Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid cells in the bone marrow. There are two main types of acute leukemia - ALL and AML. ALL is further classified using the FAB or WHO systems and is most common in children under 5 years old. The disease involves a proliferation of lymphoblasts in the bone marrow. Microscopically, ALL blasts can be classified as L1, L2, or L3 depending on their size, shape, and other characteristics. Immunophenotyping and cytogenetic testing are also used in the diagnosis and classification of ALL. Presenting symptoms are non-specific and related to low blood cell counts.
9. ALL
The acute lymphoblastic leukemias
(ALLs) are systemic neoplastic
proliferations of lymphoblasts that
have their origin in a bone marrow
lymphocyte progenitor cell.
10. ALL
• Disease of the children and young
adults
• With a peak incidence at 4yrs of age
• The most common childhood
leukemia (80%)
• More common in boys
• It can occur in adults (less frequent)
12. FAB classificationFAB classification
o L1: small cells predominate 2x the dia of
small lymphocyte, Nuclei round regular,
occasional cleft. Nucleoli not visible.
Cytoplasm is scanty. Homogeneous
population
o L2: heterogeneous in size, share features
of L1 & L3. Nuclei show clefts, Nucleoli+
o L3: homogeneous population of large
cells, 3-4x dia of small lymphocytes, nuclei
are round, oval with prominent nucleoli.
Cytoplasm abundant deeply basophilic,
Vacuolated.
13. ACUTE LYMPHOBLASTIC
LEUKEMIA, L1 (ALL-L1)
L1: small cells predominate 2x
the dia of small lymphocyte,
Nuclei round regular, occasional
cleft. Nucleoli not visible.
Cytoplasm is scanty.
Homogeneous population
16. IMMUNOPEROXIDASE STAIN
FOR TdT ON A BONE MARROW
SMEAR FROM A PATIENT WITH
ACUTE LYMPHOBLASTIC
LEUKEMIA
The nuclear distribution of the stain
corresponds to the location of TdT in
the lymphoblasts.
19. ACUTE LYMPHOBLASTIC LEUKEMIA, L2 (ALL-L2)
The lymphoblasts vary in size, have reticular chromatin, prominent nucleoli, and lack the nuclear irregularity of the
blasts. A minority of the lymphoblasts have the cytologic features of ALL-L1. (Wright-Giemsa stain)
20. ALL - L3:
Homogeneous
population of large
cells
3-4x dia of small
lymphocytes
Nuclei are round, oval
with prominent
nucleoli
Cytoplasm abundant
deeply basophilic,
vacuolated
23. ALL L3 A methyl green pyronine (MGP) stain on the left shows strong uniform staining
of the cytoplasm. On the right the cytoplasmic vacuoles stain with oil red 0.
MGP Oil red O
24. Chromosomal changes
1. Hyperdiploidy: upto 60 chr. Good
prognosis
2. Ph’ L2 Poor prognosis
3. t(1,19) pre-B ALL, Poor prognosis
4. t(8,14) L3, Poor prognosis
25. Specific CF
The presenting signs and symptoms are similar to
those of AML and are usually related to blood
cytopenias.
Lethargy, malaise, fever, and infection are the
most common.
T-cell ALL : Mediastinal mass,
Testis is involved
ALL 3 (Burkitt’s): Maxilla is involved
27. Aplastic Presentation of ALL
Rarely, patients with ALL present with pancytopenia
and a hypoplastic bone marrow. Leukemic blasts
may not be identified initially. This hypocellular
phase is typically followed by apparent bone
marrow recovery and later by overt leukemia in a
matter of weeks or a few months.
29. CYTOLOGIC FEATURES OF BLASTS IN ACUTE MYELOID
& ACUTE LYMPHOBLASTIC LEUKEMIAS
AMLAML ALLALL
Blast sizeBlast size Medium to large, uniform
Variable Small to
medium
CytoplasmCytoplasm
Fine granules may be
present
Usually scant, a few
coarse granules may
be seen
Auer rodsAuer rods
Present in 60-70% of
cases
absent
Nuclear chromatinNuclear chromatin Finely dispersed Fine to coarse
NucleoliNucleoli 2-4, prominent 1-3, indistinct
Other cell typesOther cell types
Often dysplastic changes
in maturing myeloid cells
Myeloid cells are not
dysplastic
running, RD and McKenna, RW. Tumors of the
bone marrow. Atlas of Tumor Pathology, 3rd
Series, Fascicle 9. Washington D.C.:Armed
Forces Institute of Pathology, 1993. p.100.
Disease of the children and young adults
With a peak incidence at 4yrs of age
Constitutes 80% of all childhood leukemias
It can occur in adults but, with less frequency
More common in boys
ACUTE LYMPHOBLASTIC
LEUKEMIA, L1 (ALL-L1)
The lymphoblasts in the trephine biopsy section are smaller and have more condensed nuclear chromatin than those in figure 120. (Hematoxylin and eosin stain)
Brunning, RD and McKenna, RW. Tumors of the bone marrow. Atlas of Tumor Pathology, 3rd Series, Fascicle 9. Washington D.C.:Armed Forces Institute of
Pathology, 1993. p.105.
IMMUNOPEROXIDASE STAIN FOR
TdT ON A BONE MARROW SMEAR
FROM A PATIENT WITH ACUTE
LYMPHOBLASTIC LEUKEMIA
The nuclear distribution of the stain corresponds to the location of TdT in the lymphoblasts. (Immunoperoxidase-anti-TdT reaction)
Brunning, RD and McKenna, RW. Tumors of the bone marrow. Atlas of Tumor Pathology, 3rd Series, Fascicle 9. Washington
D.C.:Armed Forces Institute of Pathology, 1993. p.118.
ACUTE LYMPHOBLASTIC
LEUKEMIA, L2 (ALL-L2)
A bone marrow smear from a 2-year-old female. The lymphoblasts vary in size and show considerable nuclear irregularity. There is a moderate amount of cytoplasm.
The nuclei have coarse chromatin and contain distinct nucleoli. (Wright-Giemsa stain)
Brunning, RD and McKenna, RW. Tumors of the bone marrow. Atlas of Tumor Pathology, 3rd Series, Fascicle 9. Washington D.C.:Armed Forces Institute of
Pathology, 1993. p.107.
ACUTE LYMPHOBLASTIC
LEUKEMIA, L2 (ALL-L2)
The lymphoblasts in this bone marrow smear from a 12-year-old male vary in size, have reticular chromatin, prominent nucleoli, and lack the nuclear irregularity of the
blasts in figure 125. A minority of the lymphoblasts have the cytologic features of ALL-L1. (Wright-Giemsa stain)
Brunning, RD and McKenna, RW. Tumors of the bone marrow. Atlas of Tumor Pathology, 3rd Series, Fascicle 9. Washington D.C.:Armed Forces Institute of Pathology,
1993. p.108.
ACUTE LYMPHOBLASTIC
LEUKEMIA, L3 (ALL-L3)
A bone marrow smear from a 19-year-old male who presented with a paraspinal mass. The marrow was heavily infiltrated with the characteristic cells of ALL-L3. There
is variation in size of the blasts but all have round or oval nuclei with coarsely reticular chromatin and deeply basophilic cytoplasm containing the characteristic
vacuoles. Nucleoli are prominent in some of the cells. Three cells on the lower left of this field are in mitosis. An eosinophil myelocyte and neutrophil promyelocyte are
also present in this field. A tissue mass commonly accompanies ALL-L3, frequently in the ileocecal region. The morphologic features of L3 are identical to those of
small noncleaved cell lymphomas. (Wright-Giemsa stain) (Fig. 37.23 (right) from McKenna RW. The bone marrow manifestations of Hodgkin's disease, the
non-Hodgkin's lymphomas, and lymphoma-like disorders. In Knowles DM, ed. Neoplastic hematopathology. Baltimore: Williams & Wilkins, 1992:1135-80.)
Brunning, RD and McKenna, RW. Tumors of the bone marrow. Atlas of Tumor Pathology, 3rd Series, Fascicle 9. Washington D.C.:Armed Forces Institute of Pathology, 1993. p.111.
Figure 134
ACUTE LYMPHOBLASTIC
LEUKEMIA, L3 (ALL-L3)
A blood smear from a young man with an elevated leukocyte count. The leukemic cells are relatively uniform with a moderate amount of deeply basophilic cytoplasm
and round nuclei. The chromatin is coarsely reticular; indistinct nucleoli can be identified in some of the blasts. The cytoplasm contains several sharply defined clear
vacuoles. Some of the vacuoles overlie the nucleus. The blood contained an unusually large number of blasts in this case. (Wright-Giemsa stain)
Brunning, RD and McKenna, RW. Tumors of the bone marrow. Atlas of Tumor Pathology, 3rd Series, Fascicle 9. Washington D.C.:Armed Forces Institute of Pathology,
1993. p.111.
ACUTE LYMPHOBLASTIC
LEUKEMIA, L3 (ALL-L3)
A bone marrow smear from a 19-year-old male who presented with a paraspinal mass. The marrow was heavily infiltrated with the characteristic cells of ALL-L3. There
is variation in size of the blasts but all have round or oval nuclei with coarsely reticular chromatin and deeply basophilic cytoplasm containing the characteristic
vacuoles. Nucleoli are prominent in some of the cells. Three cells on the lower left of this field are in mitosis. An eosinophil myelocyte and neutrophil promyelocyte are
also present in this field. A tissue mass commonly accompanies ALL-L3, frequently in the ileocecal region. The morphologic features of L3 are identical to those of
small noncleaved cell lymphomas. (Wright-Giemsa stain) (Fig. 37.23 (right) from McKenna RW. The bone marrow manifestations of Hodgkin's disease, the
non-Hodgkin's lymphomas, and lymphoma-like disorders. In Knowles DM, ed. Neoplastic hematopathology. Baltimore: Williams & Wilkins, 1992:1135-80.)
Brunning, RD and McKenna, RW. Tumors of the bone marrow. Atlas of Tumor Pathology, 3rd Series, Fascicle 9. Washington D.C.:Armed Forces Institute of Pathology, 1993. p.111.
Figure 134
ACUTE LYMPHOBLASTIC
LEUKEMIA, L3 (ALL-L3)
Bone marrow smear from an 8-year-old male. A methyl green pyronine (MGP) stain on the left shows strong uniform staining of the cytoplasm. On the right the
cytoplasmic vacuoles stain with oil red 0.
Brunning, RD and McKenna, RW. Tumors of the bone marrow. Atlas of Tumor Pathology, 3rd Series, Fascicle 9. Washington D.C.:Armed Forces Institute of
Pathology, 1993. p.113.
Brunning, RD and McKenna, RW. Tumors of the
bone marrow. Atlas of Tumor Pathology, 3rd
Series, Fascicle 9. Washington D.C.:Armed
Forces Institute of Pathology, 1993. p.100.
1- Aleukemic leukemia: Normal total leucocyte count with anemia & thrombocytopnia.Therd may be an occasional blast in teh peripheral blood smear.
2- Sub leukemic leukemia: Leucopeniam with a few blasts and anemia and thrombocytopenia.
3- Leukemoid reaction: Elevated count with a few immaure cells like myelocyte and metamyelocyte. Because of high count it may mimic leukemia. However, total count will not exceed 50K.