Leukemia is a cancer of the blood-forming tissues, usually involving the bone marrow, resulting in the production of abnormal white blood cells. Diagnosis relies on the microscopic examination of blood and bone marrow samples, a technique called morphology. By observing the shape, size, and internal features of the cells, specialists detect the visual signs of malignancy. This visual analysis guides the diagnostic and treatment process.
The Normal View: A Baseline for Comparison
The healthy production of blood cells, called hematopoiesis, creates a diverse population of mature cells with distinct appearances. Red blood cells (erythrocytes) are uniform, biconcave discs about 7.5 micrometers in diameter, lacking a nucleus and showing central pallor. Platelets are much smaller (2 to 3 micrometers) and appear as small, bluish-staining particles.
The various types of white blood cells (leukocytes) exhibit specific features denoting their maturity. Neutrophils, the most common type, have a nucleus segmented into two to five lobes, surrounded by pale pink cytoplasm containing fine granules. Lymphocytes possess a single, dark, round nucleus that occupies most of the cell volume, leaving a thin rim of blue cytoplasm.
Monocytes are the largest normal white blood cells, featuring an indented or kidney-shaped nucleus and abundant, pale gray-blue cytoplasm. The distinct features of these mature cells result from a complete differentiation process. This orderly appearance provides the benchmark against which leukemic cells are compared.
The Leukemic Hallmark: Appearance of Blast Cells
The microscopic hallmark of acute leukemia is the presence of blast cells, which are immature white blood cell precursors that have failed to mature. These blasts accumulate in the bone marrow and often spill into the peripheral blood, crowding out normal cells. They are typically larger than mature lymphocytes.
A defining characteristic is their high nucleus-to-cytoplasm ratio, where the nucleus takes up a disproportionately large volume. The nucleus has an “open” or fine chromatin pattern, reflecting active proliferation, unlike the densely clumped chromatin of mature cells.
Another feature is the presence of prominent nucleoli (distinct, dark spots within the nucleus). The cytoplasm is often scant, appears blue (basophilic), and has few or no granules. The presence of greater than 20% blast cells in the blood or bone marrow is the defining criterion for acute leukemia diagnosis.
Classifying Leukemia: Key Microscopic Distinctions
While all acute leukemias share excess blasts, subtle morphological differences classify the disease into specific types. The distinction between Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) is the primary classification challenge.
AML blasts, precursors to granulocytes and monocytes, may contain specific rod-shaped inclusions called Auer rods, which are pathognomonic for myeloid lineage. These rods appear as reddish or pink needles within the cytoplasm.
In contrast, ALL blasts (lymphocyte precursors) are often smaller than AML blasts, have less cytoplasm, and usually lack Auer rods or prominent cytoplasmic granules.
Chronic leukemias, such as Chronic Lymphocytic Leukemia (CLL) and Chronic Myeloid Leukemia (CML), involve more mature cells. CLL is characterized by a proliferation of mature-appearing but abnormal small lymphocytes, often seen smeared or “smudged” on the slide. CML is marked by an overproduction of granulocytes and their precursors at various stages of maturation, presenting a heterogeneous population.
Morphology in the Full Diagnostic Picture
The visual assessment of cell morphology is foundational, but it is only the initial step in a comprehensive leukemia diagnosis. Morphological examination can suggest a type of leukemia, but its limitations require supplementary testing for definitive confirmation, as cell appearance can sometimes overlap.
To overcome this, additional specialized tests are performed, such as flow cytometry and cytogenetics. Flow cytometry analyzes cell surface markers (proteins) to confirm the exact lineage (myeloid or lymphoid) of the leukemic cells. Cytogenetics and molecular testing examine chromosomes and genes for specific abnormalities, which are crucial for determining prognosis and selecting targeted therapy.