Master AML and ALL classification, blast morphology, cytochemistry, and immunophenotyping for ASCP BOC hematology.

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Chapter 21 โ€” ACUTE LEUKEMIAS

ASCP Board Exam ยท Lab-Focused Study Guide
Leukemogenesis ยท FAB vs WHO ยท ALL (B & T, Immunophenotype, Genetics, Prognosis) ยท AML Clinical Picture & Tumor Lysis Syndrome ยท AML with Recurrent Genetic Abnormalities (t(8;21), inv(16), t(15;17) APL, t(9;11)) ยท AML-MRC ยท Therapy-Related ยท AML NOS (M0โ€“M7) ยท Down Syndrome ยท Ambiguous Lineage ยท Cytochemistry (MPO, SBB, Esterases) ยท Practice Questions

1 ยท Priority Table & Quick Foundation

Topic Priority Why It’s Tested
WHO: โ‰ฅ20% blasts for acute leukemia (except specific recurrent genetic abnormalities) HIGH Rodak Q1
Lymphoblast vs myeloblast morphology; Auer rods HIGH Film recognition
ALL immunophenotypes: early (pro) B, common (CD10), pre-B (cytoplasmic ฮผ), T-ALL HIGH Table 35-1
ALL prognosis: age 2โ€“10 best, WBC, hyperdiploidy/t(12;21) good; t(9;22), MLL, hypodiploidy poor HIGH Case study; Rodak Q3
AML with recurrent abnormalities: t(8;21), inv(16), t(15;17) APL, t(9;11) HIGH Rodak Q2, Q6, Q7
APL: hypergranular promyelocytes, Auer rods (faggot cells*), DIC, ATRA + arsenic HIGH Emergency diagnosis
Cytochemistry: MPO, SBB, specific (chloroacetate) and nonspecific esterases, NaF inhibition HIGH Table 35-3; Rodak Q11, Q12
Tumor lysis syndrome: โ†‘ K, โ†‘ POโ‚„, โ†‘ uric acid, โ†“ Ca HIGH Rodak Q5
AML NOS subtypes and FAB M0โ€“M7 equivalents; monocytic markers (CD14, CD64, CD11b, CD36) MEDIUM Rodak Q8, Q10
Erythroid leukemias (erythroleukemia vs pure erythroid) MEDIUM Rodak Q9
Megakaryoblastic leukemia (CD41, CD42b, CD61); Down syndrome (GATA1, TAM) MEDIUM Recognition
AML-MRC, therapy-related neoplasms, ambiguous lineage (AUL, MPAL) MEDIUM Classification
Myeloid sarcoma, BPDCN, NPM1/CEBPA, FLT3 LOW Recognition
๐ŸŽฏ KEY POINT โ€” Where to spend your time

Focus: 20% blast rule and its exceptions, ALL immunophenotype and prognostic factors, the four recurrent AML translocations with their morphology and prognosis, APL + DIC, the cytochemical reaction chart, and tumor lysis syndrome. Skim: rare translocations (t(6;9), inv(3), t(1;22)), BPDCN, future gene markers.

Quick Foundation โ€” from zero

  • Acute leukemia = rapid, clonal proliferation of very immature cells (blasts) in the marrow โ€” lymphoblasts (ALL) or myeloblasts (AML).
  • Blasts crowd out normal hematopoiesis โ†’ anemia (fatigue, pallor), neutropenia (fever, infections), thrombocytopenia (bruising, bleeding).
  • It develops by โ€œmultiple hitsโ€ โ€” mutations that give growth advantage plus mutations that block differentiation โ†’ leukemic stem cells.
  • Known causes are few: radiation, benzene, prior chemotherapy (alkylating agents, topoisomerase II inhibitors), familial syndromes (e.g., Down syndrome).
  • Diagnosis: CBC and film โ†’ marrow โ†’ cytochemistry, flow cytometry and cytogenetics/molecular. WHO requires โ‰ฅ20% blasts (unless a defining translocation is present).
  • ALL is mainly a disease of children; AML is the most common leukemia of adults.
๐Ÿ’ก Analogy

The marrow is a school. In acute leukemia, one class of kindergarteners (blasts) never graduates but keeps enrolling new copies of itself until there’s no room for the other students (normal cells). The lab’s job is to figure out which school they came from: morphology is their uniform, cytochemistry is their ID badge (MPO = myeloid school), flow cytometry is the student record (CD markers), and cytogenetics is their family tree (translocations) โ€” which also predicts how they’ll do.

๐Ÿฅ Why this matters clinically

Recognizing APL is an emergency: its promyelocytes trigger DIC, and treatment (ATRA + arsenic) differs from all other AMLs. Tumor lysis syndrome can cause fatal hyperkalemia and renal failure after induction. Cytogenetics decides prognosis and therapy intensity โ€” e.g., hyperdiploid childhood ALL is cured in most children, while Ph+ ALL needs a tyrosine kinase inhibitor.

Concept Plain-English Explanation
Leukemia Greek leukos (white) + haima (blood)
Blast Most immature recognizable cell of a lineage
Auer rod Needle-like fused primary granules โ€” proves myeloid origin
Blast equivalent Cell counted as a blast: promonocytes, APL promyelocytes
Hyperdiploidy / hypodiploidy >46 / <46 chromosomes
Cytochemistry Stains detecting enzymes/lipids to identify lineage
Tumor lysis syndrome Metabolic chaos from contents of dying cancer cells
Ambiguous lineage Leukemia with no clear lineage or with markers of two lineages

2 ยท Core Content Tables

2.1 Leukemogenesis & Classification

Feature Details
Definition Rapid clonal proliferation of lymphoid or myeloid progenitors (lymphoblasts/myeloblasts) in the marrow; blasts spill into blood when marrow is overwhelmed
Causes Mostly unknown. Known: radiation, organic solvents (benzene), familial cancer predisposition, alkylating agents and chemotherapy (therapy-related leukemias)
Mechanism Stepwise โ€œmultiple hitsโ€: proliferative advantage + differentiation block โ†’ leukemic stem cells (LSCs) initiate and sustain the leukemia
FAB (1970s) Morphology + cytochemistry
WHO (2001, revised 2008) Recurring chromosomal/genetic lesions (oncogenes, tumor suppressors) plus morphology; โ‰ฅ20% marrow blasts for most acute leukemias; genetic testing required

2.2 Lymphoblast vs Myeloblast

Feature Lymphoblast Myeloblast
Size 2โ€“3ร— a normal lymphocyte (small type 1.0โ€“2.5ร—) 3โ€“5ร— a lymphocyte
Cytoplasm Scant, blue Moderate, gray
Chromatin Coarser, stains deeper Uniform, fine
Nucleoli Inconspicuous (large type: prominent + membrane irregularity) Two or more, prominent
Auer rods Never Possible
MPO / SBB Negative (<3% blasts) Usually positive

2.3 Acute Lymphoblastic Leukemia โ€” Clinical

Feature Details
Epidemiology 25% of childhood cancers; up to 75% of childhood leukemia; peak age 2โ€“5 years; rare in adults (risk โ†‘ with age; most adult patients >50)
Outcome Adults: 80โ€“90% complete remission but <40% cured
B-ALL presentation Fatigue (anemia), fever (neutropenia, infection), mucocutaneous bleeding (thrombocytopenia); lymphadenopathy, splenomegaly, hepatomegaly; bone pain (intramedullary growth)
Sanctuary sites Infiltration of meninges, testes, ovaries; lymphoblasts in CSF
T-ALL Large mediastinal mass (can compress structures); anemia, thrombocytopenia, organomegaly, bone pain; leukopenia less severe; most in teenage males with high blast counts, meningeal involvement
WBC Only about half have leukocytosis; many lack circulating lymphoblasts

2.4 B-ALL with Recurrent Genetic Abnormalities (Rodak Box 35-1) & Prognosis

Abnormality Prognosis / Notes
t(9;22)(q34;q11.2); BCR-ABL1 (Ph+ ALL) Worst ALL prognosis; more common in adults (20% adult, 2โ€“5% child); imatinib improved survival
t(v;11q23); MLL rearranged Very young infants (may occur in utero); very poor
t(12;21)(p13;q22); TEL-AML1 (ETV6-RUNX1) ~25% of childhood ALL; from a B progenitor; rare in adults; excellent (>90% cure in children)
Hyperdiploidy (>46 chromosomes) 25% of childhood B-ALL; less common in adults; very favorable in children
Hypodiploidy (<46) Poor in children and adults
t(5;14)(q31;q32); IL3-IGH Recurrent subtype (reactive eosinophilia*)
t(1;19)(q23;p13.3); E2A-PBX1 (TCF3-PBX1) Recurrent subtype
B-ALL, NOS No specific abnormality
T-ALL 50โ€“70% abnormal gene rearrangements but no specific biologic subgroups โ€” not subdivided; majority NOTCH1 gain-of-function

*Eosinophilia with t(5;14) comes from Rodak Ch. 29 (nonmalignant leukocyte disorders).

2.5 ALL Prognostic Factors

Feature Details
Main factors Age at diagnosis, lymphoblast load (tumor burden), immunophenotype, genetic abnormalities
Age Children (not infants or teens) do best
Strongest predictor Chromosomal translocations (children and adults)
Adverse Blasts in blood >20โ€“30 ร— 10โน/L, hepatosplenomegaly, lymphadenopathy; t(9;22), MLL, hypodiploidy; ETP-ALL
Favorable Hyperdiploidy, t(12;21)
No longer adverse Sex and ethnicity (with equal treatment access)
Good-prognosis children ~95% complete remission

2.6 Immunophenotypic Characteristics of ALL (Rodak Table 35-1)

ALL Subtype Immunophenotype Frequency / Notes
Early (pro/pre-pre) B-ALL CD34, CD19, cytoplasmic CD22, TdT ~5% children, 11% adults
Intermediate (common) B-ALL CD34, CD19, CD10, cytoplasmic CD22, TdT CD10 = CALLA*
Pre-B-ALL CD34 (typically negative in most mature), CD19, cytoplasmic CD22, cytoplasmic ฮผ, TdT (variable) 15% childhood, 10% adult
T-ALL CD2, CD3, CD4, CD5, CD7, CD8, TdT Mediastinal mass; ETP-ALL (CD8โˆ’, CD5 dim) poor response

Both B and T lymphoblasts usually express CD34, TdT, HLA-DR. B-cell antigens: CD19, CD20, CD22, CD24, CD79a, CD10, cytoplasmic ฮผ, PAX-5. Immunophenotyping and genetics are the most reliable indicators of origin. *CALLA (common ALL antigen) is standard terminology not used in this Rodak chapter.

2.7 AML โ€” Clinical Presentation

Feature Details
Epidemiology Most common leukemia in adults; incidence โ†‘ with age; less common in children
WBC Usually 5โ€“30 ร— 10โน/L (range 1โ€“200); myeloblasts in blood in 90%
Symptoms Pallor, fatigue, fever, bruising, bleeding; DIC and bleeding abnormalities can be significant; infiltration of gums, mucosa, skin
Organs Splenomegaly in ~half; lymphadenopathy rare; CNS involvement rare and less ominous than in ALL
Chemistry Hyperuricemia (turnover), hyperphosphatemia (lysis), hypocalcemia, hypokalemia at presentation
Diagnosis CBC, film, marrow aspirate and biopsy; marrow usually hypercellular with >20% blasts (not needed if certain genetic abnormalities present)

2.8 Tumor Lysis Syndrome (TLS)

Feature Details
Setting Malignancy (lymphomas, leukemias), especially during induction chemotherapy with high WBC/tumor burden; also without treatment
Cause Breakdown products of dying cancer cells โ†’ acute uric acid nephropathy and renal failure
Labs Hyperkalemia (can be life-threatening alone), hyperphosphatemia, hyperuricemia, hyperuricosuria, hypocalcemia
Clinical Renal failure; seizures* (hypocalcemia), arrhythmias*
Management Aggressive prophylaxis is critical

*Seizures and arrhythmias are general clinical consequences; Rodak Q5 links renal failure + seizures after chemotherapy to TLS.

2.9 WHO 2008 AML Categories (Rodak Boxes 35-2 & 35-3)

Main Category Includes
AML with recurrent genetic abnormalities t(8;21) RUNX1-RUNX1T1 ยท inv(16)/t(16;16) CBFB-MYH11 ยท APL t(15;17) PML-RARA ยท t(9;11) MLLT3-MLL ยท t(6;9) DEK-NUP214 ยท inv(3)/t(3;3) RPN1-EVI1 ยท t(1;22) RBM15-MKL1 (megakaryoblastic) ยท provisional: mutated NPM1, mutated CEBPA
AML with myelodysplasia-related changes โ‰ฅ20% blasts + multilineage dysplasia, prior MDS or MDS/MPN, or MDS-type cytogenetics
Therapy-related myeloid neoplasms After alkylating agents, radiation, topoisomerase II inhibitors
AML, not otherwise specified Morphology/FAB-like subtypes
Myeloid sarcoma Extramedullary blast mass effacing tissue
Myeloid proliferations related to Down syndrome TAM; megakaryoblastic leukemia; GATA1
Blastic plasmacytoid dendritic cell neoplasm Skin lesions โ†’ blood/marrow

2.10 AML with Recurrent Genetic Abnormalities โ€” Key Four

Translocation / Gene Frequency Morphology & Features Prognosis
t(8;21)(q22;q22); RUNX1-RUNX1T1 ~5% of AML; children and young adults Myeloblasts with dysplastic granular cytoplasm, Auer rods, some maturation (~FAB M2); pseudo-Pelger-Huรซt, hypogranulation; eosinophilia possible Favorable (worse with โˆ’7 etc.)
inv(16)(p13.1q22) or t(16;16); CBFB-MYH11 (core-binding factor) 5โ€“8%; mostly younger Myeloblasts, monoblasts, promyelocytes; marrow eosinophilia with dysplastic eosinophils (~FAB M4eo); more extramedullary disease; CNS relapse Good remission; only half cured
t(15;17)(q22;q12); PML-RARA โ€” APL 5โ€“10%; all ages, mostly young adults Differentiation block at promyelocyte (counted as blasts); hypergranular promyelocytes with Auer rods; microgranular variant (30โ€“40%): bilobed โ€œbutterflyโ€/โ€œcoin-on-coinโ€ nuclei, occasional Auer rods. Primary granule procoagulants โ†’ DIC; thromboembolism Best of all AML in adults with remission; treat with ATRA (vitamin A analogue, induces differentiation) + arsenic trioxide; some RARA variants don’t respond to ATRA
t(9;11)(p22;q23); MLLT3-MLL ~6%; usually children โ†‘ Monoblasts and immature monocytes: large, abundant cytoplasm, fine chromatin, pseudopodia, granules/vacuoles; gingival and skin involvement; DIC Intermediate to poor

Diagnosis of t(8;21), inv(16)/t(16;16) and t(15;17) AML is made on the genetic abnormality regardless of blast count.

2.11 AML with MDS-Related Changes & Therapy-Related Neoplasms

Feature Details
AML-MRC Older adults, poor prognosis; โ‰ฅ20% blasts + multilineage dysplasia, prior MDS or MDS/MPN, or MDS-associated cytogenetics, without a recurrent-abnormality AML
AML-MRC morphology Pancytopenia; neutrophil hypo/hypergranulation, pseudo-Pelger-Huรซt, bizarre segmentation; erythroid vacuoles, karyorrhexis, megaloblastoid features, ring sideroblasts; micromegakaryocytes
AML-MRC genetics Like MDS: complex karyotypes, โˆ’7/del(7q), โˆ’5/del(5q)
Therapy-related Alkylating agents, radiation, topoisomerase II inhibitors โ†’ secondary AML, MDS, MDS/MPN; 10โ€“20% of these; also after cytotoxic therapy for nonmalignant disease; morphology like AML-MRC, monocytic or AML with maturation; generally poor โ€” except t(15;17) and inv(16) cases behave like de novo

2.12 AML, Not Otherwise Specified & FAB Equivalents (Rodak Table 35-2)

WHO AML NOS Subtype FAB Key Features
Minimal differentiation M0 Blasts CD13โบ, CD33โบ, CD34โบ, CD117โบ; no Auer rods; MPO and SBB negative; <5% of AML; infants or older adults
Without maturation M1 CD13, CD33, CD117 โบ; CD34 in ~70%; blasts up to 90% of nonerythroid cells; <10% mature beyond promyelocyte; Auer rods; MPO/SBB positive
With maturation M2 >20% blasts, โ‰ฅ10% maturing neutrophil lineage cells, <20% monocytic; Auer rods, dysplasia
(APL โ€” now recurrent-abnormality category) M3 t(15;17)
Acute myelomonocytic M4 (M4eo) โ†‘ WBC; myeloid + monocytic cells in blood and marrow; monocytic cells โ‰ฅ20% of marrow cells; CD13, CD33 + CD14, CD4, CD11b, CD11c, CD64, CD36
Acute monoblastic / monocytic M5a / M5b โ‰ฅ80% of marrow cells monocytic (CD14, CD4, CD11b, CD11c, CD36, CD64, CD68); large blasts, abundant often agranular cytoplasm, prominent nucleoli; promonocytes = blast equivalents; NSE positive; <5% of AML; younger patients; skin and gingival infiltration, bleeding
Acute erythroid: erythroleukemia (erythroid/myeloid) M6 โ‰ฅ50% of nucleated marrow cells are normoblasts and โ‰ฅ20% (of nonerythroid cells*) are myeloblasts
Acute erythroid: pure erythroid leukemia โ€” โ‰ฅ50% nucleated cells pronormoblasts and โ‰ฅ30% basophilic normoblasts; erythroid >80% of marrow; myeloblasts insignificant; complex karyotypes, chromosomes 5 and 7. RBC precursors: multinucleation, megaloblastoid asynchrony, vacuoles, ring sideroblasts; nRBCs may be >50% of blood nucleated cells; aggressive
Acute megakaryoblastic M7 โ‰ฅ20% blasts, โ‰ฅ50% of megakaryocyte origin; cytopenias (sometimes thrombocytosis); blasts small to 3ร— lymphocyte, cytoplasmic blebs; CD41 (GPIIb), CD42b (GPIb), CD61 (GPIIIa), cytoplasmic VWF; excludes AML-MRC, Down syndrome, recurrent abnormalities

AML NOS: ~25% of AML; โ‰ฅ20% blasts in blood or marrow. *Rodak states ‘>20% are myeloblasts’; WHO 2008 counts myeloblasts among nonerythroid cells.

2.13 Other Myeloid Categories

Feature Details
Myeloid sarcoma Extramedullary blast proliferation that effaces tissue architecture
Down syndrome Somatic GATA1 mutations; ~10% of newborns have transient abnormal myelopoiesis (TAM) โ€” looks like AML, remits spontaneously in months; 50-fold โ†‘ AML in first 5 years; megakaryocytic; young children respond well
Blastic plasmacytoid dendritic cell neoplasm Rare, aggressive; skin lesions โ†’ blood and marrow
Future markers KIT, FLT3, ASXL1, TP53, CEBPA, NPM1 (NPM1 and CEBPA provisional in 2008)

2.14 Acute Leukemias of Ambiguous Lineage (Rodak Box 35-4)

Type Definition Synonyms / Subtypes
Acute undifferentiated leukemia (AUL) No clear evidence of differentiation along any lineage ALAL without differentiation, primitive acute leukemia, stem cell leukemia
Mixed phenotype acute leukemia (MPAL) Multiple antigens โ€” lineage can’t be assigned Biphenotypic, bilineal, mixed lineage, dual lineage, hybrid; subtypes: MPAL with t(9;22) BCR-ABL1 ยท with t(v;11q23) MLL ยท B/myeloid NOS ยท T/myeloid NOS

2.15 Cytochemical Reaction Chart (Rodak Table 35-3)

Condition MPO SBB NASDA (specific) ANBE (nonspecific) ANAE (nonspecific)
ALL โˆ’ โˆ’ โˆ’ โˆ’/+ (focal) โˆ’/+ (focal)
AML + + + โˆ’ โˆ’
AMML + + + + (diffuse) + (diffuse)
AMoL โˆ’ โˆ’/+ โˆ’ + (diffuse) + (diffuse)
Megakaryocytic โˆ’ โˆ’ โˆ’ โˆ’ + (localized)

MPO, myeloperoxidase; SBB, Sudan black B; NASDA, naphthol AS-D chloroacetate esterase; ANBE, ฮฑ-naphthyl butyrate esterase; ANAE, ฮฑ-naphthyl acetate esterase.

2.16 Cytochemistry โ€” Principles

Feature Details
Advantages Cheap, available worldwide; useful where advanced techniques are limited
Specimen Enzymatic reactions need fresh smears; nonenzymatic (SBB) can use stored specimens
Rule Only the reaction in blasts counts โ€” mature granulocytes being MPOโบ is normal
MPO Enzyme in primary granules of neutrophils, eosinophils, some monocytes (from promyelocyte on). Myeloblasts usually +; >80% of blasts + in AML without/with maturation and APL; Auer rods strongly +; lymphoblasts and lymphoid cells negative. Differentiates AML from ALL
Sudan black B Stains cellular lipids; parallels MPO; possibly more sensitive for early myeloid cells; โ†‘ intensity with maturation; monocytes โˆ’ to weak +; lymphoid cells negative (<3% of ALL blasts +)
Esterases 9 isoenzymes; separate granulocytic from monocytic cells
Specific esterase (naphthol AS-D chloroacetate) Granulocytic cells +, monocytes โˆ’ to weak; primary granules; leukemic myeloblasts + and Auer rods +
Nonspecific esterases ฮฑ-naphthyl acetate: strong in monocytes, inhibited by sodium fluoride; granulocytes and lymphoid cells negative. ฮฑ-naphthyl butyrate: diffuse + in monocytes; less sensitive but more specific; granulocytes and lymphoid โˆ’ (small dot in lymphocytes)
AMML pattern Chloroacetate + AND butyrate/acetate +; โ‰ฅ20% of cells NSE + and NaF-inhibited
Pure monocytic pattern โ‰ฅ80% of blasts NSE + and specific esterase โˆ’

3 ยท Visual Memory Hooks

๐Ÿง  20% rule
โ€œTwenty to call it acute โ€” unless 8-21, 16, or 15-17 speaks firstโ€.
๐Ÿง  ALL vs AML age
โ€œALL is for ALL the kids; AML is for Adultsโ€.
๐Ÿง  Lymphoblast vs myeloblast
โ€œLympho: Little cytoplasm, Lazy nucleoli; Myelo: More cytoplasm, Many nucleoli, Maybe Auer rodsโ€.
๐Ÿง  Auer rods
โ€œAuer rod = AML, Alwaysโ€ โ€” never in ALL.
๐Ÿง  B-ALL stages
โ€œPro-B: 34/19/22/TdT ยท Common: + CD10 ยท Pre-B: + cytoplasmic ฮผโ€.
๐Ÿง  T-ALL
โ€œTeenage boy + Thymic (mediastinal) mass = T-ALLโ€.
๐Ÿง  Good ALL
โ€œHyper is Happy; 12;21 is Terrificโ€.
๐Ÿง  Bad ALL
โ€œPhilly, MLL babies, Hypo = Horribleโ€.
๐Ÿง  t(8;21)
โ€œ8 + 21 = 29 โ†’ M2 with Auer rods, good newsโ€*.
๐Ÿง  inv(16)
โ€œInv 16 = sixteen Eosinophils (M4eo)โ€.
๐Ÿง  APL
โ€œ15;17 โ†’ Promyelocytes โ†’ DIC โ†’ ATRA + arsenicโ€.
๐Ÿง  Microgranular APL
โ€œButterfly nucleus, few visible granules โ€” still APLโ€.
๐Ÿง  t(9;11)
โ€œ9-11 โ†’ Monocytes attack gums and skinโ€.
๐Ÿง  Monocytic markers
โ€œ14, 64, 11b, 36 โ€” the monocyte crewโ€.
๐Ÿง  Megakaryoblastic
โ€œ41, 42b, 61 = platelet glycoproteins IIb, Ib, IIIaโ€.
๐Ÿง  Esterases
โ€œSpecific (chloroacetate) = granulocyte; Nonspecific = monocyte, killed by Fluorideโ€.
๐Ÿง  SBB
โ€œSudan Black = Sudan Blubber (lipids)โ€.
๐Ÿง  TLS
โ€œKโบ, POโ‚„, Uric acid UP; Calcium Comes downโ€.
๐Ÿง  Down syndrome
โ€œGATA1 โ†’ TAM โ†’ megakaryoblastsโ€.
๐Ÿง  M0
โ€œM0 = zero stains (MPO/SBB โˆ’), but CD13/33/34/117 +โ€.

*Numbers-add mnemonic is a memory device only. ‘Faggot cells’ (bundles of Auer rods in APL) is a classic term not used in Rodak.

Pattern Triggers

If you seeโ€ฆ Thinkโ€ฆ Becauseโ€ฆ
5-year-old, bruises, WBC 15, Hb 8, platelets 90, small blasts, hyperdiploidy B-ALL with favorable features Rodak case study
Teenage boy, mediastinal mass, high blast count, CD3/CD7/TdT + T-ALL
Infant <1 year with very high WBC and 11q23 MLL-rearranged ALL Very poor
Blasts CD10โบ, CD19โบ, TdTโบ, CD34โบ Common B-ALL
Blasts with Auer rods, MPO + AML
Myeloblasts with granular cytoplasm, Auer rods, maturation, young adult AML with t(8;21) RUNX1-RUNX1T1
Myelomonocytic blasts + dysplastic marrow eosinophils AML with inv(16) CBFB-MYH11
Hypergranular promyelocytes, bundles of Auer rods, DIC APL t(15;17) Emergency; ATRA
Bilobed ‘butterfly’ nuclei, few granules, DIC Microgranular APL
Child, monoblasts, gingival hypertrophy, skin lesions AML t(9;11) / monocytic leukemia
Blasts CD14, CD64, CD11b, CD36 +, NSE + inhibited by NaF Acute monoblastic/monocytic
Blasts CD61 +, cytoplasmic blebs, marrow fibrosis* Acute megakaryoblastic
โ‰ฅ50% pronormoblasts, โ‰ฅ30% basophilic normoblasts Pure erythroid leukemia
Newborn with Down syndrome, blasts, spontaneous remission Transient abnormal myelopoiesis GATA1
After chemo: โ†‘ K, โ†‘ POโ‚„, โ†‘ uric acid, โ†“ Ca, renal failure, seizures Tumor lysis syndrome
Blasts express both myeloid and B markers MPAL Ambiguous lineage
AML in elderly with multilineage dysplasia, โˆ’7 AML with MDS-related changes Poor

*Marrow fibrosis in megakaryoblastic leukemia is general knowledge, not stated in Rodak Ch. 35.

Commonly Confused Pairs

Feature A B
ALL vs AML Children; MPO/SBB โˆ’; TdT +; no Auer rods Adults; MPO/SBB +; Auer rods
B-ALL vs T-ALL CD19, CD10, CD22, CD79a CD2, CD3, CD5, CD7; mediastinal mass
Common B vs pre-B ALL CD10 + Cytoplasmic ฮผ +
t(12;21) vs t(9;22) ALL Children, excellent Adults, worst
Hyperdiploid vs hypodiploid Favorable Poor
t(8;21) vs inv(16) M2-like, Auer rods M4eo, dysplastic eosinophils
APL hypergranular vs microgranular Obvious granules, Auer rods Bilobed nuclei, granules too small to see
APL vs other AML treatment ATRA + arsenic Standard induction chemotherapy*
Specific vs nonspecific esterase Chloroacetate; granulocytes ฮฑ-naphthyl acetate/butyrate; monocytes, NaF-inhibited
ฮฑ-naphthyl acetate vs butyrate More sensitive More specific
MPO vs SBB Enzyme; fresh smear Lipid; stored smears OK; more sensitive early
AMML vs AMoL Monocytic โ‰ฅ20%, granulocytic component Monocytic โ‰ฅ80%
Erythroleukemia vs pure erythroid โ‰ฅ50% erythroid + โ‰ฅ20% myeloblasts โ‰ฅ80% erythroid, no significant myeloblasts
AUL vs MPAL No lineage markers Markers of two lineages

*Standard induction for non-APL AML is general knowledge.

Timeline Table

Event Timing Key Point Best Exam Use
FAB classification 1970s Morphology + cytochemistry History
WHO classification 2001; revised 2008 Genetics, 20% blasts History
ALL peak incidence 2โ€“5 years Children do best Epidemiology
MLL ALL Very young infants (in utero) Very poor Prognosis
TLS During induction chemotherapy High WBC risk Complication
TAM in Down syndrome Newborn; remits within months 10% of DS newborns Recognition
AML risk in Down syndrome First 5 years, 50ร— Megakaryocytic Epidemiology
Enzymatic cytochemistry Fresh smear required Enzyme degrades Pre-analytical

4 ยท Diagnostic Flowcharts

Flowchart 1 โ€” Suspected acute leukemia

Cytopenias ยฑ leukocytosis, blasts on film โ†’ Marrow aspirate and biopsy
Count blasts (include promonocytes, APL promyelocytes) โ†’ โ‰ฅ20% โ†’ acute leukemia (or any % with t(8;21), inv(16), t(15;17))
Lineage โ†’ Morphology (Auer rods), cytochemistry (MPO/SBB, esterases), flow cytometry
Genetics โ†’ Karyotype, FISH, molecular โ€” classify and prognosticate
Urgent flags โ†’ DIC (APL), TLS risk, CNS/testis involvement (ALL)
โš ๏ธ Common mistake: waiting for 20% blasts when a defining translocation such as t(15;17) is already present.

Flowchart 2 โ€” Separating ALL from AML

Auer rods present โ†’ AML (rules out ALL)
MPO or SBB โ‰ฅ3% of blasts positive โ†’ AML
MPO/SBB negative, TdT +, CD19/CD10 or CD3/CD7 โ†’ ALL (B or T)
MPO negative but CD13/CD33/CD117 + โ†’ AML with minimal differentiation (M0)
Markers of two lineages โ†’ Ambiguous lineage (MPAL)
โš ๏ธ Common mistake: calling an MPO-negative leukemia ALL without flow cytometry โ€” M0 and monocytic/megakaryocytic AML are MPO negative.

Flowchart 3 โ€” Classifying B-ALL and predicting prognosis

CD34, CD19, cCD22, TdT only โ†’ Early (pro) B-ALL
+ CD10 โ†’ Common B-ALL
+ cytoplasmic ฮผ (CD34 often โˆ’) โ†’ Pre-B-ALL
Genetics โ†’ Hyperdiploidy or t(12;21) โ†’ favorable ยท t(9;22), MLL, hypodiploidy โ†’ poor
Clinical โ†’ Age 2โ€“10 and WBC <20โ€“30 ร— 10โน/L โ†’ favorable
โš ๏ธ Common mistake: treating all ALL alike โ€” cytogenetics is the strongest predictor.

Flowchart 4 โ€” AML with a characteristic picture

Hypergranular promyelocytes / butterfly nuclei + DIC โ†’ APL โ†’ confirm t(15;17)/PML-RARA โ†’ ATRA + arsenic urgently
Granular blasts with Auer rods and maturation โ†’ Check t(8;21)
Myelomonocytic + dysplastic eosinophils โ†’ Check inv(16)/t(16;16)
Monoblasts, child, gingival/skin disease โ†’ Check t(9;11)
Multilineage dysplasia, elderly, prior MDS โ†’ AML-MRC
Prior chemo/radiation โ†’ Therapy-related myeloid neoplasm
โš ๏ธ Common mistake: missing microgranular APL because granules aren’t visible โ€” look at the bilobed nuclei and coagulation tests.

Flowchart 5 โ€” Esterase interpretation

Chloroacetate (specific) +, NSE โˆ’ โ†’ Granulocytic (AML with/without maturation)
NSE diffuse +, inhibited by NaF, chloroacetate โˆ’ โ†’ Monocytic (AMoL; โ‰ฅ80% blasts)
Both specific and NSE + populations (โ‰ฅ20% monocytic) โ†’ AMML
ANAE localized +, others โˆ’ โ†’ Megakaryoblastic (confirm CD41/CD61)
Focal NSE dots, MPO โˆ’ โ†’ Lymphoid (ALL)
โš ๏ธ Common mistake: forgetting the sodium fluoride step โ€” fluoride inhibition confirms monocytic NSE.

Flowchart 6 โ€” Tumor lysis syndrome

High tumor burden (high WBC, bulky lymphoma) starting chemotherapy โ†’ Prophylaxis (hydration, uric-acid lowering*)
Monitor โ†’ Kโบ, phosphate, uric acid, calcium, creatinine
โ†‘ K, โ†‘ POโ‚„, โ†‘ uric acid, โ†“ Ca โ†’ TLS
Renal failure, seizures, arrhythmia โ†’ Emergency treatment
โš ๏ธ Common mistake: missing hyperkalemia โ€” it alone can be fatal.

*Specific prophylactic agents (allopurinol, rasburicase) are general knowledge.

5 ยท 25 High-Yield Facts

# Fact
1 Acute leukemia is rapid clonal proliferation of lymphoblasts or myeloblasts in the marrow.
2 Leukemia develops through stepwise ‘multiple hits’ that give proliferative advantage and block differentiation.
3 WHO requires at least 20% marrow blasts, except with certain recurrent genetic abnormalities.
4 Lymphoblasts have scant blue cytoplasm; myeloblasts have moderate gray cytoplasm, fine chromatin and prominent nucleoli.
5 Auer rods indicate myeloid lineage and are strongly MPO positive.
6 ALL accounts for up to 75% of childhood leukemia, with peak incidence at 2โ€“5 years.
7 Children (not infants or teens) with ALL do best; chromosomal translocations are the strongest prognostic predictor.
8 Hyperdiploidy and t(12;21) ETV6-RUNX1 are favorable in childhood ALL.
9 t(9;22) BCR-ABL1 is the worst ALL prognosis and is more common in adults.
10 MLL (11q23)-rearranged ALL occurs in infants and has a very poor prognosis.
11 Common B-ALL expresses CD10; pre-B-ALL expresses cytoplasmic ฮผ heavy chain.
12 T-ALL typically presents in teenage males with a mediastinal mass and expresses CD2, CD3, CD5, CD7 and TdT.
13 CNS involvement is more typical of ALL than AML.
14 AML is the most common leukemia in adults; myeloblasts are in the blood in 90% of patients.
15 Tumor lysis syndrome causes hyperkalemia, hyperphosphatemia, hyperuricemia and hypocalcemia.
16 AML with t(8;21) shows granular myeloblasts with Auer rods and has a favorable prognosis.
17 AML with inv(16) shows increased marrow eosinophils with dysplastic features.
18 APL t(15;17) PML-RARA has abnormal promyelocytes and is associated with DIC.
19 APL is treated with ATRA and arsenic trioxide.
20 AML with t(9;11) occurs in children with monoblasts and gingival/skin involvement.
21 Monocytic blasts express CD14, CD4, CD11b, CD11c, CD36 and CD64.
22 Megakaryoblasts are identified by CD41, CD42b and CD61.
23 Pure erythroid leukemia has โ‰ฅ50% pronormoblasts and โ‰ฅ30% basophilic normoblasts.
24 Sudan black B stains lipids and parallels MPO.
25 Nonspecific esterase (ฮฑ-naphthyl butyrate/acetate) is diffusely positive in monocytes and inhibited by sodium fluoride.
โญ EXAM TIP โ€” The single most testable pattern

Auer rods or MPO/SBB + = AML; TdT + and MPO โˆ’ = ALL. Then match the genetics: t(8;21) Auer rods/good ยท inv(16) eosinophils/good ยท t(15;17) promyelocytes + DIC/ATRA ยท t(9;11) monocytes + gums. Childhood ALL: hyperdiploidy and t(12;21) good; Ph and MLL bad. Esterases: specific = granulocytes, nonspecific + NaF-inhibited = monocytes.

Quick Interpretation Table

Lab Finding Clinical Interpretation
5-year-old: weakness, bruises, WBC 15, Hb 8, platelets 90, abnormal cells, hyperdiploidy B-ALL; favorable: age 2โ€“10, WBC <20โ€“30, hyperdiploidy (very favorable) (Rodak case study)
20-year-old: 70% blasts, 21% monocytes, dysplastic marrow eosinophils AML with inv(16)/t(16;16) (Rodak Q2)
Swollen gums, 82% delicate blasts CD14, CD4, CD11b, CD36 + Acute monoblastic/monocytic leukemia (Rodak Q8)
WBC 3.0, trilineage dysplasia, 60% variable blasts, CD61 + Acute megakaryoblastic leukemia (Rodak Q10)
Renal failure and seizures after chemotherapy Tumor lysis syndrome (Rodak Q5)
Blasts MPO โˆ’, SBB โˆ’, CD13/CD33/CD34/CD117 + AML with minimal differentiation (M0)
Blasts CD19, CD10, TdT +, t(9;22) Ph+ B-ALL โ€” worst prognosis; add TKI
Prolonged PT/PTT, low fibrinogen, hypergranular promyelocytes APL with DIC โ€” start ATRA

๐ŸŽด Flashcards โ€” Active Recall Practice

How it works: tap the card to flip it. Then mark it โœ“ Knew It or โœ— Review Again (buttons unlock after flipping). Use ๐Ÿ”€ Shuffle to randomize and ๐Ÿ Finish anytime โ€” your summary appears at the end, and you can drill only the cards you missed.

๐Ÿ“ Practice Quiz โ€” Test Your Knowledge

How it works: tap an answer for each case. You’ll get instant feedback with the full explanation and the examiner’s trap. Your final score appears once all 10 are answered.

๐Ÿชค Trap Questions โ€” Beat the Examiner

Harder on purpose. Each question targets a real misconception. After answering you’ll see the correct reasoning, the trap explained, why the examiner wrote it, and the wrong answer most students choose.

8 ยท Rapid Revision Sheet

๐Ÿ“– READ THIS 2 HOURS BEFORE YOUR EXAM

Basics

  • Clonal blasts; multiple hits
  • Radiation, benzene, chemotherapy, familial
  • FAB 1970s (30%) โ†’ WHO 2001/2008 (20%)
  • Lymphoblast: scant blue cytoplasm
  • Myeloblast: gray cytoplasm, nucleoli, Auer rods

ALL Clinical

  • 75% of childhood leukemia; peak 2โ€“5
  • Anemia, fever, bleeding, bone pain
  • CNS, testes, ovaries
  • T-ALL: teen male, mediastinal mass
  • Adults: 80โ€“90% CR, <40% cure

ALL Phenotype

  • B and T: CD34, TdT, HLA-DR
  • Pro-B: CD19, cCD22 (5% kids, 11% adults)
  • Common: + CD10
  • Pre-B: cytoplasmic ฮผ
  • T: CD2, 3, 4, 5, 7, 8 ยท NOTCH1 ยท ETP poor

ALL Genetics

  • t(12;21) 25% kids, >90% cure
  • Hyperdiploidy 25% kids, very favorable
  • t(9;22) worst; adults 20%
  • MLL: infants, very poor
  • Hypodiploidy poor ยท translocations = strongest predictor

AML Clinical & TLS

  • Most common adult leukemia
  • WBC 5โ€“30; blasts in blood 90%
  • DIC, gums/skin, splenomegaly ยฝ
  • TLS: โ†‘K โ†‘POโ‚„ โ†‘urate โ†“Ca
  • Hyperkalemia can kill; prophylaxis

Recurrent AML

  • t(8;21) RUNX1-RUNX1T1: Auer rods, M2, good
  • inv(16) CBFB-MYH11: eos, M4eo, good
  • t(15;17) PML-RARA: APL, DIC, ATRA+As
  • t(9;11) MLLT3-MLL: monoblasts, kids, gums
  • No 20% needed: 8;21, 16, 15;17

Other AML Groups

  • AML-MRC: elderly, dysplasia, โˆ’5/โˆ’7, poor
  • Therapy-related 10โ€“20%: alkylators, topo II
  • Down: GATA1, TAM, megakaryoblastic, 50ร—
  • Myeloid sarcoma ยท BPDCN
  • AUL vs MPAL (ambiguous)

AML NOS (FAB)

  • M0: MPO/SBB โˆ’, CD13/33/34/117 +
  • M1: no maturation ยท M2: โ‰ฅ10% maturing
  • M4: โ‰ฅ20% monocytic ยท M5: โ‰ฅ80% monocytic
  • M6 erythroid ยท pure erythroid โ‰ฅ50% pro + โ‰ฅ30% baso
  • M7: CD41, CD42b, CD61; blebs

MPO & SBB

  • MPO: primary granules; AML +, ALL โˆ’
  • Auer rods strongly MPO +
  • SBB: lipids; parallels MPO; stored smears OK
  • Only blasts count
  • ALL: <3% blasts SBB +

Esterases

  • Specific (chloroacetate): granulocytes
  • Nonspecific (acetate, butyrate): monocytes
  • NaF inhibits monocytic NSE
  • Butyrate less sensitive, more specific
  • AMML: both ยท Megakaryocytic: ANAE localized

9 ยท Final Memory Map

  • โšก ACUTE LEUKEMIAS
    • General
      • Multiple-hit leukemogenesis ยท known causes
      • FAB vs WHO ยท 20% blast rule and exceptions
    • ALL
      • B-ALL (pro, common CD10, pre-B cฮผ) ยท T-ALL (mediastinum)
      • Genetics: t(12;21), hyperdiploidy (good) vs t(9;22), MLL, hypodiploidy (poor)
      • CNS/testes ยท prognosis by age, burden, genetics
    • AML โ€” Recurrent
      • t(8;21) ยท inv(16) ยท t(15;17) APL ยท t(9;11)
      • t(6;9) ยท inv(3) ยท t(1;22) ยท NPM1 ยท CEBPA
    • AML โ€” Other
      • MDS-related changes ยท therapy-related
      • NOS: M0, M1, M2, M4, M5, M6, M7
      • Myeloid sarcoma ยท Down syndrome ยท BPDCN
    • Ambiguous Lineage
      • AUL ยท MPAL
    • Lab Tools
      • Morphology ยท cytochemistry (MPO, SBB, esterases)
      • Flow cytometry ยท cytogenetics/molecular
      • Tumor lysis syndrome monitoring



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