The document provides a comprehensive overview of acute lymphoblastic leukemia (ALL), detailing its classification, etiology, clinical presentation, and genetic abnormalities. It describes different morphological types of leukemia blasts, their immunophenotypes, and various classifications such as FAB, immunological, and WHO. The document emphasizes the importance of specific genetic mutations and cytogenetic alterations in the pathogenesis and prognosis of ALL.

1. ACUTE LYMPHOBLASTIC LEUKEMIA
(ALL)
DRNILISHASHARMA
JR 1 PATHOLOGY

2. WHAT IS LEUKEMIA ??
DIVIDED INTO TWO BROAD CATEGORIES
• ACUTE MYELOID LEUKAEMIA
• ACUTE LYMPHOBLASTIC
LEUKAEMIA

5. FEATURES LYMPHOBLAST
NUCLEAR CHROMATIN COARSE FINE
NUCLEOLI 1-2 3-5
N:C RATIO HIGH HIGH
AUER ROD NEGATIVE POSITIVE
OTHER CELLS LYMPHOCYTES MYELOID PRECCURSOR
MYELO PEROXIDASE NEGATIVE POSITIVE
SUDAN BLACK B NEGATIVE POSITIVE
PAS STAIN BLOCK POSITIVITY NEGATIVE IN BLAST

6. CLASSIFICATION

7. ETIOLOGY
◦ HIGHER SOCIO-ECONOMIC STATUS
◦ GENATIC ABNORMALITY
◦ DOWN SYNDROME
◦ RADIATION EXPOSURE
◦ SMOKING
◦ INDUSTRIAL EXPOSURE TO CHEMICALS(BENZINE)

8. PATHOGENESIS
◦ APP 90% OFALLs HAVE NUMERICALOR STRUCTURALCHROMOSOMAL
CHANGES
◦ M/C IS HYPERPLOIDY, BUT HYPOPLOIDYAND VARIETY OF BALANCED
TRANSLOCATIONALSO SEEN
◦ THESE CHROMOSOMAL ABBERATIONS DYSREGULATE THE EXPRESSION AND
FUNCTION OF TRANSCRIPTION FACTORS THAT ARE REQUIRED FOR NORMAL
B AND T CELL DEVELOPMENT
◦ A HIHER FRACTION OF B- ALL HAVE LOSS OF FUNCTION MUTATION IN PAX5,
E2A, EBF
◦ UP TO 70% T-ALL HAVE GAIN OF FUNCTION MUTATION IN NOTCH1
◦ THESE MUTATIONS DISTURB THE DIFFERENTIATION OF LYMPHOID
PRECURSORSAND PROMOTE MATURATIONARREST
◦ SINGLE MUTATIONSARE NOT SUFFICIENTTO PRODUCEALL.

9. CLINICAL PRESENTATION
JOINT,EXTREMITYPAINS
CNS INVOLVEMENT
LYMPHADENOPATHY
SPLENOMEGALY
HEPATOMEGALY
GONADAL INVOLVEMENT
MEDIASTINAL MASS
ABRUPT ONSET
NON-SPECFIC SYMPTOMS
FATIGUE
PALLOR
EASY BRUISING
BLEEDING
FEVER
DYSPNOEA
DIZZINESS
WEIGHT LOSS

10. CLASSIFICATION OF ACUTE
LYMPHOBLASTIC LEUKEMIA
FAB CLASSIFICATION
IMMUNOLOGIC CLASSIFICATION
WHO CLASSIFICATION

11. FAB CLASSIFICATION(BASED ON MORPHOLOGY)
SUB TYPE MORPHOLOGY
L1
SMALL ROUND BLASTS, SCANT CYTOPLASM,
HOMOGENOUS CHROMATIN & INDISTINCT
NUCLEOLUS
L2
PLEOMORPHIC LARGER BLAST, MODERATEAMOUNT
OF CYTOPLASM, IRREGULAR NUCLEI, FINE
CHROMATIN ONE OR MORE OFTEN LARGE DISTINCT
NUCLEOLI
L3
LARGE BLASTS, MODERATEAMOUNT OF
BASOPHILIC VACUOLATED CYTOPLASM , ROUND TO
OVAL NUCLEUSWITH STIPPLED CHROMATIN & ONE
OR MORE , DISTINCT NUCLEOLI

12. L1, L2, L3 CELLSON BONE
MARROW ASPIRATION

13. DRAWBACKS OF FAB CLASSIFICATION
 IT DOES NOT INCLUDE –
a)MOLECULAR CHARACTERISTICS
b)CYTOGENETICS,
c) IMMUNOPHENOTYPING
IMMUNOLOGICAL SUB TYPE OF ALL
BIPHENOTYPIC LEUKEMIA
LIMITED RELEVANCE TO THERAPEUTIC OR PROGNOSTIC
IMPLICATION

14. IMMUNOLOGICAL CLASSIFICATION
1)B-ALL
2)T-ALL
3)MIXED –LINEAGE ACUTE LEUKEMIA
4)UNDIFFERENTIATED ACUTE LEUKEMIA

15. B-ALL
B LINEAGE MARKERS
PRO –B (8-10%) HLADR(+), Tdt(+), CD10(-),Cylg(-), Smlg(-)
COMMON(50%) HLADR(+), Tdt(+), CD10(+),Cylg(-), Smlg(-)
PRE –B(20%) HLADR(+), Tdt(+), CD10(-),Cylg(+), Smlg(-)
MATURE –B(1-2%) HLADR(+), Tdt(+), CD10(-),Cylg(-), Smlg(+)

16. T ALL
◦ PAS NEGATIVE
◦ ACID PHOSPHATE POSITIVE
◦ CD1(+), CD2(+), CD3(+), CD4(+),CD5(+),CD7(+),CD8(+),TdT,cCD3

17. MIXED LINEAGE ACUTE LEUKEMIA
(BIPHENOTYPIC LEUKEMIA )
◦ THESE COMPRISE 1-2% OF ACUTE LEUKEMIA
◦ THERE ARE TWO POPULATION OF CELLS
◦ (A) LARGE CELLS -WITH DIFFERENTIATION AS
MYELOBLAST ,WHICH ARE MPO +, SBB+ ,USUALLY
WITH AUER RODS ,OR MONOBLASTIC MORPHOLOGY
◦ (B) SMALLER BLASTS - WITH L1 MORPHOLOGY ,WITH
HAND MIRROR MORPHOLOGY .BLAST SHOWS
MIXTURE OF MYELOID &LYMPHOID ANTIGENS

18. UNDIFFERENTIATED ACUTE
LEUKEMIA
◦ BLASTS USUALLY HAVE L2 MORPHOLOGY BUT THERE
IS NO LINEAGE DIFFERENTIATION WITH EXPRESSION
OF HLA-DR , CD34, CD7 AND TdT

19. WHO CLASSIFICATION

20. B-LYMPHOBLASTIC LEUKEMIA, NOS
B LYMPHOBLASTIC LEUKEMIA ,NOS
CRITERIA
>25% blast, involving BM /PM COMMITED TO B CELL LINEAGE
AGE COMMAN IN CHILDREN
75% UNDER 6 YEARS
INCIDENCE 1_4.75/ 1 LAKH PER YEAR
MORPHOLOGY BONE MARROW ASPIRATION- BLASTS MAY BE SMALL OR LARGE
• SMALL – SCANT CYTOPLASM,CONDENSED CHROMATIN,INDISTINCT
NUCLEOLI
• LARGE MODERATE BLUE GRAY CYTOPLASM,OCCATIONALLY
VACUOLATED, DISPERSED NUCLEAR CHROMATINWITH MULTIPLE
NUCLEOLI
• 10% BLAST WITHAZUROPHILIC GRANULES
• BONE MARROW BIOPSY – RELATIVELY UNIFORM APPEARANCE WITH
ROUND TO OVAL , INDENTED OR CONVOLUTED NUCLEI ,FINELY
DISPERSED CHROMATIN & INCONSPICUOUS TO PROMINENT
NUCLEOLI.

21. IMMUNOPHENOTYPE CD19, CD79a, cyD22 +VE
CD10,Scd22, CD24,PAX5, Tdt +VE IN MOST
CASES CD20,CD34 VARIABLE EXPRESSION
GENETICS 70% CASES WITH TCR GENE
REARRANGEMENT
OTHERS- DEL6q, 9p&12p
CYTOCHEMISTRY PAS+VE,
NSE+VE
MPO –VE,
SBB -VE

24. B LYMPHOBLASTIC
LEUKEMIA WITH RECURRENT
GENETIC ABNORMALITIES

25. B-ALL WITH t(9:22)
(q34:q11.2); BCR-
ABL1
B-ALL WITH
t(V:11q23);KMT2a
REARRANGED
B-ALL WITH T(12:21)
(P13:Q22);TEL-kMT1
(ETV6-RUNX1)
NEOPLASM OF
LYMPHOBLASTWITH
TRANS B/W BCR- ABL
GENE
TRANSLOCATION
BETWEEN MLL GENE @
11q AND ANY PART OF
LARGE NO OF
DIFFERENT FUSION
PARTNER
WBC COUNT >
1LAC/MICRO LITRE
CNS INVOLMENT
TRANSLOCATION
BETWEEN ETV6 AND
RUNX1 GENE
25% OF ALL B-ALL
AGE COMMON IN ADULTS.
25% ADULT ALL
2.4%CHILDHOOD
MOST COMMON IN LESS
THAN 1 YR OF AGE
COMMON IN CHILDREN
NOT SEEN IN INFANTS
MORPHOLOGY NO UNIQUE
MORPHOLOGY
NO UNIQUE
MORPHOLOGY
NO UNIQUE
MORPHOLOGY

26. IMMUNOPHENOTYPE
S
CD10+,
CD19+,CD25+, Tdt+
CD19+, CD-,CD24-,
PRO-B+ FOR CD5
CD19+,CD10+,CD34,
CD13 FREQUENTLY
EXPRESSED
GENTICS BCR GENE FUSE
WITHABL1 GENE &
PRODUCE BCR-ABL
FUSION PROTEIN
190KD(CHILDREN)
210KD(ADULT)
MLL GENE HAVE
MANY FUSION
PARTNER
M/C AF4 (4q21)
OTHER ENL (19p14
AF9(9P22)
ETV6-RUNX1
FUSION PROTEIN
INHIBIT
TRANSCRIPTION
FACTOR RUNX1

28. B-ALL WITH HYPERDIPLOIDY B-ALL WITH HYPODIPLODY
CRITERIA BLAST CONTAIONS >50& <66
CHROMOSOMES
NO TRANSLOCATION
NO OTHER STRUCTURAL
ALTERATION
BLAST CONTAIN <46
CHROMOSOMES
AGE COMMONIN CHILDREN
RARE IN ADULT
BOTH IN CHILDRENAND
ADULTS
HAPLOID ALL (23-29 CHROM)
SEEN IN CHILDHOOD
INCIDENCE 25% 5% IF CHROMOSOME <46
1% IF CHROMOSOMES <45
MORPHOLOGY NO UNIQUE MORPHOLOGY NO UNIQUE MORPHOLOGY

29. B-ALL WITH HYPERPLOIDY B-ALL WITH HYPODIPLOIDY
IMMUNO-PHENOTYPE CD-19, CD-10+ BLAST HAVE PRE-B
CD34+ PHENOTYPE
CD45- CD19,CD10 +
GENETICS • NUMERICALINCREAS IN • LOSS OF 1 OR MORE
CHROMOSOME CHROMOSOME FROM 45
• NO STRUCTURAL CHROM TO NEAR
ABNORMALITY HAPLOID
• M/C EXTRA • DETECT BY STANDARD
CHROMOSOMESARE KARYOTYPING FISH &
21,X,14,4 FLOWCYTOMETRY.
• TRISOMY 4,10,17

30. B-ALL WITH
T(5:14)(q31:Q32);IL3-IGH
B- ALL WITH t(1:19);
(q23:P13.3); E2A-PBX1(TCF3-
PBX1)
BLAST HAVING
TRANSLOCATIO B/W IL3 GENE
&IGH GENE
RESULTING IN EOSINPHILIA
TRANSLOCATIONIN B/W E2A
GENE & PBX1 GENE
AGE BOTH IN CHILDRENAND
ADULT
COMMONIN CHILDREN
ALSO SEEN IN ADULTS
INCIDENCE RARE DISEASE <1% OF ALL 6% OF ALL CASES OF B- aLL
MORPHOLOGY BLAST WITH TYPICAL
MORPHOLOGY
INCRASING CIRCULATING
EOSINOPHIL
NO UNIQUE MORPHOLOGY
IMUNO PHENOTYPES C19,10 +
cyµ HEAVY CHAIN +
CD9 STRONGLY EXPRESSED
IN ABSENCE OF cyµ H CHAIN
C19,10 +
cyµ HEAVY CHAIN +
CD9 STRONGLY EXPRESSED
IN ABSENCE OF cyµ H CHAIN

31. T- LYMPHOBLASTIC LEUKAEMIA
CRITERIA NEOPLASM OF LYMPHOBLAST COMMITTED TO t-CELL LINEAGE
INVOLVING BM &PB
>25%BM BLAST
AGE AND SEX COMMONIN ADOLESCENTS THAN YOUNG CHILDREN
MALE > FEMALE
INCIDENCE 15% OF CHILDHOOD ALL
25% OF ADULT ALL
C/F • HIGH LEUCOCYTE COUNT
• THYMIC INFILTRATION IS VERY COMMON & MAY BE ASSOCIATED
WITH PLEURAL EFFUSION, PERICARDIAL EFFUSION & SVC
OBSTRUCTION
• MEDIASTINALMASS
• LYMPHADENOPATHY, HEPATOSPLENOMEGALY

32. MORPHOLOGY COMPOSED OF SMALL TO MEDIUM SIZED
BLAST.
NUCLEAR SHAPED – ROUND TO
IRREGULAR
SMALL BLAST WITH SCANT CYTOPLASM,
CONDENSED CHROMATIN & NO PROMINENT
NUCLEOLI
LARGE BLAST WITH FINELYDISPERED
CHROMATION& RELATIVELYPROMINENT
NUCLEOLI
MITOSIS: HIGHER THAN B- ALL
CYTOCHEMISTRY ACID PHOSPHATE POSITIVE
IMMUNOPHENOTYPE • Tdt +ve
• CD99,CD34,CD1a MOST SPECIFIC
• CD7,Cyt CD3MOSTSPECIFIC

33. IMMUNOPHENOTYPE INTRATHYMIC DIFFERENTIATION
• PRO T- cCD3+,CD7+,CD2-,CD1a -,CD34+
• PRE T- cCD3+,CD7+,CD2+,CD1a -,
CD34±ve
• CORTICAL T- cCD3+,CD7+,CD2+,CD1a+,
CD34-ve
• MEDULLARY T- cCD3+,CD7+,CD2+,CD1a-,
CD34 -,sCD3+
• CORTICAL T STAGE DOUBLE +VE FOR
CD4&8
GENETICS CLONAL REARRANGEMENT OF TCR GENE
20% OF CASES WITH IGH GENE
REARRANGEMENT
50-70% = ABNORMALKARYOTYPE
M/C INVOLVED GENE INCLUDE
TRANSCRIPTIONFACTOR TLX1 AND TLX3
50% CASES WITH MUTATION IN NOTCH1
AND HCDC4 gene

38. INVESTIGATION
◦ PERIPHERAL BLOOD SMEAR:
NORMOCYTIC NORMOCHROMIC ANAEMIA
TLC- DECREASED/ NORMAL/ INCREASE
LYMPHOBLASTS
GRANULOCYTOPENIA
THROMBOCYTOPENIA

40. ◦ BONE MARROW EXAMINATION:
1. HYPERCELLULAR d/t PROLIFERATION OF LEUKAEMIC BLASTS
2. B-ALL: THE BLAST HAVE VARIED APPEARANCE FROM A HOMOGENOUS
POPULATION OF SMALL CELLS WITH A ROUND TO SLIGHTLY IRREGULAR
NUCLEUS, CONDENSED CHROMATIN & INCONSPICUOUS NUCLEOLI TO LARGE
CELLS WITH IRREGULAR, CLEFTED OR INDENTED NUCLEI, VARIABLY
DISTRIBUTED CHROMATIN & ONE OR MORE DISTINCTNUCLEOLI.
3. CYTOPLASM IS SCANT TO MODERATE & SLIGHT BASOPHILLIC TO DEEPLY
BASOPHILLICAS CELL SIZE INCREASE
4. TALL: COMPARED WITH B- LYMPHOBLAST, T-LYMPHOBLAST SHOW GREATER
NUCLEAR CONVULATION & SIGNIFICANT NUCLEAR HYPERCHROMASIA
5. MITOTIC FIGURE: HIGHER IN T-ALLTHAN B-ALL
6. MYELOID PRECURSORS: DECREASED
7. MEGAKARYOCYTES: DECREASED

42. STAIN AML ALL
MPO + -
SBB + -
NSE
+ IN M4, M5
-
PAS +(FINE BLOCK IN M6) BLOCK+
ACID PHOSPHATASE + IN M6 (DIFFUSED) +T- ALL

45. MARKER FOR THE DIAGNOSIS OF ALL
LINEAGE ANTIGEN
PRECURSOR- B ALL CD19,CD10,CD79a,Tdt,cCD22,
HLA-DR, cCD79a
PRECURSOR-T ALL CD1,CD2,CD3,CD4,CD5,CD7,CD8
, Tdt,
cCD3

46. OTHER INVESTIGATIONS:
◦ CSF EXAMINATION FOR LYMPHOBLAST
◦ TESTICULAR BIOPSY TO RULE OUT RESIDUAL DISEASE
◦ CHEST X-RAY

47. DIFFERENTIAL DX
◦REACTIVE LYMPHOCYTOSIS DUE TO INFECTION
◦SMALL ROUND CELL TUMOR OF THE CHILD
HOOD THAT PRESENT WITH MARROW
INVOLVEMENT
◦HEMATOGONES

48. ALL vs AML
ALL AML
AGE MAINLY CHILDREN MAINLYADULTS
LYMPHADENOPATHY USUALLY + USUALLY-ve
HEPATOSPLENOMEGALY +VE MILD +VE MILD
GUM HYPERTROPHY -VE +VE IN M4/M5
SKIN INFILTRATION -VE +VE IN M4/M5
CNS INVOLVEMENT +VE IN SOME CASES +VE IN SOME
GRANULOCYTIC SARCOMA -VE +VE IN FEW CASES
MEDIASTINALMASS +VE IN T- ALL -VE
ASSOCIATED DIC -VE +VE IN M3
SERUM MURAMIDASE NORMAL IN M4/M5(MONOCYTE TYPE)
PROGNOSIS GOOD BAD

49. ALL V/S REACTIVE LYMPHOCYTOSIS
◦ THE ATYPICAL LYMPHOCYTES CAN BE DISTINGUISHED FROM
LEUKEMIC BLAST BY
1. RELATIVELY MATURE CHROMATIN PATTERN
2. LOW N:C RATIO
3. PROMINENT NUCLEOLI
ALL v/S SMALL CELL TUMOR OF THE CHILDHOOD
IMMUNOPHENOTYPING IS HELPFUL IN ARRIVING AT CORRRECT
DIAGNOSIS

50. ALL V/S HEMATOGSONES
◦ HEMATOGONES ARE THE IMMATURE LYMPHOID CELLS
APPEARING LIKE LEUKAEMIC BLAST’MAY BE SEEN IN
INFECTIONS,FOLLOWING CHEMOTHERAPY AND BONE MARROW
TRANSPLANTATION
◦ THEY CAN BE DIFFERENTIATED FROM LYMPHOBLAST IN HAVING
HIGH N:C RATIO, MORE HOMOGENOUS CHROMATIN & NO
DISCERNIBLE NUCLEOLI

52. THANK YOU 