Lymphadenopathy

Physical characteristics of normal nodes

Normal lymph nodes number around 600 in the body. It is normal to palpate cervical, axillary, and
inguinal nodes in perfectly well children, but the size should be less than 1 cm in the greatest diameter
and soft consistency.

Lymph nodes reach the largest total lymph node mass at the age of about 8–12 years and start to get
reduced with atrophy after adolescence. Therefore, in young children, 2 cm in the neck, 1 cm in the
axilla, and 1.5 cm in the inguinal region are normal values, and they do not require investigation.

Epitrochlear and supraclavicular lymph nodes need further investigation, as they may be related to
malignancy, even if they are 0.5 cm or less in size.

For any palpable lymph node, it is important to assess the following physical characteristics to help to
make the differential diagnosis:

o Site: evaluate the lymph node's location in relation to other anatomical structures.

o Size: evaluate the size of the lymph node.

o Shape: evaluate the lymph node's borders to determine if they feel regular or irregular.

o Consistency: decide if the lymph node feels soft, hard, or rubbery.

o Tenderness: take note of if the lymph node is tender on palpation.

o Mobility: evaluate if the lymph node feels mobile or is tethered to other local
structures.

o Overlying skin changes: notice any overlying skin changes such as erythema.

Examination procedure
• Do the preliminary observations of whether the child appears well or unwell?
• Check the growth parameters of head circumference, weight, and height.
Unwell children may have infective or infiltrative conditions. For example, children with
Kawasaki disease are remarkably irritable. Underweight children may have immune deficiencies,
chronic diseases, or malignancy. Overweight children may have hidradenitis suppurativa (axillary
adenopathy in the obese).
• Check the vital signs: fever and tachycardia may accompany infective or infiltrative diagnoses;
BP may be elevated with certain tumors and connective tissue disorders with renal involvement,
or decreased with sepsis or Addison disease; pulse pressure may be widened in
hyperthyroidism; respiratory rate may be elevated with infective or infiltrative conditions.
• Note any pallor (e.g. ALL), ecchymoses, purpura or petechiae (e.g. ALL, AML).
• Scan the skin; children with atopic dermatitis often have lymphadenopathy.
• Stand back and look for any asymmetry in the head and neck, and quickly scan for goiter.
Start examination

• Examine all the lymph node groups.

• Check for head and neck
o Submental
o Submandibular
o Tonsillar
o Parotid
o Pre-auricular
o Post-auricular
o Superficial cervical
o Deep cervical
o Posterior cervical
o Occipital
o Supraclavicular
1. Begin beneath the chin (submental lymph nodes), then move posteriorly beneath the jaw
(submandibular lymph nodes), move upwards at the angle of the mandible (tonsillar and parotid
lymph nodes), and examine anterior (preauricular lymph nodes) and behind the ears (posterior
auricular lymph nodes).
2. Palpate the posterior border of the sternocleidomastoid (posterior cervical chain) to the
mastoid process, then down the anterior border of the sternocleidomastoid (anterior cervical
chain) to the clavicle.
3. Perform palpation over the occipital protuberance (occipital lymph nodes).
4. Instruct the patient to tilt their head (bring their ear towards their shoulder) on either side and
palpate at the back of the posterior border of the clavicle inside the supraclavicular fossa
(supraclavicular and infraclavicular lymph nodes).
• After checking the neck, check for epitrochlear nodes. To assess for epitrochlear
lymphadenopathy:
1. Using your corresponding hand, grasp the wrist of the side to be examined (i.e., right to
right).
2. Grasp behind the olecranon process with your opposite hand's fingers. Palpate the
inside aspect of the arm immediately above the medial epicondyle of the humerus with
your thumb over the crease of the elbow.
3. Look for lymphadenopathy, which can be caused by metastatic melanoma in the arm, or
diseases that cause generalized lymphadenopathy.

• If the finding is cervical nodes only, the head and neck need to be examined thoroughly.

o The ears, nose, and throat must be examined with the auroscope, including carefully
inspecting the teeth and gums.

o If any teeth appear carious, then wear gloves to palpate them for tenderness.

o Look at the external aspects of the eyes, for conjunctivitis (which can occur with
Kawasaki disease, Parinaud's oculo-glandular syndrome [with preauricular
 lymphadenopathy] or leptospirosis), and for Horner's syndrome, which can occur
with neuroblastoma.

o Inspect and palpate the scalp for infected areas (hiding under the hair, such as tinea
capitis or a kerion).

• and then axillary nodes,

o When inspecting the right axilla, take the patient's right forearm in your right
hand and advise them to relax it completely, letting you support their weight.
This relaxes the axillary muscles.
o The left hand should then be used for palpation. When examining the left axilla,
the procedure is reversed.
o The axilla should be examined for lymph nodes in the pectoral (anterior), central
(medial), subscapular (posterior), humoral (lateral), and apical groups.

Here is an example of a systematic approach you may use:

o Palpate at the back of the lateral edge of the pectoralis major

(pectoral/anterior) with your palm facing towards you.
o Turn your hand medially, and using the pulps of your fingers, palpate against the
wall of the thorax (central/medial) with your fingertips near the apex of the
axilla.
o Now, with your palm facing away from you, feel inside the lateral edge of the
latissimus dorsi (subscapular/posterior).
o Palpate the axilla (humoral/lateral) on the inside of the arm.
o Using your fingertips, reach up into the axilla's peak (warn the patient this may
be uncomfortable).
o Repeat the assessment on the contralateral axilla.
• Inguinal and subinguinal lymph nodes, and finally popliteal lymph nodes. To assess for inguinal
lymphadenopathy:
o Request the patient to remove their pants and underwear to reveal the inguinal
region.
o Tell the patient to lie flat on the bed.
o Examine the area for any noticeable swellings or abnormalities.
o Assess the horizontal group of superficial inguinal lymph nodes by immediately
palpating inferior to the inguinal ligament (anterior superior iliac spine and
pubic tubercle).
o Place your fingers 3cm lateral to the pubic tubercle and palpate vertically
downwards over the saphenous aperture and the proximal portion of the great
saphenous vein to examine the vertical group of superficial inguinal lymph
nodes. If there are two groups of nodes enlarged, then it is considered
generalized.
• Examine the skin for any local lesions (such as herpetic infections [HSV I or II, HVZ], cat-scratch
disease's papular lesions on hands/ fingers [Bartonella henselae], any inflamed areas, reddened,
cellulitic, or purulent from staphylococcal or streptococcal infection; any generalized rash
 [rubella classically causing suboccipital lymphadenopathy; Kawasaki disease can have many
types of rash; SLE causes a malar rash]) or discoloration over the nodes themselves (purplish
discoloration classic for MAIS).
• Examine the chest for any evidence of asthma (for underlying Churg–Strauss syndrome, or
diffuse pulmonary Langerhans cell histiocytosis) or histoplasmosis (from inhaling fungal spores,
Histoplasma capsulatum).
• Examine the abdomen for hepatosplenomegaly (Malignancy [neuroblastoma, lymphoma],
ALL/AML, Toxoplasmosis, CMV, Connective tissue disorders, HIV, EBV, Syphilis).
• Examine the musculoskeletal system looking for: skeletal tenderness at the sternum, clavicles,
ribs, pelvis, tibiae (tibial infiltrates); joint tenderness; swelling; or decreased range of movement
(ALL, AML, JIA).

A brief list of typical causes for typical locations of nodes

• Cervical:
1. oropharyngeal/scalp infection (viral [usual URTI pathogens, EBV, CMV, HSV, HHV-6],
streptococcus, staphylococcus, mycobacteria [TB, MAIS]).
2. cat-derived: cat-scratch disease; toxoplasmosis.
3. Kawasaki disease.
4. Dental caries (an infectious dental hard tissues, decalcification of inorganic parts of the tooth,
then a breakdown of the organic matrix, dietary carbohydrate-modified, saliva-regulated).
• Supraclavicular:
1. (a) left side: intraabdominal malignancy; (b) right side: intra-mediastinal malignancy or infection.
2. Lymphoma.
3. TB.
• Epitrochlear:
1. hand or arm infection.
2. Cat-scratch disease.
3. Lymphoma.
• Axillary:
1. arm or chest wall infection or malignancy.
2. Animal-related: cat-scratch disease; brucellosis.
3. Lymphoma/leukemia.
• Abdominal:
1. malignancy.
2. TB.
3. Mesenteric adenitis from Yersinia enterocolitica, group A streptococcus or measles.
• Inguinal:
1. lower limb suppurative infection.
2. Perineal/Genito-urinary/venereal infection.
3. Malignancies (rhabdomyo- and non-rhabdomyosarcoma; Hodgkin's and non-Hodgkin's
lymphoma, neuroblastoma).
• Popliteal: foot or leg infection.

Causes of cervical lymphadenopathy

• MAIS complex (Mycobacterium Avium-Intracellulare-Scrofulaceum)/Malignancy (lymphoma

 [non-Hodgkin], rhabdomyosarcoma)/Mucocutaneous lymph node syndrome (Kawasaki
syndrome)

• Atopic dermatitis
• Tonsils: hypertrophy with upper respiratory tract infection (URTI)/Teeth: caries

• Cat-scratch disease (Bartonella henselae)/Chlamydia trachomatis

• HSV (gingivostomatitis)/Hodgkin disease

• EBV (Epstein-Barr virus)

• Streptococcus A

Causes of generalized lymphadenopathy

• Malignancy (neuroblastoma, leukaemia, lymphoma [non-Hodgkin])/Measles /Medications
(e.g. phenytoin, isoniazid, allopurinol) ALL/AML/Adenovirus/Autoimmune (JIA, SLE)

• TB/Toxoplasma gondii/Typhoid (salmonella typhi)

• CMV (cytomegalovirus)/Coxsackie virus/Coccidioidomycosis

• HIV/Herpes viruses: HHV-6 (roseola infantum); HVZ/Hepatitis A, B, C/Hodgkin

disease/Histiocytosis X
• EBV (Epstein-Barr virus)/Exanthemata (rubella, roseola, measles)/Enteroviruses/
Endocrinopathies (Graves, Addison)/Endocarditis

• Staphylococcus/Systemic viral infections (most common)/Sarcoidosis/Storage diseases

(Gaucher, Niemann-Pick)/Serum sickness/Septicaemia/Syphilis
Causes of lymphadenopathy (cervical [Cx] or generalized *)

• MAIS complex [Cx] (mycobacterium avium-intracellulare-scrofulaceum)/Malignancy*

(neuroblastoma, leukaemia, lymphoma [non-Hodgkin’s], rhabdomyosarcoma [Cx])/
Mucocutaneous lymph node syndrome (Kawasaki) [Cx]/Measles*/Medications* (e.g.
phenytoin, isoniazid, allopurinol)
• ALL*/AML*/Atopic dermatitis [Cx]/Adenovirus*/Autoimmune* (JIA, SLE)

• TB* (tuberculosis, tubercle bacillus, mycobacteria tuberculosis)/Toxoplasma gondii*/ Teeth:

caries [Cx]/Typhoid* (salmonella typhi)
• CMV* (cytomegalovirus)/Cat-scratch disease [Cx] (Bartonella henselae)/Chlamydia
trachomatis [Cx] Coxsackie virus*/Coccidioidomycosis*

• HIV*/Herpes viruses: HHV-6 (roseola infantum)*/HSV (gingivostomatitis) [Cx]/HVZ*/Hepatitis

A, B, C*/Hodgkin’s disease*/Histiocytosis*/Hidradenitis suppurativa (axillary adenopathy in
obese)
• EBV* (Epstein-Barr virus; infectious mononucleosis)/Exanthemata* (rubella, roseola,
 measles)/Enteroviruses*/Endocrinopathies* (Graves, Addison) Endocarditis*

• Streptococcus A [Cx]/Staphylococcus*/Systemic viral infections* (most

common)/Sarcoidosis*/Storage diseases* (Gaucher, Niemann-Pick)/Serum
sickness*/Septicaemia*/Syphilis*

Physical characteristics of pathological nodes

• Acute inflammation (acute lymphadenitis) causes a red, hot, tender, swollen lymph
node. In addition, there may be secondary torticollis (wry neck) due to reflex spasm of
adjacent muscles, especially the sternocleidomastoid muscle, such that any
movement of the neck is painful, whether active or passive.

• Acute lymph node abscess presents as a red, hot, tender swollen node that can
fluctuate has been enlarging over a few days, and may point, and then discharge pus.
These are often seen in children between 6 months and 3 years of age.
• Atypical MAIS (subacute) lymphadenitis causes swollen nodes with purple skin
discoloration overlying them, with low-grade inflammation. They tend to be soft, they
may be matted, and they are often not tender. In addition, there can be an underlying
collar-stud, 'cold' abscess (although cold means normal body temperature). These
typically present in a 1–2-year-old child for 1–2 months. If a lymph node drains
spontaneously or develops a fistulous tract, this infers a MAIS infection, particularly if
it takes a few weeks to form, whereas a fast-developing abscess that drains suggests
either staphylococcus aureus or streptococcus pyogenes.

• Reactive hyperplastic nodes present with swelling are non-tender and can be up to 3
cm in length, although if nodes of this size are noted, excisional biopsy is often the
management plan if these are present for 4–6 weeks. Reactive hyperplasia typically
occurs with common upper respiratory tract infections.
• Neoplastic (malignant) diseases typically cause rubbery, firm, or stony nodes, usually
neither tender nor discolored. Lymphoma and chronic leukemias tend to cause firmer
nodes than leukemia. However, hemorrhage within such a node can cause tenderness
and/or discoloration; immunologic stimulation and certain malignancies can also
cause tenderness, so the presence or absence of tenderness is not very
discriminatory.

• Malignant nodes can be shotty and discrete in early stages, becoming fixed to
underlying structures or matted together when the diagnosis is made.

• Primary lymph node tumors, often in cervical nodes, include Hodgkin's and non-
Hodgkin's lymphoma.

• Again, secondary lymph node tumors in cervical nodes include neuroblastoma,

 thyroid tumors, or nasopharyngeal tumors.

Differential diagnosis of cervical nodes

LATERAL NECK LUMPS OTHER THAN LYMPH NODES

1. Branchial cyst

This is derivative of 2nd and 3rd branchial clefts and is situated beneath the middle third of the
sternocleidomastoid muscle. It transilluminates, as it is full of milky cholesterol-containing fluid, and has
been described in the past as feeling like a half-empty hot water bottle. They can get infected, which is
why they are excised.

2. Cystic hygroma

These are macro-cystic lymphatic malformation, also termed 'cystic lymphangioma,' a hamartoma of the
jugular lymphatic sacs. There are two types: simple and complex.

• A simple cystic hygroma is on one side of the neck, usually situated over the anterior
triangle, brilliantly trans-illuminable, fluctuant (full of lymph), and of variable size; these
lesions can increase in size rapidly if there is internal hemorrhage, or they become
infected, and compress vital structures such as the trachea.

• Complex cystic hygromas are less common but can infiltrate neighboring structures
(including oropharynx, larynx, mediastinum, and pleura), causing upper airway
obstruction, necessitating emergent treatment such as intubation and tracheostomy
placement.

3. Vascular tumors

If these are deep enough, they do not seem vascular at first glance, as they do not appear red when as
superficial as 'strawberry' birthmarks.

There are two types worth mentioning.

• Infantile hemangioma (IH) would only be a relevant differential in an infant, as these

lesions grow rapidly until 80% of their full growth by 12 weeks of age under a few
months, if it was a deep lesion, so not readily identifiable by the 'strawberry' coloring.
Several characteristics should make it straightforward to differentiate this from a lymph
node: palpation for the thrill (as it is a vascular lesion), transient emptying/filling, and
auscultation as any hemangioma can have a bruit.

• Kaposiform hemangioendothelioma (KHE) can look like an IH, but more rapidly growing,
with the ability to cause Kasabach Merritt syndrome (KMS, which comprises a vascular
 tumor, consumptive coagulopathy, microangiopathic hemolytic anemia, and
thrombocytopenia; can lead to cardiac failure, so look for tachypnoea and
hepatomegaly, if KMS suspected).

4. Sternomastoid tumor

This can be a relevant differential only in a neonate, particularly aged 2–3 weeks old, who presents with
a lump in the vicinity of, and in line with, the sternocleidomastoid muscle. However, on closer
examination, it can be found to be within the sternocleidomastoid muscle itself. It is typically 2–3 cm
long, non-tender, and very firm, and it may be associated with a degree of angulation of the head
and/or with plagiocephaly, so the baby's head should be examined for this.

5. Recurrent parotitis with sialectasis

These can occur in a child aged 2–4 years old, can impersonate mumps or pre-auricular lymphadenitis,
and is associated with episodes of unilateral parotid swelling, which is tender, and produces purulent
fluid from the parotid duct when pressure is applied over it; these episodes last 2–4 days, but can be
quite recurrent occurring on and off for years, but generally has resolved by 10 years.

MIDLINE NECK LUMPS OTHER THAN LYMPH NODES

1. Thyroglossal cyst

its final position is in front of the trachea, which is in the midline of the neck. There can be an associated
fistula from which saliva, mucus, or pus can appear. The classic diagnostic finding is the cyst moving up
when the tongue is protruded; get the child to open the mouth, then lightly hold the cyst between
thumb and index finger, and then get the child to poke out their tongue.

These cysts are translucent when transilluminated. When infected, they tend to develop cellulitis that
spreads horizontally more than vertically. Treatment is excision of the cyst and the duct remnants,
including removing the middle third of the hyoid.

2. Ectopic thyroid

this can be found anywhere along the migratory path of descent of the thyroid gland from the foramen
caecum to the front of the trachea. The ectopic thyroid feels softer than a thyroglossal cyst. The back of
the tongue should be inspected to detect a lingual thyroid.

3. Dermoid cyst

These derive from embryonic remnants, ectodermal cells, which detach along the lines of fusion or in
the midline to be in a similar position to a thyroglossal cyst. Unlike many cysts, these do not
transilluminate because they are filled with thick, cheesy, opaque, sebaceous fluid. Dermoid cysts do not
move with swallowing or tongue protrusion, as they are not attached to the hyoid. They generally grow
slowly, are often spherical, and are not tender.

Investigations
Prompt node biopsy if:

A mnemonic for this is EXCISE:

 • Enlarged beyond 1 cm neonatal, 2 cm (and growing), in older; enlarged in many sites

• X-ray (CXR) abnormal: mediastinal mass, hilar nodes

• Concerning (Cancer, Chronic inflammatory, Connective tissue) symptoms: night sweats, loss of
weight/Cervical (deep, lower) node/CRP persistently up despite treatment (like ESR)

• Immobile (fixed)

• Supraclavicular nodes

• ENT symptoms and signs absent/ESR persistently up despite treatment (like CRP)

Investigating lymphadenopathy

In the same order as the MATCHES acronym, investigations can be remembered as:

• Malignancy; useful investigations: FBC, film, ESR, CRP, CXR (mediastinal masses: anterior or
middle: lymphoma [Hodgkin's or non-Hodgkin's]; posterior: neuroblastoma); excisional biopsy,
bone marrow biopsy (ALL, AML); MAIS: excisional biopsy

• ALL, AML: FBC and film, bone marrow biopsy

• Toxoplasmosis: serology

• Cat-scratch disease (Bartonella henselae): serology/Chlamydia trachomatis: serology, culture,

nucleic acid probe after amplification

• HSV (gingivostomatitis): HSV cell culture and PCR for HSV DNA/Hodgkin’s disease: FBC, film, CXR,
excisional biopsy

• EBV (Epstein-Barr virus): serology: EBV viral capsid antigen (VCA) IgM, EBV VCA IgG, EBV nuclear
antigens (EBNA): EBV EBNA-1 IgG; EBV EBNA IgM;

• Streptococcus A: culture, serology