From the Guidelines
Atypical lymphocytes are primarily caused by viral infections, with Epstein-Barr virus (EBV) being a common cause, resulting in infectious mononucleosis, as seen in studies such as 1.
Causes of Atypical Lymphocytes
The presence of atypical lymphocytes can be attributed to various factors, including:
- Viral infections: EBV, cytomegalovirus (CMV), hepatitis viruses, HIV, and human T-cell leukemia virus type 1 (HTLV-1) are known to cause atypical lymphocytes, as discussed in 1 and 1.
- Medications: Certain medications like phenytoin, antibiotics, and chemotherapeutic agents can trigger the formation of atypical lymphocytes.
- Autoimmune disorders: Systemic lupus erythematosus and rheumatoid arthritis are examples of autoimmune disorders that can lead to the development of atypical lymphocytes.
- Lymphoproliferative disorders: Lymphomas and leukemias may present with atypical lymphocytes, as mentioned in 1 and 1.
Characteristics of Atypical Lymphocytes
Atypical lymphocytes are activated T or B lymphocytes that respond to antigenic stimulation, characterized by:
- Larger size compared to normal lymphocytes
- Abundant cytoplasm
- Irregular nuclear contours
- Sometimes visible nucleoli Their presence in peripheral blood smears serves as an important diagnostic clue for underlying conditions, particularly viral infections, though specific diagnosis typically requires additional testing, as noted in 1 and 1.
Diagnosis and Management
Diagnosis of the underlying cause of atypical lymphocytes is crucial for appropriate management. This may involve additional testing, such as serology, molecular diagnostics, or imaging studies. Management of atypical lymphocytes depends on the underlying cause, and may include antiviral therapy, immunosuppressive therapy, or treatment of the underlying malignancy, as discussed in 1 and 1.
From the Research
Atypical Lymphocytes Causes
- Atypical lymphocytes are a common feature of infectious mononucleosis, caused by the Epstein-Barr virus (EBV) 2, 3, 4, 5
- Atypical lymphocytosis can also be seen in other conditions, including other viral infections, cancer, and immune reactions 3, 6
- The presence of atypical lymphocytes is not specific to EBV infection and can be found in other forms of atypical lymphocytosis 3
- Atypical lymphocytes constitute more than 10% of the total lymphocyte count in infectious mononucleosis 2
- The population of atypical mononuclear cells in infectious mononucleosis consists primarily of CD8+ T cells with a small fraction of CD19+ B lymphocytes 4
Associated Conditions
- Infectious mononucleosis is a risk factor for chronic fatigue syndrome 2
- Atypical lymphocytosis can be a feature of aggressive NK cell leukemia 6
- EBV infection is associated with certain cancers and autoimmune diseases, as well as complications of primary immunodeficiency in persons with certain genetic mutations 5
Diagnosis and Clinical Significance
- The diagnosis of atypical lymphocytes should be based on a combination of clinical symptoms, signs, imaging examination, cell immunophenotype, and disease outcome, rather than solely on morphological interpretation of cells 6
- The amount of atypical mononuclear cells in children with mononucleosis caused by primary EBV infection is significantly higher than for IM caused by EBV reactivation or other viruses 4
- Children failing to recover from classic IM associated with primary EBV infection within 6 months had significantly lower percentage of CD8+ atypical mononuclear cells compared to patients with normal recovery rate 4