Peripheral Smear:
Careful examination of the peripheral blood smear is of key importance to the diagnosis of leukemia. Most cases of acute leukemia have blasts or immature cells in the peripheral blood. Occasionally, patients present with no peripheral blasts (aleukemic leukemia). Peripheral smears of chronic leukemias usually show increased numbers of mature cells of a particular lineage (i.e. myeloid or lymphoid).

You should look for other peripheral blood smear abnormalities pertinent to a diagnosis of leukemia. Such abnormalities include dimorphic RBCs and other evidence of dyserythropoiesis, hypogranular neutrophils, acquired Pelger-Huet abnormality, increased nuclear excresences, and abnormal platelets. These abnormalities are evidence of myelodysplasia, a finding frequently associated with acute myeloid leukemia.

Bone Marrow:
Both bone marrow aspirate and biopsy are key parts of evaluating a suspected leukemia patient. Because leukemia arises in the marrow, the leukemic cells are generally most numerous and thus most easily examined in marrow samples. In addition, one can evaluate any remaining normal marrow elements.

Wright's stained marrow aspirate smears provide the best cytologic view of the leukemic cells and provides material for cytochemical staining. Using this method, cells are most clearly identified and any cytoplasmic or nuclear abnormalities are recognized. Leukemic cells for immunologic and genetic evaluation can be obtained from either aspirate or biopsy specimens.

Bone marrow aspirate

The biopsy provides the best evaluation of marrow celluarity and of the pattern of marrow involvement by the proliferative cells. In some leukemias marrow reticulin is increased, forming a fine fibrous network enmeshing the cells. Sometimes this leads to a dry "tap," or aspirate in which few if any cells are extracted from the marrow. In such instances the biopsy is invaluable.

Bone marrow biopsy

In most cases of leukemia the biopsy shows a diffuse infiltration of the bone marrow by leukemic cells. The presence of > 30% immature cells (blasts, promyelocytes) in the marrow is generally regarded as the minimum required for a diagnosis of acute non-lymphoblastic leukemia, (aka. AML). Normal bone marrow contains 0-5% blasts.

While most leukemias result in a hypercellular marrow, cellularity may be either hypo- or normal. Crucial to the diagnosis is the abnormal increase in the number of blasts.

Once a diagnosis of acute leukemia is made based on the morphologic findings, we need to determine the blast type to guide us to an appropriate therapy. Determination of the blast type is done by morphologic, cytochemical, immunologic, and chromosomal & molecular genetic analyses.

Normal Bone Marrow

BIOPSY:

Marrow hematopoietic cellularity ranges from 30-70%. Fat cells make up the remainder of the readily visible cells, though fibroblasts and endothelial or sinus lining cells are also present.

Immature myeloid cells are located along the bone trabeculae, with maturing neutrophils, eosinophils, etc., located more centrally, or away from bone.

Erythroid and megakaryocytic elements are found in the central areas, often near marrow sinuses. Erythroid precursors tend to cluster in red cell islands.

Megakaryocytes are relatively few in number.

Lymphocytes, plasma cells, mast cells, and macrophages are scattered about in small numbers.

Bone trabeculae are moderately thick and have only thin rims of osteoid. Occasional osteoblasts and rare osteoclasts are seen (osteoclasts & osteoblasts are common in children).

Why?

ASPIRATE:

Marrow examination generally entails a 500 cell differential of all nucleated cells.

At left is a table of the approximate ranges for normal marrow elements.

Morphological Evaluation of the Leukemias

The first and most important determination when deciding on chemotherapy and prognosis, is to determine whether the blasts are myeloid or lymphoid.

The morphology of the blasts yields strong evidence of the blast lineage. Most of the time (probably >80%) one can accurately predict the blast type from morphology alone. The key features are the chromatin pattern and the character of the cytoplasm.

ASPIRATE:

A 57 year old woman complains of unexplained fatigue and small bruises over her ankles and lower legs. The peripheral blood WBC was normal. Platelets were severely decreased in number.

Her marrow aspirate results are shown at left.

What is the most important observation made from the aspirate? Why is this important?

A. Decreased megakaryocytes
B. Normal numbers of myelocytes
C. Too little iron
D. Too many blasts
E. Decreased red cells