What is the workup for a 39-year-old male with leukopenia (white blood cell count of 3.9), lymphocytosis (51% lymphocyte predominance), and a small neck mass?

From the Guidelines

For a 39-year-old male with a white blood cell count of 3.9 with 51% lymphocyte predominance and a small neck mass, I recommend a comprehensive evaluation including a thorough physical examination, complete blood count with differential, bone marrow biopsy, serum lactate dehydrogenase levels, and a comprehensive metabolic panel, as well as imaging of the chest, abdomen, and pelvis with CT scans if necessary, as suggested by the NCCN guidelines for hairy cell leukemia 1. The initial workup should focus on identifying potential underlying causes of the leukopenia and lymphocytosis, such as viral infections, autoimmune disorders, or lymphoproliferative disorders.

• A bone marrow biopsy with or without aspirate should be obtained to evaluate the bone marrow for any abnormalities, as recommended by the NCCN guidelines 1.
• Laboratory assessments should include CBC with differential, serum lactate dehydrogenase levels, and a comprehensive metabolic panel, with close evaluation of renal function due to the potential use of drugs with renal excretion in treatment 1.
• Hepatitis B virus (HBV) testing is also recommended due to the increased risk of viral reactivation associated with immunotherapy and/or chemotherapy 1.
• The neck mass should be evaluated by an otolaryngologist or primary care physician for possible fine needle aspiration or biopsy to determine the cause of the mass.
• Additional testing may include EBV, CMV, HIV serology, tuberculosis testing, and flow cytometry if a lymphoproliferative disorder is suspected. While waiting for evaluation, it is essential to monitor for symptoms like fever, night sweats, weight loss, or enlarging lymph nodes, which could indicate a more severe underlying condition.
• The relative lymphocytosis in the setting of mild leukopenia and a neck mass raises concern for a process affecting the immune system, making timely evaluation important for proper diagnosis and treatment. In contrast to the management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy, which may involve holding or interrupting treatment and administering prednisone or IVIG 1, the initial evaluation of this patient should focus on identifying the underlying cause of the leukopenia and lymphocytosis, rather than assuming an immune-related adverse event.

From the Research

Initial Evaluation

• The patient presents with leukopenia (white blood cell count of 3.9) and lymphocytosis (51% lymphocyte predominance) 2, 3, 4.
• A small neck mass is also noted, which may be related to the lymphocytosis.

Blood Smear Examination

• A blood smear examination is necessary to verify the flagged automated hematology results and determine if a manual differential leukocyte count needs to be performed 2.
• The blood smear examination can provide a complete hematologic picture of the case, including the types and maturity of white blood cells, uniformity of white blood cells, and toxic granulations 3.

Differential Diagnosis

• The differential diagnosis for leukopenia and lymphocytosis includes infectious diseases, autoimmune disorders, and hematologic malignancies 3, 4.
• The presence of a small neck mass may suggest a lymphoproliferative disorder, such as lymphoma 4.

Further Workup

• A repeat complete blood count with peripheral smear may provide helpful information, such as the presence of blasts or abnormal lymphocytes 3, 4.
• Additional tests, such as flow cytometry or bone marrow biopsy, may be necessary to further evaluate the patient's condition 4.
• The patient's white blood cell indices, including the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and lymphocyte-monocyte ratio, may also be useful in determining the prognosis and guiding further management 5.