Lymphadenopathy can be caused by malignancies, infections, autoimmune disorders, or other miscellaneous conditions. Evaluation involves considering the patient's age, duration of lymphadenopathy, exposures, associated symptoms, and physical examination findings regarding nodal character and size. For unexplained lymphadenopathy lasting over a month, specific investigation such as biopsy may be needed. Biopsy of the largest, most suspicious node can help arrive at a diagnosis and guide further management. Persistent generalized lymphadenopathy also requires consideration of underlying causes such as HIV.

1. Lymphadenopathy and
Malignancy

2. Outline
 Introducing
 Historical Clues
 Physical Examination
 Nodal Character and Size
 Diagnosis and Management
 Lymph Node Biopsy

3. Introducing
 Lymphadenopathy :
an abnormality in the size or
character of lymph nodes
 Categories of Lymphadenopathy : MIAMI
Malignancies, Infections, Autoimmune disorders,
Miscellaneous and unusual conditions, and
Iatrogenic causes
 The most concerning to the patient and physician :
the possibility of underlying malignancy
 Low Rate of Malignancy in Primary Care :
1.1 % of pt’s presenting to the office with
unexplained lymphadenopathy

4. Historical Clues
1. Age and Duration
2. Exposures & History
3. Associated Symptoms

5. Historical Clues : Age and Duration
 Malignant rate increases with age.
 A majority of healthy children have
palpable cervical, inguinal and axillary
adenopathy. Most of them is infectious or
benign in etiology.
 Lymphadenopathy that lasts less than 2
weeks or more than 1 year with no
progressive size increase has a very low
likelihood of being neoplastic.
 Rare Exception : low-grade Hodgkin’s/
non-Hodgkin’s lymphomas and,
occasionally, chronic lymphocytic
leukemia

6. Historical Clues : Exposures & History
 Animals, biting insects, infectious
contacts, recurrent infections, chronic use
of medications. Travel-related exposures
and immunization status.
 Tobacco, alcohol, ultraviolet radiation :
raise suspicion for metastatic carcinoma
 Occupational exposures to silicon or
beryllium
 Sexual history and orientation. AIDS pt’s
 Family history

7. Medications That Can Cause Lymphadenopathy
 Allopurinol (Zyloprim)
 Atenolol (Tenormin)
 Captopril (Capoten)
 Carbamazepine (Tegretol)
 Gold
 Hydralazine (Apresoline)
 Penicillins
 Phenytoin (Dilantin)
 Primidone (Mysoline)
 Pyrimethamine (Daraprim)
 Quinidine
 Trimethoprim/sulfamethoxazole (Bactrim)
 Sulindac (Clinoril)

8. Historical Clues : Associated Symptoms
 Constitutional symptoms : fever,
fatigue, malaise with atypical
lymphocytosis → mononucleosis
syndromes
 Significant fever, night sweats,
unexplained BW loss > 10% of normal BW
→ “B” symptoms of Hodgkin’s lymphoma
 Arthralgias, muscle weakness, unusual
rash → autoimmune diseases such as RA,
SLE, dermatomyositis

9. Physical Examination
 Head and Neck LN
 Axillary LN
 Inguinal LN

10. Lymph nodes of the head and neck,
and the regions that they drain

11. Head and Neck Lymphadenopathy
 In one outpatient primary care study :
cervical LNs are palpable in 51% of adult
physicals, with the incidence declined with
age.
 Infection is the most common cause
 Most cases resolve quickly; some entities
can create persistent lymphadenopathy
for months. (ex. Atypical mycobacteria, cat-scratch
disease, toxoplasmosis, kikuchi’s lymphadenitis,
sarcoidosis, Kawasaki’s syndrome.)
 Supraclavicular nodes are the most likely
to be malignant and should always be
investigated, even in children.

12. Axillary lymphatics and the structures
that they drain

13. Axillary Lymphadenopathy
 Most of cases are nonspecific or reactive
to local injury/infection in etiology.
 Persistent lymphadenopathy is less
commonly found in the axillary nodes
than in the inguinal chain.
 Breast adenocarcinoma often metastasis
initially to the anterior and central
axillary nodes, which may be palpable
before discovery of the primary tumor.
 Antecubital or epitrochlear
lymphadenopathy can suggest lymphoma
or melanoma of the extremity.

14. Inguinal lymphatics and the structures
that they drain

15. Inguinal Lymphadenopathy
 It is common, with nodes enlarged up to
1 to 2 cm in diameter in many healthy
adults, but it is of low suspicion of
malignancy.
 Benign reactive lymphadenopathy and
infection are the most common etiologies.
 Although some tumors, such as Hodgkin’s
lymphomas, penile/ vulvar SCC,
melanoma in this area, may present with
inguinal lymphadenopathy, it is typical
presenting finding in neither case.

16. Generalized Lymphadenopathy
 Generalized lymphadenopathy :
lymphadenopathy found in two or more
distinct anatomic regions
 More likely to result from serious
infections, autoimmune diseases, and
disseminated malignancies.
 Specific testing is usually required.
 Generalized adenopathy infrequently
occurs in pt’s with neoplasms, but it is
occasionally seen in patients with
leukemias and lymphomas, or advanced
disseminated metastatic solid tumors.

17. Nodal Character and Size
 Hard and painless nodes have higher
suspicion of malignancy or granulomatous
disease.
 Viral infection typically produces
hyperplastic nodes that are bilateral,
mobile, nontender, and clearly
demarcated.
 Palpable supraclavicular, iliac, or popliteal
nodes of any size and epitrochlear nodes
larger than 5mm are considered abnormal.
 Increasing size and persistence over time
are of greater concern for malignancy
than a specific level of nodal enlargement.

18. Algorithm for evaluation,
diagnosis, and management.

20. Diagnosis and Management
 The first step : reviewing pts’ medications,
considering unusual causes of
lymphadenopathy, and reconsidering the
risk factors for neoplasm. If a diagnosis is
not suggested, and the patient is deemed
low risk for neoplasm, the regional
lymphadenopathy can be safely observed.
 It is suggested that non-inguinal
lymphadenopathy lasting more than one
month merits specific investigation or
biopsy.

21. Lymph Node Biopsy
 Once biopsy has been chosen,
ideally the largest, most suspicious,
and most accessible node is
selected, taking into 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.

22. Persistent Generalized
Lymphadenopathy (PGL)
 Lymph nodes larger than 1.5
cm in diameter in 2 or more
extrainguinal sites of 3 or more
months duration
 Nodes are non-tender,
symmetrical, and often involve
the posterior cervical, axillary,
occipital, and epitrochlear nodes
Presenting Signs and Symptoms

23. Overview
 Swelling of lymph nodes is a frequently
encountered symptom
 It is important to carry out a careful
history and physical exam
 The cause often becomes obvious, but in
more complicated cases, laboratory tests
and lymph node biopsy may be necessary
to establish a definitive diagnosis

24.  Where possible, do a CBC (FBC) and chest x-
ray before making a diagnosis of PGL
 Hilar or mediastinal lymphadenopathy on
CXR
Diagnostics

25. Management and Treatment
 No specific treatment for PGL

26. Unique features, Caveats
 Develops in up to 50% of HIV-infected individuals
 Up to one-third do not have any other symptom
on presentation (WHO clinical stage 1)
 In HIV-positive patients, PGL is a clinical
diagnosis. No further examinations are necessary,
unless there are features of another disease
 PGL may slowly regress during the course of HIV
infection and may disappear before the onset of
AIDS

27.  Cervical nodes most commonly involved
 Usual course of lymph node disease is as
follows:
Firm, discrete nodes

fluctuant nodes matted together

skin breakdown, abscesses, chronic sinuses

healing and scarring
Presenting Signs and Symptoms
Tuberculosis
lymphadenopathy

28.  Fine-needle aspiration of the involved
lymph node
 Extra-thoracic lymph node aspiration
 Positive smears for acid-fast bacilli on fine-
needle aspirates of the involved lymph
nodes (high rate in HIV patients)
 In smear-negative pulmonary TB, it is
worthwhile aspirating extra-thoracic lymph
nodes to confirm diagnosis of TB (80%
positive)
Diagnostics

29. TB abscess
as part of immune reconstitution syndrome

30. Management and Treatment
 Treatment should be started following the
national TB Guidelines.
 For further details, see Part A Module 2,
Session 3.

31. Unique features, Caveats
 One of the most common forms of extra-
pulmonary TB in HIV patients
 Fluctuant cervical nodes that develop over
weeks to months without significant
inflammation or tenderness suggest infection
with M. tuberculosis, atypical mycobacteria,
or scratch disease (Bartonella henselae).
 In severe immunocompromised patients,
tuberculosis lymphadenopathy may be acute
and resemble acute pyogenic lymphadenitis
 Miliary TB is an important consideration in
patients with generalized lymphadenopathy