This document provides guidelines for managing lymphadenopathy. It defines lymphadenopathy and differentiates between generalized and localized types. The main causes of each are described. Evaluation involves a detailed history, physical exam of lymph nodes and affected areas, and potential laboratory/imaging tests. Nodes suggesting malignancy require prompt oncology referral. The role of the internist is to map the condition and direct a symptom-guided workup. Management may include treatment or oncology referral depending on findings.

1. Lymphadenopathy
Protocol for Management
Department of Surgery
By
Eslam Emad Awesh

2. Intended issue outcome
Define Lymphadenopathy..
Differentiate between Generalized and Localized
Lymphadenopathy and Recognize their main Causes..
Understand the role of Internist in Mapping of the condition
for a better symptom-directed diagnostic workup..
Management and/or Referral to the Oncologist at the proper
time..

3. Introduction
 The lymphatic system is the part of the immune system comprising a network of
conduits called lymphatic vessels that carry a clear fluid called lymph (from Latin
lympha "water") in a unidirectional pathway.
 The widely and extensively dispersed vessel system collects tissue fluids from all
regions of the body to eventually convey them towards the heart.
 The components of the lymphatic system are :-
I. Lymph, the recovered fluid
II. Lymphatic vessels, which transport the lymph
III. Lymphatic tissue, composed of aggregates of lymphocytes and macrophages
that populate many organs of the body; and
IV. Lymphatic organs, in which these cells are especially concentrated and which
are set off from surrounding organs by connective tissue capsules

4. Defenition of Lymphadenopathy
Lymph nodes that are abnormal in size, consistency or number due to
specific or nonspecific causes.
• LYMPHADENITIS:
• Generalized or local Lymphadenopathy.
 Generalized lymphadenopathy is defined as: -
enlargement of ≥ 2 non-contiguous lymph node groups
 Regional lymphadenopathy If :
 It involves enlargement of a single node or multiple contiguous nodal
regions
 Lymphatic drainage in all organs of the body except brain, eyes, marrow
and cartilage

5. Clinical understanding
 LAD may be an incidental finding in patients being examined for various
reasons, or it may be a presenting sign or symptom of the patient's illness
 Commonly palpable and accessible lymph nodes are the cervical, axillary,
and inguinal
 Lymph nodes are common sites of metastatic cancer because cancer cells
from almost any organ can break loose, enter the lymphatic capillaries, and
lodge in the nodes
 Soft, flat, submandibular nodes (<1 cm) are often palpable in healthy
children
 Healthy adults may have palpable inguinal nodes of up to 2 cm

6. Lymphatic Organs
 Primary Lymphatic Organs :-
 The red bone marrow
 The thymus gland
(Lymphocytes originate and mature in these organs)
 Secondary Lymphatic Organs:-
 The spleen
 The lymph nodes
 Other organs, such as: the tonsils,
Payer's patches, and the appendix, ..
(All the secondary organs are the places where lymphocytes encounter and bind
with antigens, after which they proliferate and become actively engaged cells)

7. Common causes of generalized
lymphadenopathy
• EBV/CMV
• AIDS /AIDS related
complex
• Toxoplasmosis
• Secondary syphilis
Infectious
• ALL / CLL
• Lymphoma
Neoplasia
• Serum Sickness
• Drugs (Phenytoin)
• SLE
• Rheumatoid Arthritis
Hyper-
sensitivity
• Hyperthyroidism
• Lipid storage disease
Metabolic

8. Common Causes of localized lymphadenopathy
(Site Predilection)
• Viral Conjunctivitis
• Trachoma
• Cat-scratch disease
• Tularemia
• Sarcoidosis
Pre-auricular
• Rubella
• Scalp infection
Post-auricular/
Occipital
• Pharyngitis
• EBV
• Toxoplasmosis
• Sarcoidosis
Cervical
• Pharyngitis/buccal cavity
tumor
• Nasopharyngeal tumor
• Thyroid malignancy
Submandibular

9. Common Causes of localized lymphadenopathy
(Site Predilection)
• Pulmonary / Mediastinal / Esophageal Malignancy
• T.B.
• Sarcoidosis
• Toxoplasmosis
Right supraclavicular
• Intra-abdominal malignancy
• RCC
• Ovarian/Testicular /
• Prostate malignancy
Left supraclavicular (Virchow’s)
• Cancer Breast / Breast infection
• Melanoma
• Lymphoma
• Ipsilateral upper limb infection
• / Reaction to immunization
• Juvenile RA
Axillary
• Syphilis(bilateral)
• Sarcoidosis
• Infection(unilateral)
• Leprosy
• IMN
• CLL/Lymphoma
Epitrochlear

10. Common Causes of localized lymphadenopathy
(Site Predilection)
•Syphilis
•Genital herpes
• Lymphogranuloma venereum
• Chancroid
• Lower extremity/local infection
• Lymphoma
• Metastatic carcinoma from: rectum, genitalia or lower
limb(melanoma)
Inguinal
• Lymphoma
• Bronchogenic Carcinoma
• T.B.
• Sarcoidosis
• Histiocytosis
• Coccidiomycosis
Hilar
• Gut Adenocarcinoma
• Hodgkin’s disease
• T.B.
• Lymphoma
• Bladder carcinoma
Abdominal
• Lymphomas
• Leukemias
• Cat-Scratch disease
• Metastasis
• Sarcoidosis
• Granulomas
Any region

11. Hilar, mediastinal, abdominal
 >1 cm considered pathological
 Pneumonia/inflammatory process can cause unilateral hilar
disease
 Lymph adenopathy limited to abdomen likely malignant.

12. Highest rate of malignancy
 Right Supraclavicular
Mediastinum
Lungs
Upper 2/3 esophagus
 Left Supraclavicular
Virchow node
Testes/ovaries
Kidneys
Pancreas
Prostate
Stomach
Lower Esophagus

13. Chicago
Cancer
Malignancies: Hodgkins, NHL, acute
and chronic leukemias,
waldenstroms, multiple myeloma
(plastmocytomas)
Metastatic: solid tumor breast, lung,
renal, cell ovarian

14. Famous nodes
 Virchows Left supraclavicular (abdominal or thoracic
cancers)
 Sister Joseph
 Para-umbilical (gastric adenocarcinoma)
 Delphian node
 Prelaryngeal (thyroid or laryngeal cancer)
 Node of Cloquet (Rosenmuller node)
Deep inguinal near femoral canal

15. Algorithm to evaluate Lymphadenopathy
Attention to history and physical exam
Confirmatory testing
Indication for biopsy

16. Clinical assessment and applied
aspects
I. History: Detailed personal/present/past- history
II. General Examination: Review of ALL body systems
III. Local (Physical) Examination: Inspection and Palpation
IV. Investigations: Laboratory and Radiological
V. Treatment

17. GENERAL INFORMATION
I. Age: Young age: TB, Syphilis, primary malignant lymphoma. Old
age; secondary metastatic carcinoma.
I. Occupation: Brucellosis Exposure to Animals/Pets and biting insects or silicon
II. Socio economic status;
 The vast majority of cases of lymphadenopathy in children have infectious etiology.
 Lymphadenopathy that has been present for < 2 weeks has a very low chance of
representing a malignant condition
 Lymphadenopathy that has been present for > 1 year and has been stable in size
over the year, has a very low chance of being malignant (with exception of indolent
NHL and low-grade Hodgkin lymphomas)
 Presence of fever points toward a broad differential, mainly consisting of infection
or lymphoma
(Evening raise or Pel-Ebstein fever)

18.  Sexual history is also important in determining potential sexually
transmitted causes of inguinal and cervical lymphadenopathy; as: HIV,
Syphilis, HBV, HSV, CMV
 Blood Transfusion or recent transplant history: for possible infections as
CMV and HIV
 History of recent immunization
 IV- Drug Users: for possible HIV, HBV, or endocarditis
 Drug history:
 Medications that may cause lymphadenopathy(such as phenytoin)
 Others(such as cephalosporins, penicillins or sulfonamides) are more
likely to cause a serum sickness-like syndrome with fever, arthralgia
and rash in addition to lymphadenopathy
 Immunosuppressive agents

19.  Constitutional symptoms such as: fever, malaise, fatigue, cachexia,
unexplained loss of weight(>10% of body eight) and loss of appetite
 Presence of petechiae in palate of a young, may preclude IMN
 Presence of non-pitting edema with inguinal LAD may suggest filariasis
 Arthralgia, muscle weakness, unusual rashes may indicate possibility of
autoimmune diseases
 Hemiparesis of the tongue can occur if the hypoglossal nerve is involved
by affection of upper deep cervical L.N. group due to carcinoma(The
tongue will deviate towards the side of the lesion when asked to protrude
out)
 Cases are not uncommon when patient may complain of compression
symptoms as dyspnea & dysphagia due to pressure on trachea or
esophagus by the enlarged lymph nodes
 Patients with retroperitoneal node enlargement, may present with LL
edema

20.  Coexistence of splenomegaly implies a systemic disorders or a
hematological disorder as:
(IMN, Lymphoma, acute or chronic leukemia, SLE, Sarcoidosis,
Toxoplasmosis, or cat-scratch disease)
 Symptoms associated with lymphadenopathy that should be
considered red flag symptoms for malignancy include:
 Fever, night sweats, and unexplained weight loss
 A supraclavicular node
 Hard and tender L.N. with a significant size or draining an area
with a significant pathology
 Matted or Fixed node(s)
 Non-recessive node after 3 weeks period or after disappearance
of fever

21. Red flags in lymphadenopathy
1. Fever, night sweats, and unexplained weight loss
2. A supraclavicular node
3. Hard and tender L.N. with a significant size or draining an
area with a significant pathology
4. Matted or Fixed node(s)
5. Non-recessive node after 3 weeks period or after
disappearance of fever

22. Clinical Considerations
 Is the palpable mass a L.N. ?
 Acute or Chronic ?
 Epidemiological clues ?
 Site ? {Localized or Generalized}
 Number ?
 Size ?
 Character ? {surface and consistency}
 Discrete or Matted ?
 Tenderness ?
 Mobility ?
 Attachment ? And Relation to adjacent muscle ?
 Associated Systemic and/or Localizing symptoms or signs?

23. General principles of exam
Before the exam, ask the patient to
identify painful areas so that you can
examine those areas last
During the exam pay attention to
their facial expression to assess for
sign of discomfort
Remember
 Normal lymph nodes are not
palpable
 Examine the draining lymph nodes
area of any lesion
 Examine the area drained by affected
lymph nodes

24. Mapping of Different Nodes
An examination of the
lymph nodes forms part
of the routine for most
body systems.
As there is no need to
percuss or auscultate,
examination involves
inspection followed by
palpation
Don't forget to examine
the draining areas

25. Palpation
The following points are to be fulfilled during inspection:
 SSSSS (5S):
1- Site.
2- Shape.
3- Size.
4- Surface: Smooth, nodular, irregular.
5- Skin overlying the swelling (scars, colour…).
6- Other draining lymph nodes.
7- Number
8- pressure effect
 Technique: Use the pads of the index and middle finger to move the skin in circular motions over
the underlying tissues in each area
 For Serial Evaluation, documentation of “all” of the L.N. criteria is critical !!

26. Cervical Lymph nodes
1- seat the patient in a chair
2- palpate from behind (?): right hand for right side and vice versa
3- slightly bend the neck towards the side to be examined
3- use one hand at a time
4- Bimanual examination may be employed

31. Axillary Node Palpation
 The central group: near the middle
of the thoracic wall of the axilla
 The lateral group: near the upper
part of the humerus and is best
demonstrated by having the
patient’s arm elevated so that you
can feel along the axillary vein.
 With the patient’s arm still elevated,
feel along beneath the lateral edge
of the pectoralis major muscle for
the pectoral group

32. Epitrochlear node palpation: Approximately 3 cm proximal
to the medial humeral epicondyle, in the groove between the biceps
and triceps brachii. Best approached in an anterior to posterior
direction

33. Inguinal node palpation
horizontal group: along the inguinal ligament(both above and over)
vertical group: beside great saphenous vein in the proximal thigh
iliac nodes: above and deep to inguinal ligament

34. Local examination
You Have To Answer The Previous Questions of Clinical Considerations ..
►►► Note for:
Number: (single or multiple), (localized or generalized)
Site: Anatomic location can narrow the D.D.
 T.B. and Hodgkin’s ----- > cervical (earlier stages)
 Cat-scratch disease ----- > cervical and axillary
 IMN --- > cervical
 Sexually-transmitted diseases ----- > Inguinal
 Supraclavicular ----- > Highest risk of malignancy(90% in old patients)
 Paraumbilical (Sister Mary Joseph's)----- > Abdominal or pelvic neoplasm
Size (up to 1 cm is considered normal).. Except epitrochlear :if >0.5cm
N.B.=The size is usually of little importance in adding information to establish
diagnosis; however increase in size on serial examination may be of value..

35. Local examination
 Surface and Consistency (Soft, hard, firm, rubbery, fluctuant, shotty, or variable)
 Stony-hard nodes are typically a sign of cancer, usually metastatic
 Firm, rubbery nodes suggest lymphoma
 Softer nodes are the result of infections or inflammatory conditions
 Suppurant nodes may be fluctuant
 The term “shotty” refers to small nodes that feel like buckshot under the skin, as found in the
cervical nodes of children with viral illnesses
 Discrete or Matted(nodes that feel connected and seem to move as a unit)
N.B.=Nodes that are matted can be either benign (T.B., Sarcoidosis, lymphogranuloma venereum),
or malignant (metastatic carcinoma or lymphomas).
 Painless or Painful(when a lymph node increases in size its capsule stretches and causes pain, or
when there is hemorrhage into the necrotic center of a malignant node)
N.B.=The presence or absence of tenderness does not necessarily differentiate benign from
malignant nodes..

36. Local examination
 Fixed or not to the underlying skin, deep fascia or muscles
The patient is asked to contract the muscles against resistance:
 If the swelling becomes MORE apparent it is SUPERFICIAL to muscles
 If the swelling becomes LESS apparent it is DEEP to muscles
 If the swelling is NOT affected it is IN the muscle
 The overlying skin has to be noted:
 Skin redness, edema and brawny induration denote acute lymphadenitis
 Skin over tuberculous lymphadenitis becomes red and glossy when they reach the
point of bursting
 Scar often indicates previous bursting of abscess or operation
 Skin may appear tense and stretched with dilated subcutaneous veins when
overlying a rapidly growing lymphoma
 In secondary carcinoma, the skin may become fixed

37. Investigations
 The investigation of lymphadenopathy can be organized
according to where nodes occur and type of clinical symptoms
present
 Most lymphadenopathy patients do not require a biopsy and at
least half require no laboratory study
********************************************************************

38. Investigations
It includes:
I - Laboratory
II - Radiological
III - Others (as: Bronchoscopy, Mediastinoscopy or
Bone Marrow Biopsy)
IV - Node Biopsy

39. I - Laboratory:
The laboratory investigation of patients with lymphadenopathy must be tailored to elucidate the etiology suspected
from the patient's history and physical findings
 CBC with differential count : provides useful data for the diagnosis of:
 Acute or Chronic leukemia's
 EBV or CMV mononucleosis(atypical lymphocytosis)
 Pyogenic infections
 Lymphoma with a leukemic component
 Immune cytopenias (in illnesses such as SLE)
 ESR
 Serology: may demonstrate:
 Antibodies specific to: components of EBV(viral Capsid Ag), CMV, HIV, Toxoplasma, Brucella, etc
 PCR-for: CMV-DNA, T.B.
 ANA/Anti-ds DNA antibody (SLE)
 Others: In cases of hilar LAD, do:
 Serum ACE
 Tuberculin T.

40. II - Radiological:
They include:
1. Chest X-Ray (CXR)
2. Node Ultrasonography (U/S) / Color Doppler U/S
3. Abdominal: U/S and CT
4. Throat culture/urethral or cervical swab for regional
affection
5. Magnetic Resonance Imaging scans(MRI)
6. Positron Emission Tomography scans(PET)

41. 1 – CXR:
 To assess for mediastinal disease, Hilar
nodes, or for Parenchymal lung disease
(Pulmonary infiltrate)
 Mediastinal LAD would suggest:
 T.B.
 Histoplasmosis,
 Sarcoidosis
 Lymphoma
 Primary/metastatic lung cancer

42. 2 – Nodal U / S and Color Doppler U/S:
 A lymph node measuring ≥ 10 mm in the short axis is defined as
malignant
 A lymph node with a L/S ratio of ≥ 3.5 is considered reactive or benign
 A lymph node with a L/S ratio of ≤ 1.6 is considered metastatic
 A lymph node which can not be fitted to the previous categories is
considered to be “questionable”
 Malignant infiltration alters the U/S features of the lymph nodes,
resulting in enlarged nodes that are usually rounded, with definite
“internal echoes” and showing peripheral and mixed vascularity
♥♥♥Using these features, U/S has been shown to have an
accuracy of 89%– 94% in differentiating malignant from
benign cervical L.Ns.

43. Normal cervical nodes appear sonographically as somewhat
flattened, cigar-shape, hypo-echoic structures with varying
amounts of Hilar fat

44. Ultrasonography Differentiation
Benign
(No definite internal echoes)
Malignant
(Definite internal echoes)

45. 3 – Contrast Enhanced CT(CECT):
For the reveal of: mediastinal, retroperitoneal, iliac or
mesenteric nodal affection
4 – MRI:
 T1-weighted images depict lymph nodes as being
of intermediate signal intensity (similar to muscle)
 T2-weighted images show them as hyper-intense
signal

46. MRI – Sagittal scan of a large pathological
deep cervical L.N.
T1 - Weighted T2 - Weighted

47. 4 - PET:
 Most head and neck PET imaging is performed with the
radio-labeled glucose analogue FDG Fluoro-Deoxy-Glucose
which has increased uptake in viable malignant tumor due
to enhanced glycolysis
 The result can be expressed as a standardized uptake value
(SUV), with those values > 2 being considered abnormal
 PET scanning provides functional rather than anatomical
imaging

51. III – Node Biopsy:
Node Excision Biopsy:
 It is a valuable diagnostic tool
 It could be performed directly or via radiological
interventional methods or via surgery or endoscopy
 Its accuracy not only on the experience of the clinician, but
also on the cytologist who reports it
 Node should be subjected to the minimal of trauma during
removal, or it may be difficult for interpretation

52. Proper choice of node:
Choose the LARGEST node
Avoid axillary(which can show fatty involution) and inguinal
nodes(which can show scaring due to repeated infections)
Supraclavicular nodes have the highest diagnostic yield

53.  The decision to biopsy may be made:
 Early in a patient's evaluation, or
 Delayed for up to 2 weeks
N.B.-- PROMPT biopsy should be performed if the
patient's history and physical findings suggest a
MALIGNANCY:
 If a solitary, hard, non-tender cervical node is found in an
older patient who is a chronic user of tobacco, or
 If a supraclavicular adenopathy is present, or
 If there is generalized adenopathy that is firm, movable,
and suggestive of lymphoma

54. FNAC/B: should not be
performed as the first diagnostic
procedure
As most diagnoses require more
tissue, thus it often delays a
definitive diagnosis..
FNAC/B: Cannot give
information about gland
architecture..
FNAC/B: should be reserved for
thyroid nodules and for
confirmation of relapse in patients
whose primary diagnosis is
known..
FINE NEEDLE ASPIRATION

55. Investigations
 Imprints are useful, not only for showing the appearance of the cells in a cytological
preparation but when stained by a Romamowsky method, for comparison with blood or
bone marrow smears, but also for cytochemical or immunochemical studies
 Scalene node biopsy often provides useful information about the nature of underlying
lung disease
 Abdominal nodes are commonly removed in the course of staging laparotomy operations
and the sites of removal of such nodes may be indicated by small metal clips to enable
subsequent abdominal X-ray films to be compared with preoperative / pre-treatment
lymphangiogram

56. • Look at aspirated material
• Smear for AFB
• Smear for cytology
FNAC / B
• Look at cut-surface
• Fresh node for T.B. cuture
• Fresh node for immuno
phenotyping/cytochemistry
• Smear for AFB
• Node in formalin for
histology
Excision
Biopsy

58. Limited
Unexplained
Age Location History
Wait 3-4 weeks and reexamine
No indication for empiric antibiotics or steroids
Glucorticoids can be harmful and delay diagnosis can obscure
diagnosis due to lympholytic affect

59. Unexplained Generalized lymph
adenopathy
 Always requires an evaluation
 Start with CXR and CBC
 Review Medications
 PPD (purified protein derivatives), RPR (rapid plasma
regain for syphylis), Hepatitis screen, ANA (antinuclear
antibody), HIV
 No yield on above test: Biopsy most abnormal node

60. Follow-up and Treatment
• Follow-up at 2-4 weeks interval for benign causes.
• Antibiotics are given only if there is strong evidence of bacterial
infection.
• DO NOT USE GLUCOCORTICOIDS-might obscure diagnosis or delay
healing in cases of infection (EXCEPTION: life-threatening pharyngeal
obstruction by enlarged lymph tissue in Waldeyer’s ring caused by IM.)
 Surgical Care
 Surgical care usually involves a biopsy. If lymphadenitis is present, aspirate may
be needed for culture, and removal of the affected node may be indicated.

61. Diet
Diet plays little role in the pathophysiology of lymphadenopathy.
Internationally, many of the infectious etiologies may be associated with a higher risk of
malnutrition.
Activity
Limitations on activity usually involve associated acute-onset splenomegaly. Any patient
with an acutely enlarged spleen may need to be restricted from contact sports.
In infectious mononucleosis, rupture of the spleen can occur with relatively little trauma
and can be fatal.

62. Conclusion
Protocol of
Management
Attention to history
and physical exam
Confirmatory
testing
Indication for
biopsy

63. REFERENCES
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of the adult patient. 2d ed. Philadelphia: Lippincott, 1987.
Bennett JC, Plum F, eds. Cecil textbook of medicine. 20th ed. Philadelphia: Saunders, 1996.
Pangalis GA, Vassilakopoulos TP, Boussiotis VA, Fessas P. Clinical approach to
lymphadenopathy. Semin Oncol. 1993;20:570–82.
Bailey & Love's Short Practice of Surgery 26th Edition - ...
emedicine.medscape.com
ekb.eg
Leung, A; Sigalet, DL (June 2003). "Acute Abdominal Pain in Children". American Family
Physician.
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checked: 24 March 2014
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152–155. PMID 21243990.