What is the workup for lymphadenopathy (lymph node enlargement) in the neck with a single palpable lymph node?

From the Guidelines

The workup for a single enlarged lymph node in the neck should begin with a thorough history and physical examination, followed by imaging with ultrasound as the first-line modality if the node is larger than 1 cm, persists for more than 2-4 weeks, or has concerning features, and fine-needle aspiration (FNA) should be performed if the lymph node is persistent and unexplained, with progression to excisional biopsy if FNA is inconclusive or if there is high suspicion for lymphoma or malignancy. The initial evaluation should include assessment of the node's size, location, consistency, tenderness, and duration of enlargement. Laboratory tests should include a complete blood count with differential, comprehensive metabolic panel, and inflammatory markers like ESR and CRP. According to the study by 1, a diagnostic assessment based solely on fine-needle aspiration biopsy is insufficient except in unusual circumstances when in combination with immunohistochemistry it is judged to be diagnostic of HL by an expert hematopathologist or cytopathologist. The study by 1 suggests that imaging characteristics suggestive of malignant processes should be assessed when a cystic neck mass is observed, and FNA may need to be repeated, possibly with image guidance to direct the needle into any solid components or the cyst wall. The study by 1 recommends FNA as the initial pathologic test for a patient with a neck mass at increased risk of malignancy, with a high level of confidence in the evidence and a preponderance of benefit over harm. The workup follows this stepwise approach because most cervical lymphadenopathy is benign and self-limiting, often due to local infection, but persistent enlargement requires exclusion of serious conditions like lymphoma, metastatic malignancy, or granulomatous disease. Some key points to consider in the workup include:

• A thorough history and physical examination to assess the node's size, location, consistency, tenderness, and duration of enlargement
• Laboratory tests, including complete blood count with differential, comprehensive metabolic panel, and inflammatory markers like ESR and CRP
• Imaging with ultrasound as the first-line modality if the node is larger than 1 cm, persists for more than 2-4 weeks, or has concerning features
• FNA if the lymph node is persistent and unexplained, with progression to excisional biopsy if FNA is inconclusive or if there is high suspicion for lymphoma or malignancy
• Specific testing for infectious causes, such as EBV, CMV, HIV, tuberculosis, and toxoplasmosis serologies, based on clinical suspicion.

From the Research

Lymphadenopathy Workup in the Neck - One Lymph Node

• The evaluation of lymphadenopathy typically involves a combination of clinical history, physical examination, and diagnostic tests 2, 3.
• When the cause of lymphadenopathy is unknown, it should be classified as localized or generalized, with localized lymphadenopathy evaluated for etiologies associated with the region involved according to lymphatic drainage patterns 2.
• Risk factors for malignancy in lymphadenopathy include age older than 40 years, male sex, white race, supraclavicular location of the nodes, and presence of systemic symptoms such as fever, night sweats, and unexplained weight loss 2, 4, 5.
• The workup for lymphadenopathy may include blood tests, imaging, and biopsy, depending on clinical presentation, location of the lymphadenopathy, and underlying risk factors 2, 3, 4, 5.
• Ultrasound has been shown to be a useful tool in the evaluation of lymphadenopathy, with a sensitivity of 98% and negative predictive value of 97% for detecting malignant lymphadenopathy 4.
• Clinical features significantly associated with malignancy include age > 45, B symptoms, history of malignancy, and lymphadenopathy that is ≥ 2 cm, in multiple regions, bilateral, multiple nodes, or supraclavicular 4.
• Laboratory parameters significantly associated with malignancies include CRP, LDH, and thrombocytopenia 5.
• Patients with persisting cervical lymphadenopathy and over 3 weeks of antibiotic treatment should be considered for early biopsy, especially if some of the risk factors are present 5.