1. Approach to lymphadenopathy
Dr. Mohamed Haseen Basha
Assistant professor ( Pediatrics)
Faculty of Medicine
Al Maarefa College of Science and Technology

2. Definition
Lymphadenopathy is enlargement of the lymph nodes beyond this normal state. Practically this is any node >1.0 cm in greatest diameter. Lymphadenopathy refers to nodes that are abnormal in either size, consistency or number.
Certain nodes should be considered enlarged at different sizes (i.e. Epitrochlear nodes > 0.5 cm, inguinal nodes > 1.5 cm, submandibular nodes > 1.5 cm)

3. Generalized - if lymph nodes are enlarged in two or more non-contiguous areas. It almost always indicates the presence of a significant systemic disease.
Localized - if only one area is involved.
Palpable lymph nodes are normal in anterior cervical, axillary and inguinal regions in healthy children.

5. Lymph Node
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

8. 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)

9. Localized lymphadenopathy
1. Local infection in draining area
2. Metastasis from cancers
3. Lymphoma—Hodgkin’s disease
4. Scrofuloderma

10. Generalised lymphadenopathy
Infections
Viral illnesses
Ebstein Barr virus infection
Cytomegalovirus infection
Infectious mononucleosis
HIV
Bacterial
Tuberculosis
Brucellosis
Chancroid (usually localized)
Parasitic
Toxoplasmosis
Leishmaniasis
Trypanosomiasis
Fungal
Histoplasmosis
Coccidioidomycosis
Chlamydia
Lymphogranuloma venereum (usually localised)

11. Generalised lymphadenopathy
Malignant
Hematological
Hodgkin’s disease
Non-Hodgkin’s lymphoma
Acute and chronic leukaemias
Metastatic
Connective
tissue disorder
Systemic lupus erythematosus
Rheumatoid arthritis
MCTD
Infiltrative
Sarcoidosis
Histiocytosis X
Others (rare)
Drugs, e.g. Phenytoin
Mucocutaneous LN disease (Kawasaki’s disease)

12. Drugs causing lymphadenopathy
Allopurinol
Atenolol
Captopril
Carbamazepine
Gold
Hydralazine
Phenytoin
Primidone
Pyrimethamine
Quinidine
Trimethoprim / Sulfamethozole
Penicillins

13. Approach to Lymphadenopathy
Normally, lymphoid tissue enlarges until puberty and then undergoes gradual atrophy throughout the rest of life. Normal lymph nodes are most prominent in children ages 4 to 8 years old.

14. History History of fever:
History of fever is dominant in infectious mononucleosis, tuberculosis, HIV, Leishmaniasis, Disseminated fungal & parasitic infections and lymphoreticular malignancies.
Ask about:
Type and pattern of fever
Duration of fever
History of constitutional symptoms:
Constitutional symptoms, i.e.anorexia, malaise, weight loss, night sweats. These symptoms are prominent in tuberculosis and also may be seen as “B-symptoms” in patients with lymphomas.

15. History of easy bruising, petechial hemorrhages, gum bleeds, epistaxis, suggesting thrombocytopenia—may be seen in acute leukaemias.
History of onset generalized weakness, paleness of skin, shortness of breath may suggest anemia, which is an important feature of acute leukaemias and other hematological malignancies.
History of any discharge from the nodes. Formation of a sinus and discharge from the nodes is very typical of tubercular lymphadenitis.
Sexual behaviour—ask for a history of high risk behaviour.
History of joint pains, swelling, myalgias, skin rash may suggest rheumatological or connective tissue disease.
Past history—Ask for a past history of Tuberculosis or Receiving anti-tuberculosis drugs, Phenytoin intake

16. General Physical Examination
Vital signs
Fever—always measure body temperature to assess for fever. Record the temperature pattern.
Pallor—pallor of mucous membranes, lower palpebral conjunctiva, and of the skin is seen in anemia. Severe anemia may suggest a hematological malignancy such as acute leukemia or other disorders such as kala-azar
Petechiae
Ecchymosis
Gum bleeds
Epistaxis

17. Examination of Lymph Nodes
Head and Neck
Preauricular
Post auricular
Occipital
Tonsillar
Submandibular
Submental
Superficial anterior cervical
Deep cervical
Posterior cervical
Supra clavicular
Infra clavicular
The Arms
Axillary
Anterior axillary (pectoral)
Lateral (brachial)
Mid axillary (central)
Posterior (subscapular)
Epitrochlear
The Legs
Superficial superior inguinal
Superficial inferior inguinal
Popliteal (occasionally)
It is also important to examine the oropharynx for the Waldeyer’s ring of lymph nodes and the abdomen for any abdominal lymph nodes that may be enlarged and palpable.

22. 1. Site of Lymph Nodes Whether Generalised or localised
Which group(s) of lymph nodes
Generalised lymphadenopathy is most commonly due to tuberculosis, lymphoma, HIV infection.
Certain diseases may produce enlargement of specific lymph node groups. Ex:
left supraclavicular lymph node— called “Virchow‘s node”—is suggestive of metastasis from a gastrointestinal tract primary malignancy.
Waldeyer’s ring—enlargement of nodes in the posterior oropharynx and nasopharynx is seen especially in non-Hodgkin’s lymphoma.
Cervical adenopathy—commonly seen in upper respiratory infections, infectious mononucleosis, tuberculosis.

23. Occipital lymphadenopathy —usually due to scalp infection
Cervical lymphadenopathy —diseases of oral cavity, metastases from head and neck, breast, thyroid and lung malignancies.
Axillary adenopathy is mainly due to an infection of the upper limb. It may also be seen in metastasis from carcinoma of the breast and hence, examination of breasts is very important in any patient with isolated axillary node enlargement.
Inguinal lymphadenopathy is quite common especially in those walking barefoot. However, sexually transmitted diseases must always be ruled out.

24. 2. Size of Lymph Node
Measure the size of the enlarged lymph nodes, in all enlarged groups and comment on them individually.
If multiple nodes are enlarged always give the range from the size of the smallest node to the largest palpable node.
Size is important as:
Small nodes < 1 cm size are usually benign or due to reactive causes. Hence, isolated, small nodes, need not be aggressively subjected to a FNAC and/or biopsy and can be closely followed up.
Nodes > 2 cm in size are unlikely to be ‘reactive’ and should be investigated.

25. 3. Consistency and Texture
Describe the consistency of the lymph nodes as soft, firm, hard, rubbery. In many instances the consistency provides important clues to the etiology.
Soft nodes - usually benign
Hard nodes - infiltration by cancers.
Rubbery nodes - lymphomas.
4. Tethering to Each Other
Comment whether the lymph nodes are individually palpable or are all tethered to each other as a mass.
Matted, conglomerate lymph nodes are seen in tuberculosis.
Lymph nodes, though multiple in number, all still individually palpable in lymphomas.

26. 6. Sinus Formation/Discharge
5. Fixity
Assess whether the lymph nodes are fixed to the Overlying skin or Underlying structures
Fixed, immobile lymph nodes - Malignant infiltration
Lymph nodes in lymphoma - Freely mobile, unattached to overlying skin or underlying structures
Tubercular lymph nodes may be tethered to overlying skin.
6. Sinus Formation/Discharge
The presence of a draining or discharging sinus over a lymph node suggests
Tuberculosis
Actinomycosis

27. In addition to the general physical examination, perform a detailed systemic examination and examination of all suspected drainage areas.
Respiratory Examination: Evaluate for evidence of:
Tuberculosis
Pleural effusion
Mass lesion
Abdomen: palpate for
Hepatomegaly
Splenomegaly
Intra-abdominal lymph nodes
Ascites
Evaluate genitalia for possible primary tumours.
Head and neck examination, especially in patients with cervical
adenopathy.

28. Generalised lymphadenopathy with hepatosplenomegaly, the differential diagnosis would include:
a. Disseminated tuberculosis
b. Lymphoma
c. Disseminated histoplasmosis
d. Kala-azar
Enlarged nodes are matted and conglomerate - Disseminated tuberculosis
Firm, rubbery, not matted/ fixed lymph nodes - Lymphoma

29. If splenomegaly is prominent and massive, with a history o prolonged fever and travel to an endemic area- kala-azar
In a patient with severe anaemia, gum bleeds, ecchymosis, hepatosplenomegaly and lymphadenopathy - Acute leukaemia
In a patient with hard, cervical lymphadenopathy with evidence of Horner’s syndrome and/or superior vena cava obstruction- Carcinoma Bronchus

30. Differentiation between benign and malignant lymphadenopathy
Feature
Malignant
Benign
Size
> 2 cm
< 2 cm (< 1 cm )
Consistency
Hard, firm or rubbery
Soft
Duration
> 2 weeks
< 2 weeks
Mobility
Fixed
Mobile
Surroundings
Attached(Invasion)
Not attached
Location
Supraclavicular, Epitrochlear or Generalized
Inguinal, Submandibular
Tenderness
Usually non-tender
Usually tender

31. Mimicking Lymphadenopathy
Branchial cleft cyst
Cystic hygroma
Thyroglossal duct cyst
Epidermoid cyst
Sternocleidomastoid tumor

32. Management
Identify underlying cause and treat as appropriate – confirmatory tests
Bacterial infection results in large nodes that are warm, erythematous, and tender. Start on antibiotics that cover the bacterial pathogens frequently implicated in lymphadenitis, including staphylococcus aureus and streptococcus pyogenes. Reevaluate in 2-4 weeks. Biopsy if unchanged or larger.
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

33. When to Investigate ?
Patients generally should be considered for investigation and/or referral if:
Unexplained generalized lymphadenopathy
Any palpable supraclavicular or popliteal node
Significant constitutional symptoms
Hepatic or splenic enlargement
Anemia or bleeding
Unresponsiveness to antibiotic treatment
Not decreasing in size after appropriate period of observation

34. Investigations:
Complete hemogram with peripheral blood smear examination
ESR or C-reactive protein
Lactate dehydrogenase
Uric acid
Liver function tests
Purified Protein Derivative skin test (PPD)
Viral titers
Other titers - Toxoplasmosis, Bartonella henselae
Chest X-ray (PA) view will help define
- Pretracheal, mediastinal lymph node enlargement
- Lung parenchymal lesion, e.g. tuberculosis
- Lung malignancy—primary and metastasis

35. Ultrasonography and contrast enhanced CT of the abdomen to delineate
- Hepatomegaly
- Splenomegaly
- Any hepatic/splenic deposits
- Intra-abdominal lymph nodes—identification of any specific character, e.g. central hypodensity/necrosis
Patients with cervical adenopathy - to rule out head and neck cancers- CECT (head and neck)
Bone marrow aspiration and/or biopsy - Haematological malignancy
ELISA for HIV

36. Fine needle aspiration cytology (FNAC) and/or lymph node biopsy
Fine needle aspiration cytology (FNAC) and/or lymph node biopsy. This is the most important diagnostic tool in patients with lymphadenopathy. In most patients with lymphadenopathy, an initial FNAC will provide the diagnosis, e.g.
Demonstration of caseous necrosis and granulomas in TB lymphadenitis. Ziehl Neelsen staining may reveal acid-fast bacilli.
Metastatic cancers
However, a lymph node biopsy should also be performed in all patients with suspected lymphomas.

37. Indication for biopsy Increase in size over baseline in 2 weeks.
No decease in size in 4-6 weeks.
No regression to normal in 8-12 weeks.
Development of new signs and symptoms.
Persistent unexplained fever, weight loss, night sweats.
Hard nodes / fixation of nodes to surrounding tissues.

38. Lymph node biopsy
Once biopsy has been chosen , ideally the largest, most suspicious, and most accessible node is selected, taking in to account differing diagnostic yields by site.
Inguinal nodes offer the lowest yield and supraclavicular nodes have the highest.
Excisional biopsy remains the diagnostic procedure of choice.

39. Role of surgery Acute Suppurative lymphadenitis
Conservative, IV Antibiotics
Incision / drainage of Abscess
BCG Adenitis.
Anti tubercular drugs
Fistulated / adherent LN need surgical excision while non adherent lesions heal spontaneously without treatment.
Non tuberculous Mycobacterial lymphadenitis
Surgical excision is the mainstay of treatment.

40. Approach to Lymphadenopathy
Reassure Family
Lymphadenopathy
Yes
Significant Physical Signs or Symptoms?
e.g. Weight loss, Hepatosplenomegaly …
Yes No
Node(s) :
Increase in size
Not Resolving
Observe :
2-3 Weeks
Node(s) Resolving
Investigate :
(CBC, ESR …)
Observe
& Follow