Diagnosis of Acute Myeloid Leukaemia

Published on 27 Jul 2021

Acute myeloid leukaemia (AML) is a form of leukaemia, that starts in the bone marrow (which is the inner soft part of the bone that produces the new blood cells) but can advance into the blood and some other parts of the body like the central nervous system, liver, lymph nodes, spleen, and testicles.

Acute myeloid leukaemia affects the development of the myeloid cells (a group of white blood cells) that generally mature into red blood cells, white blood cells, and platelets.

AML is the most common type of acute leukaemia. There are 8 subtypes of acute myeloid leukaemia which makes it one of the main aspects that differentiate it from other types of leukaemia. The subtypes are differentiated based on the cell that leukaemia is developed from, which include

M0- Undifferentiated acute myeloblastic leukaemia (Myeloblastic)- starts in immature forms of white blood cells.
M1- Acute myeloblastic leukaemia with minimal maturation (Myeloblastic)- starts in immature forms of white blood cells.
M2- Acute myeloblastic leukaemia with maturation (Myeloblastic)- starts in immature forms of white blood cells.
M3- Acute promyelocytic leukaemia (Promyelocytic)- starts in immature forms of white blood cells.
M4- Acute myelomonocytic leukaemia (Myelomonocytic)- starts in immature forms of white blood cells.
M5- Acute monocytic leukaemia (Monocytic)- starts in immature forms of red blood cells.
M6- Acute erythroid leukaemia (Erythroleukemia)- starts in immature forms of red blood cells.
M7- Acute megakaryoblastic leukaemia (Megakaryocytic)- starts in immature forms of cells that make platelets.

The symptoms of acute myeloid leukaemia include fever, frequent infections, anaemia, easy bruising or bleeding, and joint & bone pain.

Symptoms of AML:

Acute Myeloid Leukemia (AML) is a type of cancer that affects the bone marrow and blood cells. It is characterized by the rapid growth of abnormal myeloid cells, which are immature white blood cells. The symptoms of AML can vary among individuals, and some may be nonspecific or similar to other conditions. It is important to consult with a healthcare professional for an accurate diagnosis. Here are some detailed symptoms commonly associated with AML:

Fatigue and weakness: Persistent fatigue and feeling weak, even with adequate rest, is a common symptom of AML. This can be a result of decreased production of normal blood cells.
Shortness of breath: A decrease in red blood cells, known as anaemia, can lead to shortness of breath, especially with exertion. Anaemia occurs due to the crowding out of normal blood cell production by leukaemia cells in the bone marrow.
Pale skin: Anemia caused by AML can also result in a pale or "washed out" appearance of the skin.
Easy bruising and bleeding: AML can lead to a decrease in normal blood platelets, which are responsible for blood clotting. As a result, individuals with AML may experience easy bruising, excessive bleeding from minor cuts or injuries, and frequent nosebleeds or bleeding gums.
Frequent infections: AML impairs the production of healthy white blood cells, which play a crucial role in fighting off infections. As a result, individuals with AML may be prone to frequent infections, such as respiratory infections or urinary tract infections.
Bone and joint pain: Leukemia cells can accumulate in the bone marrow and cause bone and joint pain. This pain is often described as a dull ache and can affect various areas of the body.
Enlarged lymph nodes or spleen: AML may cause the lymph nodes or spleen to become enlarged. Enlarged lymph nodes can sometimes be felt as lumps under the skin, while an enlarged spleen may cause abdominal discomfort or pain.
Weight loss and loss of appetite: Unexplained weight loss and loss of appetite may occur in individuals with AML. This can be due to the effects of the leukaemia cells on the body's metabolism.
Fever and night sweats: Some individuals with AML may experience unexplained fever, often accompanied by night sweats.

It is important to note that these symptoms can also be caused by other conditions, and the presence of these symptoms does not necessarily indicate AML. If you experience persistent or concerning symptoms, it is recommended to consult with a healthcare professional for proper evaluation and diagnosis.

Also Read: Sign and Symptoms of Acute Myeloid Leukemia

Diagnosis

Several tests are necessary to diagnose cancer. They also do tests to see if cancer has metastasized or spread to another part of the body from where it began. For instance, imaging tests can determine if cancer has spread. Imaging tests show pictures of the body from the inside. Doctors can also do tests to learn which treatments would work best.

A biopsy for the doctor to know if an area of the body has cancer for most types of cancer. In a biopsy, the doctor takes a small tissue sample for testing in a laboratory. However, the doctor may suggest other tests if a biopsy cannot help diagnose the disease.

The doctor may consider the given factors when choosing a diagnostic test:

Your signs and symptoms
The age and general health status
The type of cancer suspected
The result of earlier medical tests

In addition to a physical examination, these tests can also help to diagnose AML ^?1?-

Sample tests

Blood sample: To diagnose AML, a doctor will do blood tests to count the number of white blood cells and see if they look abnormal under the microscope. Special tests called immunophenotyping or flow cytometry and cytochemistry are sometimes used to distinguish AML from other types of leukaemia and determine the exact subtype of AML ^?2?.
Bone marrow sample:
These two procedures are similar and often done simultaneously to evaluate the bone marrow, which is the fatty, spongy tissue found inside larger bones. Bone marrow has both a liquid and a solid part. A bone marrow aspiration takes a sample of the fluid using a needle. A bone marrow biopsy removes a small quantity of solid tissue using a needle.

A pathologist then reviews the samples in a lab. Pelvic bone located by the hip is a common site for bone marrow aspiration and biopsy. Doctors generally give a medication called "anaesthesia" beforehand to numb the area. Anaesthesia is a medication that blocks the awareness of pain.
Molecular and genetic testing: Your doctor may also recommend running laboratory tests to identify specific genes, proteins, and other factors involved in leukaemia. Examining the genes in the leukaemia cells is essential because the cause of AML can be due to the buildup of mistakes (mutations) in the cell's genes. In addition to it, identifying these mutations helps diagnose the specific subtype of AML and decide treatment options. Additionally, the results of those tests can help us monitor how well the treatment is working. Mentioned below are the more common molecular or genetic tests used for AML ^?3?.
Spinal fluid: This procedure is also called a lumbar puncture or spinal tap. In this method, the cerebrospinal fluid (CSF) is removed from the spinal cord. This procedure is only recommended when there are signs of acute myeloid leukaemia spreading to the CNS system. Also, the lumbar puncture procedure is used as a treatment procedure to deliver chemotherapy drugs.
Cytochemical and immunohistochemical tests: Cytochemical and immunohistochemical tests are laboratory tests that help to determine the exact subtype of AML. Furthermore, in cytochemical tests, a specific dye stains the different types of leukaemia cells differently based on the chemicals in the cells. For AML, immunohistochemical tests and a test known as flow cytometry help to find markers on the surface of the leukaemia cells. The different subtypes of leukaemia have different and unique combinations of cell surface markers.
Cytogenetics: Cytogenetics is a way to look at a cell's chromosomes through a microscope to analyze the number, shape, size, and arrangement of the chromosomes to find genetic changes in leukaemia cells. Sometimes, a chromosome part breaks off and attaches to another chromosome, known as translocation. Other times, part of a chromosome is missing, known as deletion. A chromosome can be made more than once, most often called trisomy. The cause of some leukaemia subtypes may be chromosome translocations, deletions, or trisomies ^?4?.

Knowing if specific translocations may help doctors determine the AML subtype and plan the best treatment. Fluorescence-in-situ-hybridization (FISH) is also one of the ways to detect chromosome changes in cancer cells. It also helps diagnose and determine the subtype of leukaemia. This is done on tissue removed in aspiration or biopsy.

The molecular genetics of leukaemia cells can also determine if a person needs more or less chemotherapy or bone marrow/stem cell transplantation. This type of testing looks for minute genetic mutations, called sub-microscopic mutations.

Lab tests

Complete blood count (CBC) & Peripheral blood smear: TheCBC test measures the amounts of different cells in the blood, such as the RBCs, WBCs, and platelets. Peripheral blood smear helps in identifying the changes in the numbers and the appearance of different types of blood cells.
Routine cell exams under microscope: Samples of blood, bone marrow, or CSF are observed under a microscope to look at and classify the WBC according to their size, shape, and other traits.
Cytochemistry: The cells in the sample are exposed to chemical stains (dyes) that react with only some types of leukaemia cells. These stains induce colour changes that can be observed under a microscope, to differentiate.
Flow cytometry & Immunohistochemistry: The cells in the samples are treated with antibodies (proteins), that fasten to specific proteins on cells. These methods are used for immunophenotyping leukaemia cells, which helps in the classification of acute myeloid leukaemia. In Flow cytometry, the cells are observed under a microscope whereas special equipment is used in Immunohistochemistry.
Chromosome tests: These tests observe the chromosomes. Cytogenetics test is a type of chromosome test, where the chromosomes are observed under microsome to observe changes in chromosomes, which include deletion, inversion, addition or duplication, and translocation. Fluorescent in situ hybridization (FISH) observes specific changes in certain parts of the DNA with the help of dyes. Polymerase chain reaction (PCR) is a sensitive test that can also find the changes that are too small to be observed under a microscope. It helps find gene changes that are in only a few cells, making it good for finding small numbers of leukaemia cells in a sample, it is prescribed after or during the treatment to evaluate the treatment and make any further changes in the treatment.

Imaging tests

X-ray: A regular X-ray is suggested if any infection to other organs is suspected.
Computed tomography (CT) scan: Generally CT scans use X-rays to get the cross-sectional image of the focused organ. Sometimes CT scan can also be used to guide a biopsy needle if the abscess is suspected. Also, sometimes a PET scan is used along with a CT scan for more precise diagnosis as PET use radioactive sugars to capture a picture of the regions of high radioactivity as the cancer cells absorb large amounts of sugar, then a CT scan is used to observe the region more detailed.
Magnetic resonance imaging (MRI) scan: MRI scan gives precise images of the soft tissues like the CT scan, but instead of using x-rays like for CT scan, radio waves are used for MRI scan.
Ultrasound: This procedure uses sound waves to make an image of the internal organs or masses. Ultrasound can be used to observe lymph nodes near the surface of the body or to look inside your abdomen for enlarged lymph nodes or organs such as the liver, spleen, and kidneys. Also, it is sometimes used to guide the needle inside swollen or enlarged lymph nodes for a biopsy.

If you are diagnosed with acute myeloid leukaemia (AML), your oncologist/ doctor will discuss the treatment options that can be based on the acute myeloid leukaemia subtype, other prognostic factors, age and your overall health status.

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Reference:

Arber DA, Erba HP. Diagnosis and Treatment of Patients With Acute Myeloid Leukemia With Myelodysplasia-Related Changes (AML-MRC). Am J Clin Pathol. 2020 Nov 4;154(6):731-741. doi: 10.1093/ajcp/aqaa107. PMID: 32864703; PMCID: PMC7610263.