Lymphadenopathy

Lymphadenopathy is a term meaning "disease of the lymph

nodes." It is, however, almost synonymously used with
"swollen/enlarged lymph nodes". It could be due to infection,
auto-immune disease, or malignancy.

Types:
 Localized lymphadenopathy : due to localized spot of
infection e.g. an infected spot on the scalp will cause lymph
nodes in the neck on that same side to swell up

 Generalized lymphadenopathy : due to generalized

infection all over the body e.g. influenza

N.B. Persistent generalized lymphadenopathy:

persisting for a long time, possibly without an
apparent cause.

Generalized lymophadenopathy
Causes:
1. Infections

1. Viral

 Common upper respiratory infections

 Infectious mononucleosis
  CMV

 Acquired immunodeficiency syndrome

 Rubella

 Varicella

 Measles

2. Bacterial

 Septicemia

 Typhoid fever

 Tuberculosis

 Syphilis

 Plague

3. Protozoal - Toxoplasmosis

4. Fungal - Coccidioidomycosis

2. Autoimmune disorders and hypersensitivity states

1. Juvenile rheumatoid arthritis

2. Systemic lupus erythematosus

3. Drug reactions (eg, phenytoin, allopurinol)

4. Serum sickness

3. Storage Diseases

1. Gaucher disease
 2. Niemann-Pick disease

4. Neoplastic and proliferative disorders

1. Acute leukemias

2. Lymphomas (Hodgkin, non-Hodgkin)

3. Neuroblastoma

4. Histiocytoses

Differential diagnosis:

Disorder Associated findings Test

Epstein-Barr virus Splenomegaly in 50% of Monospot, IgM EA or VCA

patients
Toxoplasmosis 80 to 90% of patients are IgM toxoplasma antibody
asymptomatic
Cytomegalovirus Often mild symptoms; patients IgM CMV antibody, viral
may have hepatitis culture of urine or blood
Tuberculosis lymphadenitis Painless, matted cervical nodes PPD, biopsy

Secondary syphilis Rash RPR

Hepatitis B Fever, nausea, vomiting, Liver function tests, HBsAg

icterus
Lupus erythematosis Arthritis, rash, serositis, renal,
neurologic, hematologic
disorders
Rheumatoid arthritis Arthritis
Lymphoma Fever, night sweats, weight
loss in 20 to 30% of patients
Leukemia Blood dyscrasias, bruising
Clinical criteria, antinuclear
antibodies, complement
levels
Clinical criteria, rheumatoid
factor
Biopsy
Blood smear, bone marrow

Serum sickness Fever, malaise, arthralgia, Clinical criteria,

urticaria; exposure to antisera complement assays
or medications
Lyme disease Rash, arthritis IgM serology

Measles Fever, conjunctivitis, rash, Clinical criteria, serology

cough
Rubella Rash Clinical criteria, serology

Tularemia LA Fever, ulcer at inoculation site Blood culture, serology

Brucellosis Fever, sweats, malaise Blood culture, serology

Typhoid fever Fever, chills, headache, Blood culture, serology

abdominal complaints
Source: American Academy of Family Physicians.

Unexplained general lymphadenopathy:

Because generalized lymphadenopathy almost always
indicates that a significant systemic disease is present, the
clinician should consider the diseases listed in the table above 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
Causes:
1. Cervical

1. Viral upper respiratory infection

2. Infectious mononucleosis

3. Rubella

4. Catscratch disease

5. Streptococcal pharyngitis

6. Acute bacterial lymphadenitis

7. Toxoplasmosis

8. Tuberculosis/atypical mycobacterial infection

9. Acute leukemia

10. Lymphoma

11. Neuroblastoma

12. Rhabdomyosarcoma

13. Kawasaki disease

2. Submaxillary and submental

1. Oral and dental infections

2. Acute lymphadenitis
3. Occipital

1. Pediculosis capitis

2. Tinea capitis

3. Secondary to local skin infection

4. Rubella

5. Roseola

4. Preauricular

1. Local skin infection

2. Chronic ophthalmic infection

3. Catscratch disease

5. Mediastinal

1. Acute lymphoblastic leukemia

2. Lymphoma

3. Sarcoidosis

4. Cystic fibrosis

5. Tuberculosis

6. Histoplasmosis

7. Coccidioidomycosis

6. Supraclavicular

1. Lymphoma
 2. Tuberculosis

3. Histoplasmosis

4. Coccidioidomycosis

7. Axillary

1. Local infection

2. Catscratch disease

3. Brucellosis

4. Reactions to immunizations

5. Lymphoma

6. Juvenile rheumatoid arthritis

8. Abdominal

1. Acute mesenteric adenitis

2. Lymphoma

9. Inguinal

1. Local infection

2. Diaper dermatitis

3. Insect bites

4. Syphilis

5. Lymphogranuloma venereum
Differential diagnosis:
 Cervical lymphadenopathy: Cervical lymphadenopathy is a
common problem in children. Cervical nodes drain the
tongue, external ear, parotid gland, and deeper structures of
the neck, including the larynx, thyroid, and trachea.
Inflammation or direct infection of these areas causes
subsequent engorgement and hyperplasia of their respective
node groups. Adenopathy is most common in cervical nodes
in children and is usually related to infectious etiologies.
Lymphadenopathy posterior to the sternocleidomastoid is
typically a more ominous finding, with a higher risk of
serious underlying disease.

 Infectious etiologies
o
Cervical adenopathy is a common feature of many viral
infections. Infectious mononucleosis often manifests
with posterior and anterior cervical adenopathy. Firm
tender nodes that are not warm or erythematous
characterize this lymph node enlargement. Other viral
causes of cervical lymphadenopathy include
adenovirus, herpesvirus, coxsackievirus, and CMV. In
herpes gingivostomatitis, impressive submandibular
and submental adenopathy reflects the amount of oral
involvement.
o
Bacterial infections cause cervical adenopathy by
causing the draining nodes to respond to local infection
or by the infection localizing within the node itself as a
 lymphadenitis. Bacterial infection often results in
enlarged lymph nodes that are warm, erythematous,
and tender. Localized cervical lymphadenitis typically
begins as enlarged, tender, and then fluctuant nodes.
The appropriate management of a suppurative lymph
node includes both antibiotics and incision and
drainage. Antibiotic therapy should always include
coverage for Staphylococcus aureus and Streptococcus
pyogenes.
o
In patients with cervical adenopathy, determine
whether the patient has had recent or ongoing sore
throat or ear pain. Examine the oropharynx, paying
special attention to the posterior pharynx and the
dentition. The classic manifestation of group A
streptococcal pharyngitis is sore throat, fever, and
anterior cervical lymphadenopathy. Other
streptococcal infections causing cervical adenopathy
include otitis media, impetigo, and cellulitis.
o
Atypical mycobacteria cause subacute cervical
lymphadenitis, with nodes that are large and indurated
but not tender. The only definitive cure is removal of
the infected node.
o
Mycobacterium tuberculosis may manifest with a
suppurative lymph node identical to that of atypical
mycobacterium. Intradermal skin testing may be
equivocal. A biopsy may be necessary to establish the
diagnosis.
 o
Catscratch disease, caused by Bartonella henselae,
presents with subacute lymphadenopathy often in the
cervical region. The disease develops after the infected
pet (usually a kitten) inoculates the host, usually
through a scratch. Approximately 30 days later, fever,
headache, and malaise develop, along with
adenopathy that is often tender. Several lymph node
chains may be involved. Suppurative adenopathy
occurs in 10-35% of patients. Antibiotic therapy has not
been shown to shorten the course.

 Noninfectious etiologies
o
Malignant childhood tumors develop in the head and
neck region in one quarter of cases. In the first 6 years
of life, neuroblastoma, leukemia, non-Hodgkin
lymphoma, and rhabdomyosarcoma (in order of
decreasing frequency) are most common in the head
and neck region. In children older than 6 years,
Hodgkin disease and non-Hodgkin lymphoma both
predominate. Children with Hodgkin disease present
with cervical adenopathy in 80-90% of cases as
opposed to 40% of those with non-Hodgkin lymphoma.
o
Kawasaki disease is an important cause of cervical
adenopathy. These children have fever for at least 5
days, and cervical lymphadenopathy is one of the 5
diagnostic criteria (of which 4 are necessary to
establish the diagnosis).
 Submaxillary and submental lymphadenopathy: These nodes
drain the teeth, tongue, gums, and buccal mucosa. Their
enlargement is usually the result of localized infection, such
as pharyngitis, herpetic gingivostomatitis, and dental
abscess.
 Occipital lymphadenopathy: Occipital nodes drain the
posterior scalp. These nodes are palpable in 5% of healthy
children. Common etiologies of occipital lymphadenopathy
include tinea capitis, seborrheic dermatitis, insect bites,
orbital cellulitis, and pediculosis. Viral etiologies include
rubella and roseola infantum. Rarely, occipital
lymphadenopathy may be noted after enucleation of the eye
for retinoblastoma.
 Preauricular lymphadenopathy: Preauricular nodes drain the
conjunctivae, skin of the cheek, eyelids, and temporal region
of the scalp and rarely are palpable in healthy children. The
oculoglandular syndrome consists of severe conjunctivitis,
corneal ulceration, eyelid edema, and ipsilateral preauricular
lymphadenopathy. Chlamydia trachomatis and adenovirus
can cause this syndrome.
 Mediastinal lymphadenopathy

 Mediastinal nodes drain the thoracic viscera, including the

lungs, heart, thymus, and thoracic esophagus. Because these
nodes are not directly demonstrable upon physical
examination, their enlargement must be indirectly assessed.
Supraclavicular adenopathy is often associated with
mediastinal adenopathy. Mediastinal nodes may cause
cough, wheezing, dysphagia, airway erosion with
 hemoptysis, atelectasis, and the obstruction of the great
vessels, which constitutes superior vena cava syndrome.
Airway compromise may be life threatening.

 Mediastinal lymphadenopathy is usually a sign of serious

underlying disease. More than 95% of mediastinal masses
are caused by tumors or cysts. Lymphomas and acute
lymphoblastic leukemia are the most common etiologies and
usually involve the anterior mediastinum. These
malignancies are associated with a high risk of superior vena
cava syndrome and are associated with several potentially
life-threatening complications, as follows:

o The danger of sedation of patients, especially in the

supine position for scans and procedures (The prone
position actually may be safer.)

o The risk during intubation of these patients, usually at

the time of biopsy or placement of a central venous
catheter

o The risk of cardiovascular collapse during general

anesthesia because of compression of venous return or
because of previously undiagnosed pleural effusions

o The risk of losing the ability to establish a pathologic

diagnosis because of the use of steroids or radiation
therapy

 Unlike most other adenopathies, mediastinal

lymphadenopathy is less frequently a result of infection.
 Infections frequently involve the hilar region and include
histoplasmosis, coccidioidomycosis, and tuberculosis.

 Nonlymphoid mediastinal tumors may be confused with

adenopathy. These include neurogenic tumors (usually found
in the posterior mediastinum), germ cell tumors, and
teratomas.

 Nonneoplastic conditions may also be confused with

mediastinal adenopathy. These include the typically large
thymus of a child, substernal thyroid glands, bronchogenic
cysts, and abnormalities of the great vessels.

 Supraclavicular lymphadenopathy

 Supraclavicular nodes drain the head, neck, arms, superficial

thorax, lungs, mediastinum, and abdomen. Left
supraclavicular nodes also reflect intra-abdominal drainage
and enlarge in response to malignancies in that region. This
is particularly true when adenopathy in this region occurs in
the absence of other cervical adenopathy.

 Right supraclavicular nodes drain the lung and mediastinum

and are typically enlarged with intrathoracic lesions.

 Serious underlying disease is frequent in children with

supraclavicular adenopathy and always merits further
evaluation. The potential for malignancy necessitates
peripheral blood counts, skin testing for tuberculosis, and
chemical studies, including uric acid, lactate dehydrogenase,
calcium (Ca), phosphorus (P), and renal and hepatic function
 studies. Chest radiography and possibly CT scanning are
indicated.

 Several important infections may occur with supraclavicular

adenopathy, including tuberculosis, histoplasmosis, and
coccidioidomycosis.

 Early lymph node biopsy should be considered in children

with supraclavicular adenopathy.

 Axillary lymphadenopathy

 Axillary nodes drain the hand, arm, lateral chest, abdominal

walls, and the lateral portion of the breast.

 A common cause of axillary lymphadenopathy is catscratch

disease. Local axillary skin infection and irritation commonly
are associated with local adenopathy. Other etiologies
include recent immunizations in the arm (particularly with
bacille Calmette-Guerin vaccine), brucellosis, juvenile
rheumatoid arthritis, and non-Hodgkin lymphoma.

 Hidradenitis suppurativa is a condition of enlarged tender

lymph nodes that typically affects children with obesity and
is caused by recurrent abscesses of lymph nodes in the
axillary chain. The etiology is unknown, and treatment may
include antibiotics. Many patients require incision and
drainage.

 Abdominal lymphadenopathy

 Abdominal nodes drain the lower extremities, pelvis, and

abdominal organs. Although abdominal adenopathy is not
 usually demonstrable upon physical examination, abdominal
pain, backache, increased urinary frequency, constipation,
and intestinal obstruction secondary to intussusception are
possible presentations.

 Mesenteric adenitis is thought to be viral in etiology and is

characterized by right lower quadrant abdominal pain
caused by nodal enlargement near the ileocecal valve.
Differentiating mesenteric adenitis from appendicitis may be
difficult.

 Mesenteric adenopathy may be caused by non-Hodgkin

lymphoma or Hodgkin disease.

 Typhoid fever and ulcerative colitis are other etiologies of

mesenteric adenopathy.

 Iliac and inguinal lymphadenopathy: The lower extremities,

perineum, buttocks, genitalia, and lower abdominal wall drain to
these nodes. They are typically palpable in healthy children,
although they are usually no larger than 1-1.5 cm in diameter.
Regional lymphadenopathy is typically caused by infection;
however, insect bites and diaper dermatitis are also frequent.
Nonlymphoid masses that may be confused with adenopathy
include hernias, ectopic testes, and lipomas.
Unexplained 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.
Diagnosis of lymphadenopathy
Laboratory Studies

The laboratory evaluation of lymphadenopathy must be directed

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

 CBC count, including a careful evaluation of the peripheral

blood smear. An erythrocyte sedimentation rate is
nonspecific but may be helpful.

 Evaluation of hepatic and renal function and a urine analysis

are useful to identify underlying systemic disorders that may
be associated with lymphadenopathy. Additional studies,
such as lactate dehydrogenase (LDH), uric acid, calcium, and
phosphate, may be indicated if malignancy is suspected. Skin
testing for tuberculosis is usually indicated.

 In evaluating specific regional adenopathy, lymph node

aspirate for culture may be important if lymphadenitis is
clinically suspected.

 Titers for specific microorganisms may be indicated,

particularly if generalized adenopathy is present. These may
include Epstein-Barr virus, cytomegalovirus (CMV), B
 henselae, Toxoplasma species, and human
immunodeficiency virus (HIV).

Imaging Studies

Chest radiography is usually the primary screening imaging
study. Additional imaging studies are usually based on
abnormal chest radiograph findings. Chest radiography is
often helpful in elucidating mediastinal adenopathy and
underlying diseases affecting the lungs, including
tuberculosis, coccidioidomycosis, lymphomas,
neuroblastoma, histiocytoses, and Gaucher disease.

Supraclavicular adenopathy, with its high associated rate of
serious underlying disease, may be an indication for other
studies, including CT scanning of the chest, abdomen, or
both.

Nuclear medicine scanning is helpful in the evaluation of
lymphomas.

Ultrasonography may be helpful in evaluating the changes in
the lymph nodes and in evaluating the extent of lymph node
involvement in patients with lymphadenopathy.8

In children with inguinal adenopathy or abdominal
complaints, ultrasonography of the abdomen, CT scanning
of the abdomen, or both may be indicated.

Procedures
  The critical question is often whether or not to perform a
lymph node biopsy; this requires an overall assessment of
the history and physical examination as described above.
Treatment with antibiotics (covering the bacterial pathogens
frequently implicated in lymphadenitis) followed by
reevaluation in 2-4 weeks is reasonable if clinical findings
suggest lymphadenitis. Benign reactive adenopathy may be
safely observed for months.

A lymph node biopsy is performed. Note that a marking pen has

been used to outline the node before removal and that a silk
suture has been used to provide traction to assist the removal.

A lymph node 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.
  If the size, location, or character of the lymphadenopathy
suggests malignancy, the need for laboratory studies and
biopsy is more urgent. If laboratory testing is inconclusive, a
lymph node biopsy is immediately indicated.

 Fine needle aspiration and core needle biopsy yield small

samples with limited ability to perform flow cytometry and
chromosomal analysis; most pediatric hematologists and
pathologists prefer excisional biopsy.

 Excisional biopsy also has limitations and may yield a

definitive diagnosis in only 40-60% of patients because of
inadequate specimen size, improper handling, or node-
sampling error. 

 Hodgkin disease may be associated with reactive changes in

surrounding nodes, and sampling more accessible nodes
may miss the underlying malignancy. 

 Sampling inguinal nodes may yield specimens with

an architecture distorted by chronic inflammatory changes. 

 The surgeon should perform a biopsy on larger, firmer, and

most recently enlarging nodes, even if it is technically
difficult, with appropriate preparation and handling of the
specimen. If an excisional biopsy does not reveal the
diagnosis despite appropriate sampling practice, a second
biopsy may be indicated if symptoms persist or worsen.

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

 When examining the tissue, histiologic findings are often

inadequate. Flow cytometric and chromosomal analysis may
provide critical information to permit a diagnosis to be
established.

Staging

 Staging is relevant only when a specific malignancy is

diagnosed as the etiology of lymphadenopathy.
Lymph node examination
Lymph Node Groups

 occipital, preauricular, postauricular

 submental, submandibular

 cervical: anterior, posterior, deep

 clavicular: supraclavicular, infraclavicular

 axillary: anterior (pectoral), lateral, posterior (subscapular),

apical, medial

 epitrochlear

 inguinal:superficial(horizontal,vertical),deep

Inspection

 lymphedema

 surgical scars from cancer excision

 obvious masses

Palpation

 technique: use the pads of the index and middle finger to

move the skin in circular motions over the underlying tissues
in each area; palpated both sides of the neck simultaneously

 Small nodes (< size of distal phalanx of pinky finger) are

normal unless in unusual location (preauricular).
  in abnormal nodes, describe in terms of

o location

o size

o delimination (discrete or matted together)

o mobile or fixed

o consistency (soft, hard, firm)

o tenderness

Location of Nodes (And what it drains)

 preauricular - in front of tragus of ear (eye)

 postauricular - behind ear, over mastoid process (ear)

 occipital - posterior to mastoid process, at base of skull

 submental - inside mentus of the mandible (floor of mouth)

 submandibular - near submandibular salivary glands (oral

cavity)

 cervical chains

o anterior chain runs along the SCM (pharynx, tonsils)

o posterior chain runs along the trapezius

 clavicular (abdomen, thorax, breast)

o supraclavicular - Virchow’s node (ominous finding in

cancer patient)
 axillary

o lateral (arm), medial

o apical - need to push very hard

o anterior (anterior chest wall, most of breast)

o posterior (posterior chest wall, upper arm)

 epitrochlear - while shaking the patient’s hand, feel the

epitrochlear area

 inguinal - “shotty” nodes are small, mobile and discrete

(normal)