
70% as Hb, 10% as Mb, 1% mobile
storage form = Ferritin
hemochromatosis/ chronic Fe2+ toxicity
etio: inherited, ^transfusions
Px: Fe2+ depo in organ systems
Tx: phlebotomy: 250mg Fe2+/unit blood
what is the function of FA/Vit B9?
synthesis methionine, purines, pyrimidines...

Folate Reductase: doesn't require Vit B12
THFR: requires Vit B12
what are the forms of FA/Vit B9?
dietary/storage: N5-methyltetrahydrofolate
active: tetrahydrofolate
idiosyncratic neutropneia
chloramphenicol
aminopyrine
sulfonamides
chlorpromazine
phenylbutazone
thiouracil
LAD1
mut: B-chain of CD11/CD18 integrins
LAD2
mut: fucosyl transferase -> no sialylated oligo
-> selectins defective
CGD: chronic granulomatous dx
v NADPH oxidase
-X-linked: memb component NADPH oxidase
-AR: cylosolic component NADPH oxidase
MPO deficiency
defective MPO-H2O2 system
-> less microbicidal activity
Chediak-Higashi syndrome
mut LYST
-> ineffective lysosomal trafficking
Chediak-Higashi syndrome
PCV is characterized by increased sensitivity to what growth factors?
Epo, IL-3 (due to JAK2 mut)
-actual level of Epo = low/normal
CD117/c-Kit _+, tryptase + pathology?
mastocytosis
what is the shared mechanism of myeloproliferative neoplasms?
tyrosine kinase dysregulation
leukemia types by age
ALL: ped
AML: any age
CML: adults (30+)
CLL/SLL: adults
AML: Tx options
AML mgmt
-induction 3+7: cytarabine + idarubicin
-consolidation
-SCT: intermed-risk + FLT3, high-risk

AML-3: ATRA, anthracycline (idarubicin)
Sorafenib --| FLT3
AML: genetic categories
FLT3-> high risk
NPM1;CEBPA -> low risk
what is the definitive marker of a mature B cell?
sIg
why does CML->AML but CLL can't -> ALL?
mature lymphoid cells have excised DNA present in lymphoid blasts by undergoing Ig rearrangement (B-cells) or TCR rearrangement (T-cells)
B cell neoplasias: 80% lymphoid neoplasms
T/K cell neoplasias: 20% lymphoid neoplasms
which neoplasia has a bimodal age presentation?
HL: 15-35, >50yo
ALL (slight): ped >> elderly
B-ALL markers
CD10, CD19, TdT
(-) sIg
What is TdT?
maker of B, T cell blasts -> ALL diagnosis
MLL -associated translocation
phenotype intermed btw ALL, CML
assoc + partner translocations, ie chrom 4
unique clin presentation: infant leuk, Tx-related
absolute monocytopenia: etio?
hairy cell leukemia
neoplasia: genetics
CML: t(9;22) Bcr-Abl
AML-3: t(15;17) PML-RARa; FTL3-poor
ALL: hyperdiploidy -good
follicular lymphoma (18;14) Bcl-2
DLBCL: KSHV/HHV8, EBV
Burkitt (8;14) c-myc, EBV
mantle cell lymphoma: t(11;14) cyclin D1
adult T cell leuk/lymph: HTLV-1
anaplastic large cell lymphoma t(2;5): Alk -good
MDS: chrom 5
PCV, ET, PM: JAK2
what is the fastest growing neoplasia?
Burkitt lymphoma:
diagnostic criteria ^^mitotic index
what T-cell neoplasm is +CD30, prognosed by Alk, hallmark cells?
anaplastic large cell lymphoma
-CD30 normally B-cell exp
-t(2;5) Alk - good; absence - bad
what T-cell neoplasm is characterized by abscess, CD4+, and convoluted nuc?
mycosis fungoides/ Sezary synd (if leuk)
what T-cell neoplasm is +HTLV-1, ^Ca2, endemic in SE Asia?
adult T cell leukemia/lymphoma
what is the treatment of anaplastic large cell lymphoma?
Brentuximab --| CD30
=ADC, Ab-drug conjugate
eosinophilia is characteristic of what neoplasm?
peripheral T-cell lymphoma
granuloma: Langerhans cell histiocytosis
what serves as surrogate marker to PCR for detecting monoclonal B-cell?
Ig-K or λ light chains
no such surrogate for T-cells - PCR only
what is significance of peak v smear on PCR for detecting B or T cell origin?
peak = monoclonal BCR (Ig) or TCR
smear = polyclonal "
Reed Sternberg cells are characteristic of what pathology?
HL: B cell neoplasm
Waldeyer ring presentation
nHL >> HL
What pathologies show aberrant CD30?
anaplastic large cell lymphoma: also t(2;5) Alk
HL: CD30 - Reed-Sternberg cells
treatment = Brentuximab --| CD30
lymphoma staging: Ann Arbor
nodular lymphocyte predominance HL
small LC in bg; no Reed-Sternberg
(+) CD19, CD20; (-) CD15, CD30
good prognosis
which form of HL has no Reed-Sternberg cells nor CD30?
nodular lymphocyte predominance HL
(not classical)