✓ Evidence Based

Leukemia Diagnosis and Tests

Performing an accurate diagnosis is an essential part of any physician’s regular clinical practice. For this reason, during the many years needed to become a physician are dedicated to both the basic sciences and the clinical sciences. A physician through the integration of both groups of sciences will be able to diagnose a patient accurately. A great example of this is the diagnosis of leukemia.

Leukemia Diagnosis

Leukemia is a category of malignant diseases that derives from the hematologic system. It is, like any cancer, a group of diseases with abnormal qualities that allow it to bypass regulatory mechanisms. However, the abnormal qualities of the malignant cell that permit their identification through the numerous test for leukemia. Until recent years this group carried a poor prognosis. However technological advances allowed improved diagnosis and treatment has improved patients’ outcomes.

Diagnosis of leukemia

The diagnosis of leukemia is a process based on our current understanding of this group disease along with the evidence of the utility of different methods of evaluation. This process is akin to the steps needed for any diagnosis. The initial steps consist of the evaluation of the patient for risk factors and other details which will provide useful details. Later, the physical exam will be performed to complement the details gathered before to develop a working diagnosis that will orient the physician. This working diagnosis is essential in order to solicit the correct diagnostic test for leukemia.

As stated before leukemia is a category that includes a group of diverse malignancies derived from the hematologic system. Understanding its genetic and cytological characteristics will provide the essential knowledge need to understand the basis of the signs and symptoms arising from this disease and the test for leukemia.

Genetic alterations are one of the fundamental alterations in the development of cancer. Also, these will determine the clinical manifestations and utility of the test in the diagnosis of leukemia. There are many types of genetic alterations, such as deletions and missense mutations. Any type of these alterations could be found in leukemia, but chromosomal translations will be the major type involved in the development of these diseases. Chromosomal translocations can be described as defined as the shift of the location of certain parts of a chromosome to another chromosome.  As a result of these alterations, abnormal proteins might be produced which will later change cells into malignant cells. The diverse genes mutated by chromosomal translocation will produce specific types and subtypes of leukemia. This is what allows a genetic test for leukemia to identify leukemic cells and later distinguish the distinct subtypes of leukemia.  Additionally, the genetic alterations determine the cytological alterations found in the patients suffering from leukemia.

Cytological alterations are the result of diverse genetic alterations and will determine the clinical presentation of patients. Because the genetic alterations change cellular characteristics specifically in certain cells in the hematologic system, they will determine the clinical manifestations which are required for the diagnosis of leukemiaSpecifically, the hematopoietic cells are affected in leukemia and the signs and symptoms will depend on the deficiencies and lesions caused by hematopoietic malignant cells. Among the deficiencies found in leukemic patients are varied degrees of hematopoietic dysfunction. This manifest in the general test for leukemia as pancytopenia, or the decrease of mature blood cells. In pancytopenia, there is a decrease in red blood cells, white blood cells, and platelets, causing specific signs attributable to either of the three types of cellular deficiencies. However, not all types of leukemia present pancytopenia, in these cases the patient will only have a deficiency in one or two of the blood cells. Hematopoietic malignancies additionally can cause lesions resulting from damages to structures outside the blood vessels. These lesions manifest in diverse organs, including the skin, liver, nervous system and many others.

In the diagnosis of leukemia, cytological changes will also be the basis of several specific tests for leukemia, particularly relevant in the identification of subtypes. Among the cytological changes found in cells are morphological characteristics and variations in the molecular markers found in malignant cells. All hematologic cells derive from a group of stem cells, but as stem cells differentiate they will begin to change their morphological characteristics and molecular markers. Several laboratory tests are used to identify the cells because distinguishing leukemias from lymphomas and other hematologic malignancies depend on the cell types from which the malignancy originates. Additionally, the subtypes will be determined by the characteristics presented by the malignant cells. Understanding these characteristics is fundamental in the evaluation of the test result of patients.

Based on the genetic and cytological characteristics of leukemia a physician is able to diagnose leukemia and the specific subtype. In order to perform this task, a physician must evaluate a patient’s medical history and physical exam, looking for risk factors and clinical manifestations that will help him identify a possible diagnosis of leukemia. If there is the possibility of the diagnosis of leukemia, the physician should attempt to distinguish which type of leukemia is present, based on the risk factors and clinical manifestations. Afterward, the physician will order several tests for leukemia which can confirm the diagnosis and identify the specific subtype.

The cause of leukemia is not currently known but several risk factors have been identified. One of the first steps in the diagnosis of leukemia involves the identification of risk factors based on epidemiological studies. Risk factors for leukemia include exposure to carcinogens (such as smoking and chemicals) and presenting other illnesses (such as myelodysplastic syndromes and congenital syndromes). However, risk factors vary according to the type of leukemia.


Another part of the diagnosis of leukemia is the identification of signs and symptoms through the clinical interview and the physical exam. Signs and symptoms of leukemia can be classified as constitutive, intramedullary, extramedullary. The constitutive are unspecific of leukemia, they are sometimes described as flu-like. They include fatigue, malaise, anorexia, and fever. The intramedullary and extramedullary symptoms provide greater evidence for leukemia.

After the evaluation of risk factors and clinical manifestations, these must use to identify the most probable diagnosis. Based on this probable diagnosis, the physician will order a test in order to confirm the diagnosis. If a physician suspects the diagnosis of leukemia, ordering a confirmatory test is essential. The tests for leukemia include a blood test, a chemistry test, a bone marrow test, some imaging tests, a lymph node biopsy, a lumbar puncture, and a urine test. These tests additionally seek to identify lesions outside the vascular system.

Leukemia is not a single disease; it is a category of diverse diseases that all originate from the hematopoietic system. Currently, leukemia is classified into three types of leukemia, acute myelogenous leukemia, acute lymphoblastic leukemia, and chronic myelogenous leukemia. Additionally, some of the types of this group of diseases have several subtypes. Therefore, the diagnosis of leukemia should be considered in general initially but later each type should be considered individually.

When considering an acute presentation during the diagnosis of leukemia in adults, a physician should always consider acute myelogenous leukemia. This is an aggressive hematologic malignancy that represents 80% of all adult leukemias. In general, the risk of being diagnosed with acute myelogenous leukemia increases with aging, as most cases present between the ages of 60 and 70 years. This disease has several established risk factors, including environmental exposures, other medical condition and the patient’s sex (males are more commonly affected than females).

Among the environmental risk factors are smoking, chemicals, chemotherapy, and radiation. All of these are known to cause cancers but their exact mechanism in the pathogenesis of acute myelogenous leukemia is unknown. Medical conditions can also be risk factors and they are divided into two groups, hematologic disorders, and cytogenetic congenital syndromes. Some of the hematologic disorder risk factors are polycythemia vera, essential thrombocythemia, and some myelodysplastic syndromes. These disorders are not types of leukemia but share certain characteristics, which are like to be the cause of their progression into acute myelogenous leukemia. Cytogenetic congenital syndromes are also risk factors. Among these syndromes are, Down syndrome, Fanconi´s anemia, Bloom´s syndrome, ataxia-telangiectasia, Li-Fraumeni syndrome, and Kostmann syndrome.

Evaluating the risk factors for acute myelogenous leukemia is the first part in the diagnosis of leukemia, later the physician must evaluate the patient looking for constitutive, intramedullary and extramedullary signs. The constitutive clinical manifestations in acute myelogenous leukemia comprehend one of the earliest hints of the presence of this disease. These manifestations include fatigue, shortness of breath, and fever. The first two can be attributed to the patient´s anemic state. Additionally, paleness and exertion dyspnea are other signs of anemia. About 30% percent of patients will have a major infection such as pneumonia, cellulitis or septicemia. This could be a hint that leukocytes are not being produced adequately.   Also, deficiency in platelet formation causes diverse coagulative disorders like gum bleeding, petechial bleeding, and retinal bleeding.

Other clinical manifestations in the patient include the intramedullary signs and extramedullary signs. The first is mainly represented by varied degrees of bone and articular pain. Extramedullary manifestations are varied and correspond to all possible sites of malignant cell infiltration. Examples of this are chloromas in the skin and other organs. Also, the patient might present hepatomegaly or splenomegaly.

The confirmatory test for leukemia includes a complete blood cell count, a peripheral blood spread, bone marrow aspirate, and the specific molecular test.  The white cell count is usually much higher than regular levels. Additionally, in the peripheral blood, only an immature myeloid blast is observed. Also, the presence of Auer rods in the immature cells produced in acute myelogenous leukemia is a pathognomonic sign and allows the distinction with acute lymphoblastic leukemia. A bone marrow aspirate is another essential test for leukemia because it defines the diagnosis of acute myelogenous leukemia. Bone marrow aspirates with more than 20% of leukemic blasts define the presence of the disease.

The evaluation of molecular immunological markers permits the precise identification of the original of the cells. As these cells originate from myeloid, the markers must confirm this by identifying the expression of the appropriate markers (CD13, CD14, CD33, and HLA-DR). Other markers along with the molecular test like PCR and FISH allow the identification of the subtypes.

Another acute presentation of leukemia can be observed in patients diagnosed with acute lymphoblastic leukemia. This group of hematologic malignancies is less frequent than acute myelogenous leukemia. Additionally, instead of a single peak, across populations, a double peak is observed. An initial peak of cases occurs among children and young adults and the second peak occurs after the age of 60 years. Additionally, many more cases of acute lymphoblastic leukemia are identified in children than acute myelogenous leukemia, in a 4 to 1 ratio. This is particularly relevant when evaluating pediatric patients with a possible diagnosis of leukemia.

Risk factors in acute lymphoblastic leukemia are similar to those in acute myelogenous leukemia. But there are some additional ones, such as race/ethnicity and viral infections. For unknown reasons, this disease is more prevalent in white/Caucasians than in other racial/ethnic groups. The other specific risk factors are viral infections by a special type of Epstein-Barr virus and the Human T-lymphotropic virus 1 are associated with acute lymphoblastic leukemia.

Acute lymphoblastic leukemia also has particular signs and symptoms useful for its diagnosis. The constitutive signs and the clinical manifestations are similar to acute myelogenous leukemia. Also, an extramedullary manifestation may occur as well, but this disease has some findings not present in acute myelogenous leukemia. Upon the physical exam, lymph node enlargement can be palpated in patients. Also, acute lymphoblastic leukemia presents infection of the central nervous system in about 5-10% of all patients. Signs of neuronal affection include a headache, meningeal irritation, and cranial nerve paralysis.

Afterward, a diagnostic test for leukemia should be performed. The same test for acute myelogenous is regularly performed. But patients present some differences in the results. For example, white cell counts are also increased but instead myeloid blast cells, lymphoid blast cells are present. Likewise, the immunological markers will provide further evidence of the lymphoid origin of malignant cells. In the bond marrow aspirate, about 50 to 90% of the leukemic blast can be identified. The molecular test will allow the identification of specific genetic alterations associated with this group of illnesses.

Contrasting to the other two presentations, as indicated by the name, chronic myelogenous leukemia has a progressive clinical presentation. This disease has particular cytogenetics characteristics but definite risk factors have not been identified.

The time course of the clinical presentations allows the distinction between the other two groups of leukemias. However, specific signs do not. The constitutive signs are similar to the acute presentations of leukemia but due to the extended time course weight loss can occur. The extramedullary manifestations include a mixture of both acute presentations. However, lymphadenopathy suggests progression to a blast crisis.

The diagnosis is made after the confirmation through a laboratory test. The diagnostic result also provides the stages of the disease. Two essential criteria are the platelet count and the number of blast cells in the blood. In the chronic phase, the blast will represent less than 15% of cells and platelet will be above 100,000 in blood. When the patient enters a blast crisis, the number of blast increase to represent 30% of cells and platelet count decreases below 100,000. Regarding the immunological markers, about 80% will have a myeloid phenotype and the rest will have a lymphoid phenotype. Additionally, through cytogenetic testing, Philadelphia will be present. Occasionally other genetic abnormalities will be identified.

The diagnosis of leukemia is composed of several steps based on our current understanding of this hematologic malignancy. The steps try to incorporate all aspects concerning the nature and evolution of the specific malignancy. This is why it essential to differentiate leukemia from other hematologic disorders and later distinguish the type and subtype of the disease present in the patient. Only after the accurate and prompt diagnosis, the appropriate management will be implemented and the patient will recover their health and continue to enjoy life.

Get our wellness newsletter

Fitness and nutrition tips, health news, and more.

Thank you for subscribing.

Something went wrong.

Do NOT follow this link or you will be banned from the site!

Evidence Based

This article is based on scientific evidence, and written, fact-checked & medically reviewed by health experts.

Throughout this article, you'll find scientific references (clickable links to highly trusted peer-reviewed scientific papers, links denoted by the numbers in the parentheses (1, 2, 3)).