Medicine Newbie: Lymph Nodes, Lymphadenitis and Lymphadenopathy

Thursday 24 March 2016

Lymph Nodes, Lymphadenitis and Lymphadenopathy

Do we all have lymph nodes?

Yes. # of lymph nodes in the body: ~ 600

What are lymph nodes? How big are our lymph nodes?
Structure and function of lymph nodes:

Lymph nodes are small, ovoid nodules normally ranging in size from a few millimeters to 2 cm.
They are distributed in clusters along the course of lymphatic vessels located throughout the body.
The primary function of lymph nodes is to filter out microorganisms and abnormal cells that have collected in lymph fluid.
Node dimensions: In general, lymph nodes greater than 1 cm in diameter are considered to be abnormal. eg 1.7 cm x 1.8 cm x 2.2 cm ... before commencing antiobiotics (Amoxycillin + clavulanate)

Definitions:

Lymphadenopathy refers to nodes that are abnormal in either size, consistency or number.
Lymphadenitis is the inflammation or enlargement of a lymph node.

Physical examination (PE):

Careful palpation of the submandibular (bawah dagu), anterior and posterior cervical (leher), supraclavicular (pangkal leher), axillary (ketiak) and inguinal (celah kangkang) nodes can be accomplished in a short time and will identify patients with generalized lymphadenopathy.

A localised cervical lymphadenopathy is either on the right side or left side of the neck. It can be solitary or aggregated (like a bunch of grapes).

Characteristics:

Location - Depends on underlying etiology
Number - Single, local groupings (regional), or generalized (ie, multiple regions)
Size/shape - Normal lymph nodes range in size from a few millimeters to 2 cm in diameter; enlarged nodes are greater than 2-3 cm with regular/irregular shapes
Consistency - Soft, firm, rubbery, hard, fluctuant, warm
Tenderness - Suggestive of an infectious process but does not rule out malignant causes

Classification by anatomical location (the region drained by the nodes) and incidence:

1. “Generalized lymphadenopathy” if lymph nodes are enlarged in two or more non contiguous areas (25%). eg Cytomegalovirus.

2. “Localized lymphadenopathy” if only one area is involved (75%):

Head and neck (55%)
Supraclavicular (1%)
Axillary (5%)
Inguinal (14%)

Further breakdown of location of lymph nodes:

(i) Head and neck (55%)
Submandibular

tongue
submaxillary gland - dental caries/abscess
lips and mouth
conjunctivae

Submental

lower lip
floor of mouth
tip of tongue
skin of cheek

Jugular

tongue
tonsil
pinna
parotid

Posterior cervical

scalp and neck
skin of arms and pectorals
thorax
cervical and axillary nodes

Anterior cervical, mediastinal - Epstein-Barr virus (EBV) (mononucleosis)

Suboccipital

scalp and head

Postauricular

external auditory meatus
pinna
scalp

Preauricular

eyelids and conjunctivae
temporal region
pinna

(ii) Supraclavicular (1%)

Right supraclavicular node

mediastinum; mediastinal - Epstein-Barr virus (EBV) (mononucleosis)
lungs
esophagus

Left supraclavicular node

thorax
abdomen
via thoracic duct

(iii) Axillary (5%)

Axillary

arm
thoracic wall
breast

Epithrochlear

ulnar aspect of forearm and hand

INVESTIGATIONS

Skin test/Mantoux test - walk-in test done at Medical clinic (KPP). Uses 1 ml of tuberculin or purified protein derivative (PPD). To confirm the diagnosis of tuberculous lymphadenopathy; alternative is interferon-gamma release assays (IGRA). TRO TB; check for recent/past exposure to TB organism. Results are read on the 4th day: eg a 15 mm induration is considered "positive" or evidence of having antibodies/immunity to the TB organism or previous exposure - could be a recent house renovations with a coughing worker; could be a coughing husband, etc.
Blood test: ESR, FBP. TRO bacterial/viral infection. Turnaround time (TAT) for blood results is 1 week from Hematology. CBC count - Elevated WBC count may indicate an infectious etiology. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) - Elevated ESR and CRP are nonspecific indicators of inflammation.
Serology. Monospot or Epstein-Barr Virus (EBV) serologies. To confirm the diagnosis of infectious mononucleosis.
CT Scan - location, size and # of abnormal lymph nodes involved; contents of lymph node - fluid/pus or cellular. Interpretations and Radiology reports are available by the 3rd day.
CXR (chest x-ray) - Chest radiography may be helpful in determining pulmonary involvement or spread of lymphadenopathy to the chest. TRO pulmonary TB (PTB). Films are available online the same day. Radiology report is made available online.
Ultrasound. Ultrasonography may be useful for verifying lymph node involvement and taking accurate measurements of enlarged nodes. Ultrasound is not able to differentiate between benign and malignant forms of lymphadenopathy.
Node biopsy: FNAC versus excisional biopsy ... performed under local anaesthesia ... procedure does not need fasting; performed after 1 week course of antibiotics (Amoxycillin + calvulanate). Drainage if filled with pus or fluid. Aspirates, if any.
Gram stain of aspirated tissue. To evaluate bacterial etiologies.
Culture and Sensitivity (C&S). Culture of aspirated tissue or biopsy specimen. To determine the causative organism and its sensitivity to antibiotics.
Liver function tests (LFT). May indicate hepatic or systemic involvement; elevated transaminase levels can be seen in infectious mononucleosis.

CAUSES

In most cases, a careful history and physical examination will identify a readily diagnosable cause of the lymphadenopathy. Refer to the algorithm for investigating lymphadenopathy. The causes are categorized into 3 types:

Diagnostic causes:

upper respiratory tract infection (URTI),
pharyngitis (sakit tekak),
periodontal disease (penyakit gigi dan gusi),
conjunctivitis (sakit mata),
lymphadenitis (radang noda limfa),
tinea (kulat),
insect bites (gigitan serangga),
recent immunization (imunisasi terhampir),
cat-scratch disease (cakar kucing)
dermatitis (radang kulit)

Suggestive causes:

mononucleosis
syphilis
lymphoma
HIV

Unexplained causes:

if generalised - review epidemiologic clues. Patients with generalized lymphadenopathy will need further diagnostic evaluation that often includes biopsy.
if localized - review history, regional examination and epidemiologic clues. Patients with localized lymphadenopathy + a worrisome clinical picture will need further diagnostic evaluation that often includes biopsy.

LYMPHADENITIS

Infectious agents/causes and lymphadenitis and characteristics:

Bartonella henselae (catscratch disease) – Single-node involvement determined by scratch site; discrete, mobile, nontender
Coccidioides immitis (coccidioidomycosis) – Mediastinal
Cytomegalovirus – Generalized
Epstein-Barr Virus (EBV) (mononucleosis) - Anterior cervical, mediastinal, bilateral; discrete, firm, nontender
Francisella tularensis (tularemia) - Cervical, mediastinal, or generalized; tender
Histoplasma capsulatum (histoplasmosis) – Mediastinal
Atypical Mycobacterium - Cervical, submandibular, submental (usually unilateral); most commonly in immunocompetent children aged 1-5 years
Mycobacterium tuberculosis - Mediastinal, mesenteric, anterior cervical, localized disease (discrete, firm, mobile, tender); generalized hematogenous spread (soft, fluctuant, matted, and adhere to overlying, erythematous skin)
Parvovirus - Posterior auricular, posterior cervical, occipital
Rubella - Posterior auricular, posterior cervical, occipital
Salmonella – Generalized
Seborrheic dermatitis, scalp infections - Occipital, postauricular
Staphylococcus aureus adenitis - Cervical, submandibular; unilateral, firm, tender
Group A streptococcal (GAS) pharyngitis - Submandibular and anterior cervical; unilateral, firm, tender
Toxoplasma gondii - Generalized, often nontender
Viral pharyngitis - Bilateral postcervical; firm, tender
Yersinia enterocolitica - Cervical or abdominal
Yersinia pestis (plague) - Axillary, inguinal, femoral, cervical; extremely tender with overlying erythema

Immunologic or connective tissue disorders causing lymphadenitis are as follows:

Juvenile rheumatoid arthritis
Graft versus host disease

Primary diseases of lymphoid or reticuloendothelial tissue causing lymphadenitis are as follows:

Acute lymphoblastic leukemia
Lymphosarcoma
Reticulum cell sarcoma
Non-Hodgkin lymphoma
Malignant histocytosis or histocytic lymphoma
Nonendemic Burkitt tumor
Nasopharyngeal rhabdomyosarcoma
Neuroblastoma
Thyroid carcinoma, chronic lymphocytic thyroiditis
Histiocytosis X
Kikuchi disease
Benign sinus histiocytosis
Angioimmunoblastic or immunoblastic lymphadenopathy
Chronic pseudolymphomatous lymphadenopathy (chronic benign lymphadenopathy)

Immunodeficiency syndromes and phagocytic dysfunction causing lymphadenitis are as follows:

Chronic granulomatous disease of childhood
Acquired immunodeficiency syndrome
Hyperimmunoglobulin E (Job) syndrome

Metabolic and storage diseases causing lymphadenitis are as follows:

Gaucher disease
Niemann-Pick disease
Cystinosis

Hematopoietic diseases causing lymphadenitis are as follows:

Sickle cell anemia
Thalassemia
Congenital hemolytic anemia
Autoimmune hemolytic anemia

Miscellaneous disorders causing lymphadenitis are as follows:

Kawasaki disease
PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) syndrome
Sarcoidosis
Castleman disease (also known as benign giant lymph node hyperplasia)

Medications causing lymphadenitis are as follows:

Mesantoin – most commonly causes cervical lymphadenitis
Hydantoin - Generalized lymphadenopathy

REGIONAL LYMPHADENITIS

In a patient with regional lymphadenitis, knowledge of lymphatic drainage patterns and pathologic processes most likely to affect these areas can facilitate diagnostic investigation.

Cervical lymph nodes

Cervical lymph nodes receive lymphatic drainage from the head, neck, and oropharyngeal cavities.

Infections associated with cervical lymph nodes are as follows:

Skin and soft tissue infections of the face
Dental abscesses
Otitis externa
Bacterial pharyngitis
Cytomegalovirus
Adenovirus infection
Rubella
Toxoplasmosis

Malignancies associated with cervical lymph nodes are as follows:

Hodgkin lymphoma
Non-Hodgkin lymphomas
Squamous cell carcinomas of nasopharyngeal or laryngeal structures

BIOPSY

Choice of biopsy: FNAC versus Excisional biopsy

Fine-needle aspiration and cytology (FNAC) is an alternative to excisional biopsy.

Advantages of excisional biopsy:

larger tissue mass to examine
can examine the entire abnormal lymph node

Disadvantages of FNAC:

FNAC often yields a high number of non diagnostic results,
because of the small amount of tissue obtained and
the inability to examine the architecture of the lymph node.
There may be some risk of sinus tract formation, depending on the underlying pathology.

Lymph node biopsy is performed by the Pathology MO under local anaesthesia. The specimen is sent to the Pathology laboratory for processing and examination.

Pathology reports should be available within a week of performing FNAC or excisional biopsy.

Incision and drainage is the treatment for lymphadenitis with abscess formation.

For atypical mycobacterial lymphadenitis, neither incision and drainage nor FNA should be performed as either of these may increase the risk of fistula formation and drainage.

CANCEROUS OR NOT?

Is it cancer or not? Is it benign or malignant?

Physical examination findings suggestive of malignancy are as follows: