Acute Myeloid Leukemia (AML) – Morphology, Clinical Features, and Prognosis

Acute Myeloid Leukemia (AML) is a malignant disorder of the blood-forming cells, characterized by the accumulation of immature myeloid blasts in the bone marrow and blood. In this article, we’ll explore the morphological features, clinical presentation, and prognostic factors of AML in a simplified, student-friendly way — exactly as explained in my lecture series on white blood cell neoplasms.

Acute Myeloid Leukemia Morphology – Key Features

The diagnosis of AML is usually made by peripheral smear or bone marrow examination. The key finding is:

  • Increased myeloid blasts in the bone marrow or peripheral blood.

  • Cut-off: More than 20% blasts is the diagnostic threshold.

Exception:
If AML is defined by specific genetic abnormalities, the 20% cut-off does not apply. Even with fewer blasts, the diagnosis can be made if characteristic genetic changes are documented.

acute myeloid leukemia

Types of Myeloid Blasts

Morphologically, myeloid blasts can be of four main types:

  1. Myeloblasts – Large cells with delicate chromatin, 1–4 nucleoli, more cytoplasm than lymphoblasts, fine azurophilic granules (myeloperoxidase positive), and Auer rods (needle-like structures) in some cases.

  2. Monoblasts – Large folded or lobulated nuclei, no Auer rods, non-specific esterase positive.

  3. Megakaryoblastic blasts – Related to megakaryocytic lineage.

  4. Erythroid blasts – Show erythroid differentiation.

Blast Counts in Blood

  • Blast counts can vary widely between patients.

  • In many cases, the WBC count is high (>1 lakh/mm³).

  • In about 50% of cases, blasts are less than 10,000/mm³.

  • Sometimes blasts are absent in the peripheral smear despite bone marrow involvement.
    This is called aleukemic leukemia — highlighting the importance of bone marrow examination in cases of pancytopenia.

Myeloblast vs. Lymphoblast – Key Differences

Feature Myeloblast Lymphoblast
Cell of origin Myeloid stem cell Lymphoid stem cell
Size 15–20 μm 10–18 μm
Cytoplasm More abundant, basophilic, granular Scanty, agranular, blue-gray
Auer rods May be present Absent
Nucleus Round/oval, open chromatin Round/oval, dense clumped chromatin
Nucleoli 2–5 prominent 1–2 inconspicuous
Cytochemistry MPO+, Sudan Black B+, Specific esterase+ PAS+ (block positivity)

Special Stains & Immunophenotyping

When morphology is not enough, special stains and flow cytometry are used:

  • Myeloblasts: Myeloperoxidase (MPO) positive, Sudan Black B positive, specific esterase positive.

  • Monoblasts: Non-specific esterase positive.

  • Lymphoblasts: Periodic acid–Schiff (PAS) positive with block positivity.

  • Flow cytometry: Myeloblasts often express CD34 and CD33 (immature markers). More differentiated cells express CD64 and CD15.

Cytogenetic Abnormalities and Prognosis

Cytogenetics is crucial for classification, treatment decisions, and prognosis.

Common scenarios:

  • De novo AML in young adults:

    • t(8;21)

    • inv(16)

    • t(15;17) — associated with Acute Promyelocytic Leukemia (best prognosis, curable in ~90% with targeted therapy).

  • Therapy-related AML after DNA-damaging agents:

    • Monosomy 5, monosomy 7

    • TP53 mutations (poor prognosis)

  • After topoisomerase II inhibitor therapy:

    • KMT2A gene rearrangements (worst prognosis)

Acute Myeloid Leukemia – Clinical features

Symptoms and signs arise due to:

  1. Anemia – Fatigue, pallor.

  2. Neutropenia – Fever, recurrent infections (oral cavity, skin, lungs, urinary tract, kidneys). Opportunistic infections are common.

  3. Thrombocytopenia – Mucosal and cutaneous bleeding.

    • Mucosal hemorrhages: Gums, urinary tract.

    • Serosal hemorrhages: Linings of body cavities.

Myeloid Sarcoma

A localized soft tissue mass composed of myeloid blasts.
Although localized initially, it can progress to systemic AML.

Prognosis in AML

  • Overall: AML is challenging to treat.

    • ~60% achieve complete remission with chemotherapy.

    • Only 15–30% remain disease-free after 5 years.

  • Best prognosis: t(15;17) — Acute Promyelocytic Leukemia (curable in 90% of cases).

  • Worst prognosis: Age >60, AML after myelodysplastic syndrome, AML after exposure to DNA-damaging drugs.

Key Takeaways

  • Diagnosis is based on blasts >20%, except when genetic abnormalities are present.

  • Myeloblasts and lymphoblasts differ in size, cytoplasm, granules, nucleoli, and staining.

  • Special stains and flow cytometry help confirm the diagnosis.

  • Cytogenetic analysis is essential for prognosis and treatment planning.

  • Clinical presentation is mainly due to cytopenias — anemia, neutropenia, thrombocytopenia.

  • Prognosis depends on genetic changes, patient age, and clinical history.

This concludes our overview of Acute Myeloid Leukemia – Morphology, Clinical Features, and Prognosis.
For students, remember: always think morphology + genetics + clinical history when approaching a case of AML.

Click to view the video tutorial on acute myeloid leukemia

You can navigate through the virtual slides of  Acute Myeloid leukemia in the link below

Virtual Microscopy- Acute Myeloid leukemia