Acute Leukemias and their Diagnosis, Acute Myelocytic and Acute Lymphocytic Leukemia

This is a malignant neoplasm of hematopoietic cells particularly stem cells.
There is diffuse infiltration of the bone marrow by these neoplastic cells.
These cells enter the blood and may infiltrate the liver, spleen, lymph nodes and other organs.

L1	Lymphoblasts with uniform, round nuclei, and scant cytoplasm Nucleoli are not prominent.
L2	More variable lymphoblast and cytoplasm is abundant. Nucleoli are large and may see one or more nucleoli.
L3	Lymphoblasts with fine nuclear chromatin and blue to deep blue cytoplasm that contains vacuoles. Lymphoblast is large and has prominent nucleoli and these are one or more than one.

M1	Undifferentiated myeloblastic. No cytoplasmic granulation Also called acute myeloblastic leukemia with no differentiation (20 %)
M2	Differentiated myeloblastic cells and sparse granules in the cytoplasm Also called AML with maturation
M3	Acute Promyelocytic Leukemia Granules are typical of promyelocytic morphology (5 to 10 %)
M4	Acute Myeloid Monoblastic Leukemia The mixed population of myeloblastic and monocytic morphology (15 to 20 %)
M5	Acute Monoblastic Leukemia Pure monobasic morphology (10 )
M6	Acute Erythroleukemia Predominantly immature erythroblast morphology, sometimes megaloblastic appearance ( 5)
M7	Acute Megakaryoblastic leukemia Megakaryocytic Cells with shaggy borders that may show some budding ( 1%)

The malignant transformation is at the level of pluripotential cells like stem cell and these are the committed stem cells, called stem cell disorder.
There is abnormal proliferation, monoclonal expansion, and decreased apoptosis of these cells leads to the replacement of normal bone marrow cells by these malignant cells or immature cells.
Acute Leukemias has little or no maturation and may see mainly blast cells.
1. Acute Leukemias are diagnosed on the percentage of blast cells in the bone marrow.
2. 30% or more blast cells are needed to classify the disorder as acute leukemia.

These are more common in the younger age group.
1. These are more frequent in children.
2. Mostly seen before the age of 20 years.
Onset is an abrupt and fatal outcome.
1. There is a fever.
There is the rapid development of anemia.
1. There is normochromic and normocytic anemia.
2. May see nucleated RBCs.
There is thrombocytopenia.
1. May see petechiae and purpura in the skin and mucous membranes.
Leukocytes count is variable.
1. Mostly leucocytes count is less than 100,000/cmm.

Age: This is seen during the first month of life and then in the later age group.
1. 10% cases found in the children.
Sex: More common in males than women. Male: female ratio is 3:2.
Signs and symptoms:
1. Mostly these patients present with a varying degree of bone marrow failure.
1. So clinical symptoms and signs are due to anemia, leukopenia, thrombocytopenia, and infections.
2. Fever and fatigue are present in most of the patient.
3. Acute promyelocytic leukemia (M3) causes disseminated intravascular coagulopathy (DIC) and bleeding.
4. Acute myelomonocytic leukemia (M4) and acute monocytic leukemia (M5) causes gum hypertrophy.
Lab. findings :
1. WBC count is variable. 25% of the patient has >50,000/cmm, 25% has <5000/cmm and 5 to 10% has count between 5000 to 10,000/cmm.
2. WBC morphology. These are morphologically abnormal and immature cells.
3. Uric acid in 50% of the cases is raised.
4. Lactate dehydrogenase (LDH) about 50% show raised a level.
5. Bone marrow shows >20% blast cells. Promyelocytes are numerous particularly in M3.
  1. Auer rods can be seen in the cytoplasm.
  2. Cytochemical stains, peroxidase reaction and Sudan black are positive.
6. Nucleated RBCs may be seen.
7. Platelet count may be low and may see count between 30,000 to 100,000/cmm.
8. Coagulation abnormalities are also seen. PT, PTT and Thrombin time are prolonged.

Age: This is most common in childhood. Mostly occur before the age of 4 years. The peak is between 2 to 10 years.
1. These are rare after the age of 30 years.
2. The second peak may be seen in middle and old age group.
Signs and symptoms:
1. Onset is sudden. There is no preleukemic stage.
2. There are fatigue and fever.
3. There may be bleeding and infections.
4. There is an enlargement of lymph nodes, spleen, and liver.
5. There may be involvement of the central nervous system (CNS). This shows as leukemic meningitis
6. Bone pain is due to the infiltration of the leukemic cells.
Lab. Findings:
1. WBC count is variable from very high to low count.
2. There are anemia and thrombocytopenia.
Bone marrow: Very few leucocytes are seen.
1. Difficult to find normal WBCs or RBCs in the bone marrow.
2. Characteristically there are blast cells.
3. Auer rods are absent.
4. Sudan’s black and peroxidase reactions are negative.

Characteristic Features	Acute Myelocytic Leukemia	Acute Lymphocytic Leukemia
Origin of the cells	Myeloid series cells	Lymphoid series cells
Features of Blast cells	Large in size,	Small in size
	Cytoplasm is moderate	Cytoplasm is scanty
	Chromatin is fine and lacy	Chromatin is dense
	Nucleoli are prominent and >2	Nucleoli are indistinct and <2
Auer rods	Present	Absent
Sudan black and peroxidase	Positive	Negative
Bone marrow	A mixed population of myeloid cells and blast cells	Mainly blast cells and very few WBCs or RBCs
Leukocyte Alkaline phosphatase (ALP)	Positive (differentiate CML from the leukemoid reaction.	Negative
Periodic Acid-Schiff (PAS)	Positive in Erythroblast in M6 leukemia	Positive (block patterns) in L1 and L2 Negative in L3