Sandbox: Lymphadenopathy
Synonyms and keywords: Lymph nodes enlarged; Enlarged lymph nodes; Lymphadenitis; Swollen lymph nodes; Swollen/enlarged lymph nodes

# Overview
Lymphadenopathy (also known as "enlarged lymph nodes) refers to lymph nodes which are abnormal in size, number or consistency. Common causes of lymphadenopathy are infection, autoimmune disease, or malignancy.  Lymphadenopathy may be classified according to distribution into 2 groups: generalized lymphadenopathy and localized lymphadenopathy. The pathogenesis of lymphadenopathy is characterized by the inflammation of lymph nodes. This process is primarily due to an elevated rate of trafficking of lymphocytes into the node from the blood, exceeding the rate of outflow from the node. Lymph nodes may also be enlarged secondarily as a result of the activation and proliferation of antigen-specific T and B cells (clonal expansion). Lymphadenopathy is very common,  the estimated incidence of lymphadenopathy among children in the United States ranges from 35%- 45%. Patients of all age groups may develop lymphadenopathy. Lymphadenopathy is more commonly observed among children. Common complications of lymphadenopathy, may include: abscess formation, superior vena cava syndrome, and intestinal obstruction.  Diagnostic criteria for malignant lymphadenopathy, may include: node > 2 cm, node that is draining, hard, or fixed to underlying tissue, atypical location (e.g. supraclavicular node), associated risk factors (e.g. HIV or TB), fever and/or weight loss, and splenomegaly. On the other hand, diagnostic criteria for benign lymphadenopathy, may include: node < 1 cm, node that is mobile, soft-or tender, and is not fixed to underlying tissue, typical location (e.g. supraclavicular node), no associated risk factors, and palpable and painful enlargement. Laboratory findings consistent with the diagnosis of lymphadenopathy, may include: elevated lactate dehydrogenase (LDH), mild neutropenia, and leukocytosis. There is no treatment for lymphadenopathy; the mainstay of therapy is treating the underlying condition.

# Classification
- Lymphadenopathy may be classified according to distribution into 2 groups:
- Generalized lymphadenopathy
- Localized lymphadenopathy

# Pathophysiology
- The pathogenesis of lymphadenopathy is characterized by the inflammation of lymph nodes. This process is primarily due to an elevated rate of trafficking of lymphocytes into the node from the blood, exceeding the rate of outflow from the node.
- The inmune response between the antigen and lymphocyte that leads to cellular proliferation and enlargement of the lymph nodes.
- Lymph nodes may also be enlarged secondarily as a result of the activation and proliferation of antigen-specific T and B cells (clonal expansion).
- On gross pathology, characteristic findings of lymphadenopathy, include:
- Enlarged lymph node
- Soft greasy yellow areas within capsule
- On microscopic histopathological analysis, characteristic findings of lymphadenopathy will depend on the aetiology.
- Common findings, include:
Non-specific reactive follicular hyperplasia (NSRFH)
- Large spaced cortical follicles
- Tingible body macrophages, normal dark/light GC pattern
Lymph node metastasis
- Foreign cell population (usually in subcapsular sinuses)
- +/-nuclear atypia
- +/-malignant architecture
Toxoplasmosis
- Large follicles
- Epithelioid cells perifollicular & intrafollicular
- Reactive GCs
- Monocytoid cell clusters
Cat-scratch disease
- PMNs in necrotic area
- "Stellate" (or serpentine) shaped micro-abscesses
- Presence of granulomas
Dermatopathic lymphadenopathy
- Melanin-laden histiocytes
- Histiocytosis
Systemic lupus erythematosus lymphadenopathy
- Blue hematoxylin bodies
- Necrosis
- No PMNs

# Causes
- Common causes of lymphadenopathy, include:
- Infections (acute suppurative)
- Fungal
- Mycobacterial
- Viral
- Protozoal (e.g. toxoplasma)
- Bacterial (e.g. chlamydia, rickettsia, bartonella)
- Reactive
- Follicular hyperplasia
- Paracortical hyperplasia
- Sinus histiocytosis
- Granulomatous
- Neoplastic
- Drugs (e.g. cyclosporin, phenytoin, methotrexate)
- Lipid storage diseases
- IgG4-related sclerosing disease

# Epidemiology and Demographics
- Lymphadenopathy is very common.
- The estimated incidence of lymphadenopathy among children in the United States ranges from 35%- 45%.

## Age
- Patients of all age groups may develop lymphadenopathy.
- Lymphadenopathy is more commonly observed among children.

## Gender
- Lymphadenopathy affects men and women equally.

## Race
- There is no racial predilection for lymphadenopathy.

# Risk Factors
- The most common risk factors in the development of lymphadenopathy, include:
- Local soft-tissue infections
- Upper respiratory tract infection
- Foreign travel

# Natural History, Complications and Prognosis
- Patients with lymphadenopathy may be symptomatic or asymptomatic, depending on the aetiology.
- Early clinical features include palpable tenderness, pain, and fever.
- Common complications of lymphadenopathy, include:
Mediastinal lymphadenopathy
- Superior vena cava syndrome
Tracheal and bronchial obstruction
Dysphagia
Hemoptysis
- Tracheal and bronchial obstruction
- Dysphagia
- Hemoptysis
- Uric acid nephropathy
- Hyperkalemia
- Hypercalcemia
- Hypocalcemia
- Hyperphosphatemia
- Renal failure
Abdominal lymphadenopathy
- Intestinal obstruction
Superficial lymphadenopathy
- Abscess formation
- Cellulitis
- Fistulas (seen in lymphadenitis that is due to tuberculosis)
- Sepsis
- Prognosis will depend on the aetiology of the underlying disease.

# Diagnosis

## Diagnostic Criteria

### Malignant Lymphadenopathy
- Node > 2 cm
- Node that is draining, hard, or fixed to underlying tissue
- Atypical location (e.g. supraclavicular node)
- Risk factors (e.g. HIV or TB)
- Fever and/or weight loss
- Splenomegaly

### Benign Lymphadenopathy
- Node < 1 cm
- Node that is mobile, soft-or tender, and is not fixed to underlying tissue
- Common location (e.g. supraclavicular node)
- No associated risk factors
- Palpable and painful enlargement

## Symptoms
- Symptoms of lymphadenopathy may include the following:
- Constitutional symptoms
- Fever
- Weight loss
- Fatigue
- Night sweats
- Malaise
- Nausea and vomiting
- Cachexia
- A directed history should be obtained to ascertain:
- Use of drugs causing lymphadenopathy
- Travel to endemic areas
- Occupational risk (e.g. Fishermen, slaughterhouse workers, hunters, trappers)
- High risk behavior or high risk sexual behaviors (e.g. I.V drug abuse, multiple partners)

## Physical Examination
- Patients with lymphadenopathy may have a pale or normal appearance.
- Physical examination may be remarkable for:

## Vitals
- Temperature
- High grade fever
- Low grade fever
- Pulse
- Rapid (e.g. acute infections)

## Skin
- Rash may be present
- Color change (indicative of inflammation)
- Skin fistula draining pus may be present
- Ulcers

## Head

### Palpating Anterior Cervical Lymph Nodes
Lymph nodes should be examined in the following order:
- Anterior Cervical
- Posterior Cervical
- Tonsillar
- Sub-Mandibular
- Sub-Mental
- Supra-clavicular
Characteristics to be noted while palpating lymph nodes:
- Size
- Pain/ tenderness
- Increased tenderness (e.g infected lymph nodes)
- Consistency
- Matting

### Gallery
- Cervical adenopathy: massive right side cervical adenopathy and facial asymmetry due to metastatic, intraoral squamous cell cancer. Images Courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, CA.
- Cervical adenopathy: massive right side cervical adenopathy and facial asymmetry due to metastatic, intraoral squamous cell cancer.  Images Courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, CA.
- Cervical adenopathy: large right anterior cervical lymph node.  Images Courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, CA.
- Cervical lymphadenopathy. Images Courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, CA.
- Cervical Adenopathy: multiple right sided cervical lymph nodes.  Images Courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, CA.

## Laboratory Findings
- Laboratory findings consistent with the diagnosis of lymphadenopathy, may include:
Complete Blood Count
- Elevated lactate dehydrogenase (LDH)
- Mild neutropenia
- Leukocytosis
- Elevated markers of inflammation and acute phase reactants (e.g. ESR, C-reactive protein, ferritin)

## Imaging Findings
Ultrasonography
- On ultrasound, characteristic findings of lymphadenopathy, include:
- Round, hypoechoic mass (less than 1 cm)
- Extent of lymph node involvement
CT
- On CT, characteristic findings of lymphadenopathy, include:
- Most nodes: 10 mm in short-axis
- Sub-mental and sub-mandibular: 15 mm
- Retropharyngeal: 8 mm
- Loss of fatty hilum
- Focal necrosis
- Cystic necrotic nodes
- Long-to-short axis ratio (>2cm - usually benign)
- The upper limit in size of a normal node varies with location.

# Treatment
- There is no treatment for lymphadenopathy; the mainstay of therapy is treating the underlying condition.
- For instance, infectious lymphadenopathy responds well to prompt treatment with antibiotics, and usually leads to a complete recovery. However, it may take months, for swelling to disappear. The amount of time to recovery depends on the cause.