What are the common causes of lymphadenopathy. How can physicians differentiate between benign and malignant lymph node enlargement. What diagnostic approach should be taken for unexplained lymphadenopathy. When is a lymph node biopsy necessary.

Understanding Lymphadenopathy: Definition and Classification

Lymphadenopathy refers to abnormalities in the size, consistency, or number of lymph nodes. While the human body contains approximately 600 lymph nodes, only those in the submandibular, axillary, or inguinal regions are typically palpable in healthy individuals. Lymph nodes larger than 1 cm in diameter are generally considered abnormal.

A clinically useful classification system divides lymphadenopathy into two categories:

• Localized lymphadenopathy: Enlargement of lymph nodes in a single area
• Generalized lymphadenopathy: Enlargement of lymph nodes in two or more noncontiguous areas

This distinction is crucial for developing a differential diagnosis. In primary care settings, about 75% of patients with unexplained lymphadenopathy present with localized involvement, while 25% exhibit generalized lymphadenopathy.

Epidemiology of Lymphadenopathy in Primary Care

The epidemiology of lymphadenopathy in family practice is not extensively documented. However, a notable Dutch study provides valuable population-based estimates:

• Annual incidence of unexplained lymphadenopathy: 0.6% in the general population
• Referral rate to specialists: 10% of cases
• Biopsy requirement: 3.2% of cases
• Malignancy diagnosis: 1.1% of cases

These findings highlight the relatively low prevalence of malignancy in primary care settings. This contrasts sharply with the 40-60% prevalence of malignancy in lymph node biopsies performed in referral centers, a statistic that has often been misinterpreted in medical literature.

Age-Related Risk of Malignancy

In primary care, the risk of cancer in patients with unexplained lymphadenopathy varies by age:

• Patients 40 years and older: Approximately 4% risk of cancer
• Patients younger than 40: Approximately 0.4% risk of cancer

Diagnostic Approach to Lymphadenopathy

The cornerstone of lymphadenopathy evaluation is a thorough history and physical examination. This approach often reveals a readily diagnosable cause, particularly in cases of localized lymphadenopathy.

Key Steps in the Diagnostic Process

1. Detailed patient history
2. Comprehensive physical examination
3. Identification of localized vs. generalized lymphadenopathy
4. Assessment of associated symptoms and risk factors
5. Consideration of age-related risk profiles

When evaluating localized lymphadenopathy, physicians should search for adjacent precipitating lesions and examine other nodal areas to rule out generalized involvement.

Differentiating Benign and Malignant Causes

While lymphadenopathy can raise concerns about serious illnesses, it is most often the result of benign infectious causes in primary care settings. However, certain characteristics may increase suspicion for malignancy:

• Supraclavicular node involvement (highest risk for malignancy)
• Firm, fixed, or matted nodes
• Persistent enlargement over several weeks
• Associated systemic symptoms (fever, night sweats, weight loss)
• Absence of obvious infectious cause

Observation Period for Benign Cases

For patients with localized nodes and a benign clinical picture, a three- to four-week observation period is often appropriate. This allows time for self-limited conditions to resolve while monitoring for any concerning changes.

Investigating Generalized Lymphadenopathy

Generalized lymphadenopathy always warrants further clinical investigation. Potential causes include:

• Systemic infections (e.g., HIV, Epstein-Barr virus)
• Autoimmune disorders (e.g., lupus, rheumatoid arthritis)
• Malignancies (e.g., lymphoma, leukemia)
• Medications
• Sarcoidosis

A systematic approach to diagnosis may include blood tests, imaging studies, and potentially, lymph node biopsy.

When to Consider Lymph Node Biopsy

Lymph node biopsy may be indicated in cases where the cause of lymphadenopathy remains unclear after initial evaluation or when malignancy is strongly suspected. When biopsy is necessary, an excisional biopsy of the most abnormal node is preferred, as it provides the pathologist with the best opportunity to determine a diagnosis.

Indications for Lymph Node Biopsy

• Persistent unexplained lymphadenopathy
• Suspicious characteristics (e.g., hard, fixed nodes)
• Supraclavicular node involvement
• Progressively enlarging nodes
• Associated constitutional symptoms

It’s important to note that in primary care settings, only about 3% of patients with unexplained lymphadenopathy ultimately require a biopsy.

Common Benign Causes of Lymphadenopathy

In primary care, the majority of lymphadenopathy cases are due to benign causes. Some common examples include:

• Upper respiratory tract infections
• Streptococcal pharyngitis
• Infectious mononucleosis
• Dental infections
• Skin infections
• Cat scratch disease
• Toxoplasmosis

Understanding these common causes can help guide initial management and reduce unnecessary concern about more serious conditions.

Case Example: Streptococcal Pharyngitis

A child presenting with a sore throat, tender cervical nodes, and a positive rapid strep test exemplifies a clear-cut case of benign lymphadenopathy. In such instances, targeted treatment of the underlying infection typically resolves the lymph node enlargement.

Lymphadenopathy in Special Populations

Certain patient populations require special consideration when evaluating lymphadenopathy:

Pediatric Patients

Children frequently develop lymphadenopathy due to their heightened exposure to new pathogens and vigorous immune responses. Common causes in this age group include:

• Viral upper respiratory infections
• Streptococcal throat infections
• Infectious mononucleosis (in adolescents)

Malignancy is less common in children but should still be considered, particularly in cases of persistent or generalized lymphadenopathy.

Elderly Patients

In older adults, the risk of malignancy as a cause of lymphadenopathy increases. Conditions to consider include:

• Lymphoma
• Metastatic carcinoma
• Chronic lymphocytic leukemia

However, benign causes remain more common even in this age group, and a thorough evaluation is necessary to avoid unnecessary biopsies.

Immunocompromised Patients

Patients with compromised immune systems, such as those with HIV/AIDS or undergoing chemotherapy, are at increased risk for both opportunistic infections and malignancies. Lymphadenopathy in these patients requires prompt and thorough evaluation.

Diagnostic Tools and Tests for Lymphadenopathy

While history and physical examination form the foundation of lymphadenopathy evaluation, additional diagnostic tools may be necessary in certain cases:

Laboratory Tests

• Complete blood count (CBC) with differential
• Erythrocyte sedimentation rate (ESR)
• C-reactive protein (CRP)
• Specific serological tests (e.g., EBV, HIV, toxoplasmosis)

Imaging Studies

• Ultrasound: Useful for evaluating superficial lymph nodes
• CT scan: Provides detailed imaging of deep lymph nodes
• PET scan: Can help identify metabolically active nodes suggestive of malignancy

Fine Needle Aspiration (FNA)

FNA can be useful for initial evaluation of suspicious nodes, particularly in cases where infection is suspected. However, it may not provide sufficient tissue for definitive diagnosis of lymphoma.

Excisional Biopsy

The gold standard for diagnosis when malignancy is suspected, providing the pathologist with intact lymph node architecture for comprehensive evaluation.

The choice of diagnostic tests should be guided by the clinical presentation, patient characteristics, and initial findings from the history and physical examination.

Management Strategies for Lymphadenopathy

The management of lymphadenopathy depends on the underlying cause and can range from simple observation to aggressive treatment. Here are some general principles:

Benign Infectious Causes

• Treat the underlying infection (e.g., antibiotics for bacterial infections)
• Provide symptomatic relief (e.g., analgesics, warm compresses)
• Follow up to ensure resolution

Unexplained Lymphadenopathy

• Observe for 3-4 weeks in cases with benign clinical features
• Reassess regularly for changes in size or characteristics
• Consider further investigation if persistence or progression occurs

Malignant Causes

• Refer to appropriate specialist (e.g., oncologist, hematologist)
• Initiate staging and treatment planning
• Provide supportive care and patient education

It’s crucial to tailor the management approach to each individual patient, considering factors such as age, overall health status, and patient preferences.

Long-term Follow-up and Prognosis

The long-term outlook for patients with lymphadenopathy varies greatly depending on the underlying cause:

Benign Causes

Most cases of lymphadenopathy due to benign causes resolve completely with appropriate treatment or observation. Long-term complications are rare, and patients generally have an excellent prognosis.

Malignant Causes

Prognosis for malignant causes of lymphadenopathy depends on various factors, including:

• Type and stage of malignancy
• Patient’s age and overall health
• Response to treatment

Early detection and prompt treatment can significantly improve outcomes in many cases.

Follow-up Recommendations

For resolved cases of benign lymphadenopathy, routine follow-up may not be necessary. However, patients should be advised to return if they notice recurrence or new lymph node enlargement.

In cases of malignancy or chronic conditions causing lymphadenopathy, long-term follow-up is essential to monitor for recurrence, manage complications, and provide ongoing support.

Patient Education and Counseling

Effective patient education is crucial in managing lymphadenopathy and alleviating patient concerns. Key points to address include:

• Explaining the common benign nature of most lymphadenopathy cases
• Describing normal lymph node function and reasons for enlargement
• Providing guidance on when to seek medical attention for new or persistent lymphadenopathy
• Discussing the diagnostic process and potential need for further tests
• Addressing anxiety related to fear of serious illness

For patients diagnosed with malignancy, comprehensive counseling should include:

• Information about the specific diagnosis and treatment options
• Discussion of prognosis and potential complications
• Guidance on supportive care and lifestyle modifications
• Referral to support groups or psychological services as needed

By providing clear, compassionate communication, healthcare providers can help patients navigate the often complex journey of lymphadenopathy diagnosis and management.

Lymphadenopathy: Differential Diagnosis and Evaluation

ROBERT FERRER, M.D., M.P.H.

Although the finding of lymphadenopathy sometimes raises fears about serious illness, it is, in patients seen in primary care settings, usually a result of benign infectious causes. Most patients can be diagnosed on the basis of a careful history and physical examination. Localized adenopathy should prompt a search for an adjacent precipitating lesion and an examination of other nodal areas to rule out generalized lymphadenopathy. In general, lymph nodes greater than 1 cm in diameter are considered to be abnormal. Supraclavicular nodes are the most worrisome for malignancy. A three- to four-week period of observation is prudent in patients with localized nodes and a benign clinical picture. Generalized adenopathy should always prompt further clinical investigation. When a node biopsy is indicated, excisional biopsy of the most abnormal node will best enable the pathologist to determine a diagnosis.

The cause of lymphadenopathy is often obvious: for example, the child who presents with a sore throat, tender cervical nodes and a positive rapid strep test, or the patient who presents with an infection of the hand and axillary lymphadenopathy. In other cases, the diagnosis is less clear. Lymphadenopathy may be the only clinical finding or one of several nonspecific findings, and the discovery of swollen lymph nodes will often raise the specter of serious illness such as lymphoma, acquired immunodeficiency syndrome or metastatic cancer. The physician’s task is to efficiently differentiate the few patients with serious illness from the many with self-limited disease. This article reviews the evaluation of patients with a central clinical finding of lymphadenopathy, emphasizing the identification of patients with serious illness.

Definition

The body has approximately 600 lymph nodes, but only those in the submandibular, axillary or inguinal regions may normally be palpable in healthy people.¹ Lymphadenopathy refers to nodes that are abnormal in either size, consistency or number. There are various classifications of lymphadenopathy, but a simple and clinically useful system is to classify lymphadenopathy as “generalized” if lymph nodes are enlarged in two or more noncontiguous areas or “localized” if only one area is involved. Distinguishing between localized and generalized lymphadenopathy is important in formulating a differential diagnosis. In primary care patients with unexplained lymphadenopathy, approximately three fourths of patients will present with localized lymphadenopathy and one fourth with generalized lymphadenopathy (Figure 1).^2,3

Epidemiology

Our understanding of the epidemiology of lymphadenopathy in family practice is limited by the scarcity of relevant literature. Only one study⁴ provides reliable population-based estimates. Findings from this Dutch study revealed a 0.6 percent annual incidence of unexplained lymphadenopathy in the general population. Of 2,556 patients in the study who presented with unexplained lymphadenopathy to their family physicians, 256 (10 percent) were referred to a subspecialist and 82 (3.2 percent) required a biopsy, but only 29 (1.1 percent) had a malignancy.

This low prevalence of malignancy is supported by the results of two case series^2,3 from family practice departments in the United States, in which none of 80 patients and three of 238 patients with unexplained lymphadenopathy were diagnosed with malignancy. In contrast, the prevalence of malignancy in lymph node biopsies performed in referral centers is 40 to 60 percent,⁵ a statistic that has made its way into many textbooks (e.g., “In those more than 30 years of age, however, lymphadenopathy is due to a benign process only 40 percent of the time”⁶). Such assertions overestimate the probability of malignancy in patients with lymphadenopathy because they exclude the 97 percent of patients with lymphadenopathy who do not undergo a biopsy. In primary care settings, patients 40 years of age and older with unexplained lymphadenopathy have about a 4 percent risk of cancer versus a 0.4 percent risk in patients younger than age 40.⁴

Diagnostic Approach to Lymphadenopathy

The algorithm in Figure 2 provides a diagnostic framework for the evaluation of lymphadenopathy. The algorithm emphasizes that a careful history and physical examination are the core of the evaluation. In most cases, a careful history and physical examination will identify a readily diagnosable cause of the lymphadenopathy, such as upper respiratory tract infection, pharyngitis, periodontal disease, conjunctivitis, lymphadenitis, tinea, insect bites, recent immunization, cat-scratch disease or dermatitis, and no further assessment is necessary (see the “diagnostic” branch of the algorithm).

In other cases, a definitive diagnosis cannot be made on the basis of the history and physical examination alone; however, the clinical evaluation may strongly suggest a particular cause. Confirmatory testing should be performed in order to correctly identify the patient’s illness (see the “suggestive” branch of the algorithm).

A subset of patients will either have unexplained lymphadenopathy after the initial clinical evaluation or have a presumptive diagnosis that is made in the “diagnostic” or “suggestive” branches of the algorithm and is not confirmed by test results or by the clinical course. In patients with unexplained localized lymphadenopathy and a reassuring clinical picture, a three- to four-week period of observation is appropriate before biopsy. Patients with localized lymphadenopathy and a worrisome clinical picture or patients with generalized lymphadenopathy will need further diagnostic evaluation that often includes biopsy (see the “unexplained” branch of the algorithm). Fine-needle aspiration is occasionally considered an alternative to excisional biopsy but often yields a high number of nondiagnostic results because of the small amount of tissue obtained and the inability to examine the architecture of the gland.⁷ In addition, there may be some risk of sinus tract formation, depending on the underlying pathology.⁸

History

The physician should consider four key points when compiling a patient’s history.¹ First, are there localizing symptoms or signs to suggest infection or neoplasm in a specific site? Second, are there constitutional symptoms such as fever, weight loss, fatigue or night sweats to suggest disorders such as tuberculosis, lymphoma, collagen vascular diseases, unrecognized infection or malignancy? Third, are there epidemiologic clues (Table 1) such as occupational exposures, recent travel or high-risk behaviors that suggest specific disorders? Fourth, is the patient taking a medication that may cause lymphadenopathy? Some medications are known to specifically cause lymphadenopathy (e. g., phenytoin [Dilantin]), while others, such as cephalosporins, penicillins or sulfonamides, are more likely to cause a serum sickness-like syndrome with fever, arthralgias and rash in addition to lymphadenopathy (Table 2).

The rightsholder did not grant rights to reproduce this item in electronic media. For the missing item, see the original print version of this publication.

Physical Examination

When lymphadenopathy is localized, the clinician should examine the region drained by the nodes for evidence of infection, skin lesions or tumors (Table 3). Other nodal sites should also be carefully examined to exclude the possibility of generalized rather than localized lymphadenopathy. This is an important aspect of the examination, as a study of primary care physicians found that generalized lymphadenopathy was identified in only 17 percent of the patients in whom it was present.⁹ Careful palpation of the submandibular, anterior and posterior cervical, supraclavicular, axillary and inguinal nodes can be accomplished in a short time and will identify patients with generalized lymphadenopathy.

Location	Lymphatic drainage	Causes
Submandibular	Tongue, submaxillary gland, lips and mouth, conjunctivae	Infections of head, neck, sinuses, ears, eyes, scalp, pharynx
Submental	Lower lip, floor of mouth, tip of tongue, skin of cheek	Mononucleosis syndromes, Epstein-Barr virus, cytomegalovirus, toxoplasmosiss
Jugular	Tongue, tonsil, pinna, parotid	Pharyngitis organisms, rubella
Posterior cervical	Scalp and neck, skin of arms and pectorals, thorax, cervical and axillary nodes	Tuberculosis, lymphoma, head and neck malignancy
Suboccipital	Scalp and head	Local infection
Postauricular	External auditory meatus, pinna, scalp	Local infection
Preauricular	Eyelids and conjunctivae, temporal region, pinna	External auditory canal
Right supraclavicular node	Mediastinum, lungs, esophagus	Lung, retroperitoneal or gastrointestinal cancer
Left supraclavicular node	Thorax, abdomen via thoracic duct	Lymphoma, thoracic or retroperitoneal cancer, bacterial or fungal infection
Axillary	Arm, thoracic wall, breast	Infections, cat-scratch disease, lymphoma, breast cancer, silicone implants, brucellosis, melanoma
Epitrochlear	Ulnar aspect of forearm and hand	Infections, lymphoma, sarcoidosis, tularemia, secondary syphilis
Inguinal	Penis, scrotum, vulva, vagina, perineum, gluteal region, lower abdominal wall, lower anal canal	Infections of the leg or foot, STDs (e. g., herpes simplex virus, gonococcal infection, syphilis, chancroid, granuloma inguinale, lymphogranuloma venereum), lymphoma, pelvic malignancy, bubonic plague

If lymph nodes are detected, the following five characteristics should be noted and described:

Size. Nodes are generally considered to be normal if they are up to 1 cm in diameter; however, some authors suggest that epitrochlear nodes larger than 0.5 cm or inguinal nodes larger than 1.5 cm should be considered abnormal.^7,8 Little information exists to suggest that a specific diagnosis can be based on node size. However, in one series¹⁰ of 213 adults with unexplained lymphadenopathy, no patient with a lymph node smaller than 1 cm² (1 cm × 1 cm) had cancer, while cancer was present in 8 percent of those with nodes from 1 cm² to 2.25 cm² (1 cm × 1 cm to 1.5 cm × 1.5 cm) in size, and in 38 percent of those with nodes larger than 2. 25 cm² (1.5 cm × 1.5 cm). In children, lymph nodes larger than 2 cm in diameter (along with an abnormal chest radiograph and the absence of ear, nose and throat symptoms) were predictive of granulomatous diseases (i.e., tuberculosis, cat-scratch disease or sarcoidosis) or cancer (predominantly lymphomas).¹¹ These studies were performed in referral centers, and conclusions may not apply in primary care settings.

Pain/Tenderness. When a lymph node rapidly increases in size, its capsule stretches and causes pain. Pain is usually the result of an inflammatory process or suppuration, but pain may also result from hemorrhage into the necrotic center of a malignant node. The presence or absence of tenderness does not reliably differentiate benign from malignant nodes.⁴

Consistency. Stony-hard nodes are typically a sign of cancer, usually metastatic. Very firm, rubbery nodes suggest lymphoma. Softer nodes are the result of infections or inflammatory conditions. Suppurant nodes may be fluctuant. The term “shotty” refers to small nodes that feel like buckshot under the skin, as found in the cervical nodes of children with viral illnesses.

Matting. A group of nodes that feels connected and seems to move as a unit is said to be “matted.” Nodes that are matted can be either benign (e.g., tuberculosis, sarcoidosis or lymphogranuloma venereum) or malignant (e.g., metastatic carcinoma or lymphomas).

Location. The anatomic location of localized adenopathy will sometimes be helpful in narrowing the differential diagnosis. For example, cat-scratch disease typically causes cervical or axillary adenopathy, infectious mononucleosis causes cervical adenopathy and a number of sexually transmitted diseases are associated with inguinal adenopathy (Table 4).

Supraclavicular lymphadenopathy has the highest risk of malignancy, estimated as 90 percent in patients older than 40 years and 25 percent in those younger than age 40. ⁴ Having the patient perform a Valsalva’s maneuver during palpation of the supraclavicular fossae increases the chance of detecting a node. Lymphadenopathy of the right supraclavicular node is associated with cancer in the mediastinum, lungs or esophagus. The left supraclavicular (Virchow’s) node receives lymphatic flow from the thorax and abdomen, and may signal pathology in the testes, ovaries, kidneys, pancreas, prostate, stomach or gallbladder. Although rarely present, a paraumbilical (Sister Joseph’s) node may be a sign of an abdominal or pelvic neoplasm.¹²

In patients with generalized lymphadenopathy, the physical examination should focus on searching for signs of systemic illness. The most helpful findings are rash, mucous membrane lesions, hepatomegaly, splenomegaly or arthritis (Table 4). Splenomegaly and lymphadenopathy occur concurrently in many conditions, including mononucleosis-type syndromes, lymphocytic leukemia, lymphoma and sarcoidosis.

Clinical Evaluation for Algorithm’s ‘Suggestive’ Branch

Laboratory tests that may be useful in confirming the cause of lymphadenopathy are listed in Table 4. The presence of certain characteristic clinical syndromes may help the physician determine a suspected cause of lymphadenopathy.

Mononucleosis-Type Syndromes

Patients with these syndromes present with lymphadenopathy, fatigue, malaise, fever and an increased atypical lymphocyte count. Mononucleosis is most commonly due to Epstein-Barr virus infection. The presence of the typical syndrome and positive results on a heterophilic antibody test (Monospot test) confirms the diagnosis. The most common cause of heterophil-negative mononucleosis is early Epstein-Barr virus infection. False-negative results on heterophilic antibody tests are especially common in patients younger than four years of age. Epstein-Barr virus infection may be confirmed by repeating the Monospot test in seven to 10 days. Rarely is it necessary to confirm the diagnosis with IgM viral capsid antigen or early antigen antibody titers.

If Epstein-Barr virus antibodies are absent, other causes of the mononucleosis syndrome should be considered. These include toxoplasmosis, cytomegalovirus infection, streptococcal pharyngitis, hepatitis B infection and acute human immunodeficiency virus (HIV) infection. Acute infections with cytomegalovirus and Toxoplasma may be identified with IgM serology for those organisms.

Ulceroglandular Syndrome

This syndrome is defined by the presence of a skin lesion with associated regional lymphadenopathy. The classic cause is tularemia, acquired by contact with an infected rabbit or tick; more common causes include streptococcal infection (e.g., impetigo), cat-scratch disease and Lyme disease.

Oculoglandular Syndrome

This syndrome involves the combination of conjunctivitis and associated preauricular nodes. Common causes include viral kerato-conjunctivitis and cat-scratch disease resulting from an ocular lesion.

HIV Infection

Enlargement of the lymph nodes that persists for at least three months in at least two extrainguinal sites is defined as persistent generalized lymphadenopathy and is common in patients in the early stages of HIV infection. Other causes of generalized lymphadenopathy in HIV-infected patients include Kaposi’s sarcoma, cytomegalovirus infection, toxoplasmosis, tuberculosis, cryptococcosis, syphilis and lymphoma.

Unexplained Lymphadenopathy

When, after the initial evaluation and after exploration of the “diagnostic” and “suggestive” branches of the algorithm (Figure 2), a cause for the lymphadenopathy remains unexplained, the physician must decide whether to pursue a specific diagnosis. The decision will depend primarily on the clinical setting as determined by the patient’s age, the duration of the lymphadenopathy and the characteristics and location of the nodes.

Generalized Lymphadenopathy

Because generalized lymphadenopathy almost always indicates that a significant systemic disease is present, the clinician should consider the diseases listed in Table 4 and proceed with specific testing as indicated. If a diagnosis cannot be made, the clinician should obtain a biopsy of the node. The diagnostic yield of the biopsy can be maximized by obtaining an excisional biopsy of the largest and most abnormal node (which is not necessarily the most accessible node). If possible, the physician should not select inguinal and axillary nodes for biopsy, since they frequently show only reactive hyperplasia.

Localized Lymphadenopathy

If the lymphadenopathy is localized, the decision about when to biopsy is more difficult. Patients with a benign clinical history, an unremarkable physical examination and no constitutional symptoms should be reexamined in three to four weeks to see if the lymph nodes have regressed or disappeared. Patients with unexplained localized lymphadenopathy who have constitutional symptoms or signs, risk factors for malignancy or lymphadenopathy that persists for three to four weeks should undergo a biopsy. Biopsy should be avoided in patients with probable viral illness because lymph node pathology in these patients may sometimes simulate lymphoma and lead to a false-positive diagnosis of malignancy.

Initial Management

Many patients worry about the cause of their abnormal lymph nodes. To adequately address their fears, the physician should ask the patient about his or her concerns and respond to questions about specific diagnoses. When biopsy is deferred, the physician should explain to the patient the rationale for waiting. Patients should be cautioned to remain alert for the reappearance of the nodes because lymphomatous nodes have been known to temporarily regress.

Final Comment

In most patients, lymphadenopathy has a readily diagnosable infectious cause. A diagnosis of less obvious causes can often be made after considering the patient’s age, the duration of the lymphadenopathy and whether localizing signs or symptoms, constitutional signs or epidemiologic clues are present. When the cause of the lymphadenopathy remains unexplained, a three- to four-week observation period is appropriate when the clinical setting indicates a high probability of benign disease.

Swollen Lymph Nodes | Kaiser Permanente

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Overview

What are lymph nodes?

Lymph nodes are small, bean-shaped glands throughout the body. They are part of the lymph system, which carries fluid (lymph fluid), nutrients, and waste material between the body tissues and the bloodstream.

The lymph system is an important part of the immune system, the body’s defense system against disease. The lymph nodes filter lymph fluid as it flows through them, trapping bacteria, viruses, and other foreign substances, which are then destroyed by special white blood cells called lymphocytes.

Lymph nodes may be found singly or in groups. And they may be as small as the head of a pin or as large as an olive. Groups of lymph nodes can be felt in the neck, groin, and underarms. Lymph nodes generally are not tender or painful. Most lymph nodes in the body cannot be felt.

What causes swollen lymph nodes?

Lymph nodes often swell in one location when a problem such as an injury, infection, or tumor develops in or near the lymph node. Which lymph nodes are swollen can help identify the problem.

• The glands on either side of the neck, under the jaw, or behind the ears commonly swell when you have a cold or sore throat. Glands can also swell following an injury, such as a cut or bite, near the gland or when a tumor or infection occurs in the mouth, head, or neck.
• Glands in the armpit (axillary lymph nodes) may swell from an injury or infection to the arm or hand. A rare cause of axillary swelling may be breast cancer or lymphoma.
• The lymph nodes in the groin (femoral or inguinal lymph nodes) may swell from an injury or infection in the foot, leg, groin, or genitals. In rare cases, testicular cancer, lymphoma, or melanoma may cause a lump in this area.
• Glands above the collarbone (supraclavicular lymph nodes) may swell from an infection or tumor in the areas of the lungs, breasts, neck, or abdomen.

Common sites for swollen lymph nodes include the neck, groin, and underarms.

When lymph nodes swell in two or more areas of the body, it is called generalized lymphadenopathy. This may be caused by:

• A viral illness, such as measles, rubella, chickenpox (varicella), or mumps.
• Mononucleosis (Epstein-Barr virus), which results in fever, sore throat, and fatigue, or cytomegalovirus (CMV), a viral infection that causes symptoms similar to those of mononucleosis.
• A bacterial illness, such as strep throat (caused by the streptococcus bacterium) or Lyme disease (a bacterial infection spread by certain types of ticks).
• Side effects of phenytoin (Dilantin), a medicine used to prevent seizures.
• Side effects of measles-mumps-rubella (MMR) vaccination.
• Cancer, such as leukemia, Hodgkin disease, and non-Hodgkin lymphoma.
• Acquired immunodeficiency syndrome (AIDS), which develops after a person contracts HIV (human immunodeficiency virus). This virus attacks the immune system, making it difficult for the body to fight off infection and some disease.
• Syphilis, a sexually transmitted infection.

How are swollen lymph nodes treated?

Treatment for swollen glands focuses on treating the cause. For example, a bacterial infection may be treated with antibiotics, while a viral infection often goes away on its own. If cancer is suspected, a biopsy may be done to confirm the diagnosis.

Any swollen lymph nodes that don’t go away or return to normal size within about a month should be checked by your doctor.

How long will lymph nodes remain swollen?

Lymph nodes may remain swollen or firm long after an initial infection is gone. This is especially true in children, whose glands may decrease in size while remaining firm and visible for many weeks.

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  Related Information

First symptoms and prognosis with metastases

Cancer in the lymph nodes appears in 2 ways.

• Starts growing in a lymph node – this is a lymphoma.
• It enters the lymph nodes from the tumor of other organs and forms metastases.

More often lymph nodes are affected by metastases. It is this secondary lesion of the lymph nodes that we will consider in this article.

What are lymph nodes

Together with the circulatory system, our body has a lymphatic system. It consists of lymph, lymph capillaries, vessels and lymph nodes.

Lymph leaves the vessels and bathes the cells of the body, with its help oxygen and nutrients enter the cells, and carbon dioxide and metabolic products leave the cells. Also, the lymph contains a lot of white blood cells, which are necessary to fight infections. In inflammation, lymphatic fluid can accumulate in the tissues, causing swelling.

Human lymphatic system

Lymph through the lymphatic capillaries, then the vessels enter the lymph nodes. They are clusters of cells of different sizes that filter harmful substances from the lymph. They contain a large number of leukocytes and other immune cells that attack harmful objects, destroying them.

Why lymph nodes enlarge

Any pathological process in the body: infection, trauma or cancer causes enlargement and inflammation of the lymph nodes. This is due to their active work, lymphatic cells destroy incoming pathological objects.

Swollen lymph nodes is called lymphadenopathy.

Lymphadenopathy signals a pathological process in the body, and accompanying syndromes help to determine where it is located.

For example, ear pain, fever, and swollen behind-the-ear lymph nodes indicate ear inflammation.

How cancer spreads through the lymph nodes

As a tumor grows, cancer cells spread throughout the body forming metastases.

Not all tumors metastasize. For the formation of metastasis, it is necessary for the tumor to produce cells that can break away from the primary neoplasm. Then these cells must enter a blood or lymphatic vessel, gain a foothold in a new place and begin to multiply. Only then is metastasis formed.

Usually, as the tumor grows, nearby lymph nodes become inflamed and enlarged. These lymph nodes filter out and destroy cancer cells that enter them with lymph flow, which causes inflammation.

How lymph node metastases are detected

Lymph nodes are normally small and cannot be seen or palpated. But if there is an infection or neoplasm in the body, then the lymph nodes may increase. Subcutaneous lymph nodes are sometimes enlarged to such an extent that they can be felt on palpation or even seen on examination.

If cancer cells have recently entered the lymph node, it may not visually increase in size. In this case, additional examinations are required.

To assess the condition of the lymph nodes, cell samples are taken for histological examination. Cell samples are taken with a special needle – a node biopsy is performed.

Metastases in the lymph nodes

Histological examination of tissue taken from a biopsy is carried out by a pathologist. Under a microscope, cancer cells from the lymph nodes look the same as cells from a primary cancer.

For example, when a breast tumor spreads to the lymph nodes, cells taken from the nodes look like breast tumor cells.

A detailed report is made describing the cells and where they were found. If cancer cells were found in the sample, the report describes their type and number.

During surgery to remove a primary cancer, one or more lymph nodes near the tumor may be removed. Removed lymph nodes must be checked for the presence of cancer cells.

The spread of cancer cells throughout the body and the involvement of distant lymph nodes indicates a high risk of cancer recurrence after surgery. The defeat of the lymph nodes indicates the need to use additional methods of treatment – chemotherapy or radiation therapy after surgery.

Ultrasound, MRI with contrast, CT, PET-CT are also used to diagnose metastases. With their help, the state of the lymph nodes that are deep in the body is determined.

Cancer cells were found in the lymph nodes – what does it mean

When cancer cells are found in the lymph nodes, their number and the degree of tumor development are assessed. Sometimes there are so few pathological cells in the lymph nodes that they are detected only with the help of special tests. In such cases, their detection will not affect the treatment and prognosis of the disease.

If cancer cells are found only in nearby lymph nodes. Then during the operation to remove the main tumor, they are also removed. They do not have a strong influence on the prognosis of treatment and the patient’s condition.

If a large number of cancer cells are found in the lymph nodes, the enlargement of the lymph nodes is visible to the naked eye, this may indicate the rapid growth of the primary tumor and the spread of cancer throughout the body.

If the cancer has spread to distant lymph nodes, additional treatments such as chemotherapy or radiation therapy may be recommended.

It is possible for a tumor to grow from a lymph node when it grows through the connective tissue surrounding the node (capsule), such growth is called extracapsular expansion.

How the stage of cancer changes when metastases are detected in the lymph nodes

The choice of cancer treatment depends on the type of tumor and the stage of its development. Doctors use the TNM system to determine the stage.

In this system, T is the size of the primary tumor, M is the presence of metastases, and N is the involvement of the lymph nodes.

N0 – means that in the lymph nodes near the primary tumor, cancer cells were not found.

When cancer cells are found in nearby or distant lymph nodes, the stage is designated N 1,2 or 3.

The number (1,2,3) depends on how many nodes are affected, how much and how far they are located from the main tumor. Each type of cancer has its own classification.

The lower the TNM values, the easier it is to treat such cancer and the better the prognosis.

Effect of removal of lymph nodes

After removal of lymph nodes, the movement of lymph is disturbed. Part of the lymphatic fluid will begin to flow into other vessels, and some will sometimes accumulate in the tissues of the body. This results in swelling or lymphedema. The more lymph nodes are removed, the higher the risk of complications.

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Onco Wiki – Lymph Node Surgery

To assess the prognosis and the possible benefits of postoperative therapy, it is necessary to diagnose the defeat of the lymph nodes and determine the stage.

Regional lymph nodes are nodes that collect lymph for a given area of ​​the body. For example, for the skin of the anterior surface of the thigh, the regional lymph nodes will be inguinal.

To obtain accurate information about whether there are metastases in regional nodes, use:

• ultrasound-guided fine-needle biopsy of suspicious lymph nodes;
• sentinel lymph node biopsy.

According to both Russian and foreign recommendations, one should not routinely (that is, all in a row) remove regional lymph nodes in patients without signs of lymph node damage for prophylactic purposes.

If micrometastases are found after biopsy of the sentinel lymph node, then the question of performing lymph node dissection is always discussed with the doctor.

Removal of micrometastatically affected lymph nodes found on sentinel lymph node biopsy is not currently thought to prolong the life of the patient, so lymph node removal is not recommended in this case. However, the opinions of various communities on this issue differ. The Association of Clinical Oncologists of the Russian Federation refers to the study mentioned above and proposes to carefully discuss this issue, weighing the potential risks of such an operation and the expected benefits. However, the Russian Society of Clinical Oncologists believes that biopsy of the sentinel lymph node with subsequent removal of the lymph nodes (if micrometastases are detected) is a necessary procedure.

Surgical removal of lymph nodes is the preferred method for patients with initially affected lymph nodes. Even if the patient subsequently develops distant metastases, lymphadenectomy can prevent the rapid course of the disease associated with massive involvement of nodes or destruction of the skin.

The group of lymph nodes that collect lymph from the skin area affected by melanoma is removed. This removal is called lymph node dissection, or dissection for short. The main, that is, the most frequently performed, are axillary, inguinal and cervical lymphadenectomy. Rarely, popliteal and ulnar lymph node dissections are performed. For example, when melanoma is localized on the lower leg, metastases can get into the nearest lymph nodes under the knee, or they can go further into the femoral ones. Any group of affected lymph nodes can undergo lymph node dissection.

Axillary dissection removes all lymph nodes and possible tumor-bearing tissue from the axilla. Important arteries, veins and nerves pass through the armpit. The operation is planned and carried out in such a way as to remove all lymph nodes and malignant tissue without damaging these important structures. During the operation, small axillary nerves are removed. This causes numbness in the armpit and on the inside of the arm, which is often permanent.

The operation is performed under general anesthesia, that is, at this moment the patient does not feel anything, and usually takes from 60 to 90 minutes. A drain is placed in the wound to collect fluid. Most of the fluid that collects in the wound is draining lymph: the lymph nodes that collected it have been removed, and the remaining vessels continue to leak for some time after the operation. The drain is a soft, flexible silicone tube that is connected to a suction bottle and will be checked frequently by medical staff. When the active separation of fluid from the wound stops (reducing the volume of fluid in the drainage to 5-20 ml per day), the drainage is removed. Drainage can be in the wound from several days to several weeks.

When melanoma affects the lymph nodes of the groin, removal of the inguinal-femoral lymph nodes or ilio-inguinal lymph nodes (removal of nodes from the groin and pelvis) is required. These are quite traumatic and voluminous operations that are performed only under general anesthesia. Drainage is also installed in the wound. According to the rapid recovery protocols after surgical interventions, patients are encouraged to sit down and even get up on the first day after surgery. For several days after the operation, there may be pain in the surgical area, which is controlled with painkillers. You don’t need to endure the pain after the operation, the doctor will select the necessary dose of painkillers and make an appointment.

Iliopinguinal dissection is a deeper and more traumatic operation. The question of its necessity in certain situations remains controversial, since it is still unclear whether such extensive excision increases the patient’s life expectancy. The volume of operations on the lymph nodes is determined individually, taking into account the potential benefits and harms.

Lymph nodes in the neck are located from the ear on both sides of the neck to the collarbone, and also under the jaw. The neck is a complex anatomical part of the body. In order for the surgeon to gain access to the lymph nodes, several small cutaneous nerves must be removed. This leads to numbness of the operated side of the neck, ears, upper chest and back, which sometimes remains forever. The operation is also performed under general anesthesia.

There may be pain in the surgical area for several days after the operation, this can be controlled with painkillers. When the wound is closed, a drain is installed, which can be removed when the discharge from the wound stops. Unfortunately, it is not always possible to maintain the desired appearance of the neck after such operations

Operations on the lymph nodes, as with any surgical intervention, there are general surgical complications, for example:

• collection of blood under a wound with stitches;
• wound infection;
• divergence of the postoperative suture;
• excessive formation of new tissue during healing;
• formation of subcutaneous seroma – accumulation of fluid at the site of intervention. Seromas can form even if a drain has been placed in the wound. Small seromas can resolve on their own, large ones (annoying, convex, reddening, there is a feeling of stretching of the skin) must be punctured, that is, fluid should be pumped out.

More specific complications after lymph node dissection depend on which group of lymph nodes the surgeon worked on, that is, from where these lymph nodes collected lymph.

For example, in case of melanoma of the skin on the upper limbs, the operation is performed on the axillary lymph nodes. Already in the early postoperative period, dysfunction (violation of the normal range of motion) of the shoulder may occur. Almost always, this complication can be reduced to nothing with the help of physiotherapy exercises.

Complications that occur later include lymphedema (lymphatic swelling of a limb) and paresthesias. Paresthesia is a violation of neurological sensitivity, which is directly related to limb edema and compression of nerve endings.

Complications are more common after excision of inguinal lymph nodes. Inguinal lymph node dissection is performed for melanoma of the skin of the lower extremities or melanoma of the skin of the body with lymph outflow to the inguinal lymph nodes.

Patients who have undergone groin excision may benefit from wearing compression stockings for at least six months after surgery. Prevention of lymphedema (an increase in the volume of a limb due to a violation of the outflow of lymph) is very important, since the formed lymphedema requires lifelong treatment. For the upper limb, when wearing a compression sleeve, you must not forget about the glove – to prevent swelling of the hand. Similarly, in the lower limb, the foot is an integral part of compression hosiery.

When properly fitted and worn, compression garments can reduce swelling that has already developed. If the compression underwear is not properly fitted, this can lead to the onset or progression of lymphedema.