AML

Classification

For the time being, we consider the FAB (French - American - British) classification of AML. WHO classifies AML as a spectrum of neoplasms based on the molecular genetics and therapy.

M0 - undifferentiated (minimal)

M1 - without maturation (20% diff)

M2 - with maturation (30% diff)

M3 - Acute Promyelocytic Leukemia (PML - RARA)

M4 - Acute Myelo-monocytic Leukemia

M5 - Acute Monoblastic or Monocytic Leukemia

M6 - Acute Erythroid Leukemia

M7 - Acute Megakaryoblastic Leukemia

Epidemiology

Most common AML is M2(10%), followed by M1 and M4 (5-10% each). Then follows M3 (5-8%), M5 and M0 (<5% each). M7 is rare and M6 is the rarest.

AML can affect at any age. Peak age group is middle aged adults. Can occur to infants also.

Clinical presentation

  • Fever

  • Anemia

  • Thrombocytopenia

  • Neutropenia or Leukocytosis with circulating blasts

These are the non specific findings in any patients with AML. There is no point in trying to assign a class with the clinical features and blood counts alone. Although:

  • M5 has shown CNS involvement and extramedullary masses

CBC and Peripheral Smear

In majority of the cases, WBC counts are elevated. Relating it to marrow suppression, it justifies the Normocytic normochromic anemia and thrombocytopenia.

In cases of marrow failure, there will be anemia and thrombocytopenia as usual, but now with neutropenia also.

Peripheral smear shows circulating blasts. In a resource limited setup, we try to classify AML into one of the FAB classes based on morphology and cytochemistry only.

Criteria: More than or equal to 20% blasts in smear or marrow.

Blasts are morphologically 3 types.

Agranular, granular and abundantly granular (>20% of cytoplasm). The latter 2 cannot be distinguished, so we consider them as granular blasts.

The blasts morphology helps in narrowing down the diagnosis, more of which is discussed here.

For pictures, scroll down to Bone Marrow.

M0 / M1

  • Agranular blasts.

  • Large cells with scanty blue cytoplasm.

  • Open chromatin, one or more nucleoli.

  • No distinction possible without cytochemistry.

  • No lineage is evident as there are no granules.

  • Cytochemistry: MPO and SBB: unreliable or negative. (Positive in <3% for M0; >3% for M1).

M2

  • Most common AML

  • Maturating stage and lineage is evident from the granules, neutrophils, etc.

  • Abundant granules, occasionally with Auer Rods.

  • Counts should show monocytes < 5000/microL to rule out M4 or M5

  • Cytochemistry: MPO & SBB positive. NSE and PAS negative.

M3

  • Fragmented RBCs can be seen if DIC occurs.

  • Atypical promyelocytes are considered as blasts. (Blast equivalent)

  • Based on morphology, it is of 2 types

M3 - Hypergranular

  • Neutropenia or normal Total Counts.

  • Blasts show densely packed granules.

  • Largest Auer Rods among all AMLs.

  • Auer rods may be abundant arranged as criss-cross, leading to call it Faggot cells.

M3 - Microgranular

  • Very high WBC counts

  • Promyelocytes are hypogranular, that looks like monoblasts.

  • Very tiny submicroscopic granules or Auer rods, which seems like almost agranular.

  • Buttock shaped nuclei

  • Sometimes reniform or convoluted nucleus

  • MPO and SBB is strongly positive which differentiates from monoblasts.

M4/M5

  • Counts show Monocytes > 5000/microL.

  • Monoblasts are large cells with abundant cytoplasm and rounded nucleus.

  • Promonocytes will also be seen with bilobed or multilobed nucleus. They are counted as blasts (Blast equivalent)

  • Cytochemistry: MPO, SBB and NSE positive blasts.

Bone Marrow

Bone marrow aspirate shows more than or equal to 20% of nucleated cells as blasts as mentioned in the smear.

Aspirate smears should be adequate enough to count at least 500 well visualized nucleated cells for a diagnosis.

Haemophagocytosis is seen in AML M2 onwards.

M0

Marrow cells are completely replaced by agranular blasts as mentioned above.

M1

Marrow cells are completely replaced by sparsely granular blasts. Cytochemistry is as mentioned above.

Marrow cells constituted by maturing granulocytes are only <20% of all nucleated cells. Hence it is termed AML without maturation.

Since more cells are there in marrow, it is likely to find Auer rods in some blasts.

M2

By definition, >20% blasts. And:

More than or equal to 10% of the precursor cells show granulocytic maturation. (Neutrophils, myelocytes, etc upto promyelocytes)

Comparatively higher eosinophilic and basophilic counts.

But Monocytic lineage <20%.

M3

Both variants exhibit different morphology and cytochemistry as described in the smear.

Atypical promyelocytes - hypergranular and microgranular variants.

M4

Blasts more than or equal to 20% including promonocytes.

Monocytes and monoblasts are each more than or equal to 20% among all nucleated cells.

As it is termed myelomonocytic, there are myeloblasts in the aspirate.

Dual positive cells are revealed by double staining with NSE and Naphthol AS-D Chloro-esterase.


M5

Blasts more than or equal to 20% including promonocytes.

Monocytic differentiation cells constitute more than or equal to 80% among all blasts. This includes promonocytes, monoblasts and monocytes.

It is termed monocytic or monoblastic, based on the proportion. Monoblasts are >80% of all monocytic cells in Acute monoblastic leukemia.

Dual positive cells are revealed by double staining with NSE and Naphthol AS-D Chloro-esterase.

Extramedullary masses composed of monoblasts are seen too.

M6 and M7 have totally different morphologies. Will be updated.