What viral laboratory tests should be considered for a patient with nonspecific cervical lymph node enlargement and lymphocytic predominance on complete blood count (CBC) differential, with a normal computed tomography (CT) scan?

From the Guidelines

For nonspecific cervical lymph node enlargement with lymphocytic predominance on CBC differential and normal CT scan, I recommend testing for Epstein-Barr virus (EBV), cytomegalovirus (CMV), HIV, and toxoplasmosis, as these infections are commonly associated with cervical lymphadenopathy and lymphocytosis, and can have significant implications for morbidity, mortality, and quality of life if left undiagnosed or untreated. These viral labs should include EBV viral capsid antigen (VCA) IgM and IgG, EBV nuclear antigen (EBNA) antibodies, CMV IgM and IgG, HIV antibody/antigen testing, and Toxoplasma gondii IgM and IgG, as outlined in the 2013 recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM) 1. Additional considerations include testing for human herpesvirus 6 (HHV-6), adenovirus, and rubella IgM if clinically indicated, as these infections can also cause similar presentations. The pattern of antibody positivity in EBV testing, such as the presence of VCA IgM and IgG antibodies, can help determine if the infection is acute, recent, or past, and guide further management and treatment decisions 1. If these initial tests are negative and lymphadenopathy persists beyond 4-6 weeks, consider additional testing for less common causes or referral for lymph node biopsy to rule out lymphoma or other malignancies, as persistent lymphadenopathy can be a sign of underlying malignancy or other serious conditions. It is essential to prioritize these tests based on the patient's clinical presentation, medical history, and risk factors, and to consider the potential consequences of delayed or missed diagnosis on patient outcomes, including morbidity, mortality, and quality of life.

From the Research

Viral Laboratory Tests for Cervical Lymph Node Enlargement

The patient's presentation of nonspecific cervical lymph node enlargement and lymphocytic predominance on complete blood count (CBC) differential, with a normal computed tomography (CT) scan, suggests the need for further investigation into potential viral causes.

• Epstein-Barr virus (EBV) infection is a possible cause of cervical lymphadenopathy, as shown in a study published in the International Journal of Pediatric Otorhinolaryngology 2. This study found that 15% of children presenting with cervical lymphadenopathy tested positive for EBV serology.
• Other viral infections, such as filariasis, can also cause lymph node enlargement, although this is a rare differential diagnosis in European patients 3.
• The diagnosis of IgG4-related disease (IgG4-RD) should also be considered, as it can present with cervical lymphadenopathy, although this is a rare manifestation of the disease 4.
• Imaging studies, such as ultrasonography, can be useful in evaluating cervical lymphadenopathy and guiding further diagnostic testing 5.
• Serological testing, including EBV serology, may be helpful in identifying a specific cause of cervical lymphadenopathy and avoiding unnecessary excision biopsy 6.

Potential Diagnostic Tests

Based on the patient's presentation, the following viral laboratory tests may be considered:

• EBV serology testing, including heterophile antibody test, and/or EBV-specific antibodies (VCA-IgM and VCA-IgG) 2
• Other viral serology tests, such as filariasis serology, depending on the patient's travel history and exposure risk 3
• IgG4 level testing to evaluate for IgG4-RD 4