1. LEUKEMIAS Dr Mehboob Khan Pathologist

2. Leukemias are malignancies of hemtopoietic cells or tissues in which there is abnormal proliferation of hemopoietic cells with infiltration of bone marrow and lymphatic tissues
ETIOLOGY:
Molecular biology of leukemogenesis- oncogenes
Abnormalities of the chromosomes- translocation deletions
Radiation
Chemicals
Viruses
Genetic factors-Down syndrome

3. CLASSIFICATION LYMPHOID ACUTE LYMPHOID LEUKEMIA (ALL)
CHRONIC LYMPHOID LEUKEMIA (CLL)
MYELOID
ACUTE MYELOID LEUKEMIA (AML)
CHRONIC MYELOID LEUKEMIA (CML)

4. ACUTE MYELOID LEUKEMIA

6. AML -NOT OTHERWISE CLASSIFIED MORPHOLOGIC CLASSIFICATION

8. MYELOBLAST
WITH AUER ROD

9. NORMOBLASTS
MYELOBLAST

10. AML-M4
AML-M5
AML-M6
MEGAKARYOBLASTS

11. HYPERCELLULAR BONE MARROW (ALL)

13. CLINICAL FEATURES OF ACUTE LEUKEMIA:
COMMON
Anemia
Fever
Malaise
Hemorrhages, bruising and petechiae
LESS COMMON:
Infections of mouth and pharynx
Pains in bones and joints
URTI (children)
Superficial lymph node enlargement (children in ALL)
OCCASIONAL:
Abdominal pain
Skin rashes
Gum hypertrophy
Mediastinal obstruction

14. CLINICAL FEATURES DUE TO ORGAN INFILTRATION:
Tender bones
Superficial lymphadenopathy (ALL)
Splenomegaly, hepatomegaly (ALL)
Gum hypertrophy and infiltration, rectal ulceration and skin involvement (AML- myelomonocytic and and monocytic type)
Meningeal syndrome (ALL)
Testicular swelling and mediastinal compression (ALL)

15. BLOOD PICTURE: Normocytic and normochromic anemia
Total WBC count may be increased upto 500 x 10 /L
Thrombocytopenia
Peripheral blood smear- myeloblasts, promyelocytes, myelocytes , metamyelocytes, agranular neutrophils, stab cells, myelomonocytes and normoblasts
Bone marrow- hypercellular with plenty of blast cells (>75% of the marrow cell population)
THERE SHOULD BE AT LEAST
30% BLASTS IN BONE MARROW (FAB )
20% BLASTS IN BONE MARROW (WHO)
6. Tests for DIC will be positive in Promyelocytic leukemia

16. 3. CYTOCHEMISTRY
Myeloperoxidase- positive in immuture myeloid cells containing granules and auer rods but negative in M0 myeloblasts
Sudan black- positive in immature cells in AML
Non specific esterase (NSE)- positive in monocytic series (M4 and M5)
Periodic acid Schiff (PAS)- positive in immature lymphoid cells and in erythroleukaemia (M6)
Acid phosphatase – focal positive in leukaemic blasts in ALL and diffuse reaction in monocytic cells (M4 and M5)

17. (MYELOPEROXIDASE POSITIVE)
MYELOBLAST
(MYELOPEROXIDASE POSITIVE)

18. 4. IMMUNOPHENOTYPING
AML cells express CD13 and CD33 antigens
M5 shows CD41 and CD42 positivity
ALL is positive for CD10, CD19 in Pre B ALL (90%); B cell ALL (50%);
ALL T cell type are positive for CD1,CD2, CD5, CD7
5. OTHER INVESTIGATIONS
Serum muramidase- elevated in M4 and M5 AML
Serum uric acid- frequently elevated

19. COURSE AND PROGNOSIS IN AML: GOOD PROGNOSIS
Age <40 year
M2,M3 and M4 types
Blast cells with Auer rods
Total WBC <25,000/cumm
Tranlocation and inversion
Leukemia without preceding Myelodysplastic syndrome (MDS)
BAD PROGNOSIS:
Age<2 years and >55 years
M0,M6,M7 types
Total WBC >100,000/cumm
Deletions
Leukemia with preceding MDS

20. ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

21. ALL is the commonest leukemia seen in childhood
The predominant cell seen in ALL is LYMPHOBLAST
Lymphoblast has coarse nuclear chromatin and 1-2 nucleoli, high nucleus:cytoplasmic ratio (N:C), stain positve for PAS (periodic acid Schiff) and TdT (terminal deoxynucleotidyltransferase)

22. LYMPHOBLASTS
(ALL)

23. MYELOBLASTS
LYMPHOBLASTS

24. LYMPHOBLASTS in peripheral blood smear (ALL)

25. FAB CLASSIFICATION OF ALL L1 ALL
Commonest type
Best prognosis
Lymphoblasts have coarse chromatin with small nucleoli and scanty cytoplasm
L2 ALL
Lymphoblasts have heterogenous chromatin with 1-2 nucleoli, moderate cytoplasm with few vacuoles
L3 ALL
Rare and worst prognosis
Homogenous chromatin with 1-2 prominent nucleoli, abundant cytoplasm and vacolues positive for Oil O Red

26. WHO IMMUNOLOGICAL CLASSIFICATION OF ALL B CELL
More common
CD19 and Cd20 positive
Associated with pancytopenia
T CELL
Less common
CD1, CD2, CD7 positive
Associated with mediastinal mass, lympadenopathy and splenomegaly

27. (Adolescent males/ Lymphomas/Thymic mass)

28. CLINICAL FEATURES:
Same as AML
With lymphadenopathy, hepatsplenomegaly
BLOOD PICTURE:
Elevated total WBC count upto 500,000/cum
Anemia, neutropenia
Thrombocytopenia
Lymphoblasts >30% in bone marrow
BIOCHEMICAL CHANGES:
Elevated uric acid, LDH levels
Elevated serum phosphate levels
Hypocalcemia

29. PROGNOSIS IN ALL BAD PROGNOSIS GOOD PROGNOSIS Age 2-8 years Females
L1 type
Pre-B cell
Absence of mediastinal mass
Hyperdiploidy or translocations
BAD PROGNOSIS
Age < 2 year , >10 years
Male
L2 and L3 type
Pre T cell
Mediastinal mass
Ph chromosome