From the Guidelines
The workup for a patient with lymphocytosis should begin with a thorough history and physical examination, including evaluation of nutritional status and history of lymphocyte-depleting therapy, followed by a complete blood count with differential and reticulocyte counts, as well as bacterial cultures and evaluation for infection, as recommended by the American Society of Clinical Oncology 1. The initial evaluation should also include a physical examination with special attention to spleen size and a chest X-ray to evaluate for the presence of thymoma 1. Key considerations in the workup include:
- History of autoimmune disease and family history of autoimmune disease
- Evaluation of nutritional state as a potential cause of lymphocytosis
- Assessment for infections, including fungal, viral, and bacterial infections, specifically CMV and HIV
- CBC with differential and reticulocyte counts to confirm lymphocytosis and assess other cell lines
- Peripheral blood smear examination to characterize the lymphocyte population The workup should be tailored to the patient's clinical presentation, as lymphocytosis can result from benign reactive processes or malignant conditions, and age is an important consideration, with viral infections more common in younger patients and malignancies more prevalent in older adults with persistent lymphocytosis 1. Additional studies, such as flow cytometry, bone marrow aspiration, and biopsy, may be indicated if malignancy is suspected based on initial results, and imaging studies like CT scans or PET scans may be necessary if lymphoma is suspected 1. It is essential to note that the absolute lymphocyte count should not be used as the sole indicator for treatment, and other factors, such as symptoms, disease progression, and response to therapy, should be considered in the management of patients with lymphocytosis 1.
From the Research
Workup for High Lymphocytes
The workup for a patient with lymphocytosis (elevated lymphocytes) involves a thorough clinical review, including a history, examination, and preliminary investigations such as blood tests and a blood film 2.
Key Steps in the Workup
- Confirming the complete blood cell count and the WBC differential is the first step in distinguishing malignant from benign leukocytosis 3.
- Examination of the peripheral blood smear is essential to confirming the automated blood cell differential or affirming the manual differential performed on the peripheral blood smear 3.
- Separation of the leukocytosis into a myeloid versus a lymphoid process is necessary, with distinguishing a reactive lymphoid proliferation from a lymphoproliferative disorder requiring examination of lymphocyte morphology 3.
- Samples suspicious for lymphoproliferative disorders can be confirmed and characterized by flow cytometry, with molecular studies initiated in select cases 3.
Considerations in the Workup
- A repeat complete blood count with peripheral smear may provide helpful information, such as types and maturity of white blood cells, uniformity of white blood cells, and toxic granulations 4.
- The leukocyte differential may show eosinophilia in parasitic or allergic conditions, or it may reveal lymphocytosis in childhood viral illnesses 4.
- Leukocytosis is a common sign of infection, particularly bacterial, and should prompt physicians to identify other signs and symptoms of infection 4.
- Symptoms suggestive of a hematologic malignancy include fever, weight loss, bruising, or fatigue, and if malignancy cannot be excluded or another more likely cause is not suspected, referral to a hematologist/oncologist is indicated 4.
Additional Tests
- Bone marrow aspirates and biopsies may be necessary in certain situations, such as to rule out a malignancy 5.
- A "complete blood count score" model, which integrates reduced lymphocyte-monocyte ratio, elevated neutrophil-lymphocyte ratio, and elevated platelet-lymphocyte ratio, can predict inferior clinical outcomes in adult T-lymphoblastic lymphoma 6.