Lymphadenopathy Workup

The laboratory evaluation of lymphadenopathy must be directed by the history and physical examination and is based on the size and other characteristics of the nodes and the overall clinical assessment of the patient. When a laboratory evaluation is indicated, it must be driven by the clinical evaluation.^[13] The following studies are typically included:

• CBC count, including a careful evaluation of the peripheral blood smear. An erythrocyte sedimentation rate is nonspecific but may be helpful.
• Evaluation of hepatic and renal function and a urine analysis are useful to identify underlying systemic disorders that may be associated with lymphadenopathy. Additional studies, such as lactate dehydrogenase (LDH), uric acid, calcium, and phosphate, may be indicated if malignancy is suspected. Skin testing for tuberculosis is usually indicated.
• In evaluating specific regional adenopathy, lymph node aspirate for culture may be important if lymphadenitis is clinically suspected.
• Titers for specific microorganisms may be indicated, particularly if generalized adenopathy is present. These may include Epstein-Barr virus, cytomegalovirus (CMV), B henselae, Toxoplasma species, and human immunodeficiency virus (HIV).

Imaging studies may include the following:

• Chest radiography is usually the primary screening imaging study. Additional imaging studies are usually based on abnormal chest radiograph findings. Chest radiography is often helpful in elucidating mediastinal adenopathy and underlying diseases affecting the lungs, including tuberculosis, coccidioidomycosis, lymphomas, neuroblastoma, histiocytoses, and Gaucher disease.
• Supraclavicular adenopathy, with its high associated rate of serious underlying disease, may be an indication for other studies, including CT scanning of the chest, abdomen, or both.
• Positron-emission tomography (PET) scanning is not helpful as a screening tool as benign and malignant conditions may cause intense uptake.^[14] However, PET scanning is helpful in the evaluation of lymphomas once a clinical or tissue-based diagnosis is made.^[15]
• Nuclear medicine scanning is helpful in the evaluation of lymphomas.
• Ultrasonography may be helpful in evaluating the changes in the lymph nodes and in evaluating the extent of lymph node involvement in patients with lymphadenopathy.^[16]
• In children with inguinal adenopathy or abdominal complaints, ultrasonography of the abdomen, CT scanning of the abdomen, or both may be indicated.^[17]

The critical question is often whether or not to perform a lymph node biopsy; this requires an overall assessment of the history and physical examination as described above.

• Images taken during and after a lymph node biopsy are shown below.A lymph node biopsy is performed. Note that a marking pen has been used to outline the node before removal and that a silk suture has been used to provide traction to assist the removal. A lymph node after removal by means of biopsy, which was performed completely under a local anesthetic technique. A gross image of a node following excision. The cut surface of the node shows the typical fish-flesh appearance seen with lymphoma.
• Treatment with antibiotics (covering the bacterial pathogens frequently implicated in lymphadenitis) followed by reevaluation in 2-4 weeks is reasonable if clinical findings suggest lymphadenitis. Benign reactive adenopathy may be safely observed for months.^[6]
• If the size, location, or character of the lymphadenopathy suggests malignancy, the need for laboratory studies and biopsy is more urgent. If laboratory testing is inconclusive, a lymph node biopsy is immediately indicated.
• Fine needle aspiration and core needle biopsy yield small samples with limited ability to perform flow cytometry and chromosomal analysis; most pediatric hematologists and pathologists prefer excisional biopsy.
• Excisional biopsy also has limitations and may yield a definitive diagnosis in only 40-60% of patients because of inadequate specimen size, improper handling, or node-sampling error.
• Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a widespread technique for tissue sampling from hilar and mediastinal lymph nodes (LN), but the predominant finding in routine care can be a non-diagnostic cytology in over 70% of patients.^[18]
• Hodgkin disease may be associated with reactive changes in surrounding nodes, and sampling more accessible nodes may miss the underlying malignancy.
• Sampling inguinal nodes may yield specimens with an architecture distorted by chronic inflammatory changes.
• The surgeon should perform a biopsy on larger, firmer, and most recently enlarging nodes, even if it is technically difficult, with appropriate preparation and handling of the specimen. If an excisional biopsy does not reveal the diagnosis despite appropriate sampling practice, a second biopsy may be indicated if symptoms persist or worsen.

Histiologic findings depend on the underlying etiology of the lymphadenopathy. Nonspecific changes consistent with reactive adenopathy are often the only findings. This is helpful in ruling out malignancy, histiocytoses, granulomatous disorders, and storage diseases. Specific infections can be diagnosed if tissues are appropriately stained.

When examining the tissue, histiologic findings are often inadequate. Flow cytometric and chromosomal analysis may provide critical information to permit a diagnosis to be established.

Staging is relevant only when a specific malignancy is diagnosed as the etiology of lymphadenopathy.