Pathology > Basic Hematology > White Cell Disorders > Leukemia: Acute Lymphoblastic Leukemia

Leukemia: Acute Lymphoblastic Leukemia

As with all acute leukemias, acute lymphoblastic leukemia is characterized by proliferation of blasts (lymphoblasts) in the bone marrow. Commonly the peripheral blood and other organs are involved.

 

The three FAB ALL types (British J Haematology, 33:451-458, 1975) while still in use have largely been replaced by immunologic classification.

Since one must still be able to recognize lymphoblasts and distinguish them from neuroblastoma, rhabsdomyosarcoma, etc., we will use the FAB classification to review the morphology of acute lymphoblastic leukemia (ALL).

FAB Classification
Acute lymphoblastic leukemia (ALL)*

L-1

85% #

L-2

14%

L-3

(Burkitt's) 1% # childhood

Once it is established that blasts are present in the marrow, the morphologic, cytochemical, phenotypic and genotypic characteristics of the blasts must be evaluated.

Lymphoblasts are usually small and have round to oval nuclei with coarse chromatin which has a tendency to aggregate into masses. Nucleoli tend to be small and inconspicuous. The cytoplasm of lymphoblasts tends to be sparse in volume and basophilic, usually without granules, although rarely nonspecific cytoplasmic granules can be seen. Auer rods are never observed.

The morphology of lymphoblasts is quite variable and this variation forms the basis of the FAB classification.

Lymphoblasts

Nuclei

round-oval nuclei with coarse chromatin
chromatin tends to aggregate into masses

Nucleoli

usually small and inconspicuous

Cytoplasm

basophilic, sparse in volume, usually without granules (rare non-specific granules). Auer rods are never observed.


Acute Lymphoblastic Leukemia - L1

Morphology: L1 blasts are small and homogeneous. The nuclei are round and regular with little clefting and inconspicuous nucleoli. Cytoplasm is scanty and usually without vacuoles.

Staining: MPO is always negative.

Maturation: Most L1 ALLs are of pro B or pre B lineage.

 


Acute Lymphoblastic Leukemia - L2

Morphology: L2 blasts are large and heterogeneous. The nuclei are irregular and often clefted. One or more, usually large nucleoli are present. The volume of cytoplasm is variable, but often abundant and may contain vacuoles.

Maturation: L2 ALLs may be of pro B or pre B lineage, but cases of T cell ALL are more likely to have an L2 than L1 morphology.

 

Staining: L2 blasts may have granular or "chunky" PAS positivity with a negative cytoplasmic background. NSE is usually negative. MPO is always negative.

Myeloperoxidase staining of neutrophil at left. The blast is negative.


Acute Lymphoblastic Leukemia - L3 (Burkitt's leukemia)

Morphology: L3 blasts are moderate-large in size and homogeneous. The nuclei are regular and round-oval in shape. One or more prominent nucleoli are present. The volume of cytoplasm is moderate and contains prominent vacuoles.

Staining: MPO is always negative. NSE is negative, but may show focal cytoplasmic positivity. The vacuoles are PAS negative (center), but are classically positive for the neutral lipid stain Oil Red O (right).

All L3 leukemias are surface immunoglobulin (SIg) positive and are of B cell lineage.

Today the immunophenotype is the most important finding for the proper classification and treatment of acute lymphoblastic leukemia.

The major immunophenotypic classification of ALL is as follows:

B cell lineage-

     pro B ALL #
     pre B ALL $
     B (surface Ig +) ALL (Burkitt's) +

T cell lineage*-

    T cell ALL
      prothymic
      early thymocyte
      cortical (common) thymocyte
      medullary (mature) thymocyte
      mature T (peripheral) cells

* T cell ALL is usually not subclassified

**** 2YSMD do not need to know the different antigens. You should recognize CD3, CD5, and CD7 as pan T markers; CD19 as a pan B marker; CD4 as T-helper, and CD8 as T-suppressor.****

HEMATOPATHOLOGY

A 12-year-old girl is noted to be pale and lethragic by her parents. You note some petechiae on her legs.

A chest roentgenogram is normal. There is no lymphadenopathy. A CBC revealed a WBC of 25.0 x10 /L with 15% blasts.The bone marrow aspirate differential count included 32% type I blasts; 13% type II blasts; 10% type III blasts; 10% promyelocytes; 25% myelocytes; 3% PMNs and 7% monocytes. Many of the blasts contained Auer rods. There were fewer than 50% erythroblasts.

With the results of this information you make the following diagnosis:

A. Acute myelocytic leukemia, M1
B. Acute myelocytic leukemia, M2
C. Acute promyelocytic leukemia, M3
D. Acute myelocytic leukemia, M4
E. Acute myelocytic leukemia, M5

A 25-year-old woman comes to you because of a severe headache and epistaxis. She is pale and has petechiae on her arms and chest.

There is no lymphadenopathy or hepatosplenomegaly. A chest roentgenogram is normal. The WBC was 18.0 x10 /L with 10% blasts. On the bone marrow aspirate it was difficult to distinguish between Type II and III blasts and promyelocytes. There were an estimated15% type I blasts and 75% immature cells (type II and type III blasts and promyelocytes). The remainder were dysplastic myelocytes. There were fewer than 50% erythroblasts. Cytogenetic studies showed a t(15;17) chromosome abnormality.

With the results of this information you make the following diagnosis:

A. Acute myelocytic leukemia, M1
B. Acute myelocytic leukemia, M2
C. Acute promyelocytic leukemia, M3
D. Acute myelocytic leukemia, M4
E. Acute myelocytic leukemia, M5

A 45-year-old woman is referred to you from her dentist because of swollen and bleeding gums. Her conjunctiva were pale and she had been feeling exceptionally wornout.

There is mild splenomegaly. A chest roentgenogram is normal. The WBC was 23.0 x10 /L with 44% blasts. The bone marrow aspirate showed > 55% large blasts with folded nuclei and large nucleoli. The remainder were promonocytes, monocytes and a few dysplastic myelocytes. There were fewer than 50% erythroblasts. Cytogenetic studies showed a t(9;11) chromosome abnormality.

With the results of this information you make the following diagnosis:

A. Acute myelocytic leukemia, M1
B. Acute myelocytic leukemia, M2
C. Acute promyelocytic leukemia, M3
D. Acute myelomonocytic leukemia, M4
E. Acute monocytic leukemia, M5

A 37-year-old man comes to you complaining of fatigue and increasing SOB, and now a fever (the fever is what got him to see you). He has had to stop jogging.

He is pale and diaphoretic. There is no lymphadenopathy or hepatosplenomegaly. A chest roentgenogram is shows dense bilateral infiltrates c/w pneumonia. The WBC is 78.0 x10 /L with 20% blasts. On the bone marrow aspirate there were an estimated 25% type I blasts and 55% immature cells (type II and type III blasts and promyelocytes). The remainder were dysplastic myelocytes.Cytogenetic studies showed a t(8;21) chromosome abnormality.

With the results of this information you make the following diagnosis:

A. Acute myelocytic leukemia, M1
B. Acute myelocytic leukemia, M2
C. Acute promyelocytic leukemia, M3
D. Acute myelocytic leukemia, M4
E. Acute lymphoblastic leukemia

A 32-year-old man comes to you because of a persistent cough x3 weeks and noted some shortness of breath. He is pale and has several ecchymoses and petechiae on his back and legs.

He has several small axillary nodes and an ill-defined mediastinal mass. The WBC is 114.0 x10 /L with 90% blasts. The marrow aspirate showed 54% blasts; 8% promyelocytes; 15% myelocytes; 3% bands;12% segmented neutrophils; 5% eosinophils, and 3% basophils. The blasts are negative for myeloperoxidase; nonspecific esterase and PAS. Chromosome studies showed a t(10;14)(q24;q11) abnormality. Immunologic marker studies are pending.

With the results of this information you make the following diagnosis:

A. Acute myelocytic leukemia, M1
B. Acute myelocytic leukemia, M2
C. Acute promyelocytic leukemia, M3
D. Acute myelocytic leukemia, M4
E. Acute lymphoblastic leukemia

Now, assuming a T-cell phenotype, what phenotypic abnormalites might you find that would help identify these T cells as abnormal (malignant) rather than reactive?

A 25-year-old law student comes to you because of a feeling of complete exhaustion. She is pale and cachetic. She has numerous petechiae on her arms and hands.

You note several small anterior cervical nodes. The WBC is 16.0 x10 /L with 2% blasts. The marrow aspirate showed 60% blasts; 5% promyelocytes; 10% myelocytes; 5% bands;16% segmented neutrophils; 3% eosinophils, and 1% basophils. The blasts are negative for myeloperoxidase; nonspecific esterase and PAS. Chromosome studies show a t(8;14) abnormality.

With the results of this information you expect:

A. Acute lymphoblastic leukemia, pro B cell type
B. Acute lymphoblastic leukemia, pre B cell type
C. Acute lymphoblastic leukemia, B cell (Burkitt's) type
D. a translocation between c-myc and the kappa light chain gene
E. a translocation between c-myc and the lambda light chain gene

A 19-year-old undergraduate is seen by you because of headache, nausea and vomiting. She is pale and scared.

Her WBC is 22.0 x10 /L with 44% blasts in the peripheral blood. The blasts are CD10, CD19, CD20, cytoplasmic Ig, and HLADR positive, but negative for surface Ig, CD2, CD3, CD5, CD7, CD13 and CD33.

With the results of this information you expect:

A. Acute lymphoblastic leukemia, pro B cell type
B. Acute lymphoblastic leukemia, pre B cell type
C. Acute lymphoblastic leukemia, B cell (Burkitt's) type
D. Acute lymphoblastic leukemia, T cell type
E. Acute myeloblastic leukemia, M0

For information regarding clinical presentation, course of disease, and therapy see: Clinical Aspects of Leukemia.

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