Pediatric Lymph Node Disorders 

Updated: Jul 08, 2021
Author: Kenneth William Gow, MD, MSc, FRCSC, FACS, FAAP; Chief Editor: Robert K Minkes, MD, PhD 



The lymphatic system is an important component of the immune system. It includes lymphatic fluid, lymphatic vessels, lymph nodes, spleen, tonsils, adenoids, Peyer patches, and the thymus. Lymphatic fluid consists of an ultrafiltrate of blood collected within lymphatic channels, which run throughout the entire body. The fluid is slow-moving and is transported from the head and extremities to larger vessels, which then drain into the venous system. Along these channels reside approximately 600 lymph nodes.

Lymph nodes are composed of follicles and contain an abundance of lymphocytes. Lymph is filtered through the lymph node sinuses, where particulates and infectious organisms are detected and removed. Because of the exposure to immune challenges, antibody and cell-mediated immunity is mediated. As a result of such normal processes, the lymph nodes can enlarge through either proliferation of normal cells or infiltration by abnormal cells.

Lymphadenopathy is defined as the enlargement of one or more lymph nodes as a result of normal reactive process or a pathologic occurrence.[1] Whereas the (increased) size of the lymph node is the most common reference, an abnormal number or alteration in consistency may suggest a pathologic change that requires investigation and possible intervention.

Clinicians are challenged with the task of differentiating "true" enlarged lymph nodes related to a pathologic process from what are often referred to as "shotty" lymph nodes. Shotty lymph nodes are small mobile lymph nodes in the neck that are palpable and usually represent a benign change, commonly associated with viral illness.

The removal of lymph nodes to determine the etiology of their enlargement has been practiced for many years, but it is unknown when it was first performed. This procedure is often performed by general adult and pediatric surgeons, as well as by surgical specialists such as otolaryngologists. Because children often present with enlarged lymph nodes, pediatric surgeons are often the ones who treat these children, either primarily or as a referral.

A child with an enlarged lymph node is a common situation faced by clinicians. The challenge is to satisfy the parents' fears of malignancy and to do so in a safe, timely, and cost-effective manner. Organizing the possible causes of lymphadenopathy by anatomic location and origin aids the clinician in the evaluation. This article provides a rational approach to determining the etiology of the lymph node disorder, highlights various disorders to consider in treating a child with lymphadenopathy, and discusses various means of obtaining a tissue diagnosis when the cause of lymphadenopathy is uncertain.

For patient education resources, see the Blood and Lymphatic System Center, as well as Swollen Lymph Glands.


Lymph node distribution

Lymph nodes are organized in groups that drain specific regions of the body. This knowledge guides the clinician to inspect particular areas of anatomy when lymphadenopathy occurs.

Lymphatic drainage of the head and neck is traditionally divided into six regions. The most important nodes in this grouping are around the internal jugular lymph nodes. The superior aspect is termed region II; it receives lymph from the supraglottic larynx, anterior nasopharynx, and oropharynx via submental and submandibular lymph nodes (region I). The middle portion of the internal jugular chain is region III; it collects drainage from the superior hypopharynx and superior larynx via direct drainage through lymphatic capillaries. The inferior part of the chain is region IV; it collects drainage from the inferior hypopharynx, inferior larynx, and thyroid and supraclavicular regions.

Region VI sits in the anterior aspect of the neck; it contains supraclavicular, pretracheal, and thyroid nodes, which drain into region IV. Region IV of the internal jugular chain is the common collecting point for regions I-III and VI. Region V collects lymph from the scalp and posterior nasopharynx. All lymphatic drainage from region V and region IV on the internal jugular chain collect into the jugular trunk (ie, a group of nodes positioned at the internal jugular anterior brachiocephalic veins) and subsequently into the thoracic duct on the left or directly into the brachiocephalic vein on the right.

The thoracic cavity maintains a distinct collection of lymph nodes, with a slightly complex drainage route that parallels bronchi, arteries, and veins. Each major bronchial division has a collection of nodes called the intrapulmonary lymph nodes, which lie within the lungs and drain each of the lung's corresponding segments. The intrapulmonary nodes drain into a set of nodes, the left and right bronchopulmonary (hilar) lymph nodes, which are located at the junction of each lung and its main bronchi. These nodes collect the lymphatic drainage from the segments of their respective lung.

At the bifurcation of the trachea and beginning of each bronchus, three sets of nodes reside: the right and left tracheobronchial lymph nodes and the inferior tracheobronchial lymph nodes. An unusual feature of this anatomy is that the inferior tracheobronchial nodes, also known as the carinal nodes, collect lymph from the left lower lobe but drain that fluid into the right tracheobronchial lymph nodes. This is significant because a suspicious-appearing lymph node in the right hilar region should prompt evaluation of the left lower lobe and the right lung.

Aligned with the sides of the trachea are groups of nodes known as the right and left paratracheal lymph nodes, which collect lymphatic fluid from the right and left tracheobronchial nodes, respectively. The posterior thoracic cavity is drained via the intercostal lymph nodes and into the posterior mediastinal lymph nodes. The anterior thoracic cavity is drained through the parasternal lymph nodes, which are located next to the sternum in the intercostal space. The parasternal lymph nodes collect lymph from the anterior mediastinum and communicate with the medial aspect of the anterior chest wall.

The common drainage site for all of the aforementioned lymph nodes is into the jugular trunk and then into the thoracic duct on the left or directly into the brachiocephalic vein on the right.

The thoracic duct is the final common lymphatic drainage system for the lower extremities, the pelvis, the mesentery, most of the thoracic cavity, the left upper extremity, and the left head and neck. The thoracic duct is positioned on the right side of the aorta in the abdomen and receives lymph from the cisterna chyli. It ascends up through the thorax in the posterior mediastinum while receiving lymphatic drainage from the intercostal nodes. It crosses over to the left just below the carina and ascends to the level of the junction of the left internal jugular and left subclavian veins, where it connects into the venous system.

The upper intercostal nodes and right apical axillary nodes drain directly into the right brachiocephalic vein via the right bronchomediastinal trunk, and lymphatic drainage from the right side of the head and neck drain directly into the right brachiocephalic vein via the right jugular trunk.

The upper-extremity lymph node distribution consists of the cubital fossae and axillary region. The axillary group is subdivided into five subgroups. The lateral axillary group drains the upper extremity and receives lymph from the posterior axillary group, which in turn drains the posterior chest wall. The anterior axillary nodes drain lymph from the anterior chest wall. The lateral and anterior groups drain into the central axillary group, which in turn drains into the apical axillary (or subclavian) group. The apical axillary nodes drain into the thoracic duct on the left or directly into the brachiocephalic vein on the right.

The intra-abdominal lymphatic drainage parallels the arterial system. Lymph nodes lie in the mesentery, adjacent to an arterial counterpart. Each artery has a cluster of nodes that receives lymph from its corresponding arterial supply: celiac, superior, inferior mesenteric lymph nodes. These nodal groups eventually drain into the cisterna chyli, the beginning of the thoracic duct.

The additional role of the mesenteric lymphatic system is to absorb and transport long-chain fatty acids via chylomicrons. Intestinal mucosal immunity is primarily the responsibility of Peyer patches, which are unencapsulated collections of lymphatic tissue in lamina propria located on the antimesenteric side of the ileum. Mesenteric lymph nodes may become enlarged in mesenteric adenitis, a common cause of abdominal pain in children. A study that examined computed tomography (CT) scans of the abdomen showed that abdominal lymph nodes measuring up to 8 mm may be considered normal.[2]

The two groups that serve the lower extremities are the popliteal nodes and the inguinal nodes. The inguinal nodes are grouped into external and internal subtypes. The external group drains the lower extremity and lymph from the anterior abdominal wall and external genitalia. The internal inguinal nodes then drain into the external iliac nodes, which join the lymphatic drainage of the pelvis, via the internal iliac nodes, to come together in the common iliac nodes.

The two groups of common iliac nodes drain into the left and right lumbar nodes, beginning just proximal to the bifurcation of the aorta and eventually draining into the cisterna chyli, via left and right lumbar trunks. The cisterna chyli is the beginning of the thoracic duct. The kidneys and adrenal glands drain into lymph nodes around the renal vessels and subsequently into the lumbar nodes.

In most instances, lymph nodes up to 1 cm can still be considered normal. The two exceptions to this rule are the epitrochlear node, in which up to 0.5 cm is allowed, and the inguinal nodes, in which up to 1.5 cm is allowed.


The pathophysiology of lymphadenopathy differs according to the etiology. In a reactive process, a physiologic increase in the number of lymphocytes and macrophages causes the size of the node to increase. Alternatively, with changes related to pathologic processes, the node may increase in size because bacteria, fungi, viruses, or malignant or metastatic cells may fill the node.


Five broad etiologic categories lead to lymph node enlargement, as follows[3] :

  • Immune response to infective agents (eg, bacteria, viruses, fungi)
  • Inflammatory cells in infections involving the lymph node
  • Infiltration of neoplastic cells carried to the node by lymphatic or blood circulation (metastasis)
  • Localized neoplastic proliferation of lymphocytes or macrophages (eg, leukemia, lymphoma)
  • Infiltration of macrophages filled with metabolite deposits (eg, storage disorders)

Lymphadenopathy has been noted in the multisystem inflammatory syndrome in children (MIS-C; also referred to as pediatric multisystem inflammatory syndrome [PMIS], pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 [PIMS-TS], pediatric hyperinflammatory syndrome, and Kawasaki-like disease), which has appeared to correlate with COVID-19, though causing more severe symptoms.[4, 5] Further research into the possibility of a causal connection between MIS-C and SARS-CoV-2 are needed.


Lymphadenopathy is a common presentation in children; it is so common that the exact frequency may be difficult to establish. The likelihood of enlarged lymph nodes increases with age and exposure.


Virus-associated lymphadenopathy

Most commonly, upper respiratory tract infections predominate as the source of lymphadenopathy. The nodes tend to be small, soft, and bilateral and do not have warmth or erythema of the overlying skin.

Cervical adenopathy is a prominent feature of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection. Posterior cervical nodes are most commonly involved, followed by the anterior cervical chain. Children with adenovirus-associated respiratory infections may present with generalized constitutional symptoms and bilateral cervical adenopathy. Treatment is based on controlling symptoms and preventing complications instead of providing specific antiviral therapies.[6]

Bacteria-associated lymphadenopathy

The two organisms most commonly associated with lymphadenopathy are Staphylococcus aureus and group A streptococci. The clinical history often reveals a recent sore throat or cough, whereas the physical examination findings include impetigo, pharyngitis, tonsillitis, or acute otitis media. The primary sites involved include the submandibular, upper cervical, submental, occipital, and lower cervical nodal regions. Treatment involves administration of beta-lactamase–resistant antibiotics and drainage of purulence when fluctuation is present.[7]

With respect to children with acute adenitis, children hospitalized for a first episode of acute unilateral infectious adenitis generally do well. Younger patients and those with longer duration of node involvement before admission have an increased risk of surgical node drainage.[8]

Atypical mycobacteria

In the United States, atypical mycobacteria account for most cases of adenitis due to Mycobacterium infection. Numerous members are in this group, including Mycobacterium scrofulaceum and Mycobacterium avium-intracellulare complex. The onset of adenopathy may be relatively sudden; size may gradually increase over 2-3 weeks. The involved nodes usually have an overlying erythema and may be tender. The nodes may progress to fluctuance and ultimately drain spontaneously.

Treatment involves complete excision of the involved node because incision and drainage may lead to a chronically draining sinus.[9] Those dissections that may be adjacent to the marginal mandibular nerve are often associated with a transient paralysis that resolves over a few months.[10]

Mycobacterial tuberculosis

Lymph node involvement with Mycobacterium tuberculosis is commonly referred to as scrofula. It was previously a well-known manifestation of extrapulmonary tuberculosis; however, as tuberculosis has declined, so has the incidence of scrofula. Nonetheless, it is still prevalent in much of the world.

Patients with scrofula present with cervical node enlargement, most often around the paratracheal nodes or the supraclavicular nodes. Abnormal findings are observed on chest radiography in most cases. Clinical features are not helpful in distinguishing atypical from tuberculous mycobacterial infections. Nodal enlargement is usually painless; nodes are likely to suppurate and form sinuses. Performing a tuberculin test is usually helpful. Treatment involves administration of rifampin and isoniazid.[11]

Cat-scratch disease

Cat-scratch disease is a zoonotic infection that originates from animal scratches, most likely cat or kitten scratches. The primary inoculation of the skin, eye, or mucosal membrane leaves a small papule that may or may not be evident upon examination. Indeed, the papule may resolve before the lymphadenitis appears. Patients usually have accompanying constitutional symptoms, such as fever, malaise, and fatigue. The causative agent is Bartonella henselae, a gram-negative rickettsial organism. The disease is usually self-limiting and requires only supportive treatment.


Patients with lymphoma (Hodgkin disease [HD], non-Hodgkin lymphoma [NHL]), leukemia, or metastatic solid tumors may present with lymphadenopathy. The nodes are usually painless and continue to enlarge. Inflammatory signs or focuses are usually absent. Associated B symptoms of HD may be present, including fever, night sweats, weight loss, and malaise. If malignancy is suspected, a biopsy is needed to establish the diagnosis and allow important tests to be performed to guide therapy.

In a retrospective review by Oguz et al, children referred for concerning lymphadenopathy were more likely to have a malignant etiology if the lymph node was larger than 3 cm, the enlargement lasted longer than 4 weeks, supraclavicular involvement was observed, and abnormal laboratory and radiologic findings were noted.[12]

Other causes of adenopathy

Many less common disorders may also appear as lymphadenopathy.

In Kawasaki disease (ie, mucocutaneous lymph node syndrome), lymphadenitis is one of the earliest aspects of the disease. The enlarged node or group of nodes are unilateral, nonfluctuant, and usually located in the anterior triangle of the neck. Resolution of lymphadenitis is a rule.

Enlarged lymph nodes are prominent features in the course of sarcoidosis; the supraclavicular nodes and bilateral hilar nodes are involved.

Kikuchi lymphadenitis (ie, histiocytic necrotizing lymphadenitis) is a benign and rare disease of unknown origin that involves bilaterally enlarged cervical lymph nodes that are unresponsive to antibiotic therapy. Patients with Kikuchi lymphadenitis often have systemic symptoms, including fever, hepatosplenomegaly, and weight loss.

Systemic lupus erythematosus (SLE) often involves enlarged lymph nodes. Children with SLE tend to have more organ systems involved and a more severe course than adults with SLE do.

Langerhans cell histiocytosis (ie, histiocytosis X) is a syndrome with a broad clinical spectrum; its unifying pathologic feature is the derivation from Langerhans cells. The disease is believed to be a clonal neoplasm in which lymph node enlargement is common.




In most situations, performing a thorough history, a review of symptoms, and a physical examination can establish the likely etiology of the lymphadenopathy and render any further tests unnecessary.

Evaluation of the child with lymphadenopathy may begin with specific aspects of the enlarged lymph node or nodes and then expand to encompass the various aspects that may have caused it. The duration of lymph node enlargement often guides therapy. In general, benign lymphadenopathy resolves over 4-6 weeks, whereas persistent or progressive lymphadenopathy raises the possibility of malignancy.

In addition to duration, the clinician must evaluate for any associated symptoms. Other general questions include recent or past illnesses, infections, local trauma, or bites. Exposure to drugs and specifically antibiotics is also important because it may shrink the lymph nodes. If no obvious sources of infection are present, the presence of constitutional symptoms such as fever, weight loss, and night sweats are potential signs of malignancy. These are commonly referred to as B symptoms. If the patient has recurrent infections, immunodeficiencies such as HIV infection must be considered.

Information regarding family and social history is helpful to exclude associated malignancies and is useful to allay fears that cancer can run in the family. Social history may elicit potential sources of lymphadenopathy, including recent travel, drinking of unsanitized water, exposure to animals that may carry unique infections, exposure to tuberculosis (TB), exposure to typhoid, and exposure to trypanosomiasis. Information about activities such as sexual contact is also important. If the history is otherwise unremarkable, a thorough review of symptoms may establish other aspects of causation.

Physical Examination

The physical examination of a child with lymphadenopathy begins as a complete examination and then focuses on the enlarged node(s). The skin and the soft tissue drained by the enlarged node should be carefully examined for signs of inflammation, skin breakdown, and trauma. The character of the lymph node should be noted. Normal lymph nodes are described as soft, easily compressible, and freely mobile. Hyperplastic lymph nodes that develop as a response to viral infections are small, discrete, mobile, nontender, and bilateral. Usually, no accompanying cellulitis or inflammation is present.

Lymph nodes that are acutely infected with bacteria—most often S aureus or group A streptococci[6, 13] —tend to be large, warm, and tender and have surrounding erythema and edema. Infected lymph nodes may progress and develop an abscess. Chronically infected nodes tend to have discrete margins and are adherent to underlying tissues and have minimal signs of inflammation.

Nodes that are associated with malignancy tend to be larger than 2 cm, involve several groups of nodes, and occur in children older than 8 years.[14, 15] Lymphadenopathy associated with malignancy has been described as firm or rubbery, discrete, nontender, and fixed to the skin or underlying structures.[6, 15]

With a thorough physical examination, the clinician can broadly classify the lymphadenopathy as either a local or a general phenomenon. A localized lymphadenopathy usually results from abnormalities of the area in which the lymph node drains (eg, infection), though it cannot be excluded as the first sign of a precocious clinical manifestation in the course of a progressive systemic process. The appearance of a generalized lymphadenopathy suggests a systemic disease and orients the clinician more directly toward serologic and hematologic testing.

Of the regional lymphadenopathies, occipital and preauricular locations are rarely malignant; the former are often related to scalp and outer-ear infections, exanthematous diseases, and toxoplasmosis, whereas the latter are associated with infections of superficial tissue of the orbit, the middle ear, and the parotid glands. Submental lymphadenopathy requires a search for disorders in the anterior portion of the mouth and the lower lip, the submandibular portion of the face, the nose, the maxillary sinus, the mucosa of the oral cavity, the floor of the mouth, and the submental salivary gland.

Laterocervical lymphadenopathy in the upper portion of the neck can be associated with inflammatory or neoplastic disorders of the hypopharynx, the larynx, or the thyroid gland, whereas those in the lower part of the neck are related to disorders of the hypoglottic larynx, the thyroid, and the upper portion of the esophagus. Supraclavicular and epitrochlear enlargement must be considered as red flags for the potential of malignancy.

Enlarged axillary and inguinal lymph nodes are usually of benign etiology. Axillary lymphadenopathy is seen with infections of the upper extremity, chest wall, group tissue, and intrathoracic lesions. Inguinal lymphadenopathies are caused by sexually transmitted diseases of the genitalia and other infections of the perineum and pelvis.

Enlarged popliteal lymph nodes are generally associated with infections of the foot and leg. Lymphadenopathies of the mediastinum, retroperitoneum, and mesentery usually go undetected during physical examination but are sometimes suspected on the basis of compression of the surrounding structures.

The presence of general lymphadenopathy should alert the clinician to the presence of significant pathology. Any of the following common viral illnesses may produce generalized lymphadenopathy:

Even more concerning are the hematogenous malignancies (eg, leukemia, lymphomas) and other malignancies (eg, neuroblastoma, rhabdomyosarcoma). Some rare causes of generalized lymphadenopathy include autoimmune connective tissue diseases and the use of certain drugs, particularly phenytoin and carbamazepine.



Approach Considerations

Lymphadenopathy in children commonly arises from benign etiologies. A thorough history usually points the clinician in this direction. Furthermore, the physical examination guides the physician to the correct etiology by focusing on the distribution of the enlarged nodes (ie, regional or systemic), the exact characteristics of the involved nodes, and any other suspicious findings.

Alternatively, if the etiology remains unclear, laboratory studies, diagnostic imaging, or biopsy may be warranted, depending on the presumed diagnosis. If malignancy is suspected, a biopsy for histologic examination and testing is indicated.

Histologic findings vary, depending on the etiology. Staging is relevant only in cases involving a malignant etiology.

Laboratory Studies

In most patients, only the history and physical examination are needed to establish the likely diagnosis. However, if the diagnosis must be further refined, several tests can be performed. Generally, clinicians should perform the least invasive test that provides the most information. Furthermore, clinicians should tailor testing to the most likely diagnosis instead of performing a battery of tests on all patients with lymphadenopathy. Tests may include laboratory or radiologic investigations.

Various laboratory tests are available. In general, most laboratory indices of inflammation (eg, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], glycoproteins, fibrogen levels) do not contribute much to establishing the diagnosis, because most of the results are invariably elevated and do not provide useful suggestions regarding the exact etiology of the lymphadenopathy. Tests that are more specific are much more likely to help the clinician with the treatment of the patient.

A complete blood count (CBC) with a manual differentiation provides useful information. Leukemias are often accompanied by pancytopenia. A predominantly lymphocytic elevation (>1 × 109 cells/L) is practically diagnostic of mononucleosis; when the proportion of these cells is less elevated but still predominant, cytomegalovirus (CMV) and toxoplasmosis must be considered. Finding medium-to-large lymphocytes that can be classified as in transformation or activated is useful to indicate a viral infection.

Other useful tests may be performed to confirm or exclude specific clinical suspicions. Serum lactate dehydrogenase (LDH) may be used to determine the turnover rate of cells in the case of leukemia or lymphoma. Other tests (eg, tuberculin skin test; monospot; and titers for Epstein-Barr virus [EBV], CMV, cat-scratch disease, or toxoplasmosis) may be performed to evaluate for specific etiologies.

Imaging Studies

Chest radiography

Chest radiography may be useful to assess for potential sources of infection (eg, bacterial pneumonias or tuberculosis) and hilar adenopathy in the case of malignancy. Indeed, because numerous reports describe airway collapse with anesthetics in the case of a large anterior mediastinal mass, chest radiography should be considered before any general anesthetic is administered (see the image below).

A preoperative radiograph showing a narrowed trach A preoperative radiograph showing a narrowed trachea secondary to an anterior mediastinal mass.


Ultrasonography (US) may be performed to distinguish the nature of the node if it is difficult to palpate. Furthermore, it may be used to distinguish the abnormality from other potential anatomic structures (eg, dermoid cysts, thyroglossal duct cysts, branchial cleft cysts, inguinal hernias, undescended testicles). US may reveal relations to contiguous structures and offer information about the content of the enlarged lymph node or nodes (ie, solid vs liquid or gas, homogeneous vs nonhomogenous). Finally, in some studies, US has been used in an effort to establish etiology on the basis of sonographic characteristics.

A study by Zakaria et al, which compared sonoelastography (ultrasound elastography) with B-mode US and color Doppler US in 177 lymph nodes from 128 children (age range, 11 months to 12 years), suggested that sonoelastography may be superior to other US modalities for helping distinguish benign from malignant lesions.[16]  A subsequent study by Elgendy et al found sonoelastography useful in diagnosing malignant cervical lymphadenopathy but concluded that it was not a replacement for surgical biopsy.[17] Further studies with more patients are needed.

Computed tomography

Computed tomography (CT) is useful for depicting deep lymph nodes, especially in the thoracic and abdominal cavities. It may be the only noninvasive technique available to evaluate these areas for other potential areas of lymphadenopathy and determine a potential source of malignancy (eg, neuroblastoma, Burkitt lymphoma, rhabdomyosarcoma). Furthermore, chest CT may add to the information obtained from chest radiography and may depict an anterior mediastinal mass, as well as the extent of tracheal or bronchial airway compression (see the images below).

A CT scan showing an anterior mediastinal mass and A CT scan showing an anterior mediastinal mass and compression of the trachea.
A CT scan showing an anterior mediastinal mass and A CT scan showing an anterior mediastinal mass and compression of the left mainstem bronchus.

A preliminary study by Cahalane et al found that the addition of textural analysis to pediatric CT protocols improved the ability of CT to distinguish benign from malignant lymphadenopathy, thereby potentially reducing the need for follow-up imaging and tissue sampling, as well as associated radiation exposure.[18] Additional studies will be needed to determine the clinical applicability of textural analysis in this setting.

Fluorodeoxyglucose positron emission tomography

18F-Fluorodeoxyglucose positron emission tomography (18FFDG-PET) has been used in adult patients with lymphoma and, subsequently, in children to assist in diagnosis and to monitor disease during therapy.[19] It has been applied to both Hodgkin and non-Hodgkin lymphomas, with promising findings. However, clinicians must be cautious with the use of 18FFDG-PET because a high number of false-positive results in children have been reported as a consequence of a higher inflammatory reaction to inciting agents.


Fine-needle aspiration (FNA) biopsy (FNAB) has been used extensively in adults and has also been described in children.[20, 21, 22, 23] The cited advantages of FNAB include the following[21] :

  • It can be performed in the outpatient department
  • It is simple and rapid
  • It does not require general anesthesia
  • It has low morbidity
  • It is cost-effective
  • It produces minimal scarring

The sensitivity and specificity of FNAB in determining the etiology of lymphadenopathy are higher than 90%.[21, 23] Most patients who have a benign diagnosis on FNAB do not undergo surgical biopsy. However, in most centers, FNAB is still not practiced in children. Furthermore, whether the advantages of FNAB outweigh the perceived limits remains to be established. These limits include the following:

  • Center dependence on pathologists who are accustomed to making diagnoses on the basis of FNAB alone
  • Potential risk of seeding a tract with malignancy
  • Continued need for at least conscious sedation in most children

Most oncology protocols now require special studies to be performed on the nodal tissue, including cytogenetics, flow cytometry, electron microscopy, and special stains that FNAB does not allow.

To obtain larger samples, some investigators have used core needle biopsy (CNB) techniques with US or CT guidance.[24] This allows procurement of more tissue, which may be needed in difficult diagnoses.

Endobronchial US-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic US with echobronchoscope-guided FNA (EUS-B-FNA) have been found to be safe and to have a fair-to-good diagnostic yield in children with mediastinal lymphadenopathy.[25, 26]



Approach Considerations

Lymph node enlargement is a common feature of various benign and malignant disorders that affect children. If the history and physical examination are thorough, the etiology of most lymphadenopathies can be determined without further investigation. However, if the diagnosis requires confirmation or is in doubt, the results from a carefully chosen combination of skin tests, serologic tests, and/or diagnostic imaging tests may establish the correct diagnosis. If the diagnosis is still unclear or if tissue is required in the case of a potential malignancy, the results from a careful lymph node biopsy can most certainly confirm the correct diagnosis.

An absolute contraindication for lymph node biopsy is recognized if the etiology is clear and if the lymphadenopathy is expected to improve with no further management. A relative contraindication is recognized if the suspected etiology can be treated expectantly (eg, in cases of bacterial infection of the node where administration of antibiotics is expected to improve the clinical scenario without a need for biopsy). Another relative contraindication is acknowledged if an anterior mediastinal mass is noted on chest radiography and considered to be a high anesthetic risk. In this situation, the anesthetic risks must be balanced against the need for obtaining tissue.

Lymphadenopathy is present in a vast array of disorders, and discussing the future of lymphadenopathy is difficult because of the number of diseases involved. The diagnosis of lymph node disorders will improve as molecular tools become more available. Having these tools will allow clinicians to diagnose the etiology with more exact science and less invasive means. The use of fine-needle aspiration (FNA) biopsy (FNAB) in children will become more frequent as more experience is obtained in centers that had not been employing this technique in pediatric cases.[27, 20]

Medical Therapy

The medical therapy chosen is based on the most likely etiology if a biopsy has not been performed.

In the case of bacterial infection, the most likely culprits include Staphylococcus and Streptococcus species; therefore, a beta-lactamase–resistant antibiotic is chosen. In patients with tuberculosis, rifampin and isoniazid are chosen.

In cases of nontuberculous mycobacterial adenitis, most still advocate surgical management. However, some patients with lymphadenopathy in anatomic locations of concern may benefit from drugs such as clarithromycin, azithromycin, rifampin, rifabutin, or ethambutol.[28]

Most patients with viral etiology for lymphadenopathy may be treated expectantly.

Patients with some of the more obscure diagnoses, such as Kawasaki disease, systemic lupus erythematosus (SLE), and Langerhans cells histiocytosis, may require immunosuppressants.

Surgical Therapy

Enlargement of a cervical lymph node to a diameter of 1 cm or greater is regarded as abnormal and warrants consideration of biopsy if the diagnosis is otherwise uncertain. Biopsy of the lymph node may involve one of two methods. The most commonly used method is the surgical biopsy, in which either a portion of the node or the complete node is excised.

Before the procedure, the patient and family are instructed in the steps involved and the risks and benefits; a consent form is obtained. Before removal of the node, the surgeon should discuss the case with the pathologist so that the appropriate tests may be immediately performed after the specimen is received. The procedure is performed either in the operating room suite with general anesthesia or in a minor procedure room with conscious sedation.

Procedural details

An incision is made in the skin overlying the enlarged node, and the surrounding tissue is carefully dissected away from the node. Care must be taken to avoid surrounding nerves, especially in areas around the neck. To assist in the removal of the node, a suture on a noncutting needle may be placed through the center of the node to provide traction so that it can be pulled into view (see the images below). This measure also minimizes crush artifact that may result from excessive handling of the lymph node.

A lymph node biopsy is performed. Note that a mark 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, whi A lymph node after removal by means of biopsy, which was performed completely under a local anesthetic technique.

The node must then be sent fresh to the pathologist for processing (see the image below). This is to allow all possible tests to be performed; fixation of the lymph node precludes performance of some important tests (eg, flow cytology, cytogenetics). Usually, one large node or a group of smaller nodes is sent to the pathologist for diagnosis.

A gross image of a node following excision. The cu A gross image of a node following excision. The cut surface of the node shows the typical fish-flesh appearance seen with lymphoma.

Although lymph node biopsy via an open technique has been the standard approach, the advent of minimally invasive techniques has led surgeons to apply these methods to lymph node biopsies in the thoracic cavity and the abdomen.

Whereas percutaneous lymph node biopsy guided by ultrasonography (US) or computed tomography (CT) often does not supply sufficient tissue for histopathologic diagnosis of a lymphoma, laparoscopic lymph node biopsy has the advantage of obtaining the entire lymph node while avoiding the invasiveness and possible complications of a laparotomy.[29]

Postprocedural Care

Lymph node biopsies are usually performed on an outpatient basis. Before the patient is discharged from the hospital, the wound is assessed for swelling and bleeding. The wound area should be kept dry for at least 2 days, and appropriate analgesia should be administered.

Patients and their families should be contacted with the results as soon as the report is finalized. If further therapy is necessary, patients should return to the hospital or be referred to the appropriate specialists for therapy.


The known complications of the biopsy itself arise from injury to surrounding structures around the node, including soft tissue, blood vessels, and nerves. Other potential complications in patients with malignancy include the following:

  • Spread of tumor cells in the area of the biopsy
  • Production of a draining sinus in the case of atypical mycobacterial infection (if the entire node is not excised)
  • Risks associated with general anesthetics, especially if the patient has an anterior mediastinal mass