AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

Lymph nodes are considered to be the fortresses that aid immunologic defense. A common problem that many clinicians face occurs when a child presents with an enlarged lymph node. The clinician is challenged to satisfy the parental fears of malignancy and to do so in a timely and cost-effective manner. Organizing the possible causes of lymphadenopathy by anatomic location and origin aids the clinician in the evaluation. In this article, a rational approach is provided to determine the etiology of the lymph node disorder, and various disorders are highlighted to consider when treating a child with lymphadenopathy. Furthermore, various means are discussed for obtaining a tissue diagnosis when the cause of lymphadenopathy is uncertain.

History of the Procedure

The removal of lymph nodes to determine the etiology of their enlargement has been practiced for many years. The procedure is simple, and a true history has not been defined. Nonetheless, the removal of lymph nodes is a procedure that is performed by almost all surgeons. Because children often present with enlarged lymph nodes, pediatric surgeons are often the ones who either treat these children primarily or as a referral.

Problem

Lymphadenopathy is the enlargement of one or more lymph nodes as a result of normal reactive effects or a pathologic occurrence.

Frequency

Lymphadenopathy is a common presentation in children; it is so common that the exact frequency may be difficult to establish.

Etiology

Essentially, the following 5 broad etiologic categories lead to lymph node enlargement:¹

• An immune response to infective agents (eg, bacteria, virus, fungus)
• 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)

Pathophysiology

The pathophysiology of lymphadenopathy differs on the basis of etiology. If the inciting cause is one of reaction, a physiologic increase in the number of lymphocytes and macrophages causes the size of the node to increase. Alternatively, in increases in size related to pathologic processes, the node may increase in size because bacteria, fungus, virus, or metastatic cells may fill the node.

Clinical

History

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

Evaluation of the child with lymphadenopathy may begin with specific aspects of the enlarged lymph node or nodes first and then expand to encompass the various aspects that may have caused it. Important features with regard to the lymph nodes include the duration, the rate of enlargement, and 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 have an effect on the enlarged lymph nodes. If no obvious sources of infection are present, the presence of constitutional symptoms such as fever, weight loss, and night sweats are all potential indications for malignancy. If the patient has recurrent infections, immunodeficiencies such as human immunodeficiency virus (HIV) 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 drinking of unsanitized water, exposure to animals that may carry unique infections, exposure to tuberculosis (TB), typhoid, and trypanosomiasis. Activities such as sexual contact are also important to obtain. If the history is otherwise unremarkable, a thorough review of symptoms may establish other aspects of cause.

Physical examination

The physical examination of a child with lymphadenopathy starts at the enlarged nodes and then proceeds to a complete examination. The skin and the soft tissue drained by the enlarge node should be carefully examined for signs of inflammation, skin breakdown, and trauma. The character of the lymph node should be noted. Hyperplastic lymph nodes that develop as a response to viral infections are small, discrete, mobile, nontender, and bilateral and are often described as shotty. Usually, no accompanying cellulitis or inflammation is present.

Lymph nodes that are acutely infected with bacteria, most often Staphylococcus aureus or group B streptococci,^{2, 3} tend to be large, warm, and tender and have surrounding erythema and edema. 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.^{4, 5} Lymphadenopathy associated with malignancy has been described as firm or rubbery, discrete, nontender, and fixed to the skin or underlying structures.^{2, 5}

With a thorough physical examination, the clinician is able to broadly classify whether the lymphadenopathy is a local or a general phenomenon. A localized lymphadenopathy usually results from abnormalities of the area in which the lymph node drains, although 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 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.

Axillary lymphadenopathy is seen with infections of the upper extremity, chest wall, breast 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 are not usually detected at the time of physical examination but are sometimes suspected by compression of the surrounding structures.

The presence of general lymphadenopathy should alert the clinician to the presence of significant pathology. Any of the common viral illnesses may produce generalized lymphadenopathy (eg, Epstein-Barr virus [EBV], cytomegalovirus [CMV], HIV). 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 use of certain drugs, particularly phenytoin and carbamazepine.

INDICATIONS

Section 3 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

Lymphadenopathy in children generally occurs following benign etiologies. Indeed, a thorough history almost always points the clinician in this direction. Furthermore, in most scenarios, the physical examination guides the physician to the correct etiology by focusing on whether the enlarged nodes are regional or systemic, the exact characteristics of the involved nodes, and any other suspicious findings. Alternatively, if the etiology is still questionable, further investigations such as laboratory and radiographic tests are warranted and are based on a likely diagnosis. Ultimately, if malignancy is suspected, a definitive biopsy may need to be performed.

RELEVANT ANATOMY

Section 4 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

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 6 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 internal jugular 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 then 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 bronchi 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, 3 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, pelvis, mesentery, most of the thoracic cavity, left upper extremity, and 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 vein, 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 5 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 recent study that examined CT scans of the abdomen showed that abdominal lymph nodes measuring up to 8 mm may be considered normal.⁶

The 2 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 2 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 2 exceptions to this rule include 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.

CONTRAINDICATIONS

Section 5 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

An absolute contraindication to lymph node biopsy is recognized if the etiology is clear and if the lymphadenopathy is expected to improve with no further management. This contraindication applies in most cases.

A relative contraindication is recognized if the suspected etiology can be treated expectantly (eg, in cases of bacterial infection of the node in which the use 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 need to be balanced with the need for obtaining tissue.

WORKUP

Section 6 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

Lab Studies

• In most patients, only the history and physical examination are needed to establish the likely diagnosis. However, if the diagnosis needs to 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 tests 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, C-reactive protein, glycoproteins, fibrogen levels) do not contribute much to establishing the diagnosis because most of the results are invariably elevated and do not provide a suggestion 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 CBC count with a manual differentiation provides useful information. Leukemias are often accompanied by pancytopenia. A predominantly lymphocytic elevation (>1 X 109 cells/L) is practically diagnostic of mononucleosis; when the proportion of these cells is less elevated but still predominant, 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, such as tuberculin skin test; monospot; and titers for EBV, CMV, catscratch disease, or toxoplasmosis, may be performed to evaluate for specific etiologies.

Imaging Studies

• Chest radiography may be useful to assess for potential sources of infection, such as 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 Media file 1).
• Ultrasonography may be performed to distinguish the lymph nodal nature if palpation is not sufficient. 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). Ultrasonography may reveal relationships to contiguous structures and offer information about the content of the enlarged lymph node or nodes (ie, solid, liquid, gas, homogeneous or nonhomogenous). Finally, in some current studies, ultrasonography has been used in an effort to establish etiology based on ultrasonographic characteristics.
• CT scanning is useful to depict deep lymph nodes, especially in the thoracic and abdominal cavities. This 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 scanning 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 Media files 2-3).
• 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has been used in adult patients with lymphoma and, more recently, in children to assist in diagnosis and to monitor disease during therapy.⁷ Its use has been applied to both Hodgkin and non-Hodgkin lymphomas, with promising findings. However, clinicians must be cautious with use of 18F-FDG PET because a high number of false positive results in children have been reported due to higher inflammatory reaction to inciting agents.

Diagnostic Procedures

• Fine-needle aspiration (FNA) biopsy has been used extensively in adults and is now being described in children.^{8, 9, 10} The cited advantages of FNA biopsy include the fact that it can be performed in the outpatient department, that it is simple and rapid, that it does not require a general anesthetic, that it has low morbidity, that it is cost effective, and that it produces minimal scarring.⁸
• The sensitivity and specificity of FNA biopsy in determining the etiology of lymphadenopathy are more than 90%.^{8, 10} Most patients who have a benign diagnosis on FNA biopsy do not undergo surgical biopsy. However, in most centers, FNA is still not practiced in children. Furthermore, whether the advantages of FNA outweigh the perceived limits has not been established. These limits include center dependence on pathologists who are accustomed to making diagnoses on FNA alone, the potential risk of seeding a tract with malignancy, and the 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 FNA does not allow.
• To obtain more tissue, some investigators have used core needle techniques with ultrasonography or CT guidance.¹¹ This allows procurement of more tissue, which may be needed in difficult diagnoses.

TREATMENT

Section 7 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

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.¹²
• 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 1 cm in diameter is considered abnormal and should be considered for biopsy. 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.

Preoperative details

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 pathologist should be informed about the biopsy so the appropriate tests may be immediately performed after the specimen is received. The procedure is performed either in the operating room suite under general anesthetic or in a minor procedure room under conscious sedation.

Intraoperative 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 may be placed through the center of the node to provide traction to pull the node into view (see Media files 4-5). The node must then be sent fresh to the pathologist for processing (see Media file 6). Usually one large node or a group of smaller nodes is sent to the pathologist for diagnosis.

Although lymph node biopsy via an open technique is the standard approach, with the advent of minimally invasive techniques, surgeons are applying these methods to lymph node biopsies in the thoracic cavity and the abdomen. Although ultrasonography or CT-guided percutaneous lymph node biopsy often does not supply sufficient tissue for the histopathologic diagnosis of a lymphoma, laparoscopic lymph node biopsy has the advantage of obtaining the entire lymph node and avoiding the invasiveness and possible complications of a laparotomy.¹³

Postoperative details

Lymph node biopsies are usually performed on an outpatient basis. Before the patient is discharged from the hospital, he or she is usually treated in the day surgery area, where 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.

Follow-up

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.

COMPLICATIONS

Section 8 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

The known complications of the biopsy itself arise from the injury of surrounding structures around the node, including the soft tissue, blood vessels, and nerves. Other potential complications in patients with malignancy include the spread of tumor cells in the area of the biopsy, production of a draining sinus in the case of atypical Mycobacterium infection (if the entire node is not excised), and the risks associated with general anesthetics, especially if the patient has an anterior mediastinal mass.

OUTCOME AND PROGNOSIS

Section 9 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

Viral-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 EBV and CMV. Posterior cervical nodes are most commonly involved, followed by the anterior cervical chain. Children with adenoviral-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.²

Bacterial-associated lymphadenopathy

The 2 most common organisms associated with lymphadenopathy include S aureus and group B 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. The treatment involves administration of b-lactamase–resistant antibiotics and drainage of purulence when fluctuation is present.¹⁴

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.¹⁵

Atypical mycobacterium

In the United States, atypical Mycobacterium account for most cases of adenitis due to Mycobacterium infection. Numerous members are in this group, including Mycobacterium scrofulaceum and Mycobacterium avium-intracellulare. 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 spontaneously drain. Treatment involves complete excision of the involved node because incision and drainage may lead to a chronically draining sinus.¹⁶ Those dissections that may be adjacent to the marginal mandibular nerve are often associated with a transient paralysis that resolves over a few months.¹⁷

Mycobacterium 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.¹⁸

Catscratch disease

Catscratch 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.

Malignancies

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 in size, the enlargement lasted longer than 4 weeks, supraclavicular involvement was observed, and abnormal laboratory and radiological findings were noted.¹⁹

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.

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.

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.

FUTURE AND CONTROVERSIES

Section 10 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

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 needs to be confirmed 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.

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 FNA in children will become more frequent as more experience is obtained in centers that are currently not using this technique.

For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Swollen Lymph Glands.

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

Media file 1:  A preoperative radiograph showing a narrowed trachea secondary to an anterior mediastinal mass.
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Media file 2:  A CT scan showing an anterior mediastinal mass and compression of the trachea.
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Media file 3:  A CT scan showing an anterior mediastinal mass and compression of the left mainstem bronchus.
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Media file 4:  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.
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Media file 5:  A lymph node after removal by means of biopsy, which was performed completely under a local anesthetic technique.
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Media file 6:  A gross image of a node following excision. The cut surface of the node shows the typical fish-flesh appearance seen with lymphoma.
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REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Indications
• Relevant Anatomy
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• Multimedia
• References

1. Ghirardelli ML, Jemos V, Gobbi PG. Diagnostic approach to lymph node enlargement. Haematologica. Mar 1999;84(3):242-7. [Medline].
2. Kelly CS, Kelly RE Jr. Lymphadenopathy in children. Pediatr Clin North Am. Aug 1998;45(4):875-88. [Medline].
3. Segal GH, Perkins SL, Kjeldsberg CR. Benign lymphadenopathies in children and adolescents. Semin Diagn Pathol. Nov 1995;12(4):288-302. [Medline].
4. Karadeniz C, Oguz A, Ezer U, et al. The etiology of peripheral lymphadenopathy in children. Pediatr Hematol Oncol. Nov-Dec 1999;16(6):525-31. [Medline].
5. Soldes OS, Younger JG, Hirschl RB. Predictors of malignancy in childhood peripheral lymphadenopathy. J Pediatr Surg. Oct 1999;34(10):1447-52. [Medline].
6. Karmazyn B, Werner EA, Rejaie B, Applegate KE. Mesenteric lymph nodes in children: what is normal?. Pediatr Radiol. Aug 2005;35(8):774-7. [Medline].
7. Depas G, De Barsy C, Jerusalem G, et al. 18F-FDG PET in children with lymphomas. Eur J Nucl Med Mol Imaging. Jan 2005;32(1):31-8. [Medline].
8. van de Schoot L, Aronson DC, Behrendt H, Bras J. The role of fine-needle aspiration cytology in children with persistent or suspicious lymphadenopathy. J Pediatr Surg. Jan 2001;36(1):7-11. [Medline].
9. Ponder TB, Smith D, Ramzy I. Lymphadenopathy in children and adolescents: role of fine-needle aspiration in management. Cancer Detect Prev. 2000;24(3):228-33. [Medline].
10. Buchino JJ, Jones VF. Fine needle aspiration in the evaluation of children with lymphadenopathy. Arch Pediatr Adolesc Med. Dec 1994;148(12):1327-30. [Medline].
11. Sklair-Levy M, Amir G, Spectre G, et al. Image-guided cutting-edge-needle biopsy of peripheral lymph nodes and superficial masses for the diagnosis of lymphoma. J Comput Assist Tomogr. May-Jun 2005;29(3):369-72. [Medline].
12. Loeffler AM. Treatment options for nontuberculous mycobacterial adenitis in children. Pediatr Infect Dis J. Oct 2004;23(10):957-8. [Medline]. [Full Text].
13. Casaccia M, Torelli P, Cavaliere D, et al. Laparoscopic lymph node biopsy in intra-abdominal lymphoma: high diagnostic accuracy achieved with a minimally invasive procedure. Surg Laparosc Endosc Percutan Tech. Jun 2007;17(3):175-8. [Medline].
14. Bodenstein L, Altman RP. Cervical lymphadenitis in infants and children. Semin Pediatr Surg. Aug 1994;3(3):134-41. [Medline].
15. Luu TM, Chevalier I, Gauthier M, et al. Acute adenitis in children: clinical course and factors predictive of surgical drainage. J Paediatr Child Health. May-Jun 2005;41(5-6):273-7. [Medline].
16. Evans MJ, Smith NM, Thornton CM, et al. Atypical mycobacterial lymphadenitis in childhood--a clinicopathological study of 17 cases. J Clin Pathol. Dec 1998;51(12):925-7. [Medline].
17. Pumberger W, Hallwirth U, Pawlowsky J, Pomberger G. Cervicofacial lymphadenitis due to atypical mycobacteria: a surgical disease. Pediatr Dermatol. Jan-Feb 2004;21(1):24-9. [Medline].
18. Waagner DC. The clinical presentation of tuberculous disease in children. Pediatr Ann. Oct 1993;22(10):622-8. [Medline].
19. Oguz A, Karadeniz C, Temel EA, Citak EC, Okur FV. Evaluation of peripheral lymphadenopathy in children. Pediatr Hematol Oncol. Oct-Nov 2006;23(7):549-61. [Medline].

Article Last Updated: Jan 14, 2008