YEDITEPE UNIVERSITYMEDICAL FACULTY

APPROACH TO THE PATIENT WITH LYMPHADENOPATHY

Assoc. Prof. Dr. Hülya AKAN

Objectives

Approach to Adenopathy Who to investigate When to investigate How to define risk for underlying

malignancy

DEFINITION

Lymph node size depends on the person's age, the location of the lymph node in the body, and antecedent immunological events.

In neonates, lymph nodes are barely perceptible, but a progressive increase in total lymph node mass is observed until later childhood.

Lymph node atrophy begins during adolescence and continues through later life.

Lymph Nodes 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

Lymphadenopathy - node greater than 1cm in size

Why do lymph nodes enlarge? 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)

Epidemiology

0.6% annual incidence of unexplained adenopathy in the general population

10% were referred to a subspecialist and 3.2 % required a biopsy and 1.1% had a malignancy

When to worry?

Age Characteristics of the node Location of the node Clinical setting associated with

lymphadenopathy

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

Characteristics of the node 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 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

Location of the node

Epitroclear nodes Unlikely to be reactive

Isolated inguinal adenopathy Less likely to be associated with

malignancy

Clinical Setting

B symptoms – fever, night sweats, weight loss

Fatigue Pruritis Evidence of other medical conditions

– connective tissue disease Young patient – mononucleosis type

of syndrome

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 Epidemiological clues

Occupational exposures, recent travel, high-risk behaviour

Medications – serum-sickness syndrome

Physical Exam

Full nodal examination – nodal characteristics

Organomegaly Localized – examine area drained

by the nodes for evidence of infection, skin lesions or tumours

Physical Examination

When lymphadenopathy is localized, the clinician should examine the region drained by the nodes for evidence of infection, skin lesions or tumors

Careful palpation of the submandibular, anterior and posterior cervical, supraclavicular, axillary and inguinal nodes can be accomplished in a short time and will identify patients with generalized lymphadenopathy.

Physical Examination If lymph nodes are detected, the following five

characteristics should be noted and described: 1-Size : Nodes are generally considered to be

normal if they are up to 1 cm in diameter however, some authors suggest that epitrochlear nodes larger than 0.5 cm or inguinal nodes larger than 1.5 cm should be considered abnormal

2-Pain/Tenderness: When a lymph node rapidly increases in size, its capsule stretches and causes pain. The presence or absence of tenderness does not reliably differentiate benign from malignant nodes.

Physical Examination3-Consistency : Stony-hard nodes are typically

a sign of cancer, usually metastatic. Very firm, rubbery nodes suggest lymphoma. Softer nodes are the result of infections or inflammatory conditions. Suppurant nodes may be fluctuant.

4- Matting : A group of nodes that feels connected and seems to move as a unit is said to be "matted." Nodes that are matted can be either benign (e.g., tuberculosis, sarcoidosis or lymphogranuloma venereum) or malignant (e.g., metastatic carcinoma or lymphomas).

Physical Examination

5- Location : The anatomic location of localized adenopathy will sometimes be helpful in narrowing the differential diagnosis. For example, cat-scratch disease typically causes occipital adenopathy, infectious mononucleosis causes cervical adenopathy and a number of sexually transmitted diseases are associated with inguinal adenopathy

Physical Examination In patients with generalized

lymphadenopathy, the physical examination should focus on searching for signs of systemic illness. The most helpful findings are rash, mucous membrane lesions, hepatomegaly, splenomegaly or arthritis

Splenomegaly and lymphadenopathy occur concurrently in many conditions, including mononucleosis-type syndromes, lymphocytic leukemia, lymphoma and sarcoidosis.

Approach to Lymphadenopathy In most cases, a careful history and

physical examination will identify a readily diagnosable cause of the lymphadenopathy, such as upper respiratory tract infection, pharyngitis, periodontal disease, conjunctivitis, lymphadenitis, tinea, insect bites, recent immunization, cat-scratch disease or dermatitis, and no further assessment is necessary

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

Drugs Allopurinol Atenolol Captopril Carbamazepine Gold Hydralazine Penicillins

Phenytoin Primidone Pyrimethamine Quinidine Trimethoprim/

Sulfamethozole Suldinac

Management

Identify underlying cause and treat as appropriate – confirmatory tests

Generalized adenopathy – usually has identifiable cause

Localized adenopathy 3-4 week observation period for

resolution if not high clinical suspicion for malignancy

Biopsy if risk for malignancy - excisional

Fine Needle Aspirate

Convenient, less invasive, quicker turn-around time

Most patients with a benign diagnosis on FNA biopsy do not undergo a surgical biopsy

Confirmatory tests 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

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

Titers for specific microorganisms may be indicated, particularly if generalized adenopathy is present. These may include Epstein-Barr virus, CMV, Toxoplasma species, and HIV.

Chest radiography is usually the primary screening imaging study

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.

Conclusions Lymphadenopathy – initial presenting

symptom Reactive vs Malignant

Probability History Physical Exam

Biopsy if not resolved in 3-4 weeks for low risk patients

Biopsy all high risk patients – excisional biopsy

Epidemiologic Clues to the Diagnosis of Lymphadenopathy General

Cat

Undercooked meat

Tick bite

Tuberculosis

Recent blood transfusion or transplant

High-risk sexual behavior

Intravenous drug use

Cat-scratch disease, toxoplasmosis

Toxoplasmosis

Lyme disease, tularemia

Tuberculous adenitis

Cytomegalovirus, HIV

HIV, syphilis, herpes simplex virus, cytomegalovirus, hepatitis B infection HIV, endocarditis, hepatitis B infection

Epidemiologic Clues to the Diagnosis of Lymphadenopathy

Occupational Hunters, trappers

Fishermen, fishmongers, slaughterhouse workers

Tularemia

Erysipeloid

Epidemiologic Clues to the Diagnosis of Lymphadenopathy Travel-related

Arizona, southern California, New Mexico, western Texas

Southwestern United States Southeastern or central United States

Southeast Asia, India, northern Australia

Central or west Africa

Central or South America

East Africa, Mediterranean, China, Latin America

Mexico, Peru, Chile, India, Pakistan, Egypt, Indonesia

Coccidioidomycosis

Bubonic plague

Histoplasmosis Scrub typhus African trypanosomiasis (sleeping

sickness)

American trypanosomiasis (Chagas' disease)

Kala-azar (leishmaniasis)

Typhoid fever