hema lymph pathologies

294 terms by medmasha Plus

Create a new folder

Advertisement Upgrade to remove ads

RBC, WBC disorders


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


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
macro-ovalocytes, hyperseg PMN

Vit B12 deficiency: imaging

Vit B12 deficiency: histo

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


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

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


^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


ANC <1.8K/uL
suppressed HSC/ committed precursors
Rx: alkylating agent, antimetab, aminopyrine, sulfonamides, chlorpromazine, chloramphenicol, phenylbutazone, thiouracil
neoplasia: large granular lymphocytic leukemia
ineffective hematopoiesis/MDS
^destruction/use: i2, splenic seq, ^margination


ANC <500/uL
#1 etio: Rx
-dose dept: alkylating agents, antimetabolites
-idiosyncratic: chloramphenicol, aminopyrine, sulfonamides, chlorpromazine, phenylbutazone, thiouracil


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


defect: B-chain of Cd11/18 integrins
-> no ^aff binding of PMN @site i2


defect: fucosyl transferase -> mut selectin ligand
-> no rolling adhesion @site i2: selectin + ligand


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


peripheral T-cell lymphoma




chronic i2, ie IBD
collagen vasc dx: SLE


>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


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

myeloproliferative neoplasia: histo

myeloproliferative: compare


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

BCR-Abl rearrangement: Philadelphia protein = P210 fusion prot

BCR-Abl = tyrosine kinase
inhibited by Imatinib/Gleevec
WBC >20K/uL

CML presentation

hepatosplenomegaly - LUQ pain

CML pathology

leukocytosis >> 20K/uL: all stages maturation
BM <10% blasts, hypercellular, mild fibrosis
spleen: extramedullary hematopoiesis

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


^RBC mass: hyperviscosity syndrome

PCV: labs

^RBC, Hb, HCT: normocytic unless Fe2+ def
Epo: low/normal (high sens)
BM: hypercellular: ^RBC, vFe2+, ^megakaryo
spleen: extramedullary hematopoiesis

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

ET: essential thrombocytosis

^platelets + abnorm fcn: plt >1M/uL
circulating megakaryocyte fragments
JAK2 mut 50%, MPL mut 5-10%


^mast cells + abnorm fcn
etio: c-Kit RTK mut (CD117), tryptase +
urticaria pigmentosa 50% ped, systemic 10%

mastocytosis histo


>20% blasts in BM
20% leuk, 85% adult leuk; ^incid post-mid age

AML etiology

100% untreated CML->AML
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

granulocytic Sa

AML: acute promyelocytic leukemia

t(15;17) PML-RARa --| RAR-a gene
promyelocytes: granulocytes + Auer rods
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


cytopenia, macrocytic anemia, abnorm granulo
BM: hypercellular, ^blasts, cytogen weird

Langerhans cell histiocytosis

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)

LBL: lymphoblastic lymphoma

<25% blasts in BM

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


very acute onset + progress (weeks)
anemia + thrombocytopenia - severe
bone pain: LC blasts highjack BM + divide!


blood: leukocytosis + blasts (50/50%), anemia,
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


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


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%

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

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?

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
Adult T-cell leuk/lymph: HTLV-1

what is the ratio of B/T lymphoid neoplasms?

B 80%, T20%

plasma cell neoplasms

smoldering myeloma
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


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

Burkitt lymphoma/leukemia

endemic: equit Afria; ped; 95% EBV, extranodal
sporadic: US, ped/adult, extranodal - abdomen
HIV-assoc: EBV 25%

90% cure in ped

See More

Please allow access to your computer’s microphone to use Voice Recording.

Having trouble? Click here for help.

We can’t access your microphone!

Click the icon above to update your browser permissions above and try again


Reload the page to try again!


Press Cmd-0 to reset your zoom

Press Ctrl-0 to reset your zoom

It looks like your browser might be zoomed in or out. Your browser needs to be zoomed to a normal size to record audio.

Please upgrade Flash or install Chrome
to use Voice Recording.

For more help, see our troubleshooting page.

Your microphone is muted

For help fixing this issue, see this FAQ.

Star this term

You can study starred terms together

NEW! Voice Recording

Create Set