Generalized lymphadenopathy refers to the enlargement of lymph nodes in two or more non-contiguous regions of the body. It is most often caused by viral infections like infectious mononucleosis, but can also be due to bacterial infections, malignancies, autoimmune disorders, and storage diseases. A thorough history and physical exam are important to determine the cause, looking at factors like duration of lymphadenopathy, associated symptoms, epidemiological clues, characteristics of enlarged lymph nodes, and presence of systemic involvement. Further laboratory and radiological testing may be needed based on the clinical picture.

1. GENERALISED
LYMPHADENOPATHY
By
- Dr. Neet Chotai ( MS )

2. 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 in a unidirectional pathway.
• These widely and extensively dispersed vessel
system collects tissue fluids from all regions of the
body to eventually convey them towards the heart.

3. • The components of the lymphatic system are :
• Lymph, the recovered fluid
• Lymphatic vessels, which transport the lymph
• Lymphatic tissue, composed of aggregates of
lymphocytes and macrophages that populate in
many organs of the body; and
• Lymphatic organs, in which these cells are especially
concentrated and which are set off from
surrounding organs by connective tissue capsules

4. Anatomy of The lymph nodes
• Lymph nodes are bean-shaped organs found in
clusters along the distribution of lymph channels of
the body.
• Usually 1-25 mm in length.
• There are over 800 lymph nodes in the body.
• The superficial nodes are located in the
subcutaneous connective tissue, and the deeper
nodes lie beneath the fascia & muscles and within
various body cavities.

5. • The lymph node is a junction that slows down
lymph flow and allows time for cleansing it of
foreign matter.
• On its way to the bloodstream, lymph flows through
one lymph node after another and thus becomes
quite thoroughly cleansed of most impurities.

6. STRUCTURE OF LYMPH NODE:-
• Outermost is the covering called Capsule composed
of fibrous connective tissue.
- Capsule contains the parenchyma or stroma
• Stroma is differentiated into cortex & medulla.
• Trabeculae extend from cortex to medulla.

7. Outer Cortex :-
- Filled with lymph follicles.
- Outer edge of follicle contains more T cells.
- Follicles have inner germinal center which is the site
of B-cell proliferation.
Inner medulla :-
- Medullary cords of lymphocytes, macrophages, plasma
cells.

9. • Cytology of the lymph node:-
The normal or reactive lymph node is composed of
 Transient B and T lymphocytes
 Antigen processing and presenting cells
 Replicating B and T lymphocytes (in response to
antigen)
 Persistent and transient final effector cells
 Macrophages

10. • B lymphocytes are located primarily in the follicles and
perifollicular areas
• T lymphocytes are found primarily in the interfollicular
or paracortical areas of the lymph node.

12. Lymph nodes of clinical importance have been put
under 5 main groups:
➢ Cervical groups
➢ Axillary groups
➢ Inguinal groups
➢ Epitrochlear lymph nodes
➢ Popliteal lymph nodes

14. 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)

16. Lymphadenopathy:
- Refers to lymph nodes that are abnormal in:
»Size
»Number
»Consistency
- Whether as a result of normal reactive process or
pathology.
- Abnormalities may be localized or generalized.

17. Pathophysiology
Lymphadenopathy can be caused by:
1. An increase in normal lymphocytes and macrophages during a
response to an antigen (e.g. viral illness)
2.Nodal infiltration by inflammatory cells in response to an
infection in the nodes themselves (lymphadenitis)
3.Proliferation of neoplastic lymphocytes or macrophages
(lymphoma)
4.Infiltration of nodes by metabolite-laden macrophages in
storage diseases (Gaucher disease)

18. • Generalized lymphadenopathy : -
 Enlargement of ≥ 2 non-contiguous lymph node
groups
• Regional lymphadenopathy : -
 It involves enlargement of a single node or
multiple contiguous nodal regions

19. • It 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,
– inguinal

20. • Lymph nodes are common sites of metastatic cancer
because cancer cells from almost any organ can
break/loose, and 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.

21. Generalized lymphadenopathy
It is defined as enlargement of more than 2
noncontiguous lymph node groups.
Common causes of generalized lymphadenopathy
• Infections
• Autoimmune disorders and hypersensitivity
states
• Neoplastic and proliferative disorders

22. Generalized Lymphadenopathy

23. Infections :
1.Viral
2.Infectious mononucleosis
3.CMV
4.Acquired immunodeficiency syndrome
5.Rubella
6.Varicella
7.Measles

24. 8. Septicemia
9. Typhoid fever
10. Tuberculosis
11. Syphilis
12. Plague
13. Protozoal – Toxoplasmosis
14. Fungal - Coccidioidomycosis

25. Autoimmune disorders and hypersensitivity states
1.Juvenile rheumatoid arthritis
2.Systemic lupus erythematosus
3.Drug reactions (e.g., phenytoin, allopurinol)
4.Serum sickness

26. Neoplastic and proliferative disorders
1.Acute leukemias
2.Lymphomas (Hodgkin, non-Hodgkin)
3.Neuroblastoma
4.Histiocytoses II.
Storage Diseases
1.Gaucher disease
2.Niemann-Pick disease

27. Infection
• Generalized Lymphadenopathy is most often
associated with systemic viral infections.
• IMN results in widespread adenopathy.
• Roseola infantum (caused by human herpes virus
6), CMV, varicella, and adenovirus all cause
generalized lymphadenopathy.

28. • Although usually associated with localized node
enlargement, some bacterial infections cause
generalized adenopathy .
e.g.
– typhoid fever caused by Salmonella typhi,
– syphilis, and
– tuberculosis

29. Malignant etiologies
• Malignancy often is associated with constitutional
signs, such as fever, anorexia, nonspecific aches
and pains, weight loss, and night sweats like in
acute leukemias and lymphomas.
• Generalized LAP is present at diagnosis in 70% of
children with (ALL) and in 31% of children with
(AML).

30. • The lymphomas more often present with regional
lymphadenopathy, but generalized lymphadenopathy
occurs.
• 1/3rd of children with Hodgkin disease and 10% with
non-Hodgkin lymphoma display them.

31. • Malignancies usually present with nodes that tend
to be firmer and less mobile or matted; however,
this finding can be misleading.
• Benign reactive lymph nodes may be associated
with fibrotic reactions that make them firm.

32. Storage diseases
• In Niemann-Pick disease, sphingomyelin and other
lipids accumulate in the spleen, liver, lymph nodes,
and central nervous system.
• In Gaucher disease, the accumulation of the
glucosylceramide leads to the engorgement of the
spleen, lymph nodes, and the bone marrow.

33. Drug reaction
• Within a couple of weeks of initiating phenytoin,
some patients experience regional or generalized LN
enlargement, followed by a severe maculopapular
rash, fever, hepatosplenomegaly, jaundice, and
anemia.
• Several other drugs cause similar symptoms,
including,
– pyrimethamine,
– phenylbutazone,
– allopurinol, and
– isoniazid

34. Other non-neoplastic etiologies
• Rare non-neoplastic causes of generalized LAP
include Langerhans cell histiocytosis.
• Autoimmune causes include juvenile rheumatoid
arthritis, which often presents with adenopathy,
especially during the acute phases of the disease.
• Sarcoidosis and graft verses host disease also can
cause LAP.

35. Starting with the History
1. Age of the child :
• In Neonates, It needs investigations because LN are
not palpable during neonatal period.
• With time during childhood period there is antigenic
exposure so some LN may palpable in the body like
cervical up to 2 cm , axillary 1 cm, inguinal 1.5 cm
but if more than these measures LNs are
considered enlarged.

36. • The peak prevalence of leukemia is in children
younger than 10 years, whereas Hodgkin disease is
observed more often in adolescents.
2.Duration:
• If it is of short duration (less than 2 weeks) infection
is suspected.
• If it is of long duration ( more than 2 weeks but less
than 1 year) there is possibility of malignant etiology.
• If more than one year other pathologies should be
thought of like connective tissue disease.

37. 3. The Exposure history as well as the Travel history:
• Exposure to Animals/Pets and biting insects.
• Cat-scratch disease
• Exposure to infectious contacts
• Consuming Undercooked meat for possible
Toxoplasmosis
• Environmental exposure such as tobacco, alcohol, and
ultraviolet radiation may raise suspicion for metastatic
carcinoma of the internal organs, cancers of the head
and neck, and skin malignancies
• Occupational exposure to silicon or beryllium

38. • 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

39. • 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

40. Symptoms
• 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 and Presence of non-pitting lower
limb edema with inguinal LAD may suggest
filariasis.
• Arthralgia, muscle weakness, unusual rashes may
indicate possibility of autoimmune diseases.

41. • 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.

42. • Patients with retroperitoneal node enlargement,
may present with LL edema.
• Coexistence of splenomegaly implies a systemic
disorders or a hematological disorder as:
– IMN,
– Lymphoma,
– acute or chronic leukemia,
– SLE,
– Sarcoidosis,
– Toxoplasmosis,
– cat-scratch disease

43. • 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

44. Red flags in lymphadenopathy

45. Other signs
• Signs of anemia like tachycardia, pale conjunctiva,
may be associated with malignancy or autoimmune
disease.
• Dermatological changes:- Petechiae, bruising,
bleeding may be associated with malignancy
• Wt and growth:- poor growth may be associated with
malignancy.

46. Clinical Considerations
The normally palpable L.Ns. Are:
• Submandibular
• Axillary
• Inguinal

47. 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?

48. Local examination
• 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

49. • Size (up to 1 cm is considered normal).. Except
epitrochlear : if >0.5 cm
• 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( or Pellets) under the skin, as found in the cervical
nodes of children with viral illnesses.

50. • Discrete or Matted (nodes that feel connected and
seem to move as a unit)
- 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).

51. • 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

52. • 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.

53. Investigations
• The investigation of lymphadenopathy can be
organized according to where nodes occur and
type of clinical symptoms present.
It includes:
I - Laboratory
II - Radiological
III - Others (as: Bronchoscopy, Mediastinoscopy or
Bone Marrow Biopsy)
IV - Node Biopsy

54. I - Laboratory:
 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 disease such as SLE)

55.  ESR
 Serology: may demonstrate:
 Antibodies specific to: components of EBV(viral
Capsid Ag), CMV, HIV, Toxoplasma, Brucella, etc
 PCR-for: CMV-DNA, T.B.
 Antinuclear antibody (SLE)
 Others: In cases of hilar Lymphadenopathy, do:
 Serum ACE
 Tuberculin T.

56. II - Radiological:
They include:
1. Chest X-Ray (CXR)
2. Node Ultrasonography (U/S)
3. Abdominal: U/S and CT
4. Magnetic Resonance Imaging scans(MRI)
5. Positron Emission Tomography scans(PET)
6. Lymphography

57. 1 Chest X Ray:
 To assess for mediastinal disease, Hilar nodes, or
for Parenchymal lung disease (Pulmonary infiltrate)
 Mediastinal Lymphadenopathy would suggest:
 T.B.
 Histoplasmosis,
 Sarcoidosis
 Lymphoma
 Primary/metastatic lung cancer

58. 2 – Nodal U / S and Color Doppler U/S:
• Normal and reactive nodes tend to be hypoechoic
compared with adjucent muscles.
• And oval (S/L <0.5)
• Color doppler shows hilar vascularity/avascular and
low vascular resistance.

59. • Malignant nodes :
• Round without echogenic hilum
• Intranodal cystic necrosis/reticulum
• Eccentric cortical hypertrophy
• Illdefined borders

60. 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.

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

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

63. 3 – Contrast Enhanced CT(CECT):
For the reveal of: mediastinal, retroperitoneal, iliac
or mesenteric nodal affection
4 – MRI:
 T1-weighted images show lymph nodes as being of
intermediate signal intensity (similar to muscle)
 T2-weighted images show them as hyper-intense
signal

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

65. 5 - 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

68. 6. Lymphography
• MRI and CT scan have replaced this procedure
almost completely.
• However it is useful to see extent of lymphomas and
to evaluate staging.

70. III – Node Biopsy:
Node Excision Biopsy:
It is a valuable diagnostic tool
Its accuracy not only on the experience of the clinician,
but also on the pathologist who reports it
Node should be subjected to the minimal of trauma
during removal, or it may be difficult for interpretation

71. • 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

75. Scalene node biopsy
Often provides useful information about the nature
of underlying lung disease
Abdominal nodes
These are commonly removed in the course of staging
laparotomy operations.
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.

76. • Look at aspirated material
• Smear for AFB
• Smear for cytologyFNAC
• Look at cut-surface
• Fresh node for T.B.cuture
• Fresh node
forimmunophenotyping/cytochemistry
• Smear for AFB
• Node in formalin for histology
Excision Biopsy

77. Indications of biopsy
1. Failure to reach diagnosis by non invasive
investigation
2. if there is persistent or unexplained fever, weight
loss, night sweats, hard nodes, or fixation of the
nodes to surrounding tissues.
3. If there is continuous enlargement over 2 weeks
4. no decrease in size in 4–6 wk
5. no regression to "normal" in 8–12 wk
6. development of new signs and symptoms.
7. no respond to antibiotics

78. Treatment and Follow-up
• Patients with unexplained localized
lymphadenopathy and a reassuring
clinical picture
• -------------> 2 – 4 week period of
observation is appropriate before
biopsy, for re-evaluation of node(s)-
increase in size

79. • Patients with localized lymphadenopathy and a
worrisome clinical picture or patients with
generalized lymphadenopathy
• -----------> further diagnostic evaluation that
often includes Biopsy

80. Treatment and Follow-up
• Antibiotics are given only if there is strong evidence
of bacterial infection
• DO NOT USE GLUCOCORTICOIDS, which might
obscure some diagnosis (because of their
lympholytic effect) or might delay healing/activate
underlying infection.. (Except in life-threatening
pharyngeal obstruction by enlarged lymph tissue in
Waldeyer’s ring caused by EBV)

81. • Drainage is required if an abscess formed
• Treat primary cause

82. Treatment of lymphadenopathy in
suppurative bacterial lymphadenitis:
• Oral or IV antibiotics depending on severity of
infection
• I & D
• surgical excision

83. Treatment of tubercular
lymphadenopathy:
• FNAC of node
• Start antitubercular therapy

84. Treatment of lymphadenopathy in
kawasaki disesae:
• IVIG and aspirin

85. Treatment of lymphadenopathy in
syphilis:
• IM Benzathine
Penicillin/doxycycline/azithromycin

86. Treatment of lymphadenopathy in
sarcoidosis:
• Spontaneous remission.
• steroids

87. Treatment of lymphadenopathy in infectious
mononucleosis:
• Mainly supportive.
• Tonsillar hyertrophy can produce airway obstruction
need to place nasopharyngeal tube and start
steroids.

88. Treatment of lymphadenopathy in
lymphomas:
• Optimal management relies on accurate
histological classification and anatomical and
biological staging.
• Chemotherapy

89. Treatment of malignant
lymphadenopathy:
• Treatment of primary tumour ( surgical
excision/Radiotherapy/Chemotherapy)
• Block dissection
• Radiothertapy
• Chemotherapy

90. Complications:
• Mediastinal adenopathy can cause superior vena cava
syndrome with obstruction of blood flow; bronchial or
tracheal obstruction with cough, wheezing, and
ultimately respiratory tract obstruction (which can be life
threatening); and dysphagia from esophageal
compression.
• Occasionally, erosion of a node into a bronchus or trachea
can result in hemoptysis.

91. • When the diagnosis of an underlying malignancy is
missed, serious metabolic complications can occur like:
 uric acid nephropathy,
hyperkalemia,
hypercalcemia,
 hypocalcemia,
hyperphosphatemia, and
acid renal failure.
• Abdominal adenopathy can cause abdominal or back
pain, constipation, and urinary frequency. Intestinal
obstruction caused by intussusception can be life
threatening

92. Prognosis:
• The prognosis of lymphadenopathy is almost entirely
dependent on the underlying etiology.
• Patients with specific complications, such as superior
vena cava syndrome, are at risk unless this specific
complication is managed. Their prognosis is dependent
on the management of the neoplastic process resulting
in superior vena cava syndrome.

93. THANK YOU….