Diagnostic approach to lymphadenopathy

◼ Anatomy
◼ Collection of lymphoid cells attached to both vascular and lymphatic systems
◼ Over 600 lymph nodes in the body
◼ Function
◼ To provide optimal sites for the concentration of free or cell-associated antigens
and recirculating lymphocytes – “sensitization of the immune response”
◼ To allow contact between B-cells, T-cells and macrophages

Why do lymph nodes enlarge?

◼ Definition : Lymphadenopathy - node greater than 1cm in size
◼ Increase in the number of benign lymphocytes and macrophages in response to antigens
◼ Infiltration of inflammatory cells in infection (lymphadenitis)
◼ In situ proliferation of malignant lymphocytes or macrophages
◼ Infiltration by metastatic malignant cells
◼ Infiltration of lymph nodes by metabolite laden macrophages (lipid storage diseases)

When to worry?
◼ Age
◼ Children/young adults – more likely to respond to minor stimuli with lymphoid
hyperplasia
◼ Lymph nodes in patients less than the age of 30 are clinically benign in 80% of
cases whereas in patients over the age of 50 only 40% are benign
◼ Biopsies done in patients less than 25 yrs have a incidence of malignancy of
<20% vs the over-50 age group has an incidence of malignancy of 55-80%
◼ Characteristics of the node
◼ Nodes lasting less than 2 weeks or greater than one year with no progression of
size have a low likelihood of being neoplastic – excludes low grade lymphoma
◼ Cervical nodes – up to 56% of young adults have adenopathy on clinical exam
◼ Inguinal adenopathy is common – up to 1-2 cm in size and often benign reactive
nodes
◼ Consistency – Hard/Firm vs Soft/Shotty; Fluctuant
◼ Mobile vs Fixed/Matted
◼ Tender vs Painless
 ◼ Clearly demarcated
◼ Size
◼ When to worry – 1.5-2cm in size
◼ Epitroclear nodes over 0.5cm; Inguinal over 1.5cm
◼ Duration and Rate of Growth

◼ Location of the node

◼ Cervical
◼ The anterior cervical lymph nodes are often enlarged because of one of
a variety of infections of the head and neck or to some systemic
infections such as infectious mononucleosis caused by Epstein-Barr
virus (EBV), cytomegalovirus infection, or toxoplasmosis. Posterior
cervical lymphadenopathy may occur with EBV infection, tuberculosis,
lymphoma, Kikuchi disease (see below), or head and neck malignancy
(either lymphomas or metastatic squamous cell carcinoma)
◼ Inflamed cervical nodes that develop over a few days and progress to
fluctuation, especially in children, are typically caused by
staphylococcal and streptococcal infections
◼ Multiple enlarged cervical nodes that develop over weeks to months and
become fluctuant or matted without significant inflammation or
tenderness, and uncommonly with fever, suggest infection with
Mycobacterium tuberculosis or atypical mycobacteria.
◼ Hard cervical nodes, particularly in older patients and in smokers,
suggest head and neck metastatic cancer (eg, oropharynx, nasopharynx,
larynx, thyroid, esophagus)
◼ Supraclavicular lymphadenopathy
◼ Highest risk of malignancy – estimated as 90% in patients older than 40
years vs 25% in those younger than 40 yrs
◼ Right sided node – cancer in mediastinum, lungs, esophagus
◼ Left sided node (Virchow’s) – testes, ovaries, kidneys, pancreas,
stomach, gallbladder or prostate
◼ Paraumbilical node (Sister Joseph’s)
◼ Abdominal or pelvic neoplasm
◼ Epitroclear nodes
 ◼ The epitrochlear nodes are not normally palpable. Palpable epitrochlear
nodes are always pathologic. The differential diagnosis includes
infections of the forearm or hand, lymphoma, sarcoidosis, tularemia, and
secondary syphilis
◼ Isolated inguinal adenopathy
◼ Inguinal lymphadenopathy is usually caused by lower extremity
infection, sexually transmitted diseases, or cancer
◼ Less likely to be associated with malignancy

◼ Clinical setting associated with lymphadenopathy

◼ B symptoms – fever, night sweats, weight loss
◼ Fatigue
◼ Pruritis
◼ Evidence of other medical conditions – connective tissue disease
◼ Young patient – mononucleosis type of syndrome

APPROACH TO DIAGNOSTIC
The cause of lymphadenopathy is often obvious after a complete history and physical
examination. In more difficult cases, laboratory tests and lymph node biopsy may be necessary.
History
◼ Identifiable cause for the lymphadenopathy?
◼ Localizing symptoms or signs to suggest infection/neoplasm/trauma at a
particular site
◼ URTI, pharyngitis, periodontal disease, conjunctivitis, insect bites,
recent immunization etc
◼ Constitutional symptoms such as fever, night sweats, or weight loss suggesting
tuberculosis, lymphoma, or other malignancy; fever typically accompanies
lymphadenopathy for the majority of the infectious etiologies.
◼ Exposures likely to be associated with infection (eg, cat scratches [cat scratch disease],
undercooked meat [toxoplasmosis], tick bite [Lyme disease]), travel to areas with high
rates of endemic infection, high risk behavior (eg, sexual behavior, injection drug use)
◼ Epidemiological clues
 ◼ Occupational exposures, recent travel, high-risk behaviour
◼ Medications : A number of medications can cause serum sickness that is characterized
by fever, arthralgias, rash, and generalized lymphadenopathy
Physical Exam
◼ Full nodal examination – nodal characteristics
◼ Location — Localized lymphadenopathy suggests local causes and should
prompt a search for pathology in the area of node drainage, although some
systemic diseases such as plague, tularemia, and aggressive lymphomas can
present with local adenopathy. Generalized adenopathy is usually a
manifestation of systemic disease.
◼ Size — Abnormal nodes are generally greater than 1 cm in diameter. In one
series, no patient with a lymph node smaller than 1 cm2 had cancer, compared
with 8 and 38 percent of those with nodes 1 to 2.25 and greater than 2.25 cm2,
respectively. The term "shotty" is sometimes used to describe multiple, small
nodes, but has no particular diagnostic significance.
◼ Consistency — Hard nodes are found in cancers that induce fibrosis (scirrhous
changes) and when previous inflammation has left fibrosis. Firm, rubbery
nodes are found in lymphomas and chronic leukemia; nodes in acute leukemia
tend to be softer.
◼ Fixation — Normal lymph nodes are freely movable in the subcutaneous
space. Abnormal nodes can become fixed to adjacent tissues (eg, deep fascia)
by invading cancers or inflammation in tissue surrounding the nodes. They can
also become fixed to each other ("matted") by the same processes.
◼ Tenderness — Tenderness suggests recent, rapid enlargement that has put pain
receptors in the capsule under tension. This typically occurs with
inflammatory processes, but can also result from hemorrhage into a node,
immunologic stimulation, and malignancy.
◼ Organomegaly
◼ Localized – examine area drained by the nodes for evidence of infection, skin lesions
or tumours

Approach to Lymphadenopathy
◼ Localized – one area involved
◼ Generalized – two or more non-contiguous areas
Generalized Lymphadenopathy
◼ Malignancy – lymphoma, leukemia, Kaposi’s sarcoma, metastases
◼ Autoimmune – SLE, RA, Sjogren’s syndrome, Still’s disease, Dermatomyositis
◼ Infectious – Brucellosis, Cat-scratch disease, CMV, HIV, EBV, Rubella, Tuberculosis,
Tularemia, Typhoid Fever, Syphilis, viral hepatitis, Pharyngitis
◼ Other – Kawasaki’s disease, sarcoidosis, amyloidosis, lipid storage diseases,
hyperthyroidism, necrotizing lymphadenitis, histiocytosis X, Castlemen’s disease
◼ Medication
Drugs that cause lymphadenopathy
◼ Allopurinol
◼ Atenolol
◼ Captopril
◼ Carbamazepine
◼ Gold
◼ Hydralazine
◼ Penicillins
◼ Phenytoin
◼ Primidone
◼ Pyrimethamine
◼ Quinidine
◼ Trimethoprim/Sulfamethozole
◼ Suldinac