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64 Cards in this Set

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FAB Classification vs WHO Classification

FAB


- morphology


- cytochemistry




WHO


- clinical features & morphology


- immunophenotyping


- genetic features

Clinical Findings - Leukemias

anemia


thrombocytopenia (bleeding)


neutropenia (infections) or neutrophilia


bone pain (expansion of marrow)


weight loss


hepato/spleno/lymphadenopathy


rashes, tumors, CNS involvement

Acute vs Chronic Leukemias - key differences

ACUTE > 20-30% blasts


arrested maturation/hiatus development


↓ to ↑ WBCs, N to ↓Plt




CHRONIC < 20% blasts


normal maturation (uncontrolled)


↑ to ↑↑↑ WBCs, N to ↑ Plts

MPO cytochemical stain

Myeloperoxidase
Differs AML from ALL

granule peroxidases oxidizes dye substrate to black/brown precipitate
CONSIDER BLASTS ONLY!
Positive = >5% cells w/ precipitate
Positive = AML

Myeloperoxidase


Differs AML from ALL


granule peroxidases oxidizes dye substrate to black/brown precipitate


CONSIDER BLASTS ONLY!


Positive = >5% cells w/ precipitate


Positive = AML

SBB cytochemical stain

Sudan Black B
Differs AML from ALL
stains lipids found in granules of neutrophils and monos to black 
CONSIDER BLASTS ONLY!

Positive = >5% cells w/ black
Positive = AML
Sudan Black B
Differs AML from ALL
stains lipids found in granules of neutrophils and monos to black
CONSIDER BLASTS ONLY!

Positive = >5% cells w/ black
Positive = AML

Specific Esterase cytochemical stain results

Specific Esterase 

Differs btw myelo and mono
CONSIDER BLASTS ONLY!

Positive = >5% cells w/ red
Positive = AML - myelocytic


Specific Esterase


Differs btw myelo and mono

CONSIDER BLASTS ONLY!

Positive = >5% cells w/ red
Positive = AML - myelocytic


Specific Esterase cytochemical stain principle
Specific Esterase
Used to differentiate myelos from monos
Myelos stain red

napthol AS-D chloroacetate hydrolyzes substrate, releasing napthol compound that combines w/ a diazonium salt that precipitates red

Non-Specific Esterase cytochemical stain results
Non-Specific Esterase 

Differs myelo from mono
Monos - strong positive
Myelos can be weak positive

CONSIDER BLASTS ONLY!
Positive = >5% cells w/ black

Positive = AML - monocytic

Non-Specific Esterase


Differs myelo from mono


Monos - strong positive


Myelos can be weak positive


CONSIDER BLASTS ONLY!


Positive = >5% cells w/ black


Positive = AML - monocytic

Non-Specific Esterase stain principle
Non-Specific Esterase
Used to differentiate myelos from monos
Monos stain black (strong positive)

alpha napthyl acetate hydrolyzes substrate, releasing napthol compound that combines w/ a diazonium salt that precipitates black
Non-Specific Esterase cytochemical stain
results w/ NaF

Used to confirm Non-Specific Esterase if weakly positive - NaF inhibits the rxn in monocytes




Interpretation


NSE is weak pos/NaF weak pos = myelo


NSE is weak pos/NaF neg = mono

Remember!

Cytochemicals stain mature cells too! You're only looking at the percentage of stained blasts!

PAS cytochemical Stain results

Periodic Acid Schiff
Differs lymphs and erythros from myelo/monoblasts 

CONSIDER BLASTS ONLY!
Coarse pink only! Not diffuse
Positive = >5% cells coarse pink
Positive = malignant lymph, rbc, megakaryoblasts will be diffuse

Periodic Acid Schiff


Differs lymphs and erythros from myelo/monoblasts


CONSIDER BLASTS ONLY!


Coarse pink only! Not diffuse


Positive = >5% cells coarse pink


Positive = malignant lymph, rbc, megakaryoblasts will be diffuse

PAS cytochemical Stain principle

Periodic Acid Schiff (PAS)


Periodic acid oxidizes glycogen and other HMW carbs to aldehydes that react w/ Schiff reagent to stain bright pink




pos = coarse pink only - not diffuse


pos = malignant lymps, RBCs or megakaryos

LAP cytochemical stain principle

Leukocyte Alkaline Phosphatase (LAP)


Used to differ btw leukemia & leukamoid rxn. LAP enzyme found in secondary granules of PMNs hydrolyzes substrate (napthol-AS-BI phosphate), and forms red precipitate.




Interpretation - 100 cells scored 0-4


Normal = 15-70 L Rxn = 150-365,


CML = 0-24 CML of childhood = high

LAP cytochemical stain results

Leukocyte ALP
Differs leukamoid rxn from CML 
100 PMNs graded (black precipitate)  N = 15-70      
Leukamoid Rxn = 150-365
CML = 0-24   
CML of childhood = high LAP
Leukocyte ALP
Differs leukamoid rxn from CML
100 PMNs graded (black precipitate) N = 15-70
Leukamoid Rxn = 150-365
CML = 0-24
CML of childhood = high LAP

TRAP cytochemical stain principle

Tartrate Resistant Acid Phosphatase (TRAP)

Acid Phos present in almost all nonerythroid cells hydrolyzes substrate (napthol AS-BI phosphate), and forms red precipitate. Treatment with Tartaric Acid inactivates normal acid phosphatases. Hairy cell isoforms of acid phosphatase are not inactivated and stain red.

pos (red) = Hairy cells

TdT immunofluorescent stain

Terminal Deoxyribonucleotidal Transferase (TdT)
cell marker of lymph precursors only - immunoperoxidase or immunofluorescent techniques

pos = ALL - L1 and L2 (some AML)
Terminal Deoxyribonucleotidal Transferase (TdT)
cell marker of lymph precursors only - immunoperoxidase or immunofluorescent techniques

pos = ALL - L1 and L2 (some AML)

AML M0

M0 - Acute Myeloblastic Leukemia


w/o Cytological Maturation




>30% non-committed blasts


ALL STAINS NEG




5% adult AMLs, poor prognosis

Remember!

Until the marrow is entirely replaced by the malignant population, normal cells will continue to mature and be present alongside the blast/abnormal population.

AML M1

M1 - Acute Myeloblastic Leukemia
w/o Maturation


>30% myeloblasts
MPO/SBB +, SE +, NSE +/=, NaF +/=, PAS =
possible auer rods, ↑ WBC, ↓Plt

15% AMLs (adults and neonates), aggressive

AML M2

M2 - Acute Myeloblastic Leukemia


w/ Maturation




>30% myeloblasts - pros and beyond


MPO/SBB +, SE +, NSE +/=, NaF +/=, PAS =


possible auer rods, ↑ WBC, ↓Plt




25% of adult AMLs, may be blast crisis of CML

APL M3

M3 - Acute Promyelocytic Leukemia




>30% myeloblasts & pros (heavy granulation)


MPO/SBB +, SE +, NSE +/-, NaF +/=, PAS =


frequent auer rods, ↑ WBC, ↓Plt




usually an adult AMLs, DIC possible complication of treatment

APL M3m

M3m - Microgranular Varient of APL




>30% myeloblasts & pros (no granulation)


MPO/SBB +, SE +, NSE +/=, NaF +/=, PAS =


some abnormal nuclear shapes


frequent auer rods, ↑ WBC, ↓Plt




may be mistaken for AML or AMoL

AMML M4

M4 - Acute Myelomonocytic Leukemia




>30% myeloblasts & monoblasts


MPO/SBB +, SE +, NSE +/-, NaF +/=, PAS =


possible auer rods, ↑ WBC, ↓Plt




20% of adult AMLs, can invade skin, gums, etc.

AMML M4Eo

M4Eo - Acute Myelomonocytic Leukemia


w/ Eosinophilia




>30% myeloblasts/monoblasts & marrow eos


MPO/SBB +, SE +, NSE +/-, NaF +/=, PAS =


possible auer rods, ↑ WBC, ↓Plt





AMoL M5a

M5a - Acute Monocytic Leukemia


poorly differentiated




>30% monoblasts


MPO/SBB +, SE =, NSE +++, NaF =, PAS =


rare auer rods, ↑ to ↑↑↑ WBC, ↓Plt




usually kids/young adults, can invade tissues

AMoL M5b

M5b - Acute Monocytic Leukemia


differentiated




>30% monoblasts w/ lots of pros and monos


MPO/SBB +, SE =, NSE +++, NaF =, PAS =


rare auer rods, ↑ WBC, ↓Plt




usually kids/young adults, can invade tissues

AEL M6a

M6a - Acute Erythrocytic Leukemia (DiGuglielmo)




>50% rbc precursors & >20% myeloblasts


MPO/SBB =, SE =, NSE =, NaF =, PAS +


many/bizarre Plt, BM erythroidhyperplasia


often ↑MCV and anemia


looks like left shift w/ lots of nrbcs

AEL M6b

M6b - Acute Erythrocytic Leukemia (DiGuglielmo)




>80% nrbcs of marrow cellularity/no myelo


MPO/SBB =, SE =, NSE =, NaF =, PAS +


many/bizarre Plt, BM erythroidhyperplasia


often ↑MCV and anemia


looks like left shift w/ lots of nrbcs

AML M7

M7 - Acute Megakaryocytic Leukemia




>30% megakaryoblasts in marrow


MPO/SBB =, SE =, NSE =, NaF =, PAS +


bizarre Plt possible




rarest AML, associated w/ myelofibrosis (dry tap possible)

ALL L1

L1 - Acute Lymphocytic Leukemia




small lymphoblasts


(clefting, scanty cytoplasm, uniform pop.)


MPO/SBB =, SE =, NSE =, NaF =, PAS +, TdT +


↓ Plt and WBC (sometimes WBC very high)


CNS infiltration common



ALL L2

L2 - Acute Lymphocytic Leukemia




large lymphoblasts


(irregular nuc, often moderate cytoplasm, heterogeneous population)


MPO/SBB =, SE =, NSE =, NaF =, PAS +, TdT +


↓ Plt and WBC (sometimes WBC very high)


CNS infiltration common

ALL L3

L3 - Acute Lymphocytic Leukemia

leukemic conversion of Burkitt's lymphoma
large blasts w/ very basophilic cytoplasm
punch-out vacuoles
MPO/SBB =, SE =, NSE =, NaF =, PAS +, TdT =

Common characteristics of Myeloproliferative Disorders (includes CMLs)

panhyperplasia in BM


extramedullary hematapoiesis


BM fibrosis


frequent termination in acute leukemia


increased megakaryos in BM (often abnormal)


Plt dysfunction


cytogenic abnormalities

Chronic Myelogenous Leukemia (CML)

Chronic Myelogenous Leukemia (CML)


↑↑↑ WBC (blood resembles BM) - mature & immature w/ <10% blasts


looks like left shift w/ LOW LAP


hypercellular marrow (10-50:1)


possible pseudo Pelger-Huets & Gauchers


usually age 45+, abn Ph22, can transform to M2 & other AMLs


eos and baso varients (rare, aggressive, poor prognosis)





Chronic Neutrophilic leukemia

Chronic Neutrophilic leukemia

↑↑↑ WBC, ↓ Plt
persistent PMNs w/o left shift/sepsis
HIGH LAP
possible toxic granules and dohle bodies

Chronic Monocytic Leukemia

Chronic Monocytic Leukemia

very rare
no longer WHO classified

Polycythemias


(Myeloproliferative Disorder)

Increased RBCs




Polycythemia Vera: malignancy (↑ LAP)


2° Polycythemia: non-pathological compensation for low 02 (LAP normal)


Relative Erythrocytosis: same number of RBCs w/ low plasma volume (LAP normal, ↑ Hct)

Polycythemia Vera


(Myeloproliferative Disorder)

Polycythemia Vera - malignant increase in red cell mass




↑ LAP, ↑ WBCs & Plts, normal O2 Sat


extramedullary hematapoisis


BM hypercellullar (erythro/myelo/megakaryo)


disease progression leads to ↑ aniso/poik (tear drops), Fe deficiciency


JAK2 gene mutation

Essential Thrombocythemia


(Myeloproliferative Disorder)

Essential Thrombocythemia

↑↑↑ Plt, spontaneous Plt aggregation/dysfn
giant bizarre Plts, megakaryo fragments

↑ WBC w/o left shift (neutrophilia)
thrombocytic & hemorrhagic complications
30-50% JAK2 mutation

Remember!

A shift to the left/leukamoid reaction is not just increased WBCs




Left shift is increased immature WBCs




Neutrophilia is just an increase in WBCs

Chronic Ideopathic Myelofibrosis


(Myeloproliferative Disorder)

Chronic Ideopathic Myelofibrosis

↑ immature WBCs & nRBCs in blood
tear drops, abn megakaryos, ↑Plt
Poss Plt agranular, micro, impaired aggreg
extramedullary hematapoiesis (crowding)
marrow fibrosis, anemia
JAK2 mutation

Myelodysplastic Syndromes

Myelodysplastic Syndromes

- diverse diseases (mild anemia to preleukemias)
- common chromosomal defects: del 5q, monosomy 7, trisomy 8, deletions in 11, 12, and 20
- median age 70 years
Myelodysplastic Syndromes - Dyserythropoiesis
Myelodysplastic Syndromes
Dyserythropoiesis


any weird RBC morphology
oval macrocytes, asynchronism, baso stippling
sideroblasts, ringed sideroblasts, pappenheimer
ineffective hematapoiesis/increased apoptosis
Myelodysplastic Syndromes - Dysmyelopoiesis
Myelodysplastic Syndromes
Dysmyelopoiesis

usually neutropenia, hypogranulation
usually hyposegmentation (pseudo P-H)
asynch. (basophilic zones - pseudo dohle)
cell mixes of eos/baso
hybrid myelomonocytes
Myelodysplastic Syndromes -
Dysmegakaryopoiesis
Myelodysplastic Syndromes
Dysmegakaryopoiesis

usually thrombocytopenia
micromegakaryocytes
hypo or hypersegmentation
hypo or agranular
giant Plts

Refractory Anemia (RA) and (RARS)


(Myelodysplastic Syndrome)

Refractory Anemia

Blood: anemia, ↓ WBC & Plt, no/rare blasts

BM: erythroid dysplasia only, ↑ Fe stores
< 5% blasts
RA: < 15% ringed sideroblasts
RARS > 15% ringed sideroblasts
Refractory Cytopenia w/ Multilineage Dysplasia (RCMD) and (RCMD-RS)

(Myelodysplastic Syndrome)
Refractory Cytopenia
w/ Multilineage Dysplasia (RCMD)


Blood: bi or pancytopenia, no/rare blasts, no monos/auer rods
BM: > 10% dysplasia of eryrthroid & 1 or more other myeloid types
< 5% blasts, no auer rods
RCMD: < 15% ringed sideroblasts
RCMD-RS > 15% ringed sideroblasts

Refractory Anemia w/ Excess Blasts
(RAEB-1 &2)

(Myelodysplastic Syndrome)
Refractory Anemia w/ Excess Blasts
(RAEB-1 &2)

Blood: cytopenias, no monos/auers
RAEB-1: < 5% blasts, RAEB-2: 5-9% blasts

BM: uni or multilineage dysplasia
RAEB-1: 5-9% blasts, RAEB-2 10-19% blasts

Unclassified MDS

Unclassified MDS




Blood: cytopenia, no/rare blasts




BM: myelo or megakaryodysplasia


NO ERYTHRODYSPLASIA


< 5% blasts

Chronic Myelomonocytic Leukemia




(Myelodysplastic/Myeloproliferative Disease)

Chronic Myelomonocytic Leukemia

typical dyspoiesis of MDS
increased WBCs (monos, promonos, granulos, immature granulos)
< 20% blasts

CLL/SLL

Chronic/Small Lymphocytic Leukemia




SLL: involves lymph nodes & lymph organs


CLL: blood & BM lymphocytosis




- most common chronic leukemia


- usually older adults


- 95% are B cell

CLL/SLL lab findings

CLL/SLL


variable WBC


predominance of small mature lymphs


many smudge cells


suppression of all Ig - infection


slow marrow infiltration


can develop autoimmune disease


PAS +

Hairy Cell Leukemia

Hairy Cell Leukemia

lymph w/ mono features
PAS =, SBB +, NSE +, TRAP +
phagocytic, produce Ig

splenomegaly, pancytopenia
often low WBC, dry tap

Hodgkin's Lymphoma

Hodgkin's Lymphoma




malignant clone - usually B cells


Reed-Sternberg cell: large bi/multi nuc (red) w/


clear zone (owl eyes)


Hodgkin cell: mononuclear version


cells are usually few in number

Non-Hodgkin's Lymphoma

Non-Hodgkin's Lymphoma

- lymphocytic malignancy
- inciting agents/mutagenic factors: chemicals, radiation, viruses
- damage to genetic code regulating immune cell growth and reproduction

Cutaneous T cell Lymphoma & Sezary Syndrome

Cutaneous T cell Lymphoma
- skin lymphoma w/ characteristic lesions

Sezary Syndrome
- progression of above to blood
- Sezary cell: mature lymph w/ convoluted, cerebriform nuclear folds


Solitary Plasmacytoma

Solitary Plasmacytoma (Plasma Cell Disorder)

- malignant clone of plasma cells
- localized to one area of bone or soft tissue
- most often develops to Multiple Myeloma

Multiple Myeloma test results

Multiple Myeloma (plasma cell Disorder)

- M-spike: monoclonal Ig (usually IgG) diagnose & id w/ SPE & IEP
- suppression of normal normal Ig
- ↑ ESR & bleeding (abn Ig polymerize and ↑ viscosity/bind Plt)
- 25% of MM plasma cells secrete only light chains (renal fail)
- plasma cells produce osteoclast activating factor
- breaks down bone- increased serum Ca++ and Phosphorous

Multiple Myeloma differentials

Multiple Myeloma (plasma cell Disorder)




- few if any plasma cells in blood


- can see Russell Bodies, Mott & Flame cells


- can see immature plasma cells, abn nuc, loss of halo


- rouleaux (abn Ig polymerize/incr viscosity)


- suppression of normal plasma cells

Plasma Cell Leukemia

Plasma Cell Leukemia

- terminal acute phase of Multiple Myeloma
- plasma cells in blood

Waldenstrom's Macroglobulinemia

Waldenstrom's Macroglobulinemia
- malignant lymphocyte/plasma cell proliferation disorder
- monoclonal production of IgM
- neurological issues, infections
- bleeding (Plt coated w/ IgM, interferes w/ fibrin clot formation)
- rouleaux
- cryoglobulin (cold-initiated protein precipitation): Raynaud's phenomenon, thrombosis, renal damage

Monoclonal Gammopathy


of Undetermined Significance

Monoclonal Gammopathy
of Undetermined Significance


- 3% of all adults over 70 years
- milder plasmacytosis in BM w/ no other abnormalities
- +/- 20% progress to Multiple Myeloma

Heavy Chain Disease (HCD)

Heavy Chain Disease (HCD)

very rare
excessive production of heavy chain Ab subunit