1. YEDITEPE UNIVERSITY MEDICAL FACULTY
APPROACH TO THE PATIENT WITH
LYMPHADENOPATHY
Assoc. Prof. Dr. Hülya AKAN

2. Objectives Approach to Adenopathy Who to investigate
When to investigate
How to define risk for underlying malignancy

3. 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.

5. 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

6. 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)

7. 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

8. When to worry? Age Characteristics of the node Location of the node
Clinical setting associated with lymphadenopathy

9. 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%

10. 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

11. 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

12. 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

13. Location of the node Epitroclear nodes Isolated inguinal adenopathy
Unlikely to be reactive
Isolated inguinal adenopathy
Less likely to be associated with malignancy

14. 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

15. 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

16. Physical Exam Full nodal examination – nodal characteristics
Organomegaly
Localized – examine area drained by the nodes for evidence of infection, skin lesions or tumours

17. 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.

18. 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.

19. Physical Examination
3-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).

20. 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

21. 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.

22. 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

23. Approach to Lymphadenopathy
Localized – one area involved
Generalized – two or more non-contiguous areas

28. 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

29. Drugs Allopurinol Atenolol Captopril Carbamazepine Gold Hydralazine
Penicillins
Phenytoin
Primidone
Pyrimethamine
Quinidine
Trimethoprim/Sulfamethozole
Suldinac

30. 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

31. 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

32. 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.

33. 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.

34. 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.

35. 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

36. 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

37. Epidemiologic Clues to the Diagnosis of Lymphadenopathy
Occupational Hunters, trappers
Fishermen, fishmongers, slaughterhouse workers
Tularemia
Erysipeloid

38. 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