Clinical Work Up Of A Patient With Lymph adenopathy. by anil haripriya
CLINICAL WORK UP OF A PATIENT WITH
LYMPH NODE ENLARGEMENT
The lymph nodes are major components of the lymphatic system placed in
small groups or chains at strategic locations where they drain the lymphatic
vessels of various anatomic regions. They are composed of dense accumulation
of lymphoid tissues. A normal lymph node is ovoid, round or bean shaped and
vary in size from 2 mm to 20mm in longitudinal diameter. The location of each
group of lymph nodes in the mammalian body is relatively constant receiving
lymph from a specific region by multiple afferent lymphatic vessels which enter on
its convex border. The efferent lymphatic vessels along with blood vessels are
situated in the hilum.
The drainage of lymph involves not only the mechanical filtration of the
foreign Protein, viral and bacterial particles present in the lymph but also the
recognition and processing of antigens. The lymph nodes exhibit a complex
architecture in which a variety of cell populations are arranged in distinct
interfacing compartments. This provides a favorable environment in which the
various cellular components can process antigens, interact, and generate the
immune response. Afferent lymph, containing lymphocytes, macrophages, and
antigens, enters the lymph node via the subcapsular space and drains through
paracortical and medullary areas into medullary sinuses that converge to form
efferent lymphatic vessels through which lymph exits. B cells from bone marrow
and T cells from the thymus enter lymph nodes from the circulation by binding to
specific receptors on cells of post capillary high endothelial venules. After
activation by antigen and clonal expansion, sensitized T and B cells and antibody
secreting plasma cells leave the node in efferent lymph and rejoin the peripheral
blood circulation via the thoracic duct.
Removal of macro molecules and excessive fluid from the interstitium also
takes place through lymphatics. Large molecules that escape into the tissue fluid
have considerable difficulty in re-entering the vascular compartment. Proteins
such as albumin, globulins, and fibrinogen that enter the interstitial fluid are
usually returned to the plasma through the lymphatics and it passes through a
lymph node where the foreign bodies are removed.
LYMPH NODE GROUPS:
It is estimated that 500 to 600 lymph nodes exist in humans. These nodes
are located in groups along the course of the lymphatic vessels, whose contents
pass through the regional nodes to the main drainage systems of the thoracic duct
and right lymphatic ducts. In good health lymph nodes are usually not palpable.
It is important to understand the basic functional anatomy of the lymphatic
system to understand pathogenesis of lymph node enlargement. Major lymph
node groups of the body may be classified into superficial and deep lymph
nodes. Broadly all lymph node groups which are within the reach of an examiner
without assistance of investigative radiographic techniques form the superficial
group; involvement of which is easy to diagnose and manage. It is the deep
group which poses problems for diagnosis and management.
Fig. 1 : Functional architecture of the lymph node
MAJOR LYMPH NODE GROUPS:
SUPERFICIAL LYMPH NODE DEEP LYMPH NODE GROUPS
1.Superficial Cervical lymph 1. Deep Cervical lymph nodes
2. Supra clavicular lymph nodes 2. Intra thoracic lymph nodes
3. Extra thoracic lymph nodes 3. Para-aortic Lymph node
4. Inguinal lymph nodes 4. Peri portal lymph nodes
5. Epitrochlear lymph nodes 5. Iliac lymph nodes
6. Mesenteric group of
nodes. (Lymph nodes along the
named vessels. eg. Superior and
Other unnamed lymph nodes
LYMPH NODES OF THE HEAD AND NECK
Approximately 75 nodes are present on each side of the neck, most of
which are in the deep jugular and spinal accessory chains. Cervical group of
lymph nodes are divided into superficial and deep group.
Superficial group of lymph nodes are arranged in circular chain and consist of
(a) Occipital - one or two nodes situated midway between the mastoid process
and the external occipital protuberance. They drain the back of the scalp.
(b) Post auricular nodes: Situated on the mastoid process behind the
pinna. They drain the temporal region of the scalp, back of the pinna, and
external auditory meatus.
(c) Pre-auricular nodes: Situated immediately in front of the tragus, the
situation is so definite that a swelling not exactly in front of the tragus cannot
arise from this node. The node lies superficial to the parotid fascia. It drains
the outer surface of the pinna and side of the scalp.
(d) Parotid nodes: These nodes are situated both in the substance of the
parotid salivary gland and deep to it i.e. between it and the side wall of the
Pharynx. The deeper nodes drain (a) the nasopharynx (b) the back of the
nose. The more superficial receive lymph from (a) the eyelids, (b) front of the
scalp. (c) external auditary meatus (d) lymparic cavity.
(e) Submental nodes receives drainage from the skin of the chin, the
midportion of the lower lip, the tip of the tongue, the anterior oral cavity, and
the nasal vestibule.
(f) Submandibular: nodes receive drainage from the submental area, the
lower nasal cavity, the upper lip, the lateral lower lip, the anterior oral cavity,
and the skin of the midface. The submandibular nodes drain into the superior
deep jugular vein.
(g) Facial nodes: consists of superficial and deep groups.
Superficial group consists of
(a) Infraorbital: just below the orbit
(b) Buccinator: on the muscle of this name lateral to the angle of the mouth.
(c) Supramandibular: on the mandible in front of the masseter around the
These nodes receive lymph from conjunctiva and eyelids, nose and the
Deep Group: These lie around the maxillary vessels in relation to the external
pterygoid muscle. They drain (a) the temporal tossa (b) infratemporal fossa
(c) back of the nose (d) pharynx.
(h) Superficial Cervical nodes: These lie on the outer surface of the
sternomastoid around the external Jugular vein. They drain the parotid
region and lower part of the ear.
(i) Anterior cervical nodes: These lie near the middle line of the neck in front of
the larynx and trachea. They consist of superficial and deep set of nodes.
Superficial Set: Lie in relation to the anterior Jugular vein and drain the skin of
Deep Set consists of:
(a) The infra hyoid nodes: These lie on the thyrohyoid membrane and
drain the front of the larynx.
(b) The prelaryngeal nodes: These lie on the cricothyroid ligament and
drain the larynx. Their afferents pass through a small foramen in the
middle of the cricothyroid ligament. These nodes are often the first to
become enlarged in the cancer of larynx. These nodes assist in the
drainage of the thyroid.
(c) The pre tracheal nodes: These lie in relation to the inferior thyroid
veins in front of the trachea and drain the thyroid and trachea.
Efferents of the circular chain: The deep cervical chain receives ultimately all the
nodes enumerated above. It receives the efferents directly from all these node
groups except the facial and sub mental. The efferents from these two groups
pass first to the submandibular nodes.
CERVICAL LYMPH NODES.
Vertical chain of the deep cervical nodes:
This consists of a number of large nodes lying in relation to the carotid
sheath. A few members of this group occupy an outlying position behind the
pharynx and are called the retropharyngeal nodes. They drain the back of the
nose and pharynx and the auditory tube.
The vertical chain of deep cervical nodes, lies alongside the pharynx,
trachea, and oesophagus and extends from the base of skull to the root of the
neck. They are arbitrarily divided into superior deep cervical and inferior deep
cervical groups by the point of bifurcation of the common carotid (or, alternatively,
by the Omohyoid). The nodes of both groups are in very intimate relationship with
the internal jugular vein. Some of the nodes of the inferior group project beyond
the posterior border of the sternomastoid into the posterior triangle of the
neck (Supraclavicular). The Spinal accessory nodes are located along the spinal
accessory nerves and receive drainage from the parietal and occipital regions of
the scalp and the nape of the neck and from the upper retropharyngeal and
parapharyngeal nodes draining the nasopharynx, oropharynx and paranasal
sinuses. The upper spinal accessory nodes drain into the upper jugular nodes
and into the lower spinal accessory nodes, which in turn drain into the
There are a few small nodes of deep cervical group which lie in the groove
between the trachea and oesophagus alongside the recurrent nerve. They are
called paratracheal nodes and assist in the drainage of the thyroid.
Two of the deep cervical group are named Jugulodigastric, which is the
main node draining the tonsils and is situated just below the angle of mandible in
the angle between the internal jugular and common fascial vein. JUGULO-
OMOHYOID node is situated on the common carotid just above the point where
the anterior belly of the Omohyoid crosses the vessel. It plays a very important
part in the lymph drainage of the tongue, receiving some vessels from the apex
which take a circuitons route to reach the neck. The anterior Scalene (Virchow’s)
nodes received drainage from the thoracic duct and are located at the junction of
the thoracic duct and left subclavian vein. They usually are the site of metastasis
from Infraclavicular primary cancers. The supraclavicular nodes receive drainage
from the spinal accessory nodes and from infraclavicular primary cancers.
The deep cervical nodes receive the lymph from the entire head and neck
either directly or indirectly from the nodes of the circular chain. The lymph from
the deep cervical chain i.e. all the lymph from that half of the head and neck, is
collected into one trunk, the jugular lymph trunk, which leaves the inferior deep
cervical nodes. On the right side this trunk enters the junction of the
subclavian vein and the internal jugular vein. On the left side the trunk enters the
Level of Nodes in Neck Dissection:
The terminology for the classification for neck dissections has been very
confusing, this is especially important when discussing the results of treatment of
neck disease because there are so many variations of neck dissections. In an
effort to make the terminology more uniform. Suen and Goepert in 1987
proposed a classification of neck dissections based on specific nodal groups
removed. Their recommended terminology for the nodal group was based on a
modification of the Memorial Stoan-Kettering Cancer Centre classification.
This classification assigns five level of distribution to the different nodal groups.
Level I is subdivided into Level I-A (submental triangle nodes) and Level I-B
Level II includes two subgroups, Level II-A (Jugular nodes including the
subdigastric area down to the carotid bifurcation, and the nodes surrounding the
spinal accessory nerve from the jugular foramen to the posterior border of the
sternocleidomastoid muscle) and Level II-B the (lymph nodes in the upper
posterior cervical triangle above the entrance of the spinal accessory nerve into
Level III indicates the jugular nodes between the carotid bifurcation and the level
of the carotid sheath where the omohyoid muscle crosses this structure and the
posterior margin of SCM muscle.
Level IV includes sub group IV-A (Jugular nodes between the omohyoid muscle
and the level of the clavicle and to the Posterior border of the sterno
cleidomastoid muscle) Level IV-B (the lymph nodes in the supra clavicular space
lateral to the posterior border of the SCM muscle and candal to the omohyoid
Level V includes the nodes in the posterior cervical triangle created by the
posterior edge of the sterno cleidomastoid muscle, the level of the entrance of the
spinal accessory nerve, the trapezius muscle, and the posterior belly of the
AXILLARY LYMPH NODES:
The major and primary route of drainage of lymphatics from the breast is by
axillary pathway. There are five set of lymph nodes in the axilla namely the
anterior, posterior, lateral, central and apical set. There are about 35 to 50 lymph
nodes in each axilla.
Anterior set situated along the lateral thoracic veins under the anterior axillary
fold. They lie mainly on the 3rd rib. The axillary tail of Spence is in actual contact
with those nodes and therefore cancer involving this process may be
misdiagnosed as an enlarged node.
Posterior set lie along the posterior axillary fold in relationship to the subscapular
Lateral Set: lie along the upper part of the humerus in relation to the axillary vein.
Central Set: is situated in the fat of the upper part of the axilla. The
intercostobrachial nerve passes outwards amongst these nodes. Enlargement of
these nodes, such as occurs in cancer, may, by pressure on the nerve, cause
pain in the distribution of the nerve along the inner border of the arm. Occasionally
the central lymph node is involved in carcinoma stomach via Perigastric and para
oesophageal to mediastinal and from mediastinal to central node and it is termed
as Irish node.
Apical Set: These are also called the infraclavicular nodes. They are very
important and constant in position being bounded below by the first intercostal
space, behind by the axillary vein, infront by the costocoracoid membrane. These
nodes lie very deeply, but can be palpated by pushing the fingers of one hand into
the axillary apex from below, and the fingers of the other hand behind the clavicle
They are of great importance because they receive one vessel directly from
the upper part of the breast and ultimately most of the lymph from the breast. A
single trunk leaves the apical group on each side of the subclavian vein, and
enters the junction of the jugular and subclavian vein, or may join the thoracic duct
on the left.
These nodes can conveniently be subdivided into three main groups
according to their relationship with the pectoralis minor muscle, nodes at level 1
lie below the muscle, level 2 lymph glands lie behind it, and those of level 3 are in
the apex of axilla above the muscle. The majority of lymph drains from nodes at
level 1 sequentially to those at level 2 and 3.
INGUINAL LYMPH NODES:
The lymph nodes of the lower limb are divided into superficial and deep
group. The superficial lymph nodes are readily palpable in the groin and are
subdivided into proximal set just below and parallel to the inguinal ligament
(horizontal chain) and a distal group arranged along the upper end of long
saphenous vein (vertical chain). Deep inguinal lymph nodes lie in the femoral
triangle along side the upper part of the femoral vein. One of these deep inguinal
node lies in femoral canal called node of Cloquet.
LYMPH NODE ENLARGEMENT:
Lymph node enlargement may occur because of proliferation of cells of the
lymphocyte and monocyte-macrophage systems usually in response to antigenic
stimulus or infiltration by inflammatory cells in infections involving lymph nodes
(lymphadenitis), In situ proliferation of malignant lymphocytes or
macrophages, infiltration of nodes by metastatic malignant cells or infiltration of
lymph nodes by metabolite laden macrophages in lipid storage diseases.
In normal immune responses, antigen stimulation of macrophages and
lymphocytes in lymph nodes expert profound influences on lymphocytic
traffic. One of the earliest effects of the antigen is to increase the blood flow
through the affected node, which may reach 10 to 25 times of normal
levels. Lymphocytes accumulate in antigen stimulated nodes by increase in traffic
through the node, decreased egress of lymphocyte from antigen stimulated
nodes, and proliferation of responding T and B cells. A lymph node may thus
reach 15 times its normal size 5 to 10 days after antigen stimulation.
DISEASES ASSOCIATED WITH LYMPHADENOPATHY:
In childhood, the lymphoid system grows rapidly. Possibly as a result of
antigenic stimulation, and lymph node enlargement in some parts of the body is
an almost universal finding. Thus nearly all children under 12 years have
palpable cervical, axillary and inguinal nodes. In adults inguinal node
enlargement is commonplace, presumably secondary to repeated immunological
or inflammatory stimuli generated by multiple minor injuries to the lower
extremity. Enlargement of other superficial nodes is unusual but occasionally
occurs for the same reason, such as repeated hand injuries in manual labourers.
History and Examination:
Enlargement of lymph nodes require investigation when there are one or
more new nodes present equal to or greater than 1 cm in diameter, and not
known to arise from a previously recognised cause. However, this is not a rigid
criterion and under certain circumstances new multiple or single smaller lymph
nodes may warrant investigation. While taking history of the patient with lymph
node enlargement following points are particularly noted:
1. Age : Hodgkin’s disease, tuberculosis, syphilisare disease of the young,
whereas secondary involvement of lymph node occurs in old age
2. Duration: In acute lymphadenitis is short, whereas it is long in chronic
lymphadenitis like tuberculosis etc.
3. Which group was first affected? In case of generalised involvement of
the lymph nodes the physician should know which group was first affected
as it may give some clue to the diagnosis for example cervical group is first
affected in many cases of Hodgkin’s lymphoma.
4. Pain: lymph nodes are painful in both acute and chronic
lymphadenitis but are painless in syphillis, lymphosarcoma, secondary
5. Fever: evening rise in temperature is a characteristic feature of
tuberculosis. In filaria periodic fever is very common. In Hodgkin’s disease
intermittent bouts of recurrent fever is quite peculiar. So called Pel-Ebstain
type of fever.
6. Primary focus: whenever the lymph nodes are enlarged, it is usual
practice to look for the primary focus in the drainage area of the lymph
nodes for the reason of lymph node enlargement.
On examination : The following Important factors should be considered in
assessing the significance of enlarged lymph nodes
1. The Node location: The location of enlarged lymph nodes may
suggest important clues to diagnosis. Enlarged posterior cervical lymph nodes
are frequently present in scalp infections, Toxoplasmosis, and rubella, where
as anterior auricular, nodes suggest infections of the eyelids and conjunctiva,
Lymphomas commonly involve cervical lymph nodes and can
occasionally involve posterior auricular and occipital nodes as well. Enlarged
suppurative cervical nodes are seen in mycobacterial lymphadenitis. Unilateral
jugular or mandibular lymph node enlargement suggests lymphoma or non
lymphoid head and neck malignancy. Supraclavicular and Scalene lymph
node enlargement is always significant and frequently results from metastasis
from intrathoracic or gastrointestinal malignancies or from lymphoma.
Virchow’s node is an enlarged left supraclavicular lymph node infiltrated with
metastatic tumor usually from the gastrointestinal tract. Unilateral axillary
adenopathy can be seen with breast carcinoma, infections of the upper
extremity and cat scratch disease. Unilateral epitrochlear node enlargement is
usually due to hand infections, bilateral epitrochlear node enlargement is seen
in Sarcoidosis and secondary Syphillis. Bilateral inguinal adenopathy can be
seen in variety of venereal infections, however, lymphogranuloma venereum
and syphilis are associated with unilateral inguinal adenopathy. Progressive
inguinal lymphnode enlargement without obvious infection suggests malignant
disease. Femoral node enlargement has been reported to occur in Pasteurella
Pestis infection and lymphomas.
Enlargement of deeply situated lymph nodes may present by indirect
evidence. Certain symptoms should raise the suspicion of hilar or mediastinal
node enlargement. These patients may present with cough or wheezing due to
airway compression, recurrent laryngeal nerve compression with hoarseness,
paralysis of diaphragm, dysphagia with oesophageal compression and swelling
of the neck, face, or arm due to superior vena cava or subclavian vein
compression. Enlarged retroperitoneal lymph nodes may present as oedema
of lower limbs. Intra abdominal lymph nodes may sometimes be palpable in
2. The physical characteristics of the peripheral lymph nodes are
important. Nodes of lymphomas tend to be rubbery and firm and discrete but
occasionally they are matted. Tuberculous lymph node are matted and
tender. Nodes involved with metastatic carcinoma are usually hard and may
be fixed to underlying tissue. In acute infections, nodes are tender,
asymmetrically enlarged, matted together and the overlying skin may be
3. The clinical setting is also important in assessing lymphadenopathy. In a
young college student with fever and recent onset of lymph node enlargement,
infectious mono nucleosis syndromes are important to consider. In
homosexuals, hemophiliacs, and intravenous drug abusers with systemic
lymphadenopathy, the acquired immunodeficiency syndrome (AIDS) should
be considered. In all case of lymphadenopathy Liver and Spleen should be
palpated for enlargement and nodularity.
Good physical examination techniques for palpation and assessment of lymph
nodes are essential for providing useful information on which diagnostic and
therapeutic decisions can be based. For serial evaluation of nodes, the
documentation of each node with regard to size, location, consistency soft and
mobility at each examination is critical. For cervical nodes the examiner may
stand behind or in front of the seated patient to palpate the the neck and to
examine in sequence the sites of various groups of nodes.
Central axillary nodes are located near the middle of the thoracic wall of the
axilla, lateral axillary nodes are located near the upper part of the humerus
along the axillary vein and are best felt by having the patients arm
elevated. Subscapular nodes can be felt under the anterior edge of the
latissmus dorsi muscle and pectoral nodes are beneath the lateral edge of the
pectoralis major muscle. Infraclavicular nodes can be felt under the distal end
of clavicle and may require bimannual palpation.
Epitrochlear nodes are located approximately 3 cm proximal to the
medial humeral epicondyle. Palpation of epitrochlear nodes is best
accomplished by paplation of epitrochlear node area in an anterior to posterior
Enlarged abdominal lymph nodes can be difficult to palpate and may
be felt if the patient has shallow abdominal cavity. Pelvic nodes are best
evaluated with deep palpation of the lower abdomen by rolling the extended
finger over the pelvic brim.
CAUSES OF LYMPH NODE ENLARGEMENT:
Bacterial: Streptococci, staphylococci, anthrax, brucellosis, Pasteurella,
Salmonella, Haemophilus, ducreyi;Mycobacterial infections: Tuberculosis, leprosy
Viral: Infectious mononucleosis syndrome (cytomegalovirus, EB Virus), Human
Immunodeficiency virus type I, rubella, Varicella-herpes zoster.
Fungal: Coccidioidomycosis, histoplasmosis
Chlamydial infections: Lymphogranuloma veneram, trachoma.
Parasitic injections:Microfilariasis, trypanosomiasis.
Spirochetal-diseases: Syphillis, yaws, leptospirosis, toxoplasmosis
A. HEMATOLOGIC – Hodgkin’s disease, lymphomas, malignant histiocytosis
B. METASTATIC TUMORS OF LYMPH NODES: Breast, Melanoma, Seminoma,
tumors of lung, prostate, kidney, head and neck, gastrointestinal tract, Kapsoi’s
C. IMMUNOLOGICAL DISEASES
a) Rheumatoid arthritis
b) Systemic lypus erythematosis
d) Serum Sickness
e) Drug reactions: Phenytoin, hydralazine, Allopurinol.
f) Angio immunoblastic lymphadenopathy.
D. ENDOCRINE DISEASE: hyperthyroidism
E. LIPID STORAGE DISEASE: Gaucher’s and Niemann-Pick diseases
a) Giant follicular lymph node hyperplasia
b) Sinus histiocytosis
c) Dermatopathic lymphadenitis
f) Muco cutaneous lymph node syndrome.
The investigation of lymphadenopathy can be organised according to where
nodes occur and type of clinical symptoms present. Most lymphadenopathy
patients do not require a biopsy and atleast half require no laboratory study. If
the patients history and physical findings point to a benign cause for
lymphadenopathy, then careful follow up at 2 to 4 week interval can be
employed. The patient should be instructed to return for re-evaluation if the
node(s) increase in size.
Routine investigations should include a full blood count, erythrocyte
sedimentation rate, and the exam ination of blood film. These may be
diagnostic in Leukemia, or point to a viral cause such as glandular
fever. Additional investigations might include a chest radiograph, biochemical
profile, and antibody screening for an infective cause together with specific
microbial cultures as appropriate.
Chest Radiograph: Useful in assessment of the amount of medistinal disease,
hilar nodes and parenchymal lung lesion. Hilar and mediastinal gland
enlargement is seen in Tuberculosis, sarcoidosis, lymphomas, metastatic
carcinoma and coccidioidomycosis and histoplasmosis.
ULTRASONOGRAPHY: Is useful in screening patients suspected of abdominal
lymph node enlargement due to tuberculosis or lymphoma or secondary to some
malignancy. Its resolution is not as good as that obtained with CT. It is mainly
useful as a quick guide to treatment response, but even then it is highly operator
COLOUR DOPPLER SONOGRAPHY : Colour Doppler Sonography is proving
useful in differentiating benign from malignant cervical lymphadenopathy. On
colour doppler the patterns of hilar vascularity, central nodal vascularity and
peripheral vascularity are assessed. The highest resistive index and pulsatility
index are measured from special wave forms. Unlike nodes with benign reactive
disease 98% nodes with malignant disease and 100% of tuberculous nodes show
abnormal patterns of nodal vascularity. Also high values for the resistive and
pulsatility indexes were highly specific for malignant lymphadenopathy.
CONTRAST ENHANCED CT (CECT): In recent year CT has become the main
radiological technique for assessing lymph node enlargement in the mediastinum,
abdomen and pelvis. It is non invasive and has the advantage of simplicity. It is
particularly effective in revealing enlargement of and can also detect enlarged
nodes in the mediastinum that may not have been apparent on plain chest
radiograph. It may also detect large deposits in the liver and spleen. In
mediastinal tuberculous lymphadenitis, CT findings of nodes with central low
attenuation and peripheral rim enhancement suggests active disease, and
findings of homogenous and calcified nodes suggested inactive disease. Low
attenuation areas within the nodes had pathologic correspondence with areas of
caseation necrosis and may be a reliable indicator for disease activity. In
abdominal tuberculous lymphadenopathy contrast enhanced CT appearance is of
peripheral rim enhancement and of multilocular appearance. The enlarged lymph
nodes of TB were less than 4cm in diameter. Lymphadenopathy caused by
hematogenous dissemination often accompanied splenic involvement showing
multiple low density foci in the spleen. The predominant sites
of lymphadenopathy of disseminated TB were hepatoduodenal, ligamentous,
hepatogastric ligamentous, mesenteric and both upper and lower portions of the
retroperitoneal lymph nodes, where as non-disseminated Tuberculosis all the
above lymph nodes excluding the lower retroperitoneal lymph nodes. CT can
neither detect disease in normal sized lymph nodes nor distinguish infiltration
from reactive hymperplasia. In lymphomas it is particularly effective in revealing
enlargement of retroperitoneal, iliac and mesenteric lymph node groups and can
also detect enlarged nodes in the mediastinum that may not have been apparent
on the plain chest radiograph.
M.R. EVALUATION : Magnetic resonance imaging (MRI) can help in
distinguishing lymph node enlargement due to various etiology namely
Tuberculosis, Hodgkin’s lymphoma and metastatic lymph node enlargement
Tuberculous lymph nodes appeared iso-intense in both T1W1 and T2W1, on
contrast injectionmultiple hypointense foci can be seen. The metastatic lymph
nodes revealed solitary or multiple hypointense foci in T2W1, whereas the
lymphomatous lymph nodes revealed heterogenous intensity. Though the
lymphomatous nodes revealed mild to moderate type of enhancement, the
metastatic nodes revealed dense enhancement of the multiple foci which were
seen in non contrast images.
FINE NEEDLE ASPIRATION CYTOLOGY/BIOPSY (FNAC/B): This is a simple
procedure, when one of the peripheral lymph nodes is involved. However
aspiration of deep central lymph nodes require the assistance of radiological
interventional methods, surgery or endoscopy. Central lymph nodes are localized
and aspirated under fluoroscopic, ultrasonographic or CT (computed tomographic)
guidance. Fiberoptic bronchoscopy, thoracoscopy and medistianoscopy can aid
in aspirating mediastinal lymph nodes. It may be possible to visualize abdominal
lymph nodes and aspirate them by laproscopic procedures.
However the accuracy of FNAC deplends on the experience of the clinician
taking the biopsy and the cytologist who reports it. For a reasonably competent
cytologist certain diagnoses are relatively easy. Well differentiated squamous or
adenocarcinoma present no real problems, nor does the confirmation of highly
malignant cells. Malignant lymphoma can usually be distinguished from
carcinoma or reactive lymph node. Malignant lymphocytes in a neck node with a
normal blood film confirm the diagnosis of Lymphoma. In cases of
granulomatous lymph node enlargement Fine needle aspirations could be a
valuable method for cytological and bacteriological studies. The histopathological
criteria used for diagnosis for tuberculosis is presence of chronic granuloma
consisting of epitheloid cells, and presence of necrotic material with or without
epitheloid cells. The entire smear is stained with Z-N stain and should be
searched for AFB under oil immersion and part of aspirated material should be
cultured on a pair of Lowenstein Jensen (LJ) medium, and incubated at 37 C for 8
weeks. The growth once evident is examined by Z-N staining for acid fast bacilli.
Gaining experience in Fine needle aspiration cytology has considerably
reduced the number of lymph node biopsies required to come to a diagnosis in
clinical enlargement of lymph nodes. When tissue is required by pathologist for
the diagnosis sometimes Drill biopsy or Needle biopsy may prove to be useful.
LYMPH NODE BIOPSY:
There are five main reasons for performing a lymph node biopsy. They are:
1. To make a diagnosis in a case of persistent unexplained lymph node
How long should one abserve an unexplained enlarged lymph node
before removing it for biopsy? It is impossible to give a generally
applicable answer to this question. So, much will depend on the
circumstances of the case. A rubbery or hard node demands immediate
exploration regardless of the length of history. Conversely, soft and
moderately enlarged nodes, especially in children, should seldom be
removed at all unless there are other indications.
2. To confirm a diagnosis suspected on other grounds. The clinical history
or findings on physical examination may be highly suggestive of malignant
disease, but even where the primary tumor is obvious, removal of an
involved lymph node may be indicated, for example, to discover the
histological type of a bronchial carcinoma, as a necessary basis for
planning treatment. In the same way, the presence of multiple nodes in
different groups may suggest a malignant lymphoma, but lymph node
biopsy is necessary to confirm and elaborate on this diagnosis.
3. To make a diagnosis or assist in the investigation of a patient who has
unexplained symptoms, such as fever or loss of weight, accompanied by
4. To assess the extent of spread of known malignant disease.
5. To monitor the progress of disease in patients with malignant
lymphoma. Two specific indications of biopsy are: a) enlarged nodes
persisting after therapy which would normally be effective in that particular
disease and situation; b) enlarged nodes which appear in a patient
previously in remission after effective therapy.
Technique of lymph node biopsy:
It may be easy enough to remove a normal lymph node, but it often requires
great skill to remove intact an enlarged and diseased node. For the interpretation
of a difficult lymph node biopsy it is important not only that the node should be
intact, if possible, but that it should be subjected to the minimum of trauma in the
process of removal. A badly traumatized biopsy may be completely
Choice of node for biopsy is also important. If there is only a single
enlarged node then clearly that is the one to remove. If, on the other hand, there
is widespread lymphadenopathy, then other considerations apply. Inguinal nodes
should be avoided where possible in adults, because they so ofen show scarring
or other evidence of past lymphadenitis which may complicate
interpretation. Axillary nodes not infrequently show fatty involution of their
centres, so that from the histopathologist’s point of view, cervical nodes are
generally to be preferred.
The most accessible node is not always the best one to remove and,
generally, speaking, the best node from the point of view of the pathologist is the
largest one available. All too often the surgeon is tempted to remove a smaller
more accessible node, but this may not be representative and the diagnosis may
consequently be missed. If there are multiple enlarged nodes, the removal of
several nodes may be easily achieved and may give more information than can
be obtained from a single node, for even two adjacent nodes do not always look
alike. However, there are occasions when it is necessary to obtain material from
thoracic or abdominal nodes. Mediastinal nodes may be biopsied on
mediastinoscopy, but it is often difficult to get a satisfactory (i.e. untraumatized)
biopsy by this means and it may be necessary to resort to open operation to make
a diagnosis. Scalane node biopsy often provides useful information about the
nature of underlying lung disease eg. Sarcoidosis or Carcinoma. 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/pretreatment
On receipts, the fresh node should be cleanly sliced in half with a new
scalpel blade. If the history or the appearance of the node suggest infection, one
half of the node should be immediately placed in a dry sterile container for the
appropriate bacteriological, virological investigations. The other half of the node
may then be placed in fixative. An excised lymph node should be handled with
circumspection where a diagnosis of HIV infection seems likely, and gloves
should always be worn when handling fresh specimens.
Imprints are useful, not only for showing the appearance of the cells in a
cytological preparation but when stained by a Romamowsky method, for
comparision with blood or bone marrow smears, but also for cytochemical or
Bilateral lower limb lymphangiography is an excellent method for defining
abnormalities in the femoral, inguinal, iliac and para-aortic area lymph nodes, and
is reportedly accurate in detecting abnormalities in these areas in about 80
percent of cases. However, the technique does not help in defining abdominal
nodes above the level of the kidneys or mesentric nodes, which may, in part
account for the 10 to 25 percent of equivocal or false negative results. False
positive results are quite rare. One advantage is that the dye remains in the
lymph nodes for some time, and can be used to follow the progress of disease
during therapy. It is also capable of demonstrating disordered architecture in
normal sized lymph nodes.
The use of lymphangiography has declined significantly after introduction of
CT scanning, although the two techniques are in fact complimentary, with similar
individual sensivities and specificities. Lymphangiography can be unpleasant for
the patients unless skillfully performed.
CT Lymphangiography Ultrasound
Thin patients especially
good for nodes in the
Internal node structure hilum of liver and spleen
Mesentric and high para-
can be seen. Images and mesentric lymph
Advantages aortic lymphnodes can
persist for month or nodes
useful for guidance of
Of little value for
diagnosis of malignancy
Needs fat for resolution
in normal size nodes
thus not good in thin Poor for low para-aortic
patients and illiac nodes due to
Disadvantages Does not image nodes in
interface from intestinal
hilum of liver and spleen
Cannot determine gas.
or in mesentry. May
internal node structure
have reaction to contrast
The lymphomas are malignant neoplastic proliferations of cells of the immune
system. The lymph nodes are the sites most frequently involved and progressive
lymphadenopathy is the most common presentation.
Historically the lymphomas have been separated on histological grounds into
Hodgkin’s disease and the non-Hodgkin’s lymphomas this distinction is being
partially eroded with better understanding of the biology of these
conditions. Immunologically, the majority of non-Hodgkin lymphomas (of any
histological sub type) are of B cell origin, with about 10 to 20 percent expressing a T
Non-Hodgkin lymphoma accounts for more than three quarters of the cases of
lymphoma. Thirty one percent of all lymphomas presented in an extra nodal site
such as the gut or skin, of which only four percent were Hodgkin’s
disease. Diagnosis of lymphoma should always be considered in a patient
presenting with signs or symptoms affecting multiple systems or with a pyrexia of
unknown origin, ill-defined malaise, or unexpected weight loss.
The most common manifestation of lymphoma is lymphadenopathy. Most
clinical presentations of Hodgkin’s disease involve superficial nodes in the neck or
axillae, although involvement of internal lymph nodes (principally mediastinal and
para aortic) will be frequently revealed by further investigation. Involvement of
lymphoid tissue in other sites (extranodal involvement) is much more common in non
Hodgkin’s lymphoma than in Hodgkin’s disease. Indeed, primary extra nodal
lymphomas are virtually always of the non-Hodgkin’s variety. Extranodal sites most
commonly involved are the submucosal tissues of the intestinal tract (including the
naso-oropharyngeal area, Waldeyer’s ring), the bone marrow, liver and bronchial
mucosa, no site is immune.
Hodgkin’s disease appears to spread from node to contiguous mode via the
lymphaties. It is thus more likely to be localized than widespread. Non-Hodgkin’s
lymphoma spread via the blood stream, and often involve cells that normally
recirculate widely and continue to do so after malignant transformation, they are thus
best considered as systemic disorder.
In general the incidence of lymphomas increase with age, and most patients
that develop lymphoma are middle aged or elderly. The principal exception is
Hodgkin’s disease, which has in addition, a peak incidence early in the third decade.
The diagnosis of lymphoma is often strongly suggested by the history and
clinical examination, but biopsy of a lymph node or other affected tissue is required
to establish the diagnosis and to distinguish between Hodgkin’s disease and non-
Surgical lymph node biopsy remains the ‘gold standard’ for determining the
histological sub type of lymphoma. However, Fine needle aspiration of enlarged
lymph nodes can be useful in distinguishing reactive from pathological lymph
nodes. The histology of the lymphomas is frequently difficult to interpret and every
effort should be made to obtain an adequate sample and to handle it correctly. Much
additional knowledge can be obtained about the origin of the lymphoma from
immuno-chemistry, which may require a specimen of fresh frozen tissue. Biopsy
samples should not, therefore, be placed automatically into formalin or other
fixatives, it is essential to alert the histopathologist before the biopsy is done to
ensure prompt and correct handling.
Pathological diagnosis of Hodgkin’s disease is the presence of characteristic
giant cells of the Reedsternberg type in an appropriate histological setting.
Rye histological classification of Hodgkin’s disease:
Subgroup Major Histological features Approximate Frequency
Lymphocyte Abundant normal appearing lymphocytes 2-10%
Predominance with or without benign histiocytes,
Nodular Sclerosis Nodules of lymphoid infiltrate of varying size,
separated by bands of collagen and containing 40-80%
numerous “lacunar cell” variants of R-S cells
Mixed cellularity Pleomorphic infiltrate of eosinophils,
Plasma cells, histiocytes and lymphocytes 20-40%
With numerous R-S cells
Lymphocytic Paucity of lymphocytes with numerous R-S cells
Depletion often bizarre in appearance, may have diffuse fibrosis 2-15%
or reticular fibres
It has been said that nowhere in the field of pathology has there been more
confusion (and debate) than in the nomenclature and classification of the Non-
Hodgkin’s lymphoma. The most widely used classification is the Rappaport system.
Modified Rappaport classification of Non-Hodgkin’s Lymphoma
Nodular Sub types
Lymphocytic poorly differentiated
Mixed lymphocytic and histiocytic
Diffuse sub types
Lymphocytic well differentiated
Lymphocytic poorly differentiated
Mixed, lymphocytic and histiocytic
Undifferentiated (Burkitt’s or non-Burkitt’s types)
It is important to determine as accurately as possible the full extent of
involvement with Hodgkin’s disease, as this has an important bearing on Prognosis
and selection of treatment. Truly localized disease can be effectively
treated with radiotherapy with a very high chance of cure. Chemotherapy is
appropriate for more widespread disease. The staging classification agreed at a
meeting in Ann Arbor is in Widespread use.
Ann Arbor staging classification
Stage I Involvement of a single lymph node region (I) or of a single extralymphatic
organ or site (IE)
Sage II Involvement of two or more lymph node regions on the same side of
diaphragm (II) or localized involvement of extralymphatic organ or site
and of one or more lymph node regions on the same side of the
Stage III Involvement of lymph nodes on both sides of the diaphragm (III). There
may be splenic involvement (IIIs), or localized involvement of extra
lymphatic organ or site (IIIE).
Stage IV Involvement of extranodal sites, other than by direct invasion from an
affected node, with or without lymph node involvement.
For each stage, qualifier ‘A’ or ‘B’ is used. ‘A’ denotes the absence and ‘B’
presence of typical symptoms: weight loss, fever, drenching night sweats.
Staging Laparotomy: The use of staging laparotomy has markedly declined in
recent years in response to number of factors:
(a) advent of CECT, which is non invasive and delinerates the intra
abdominal lymph nodes, it can also show splenic & liver infiltrates.
(b) absence of clear survival advantage for groups of patients who
have been staged by laparotomy.
(c) success of chemotherapeutic regimens in controlling the disease
and increasing tendency to use chemotherapy in earlier stage of
(d) Splenectomy carries a small but significant morbidity, risk of
overwhelming post splenectomy infection.
Staging laparotomy should include detailed inspection of the abdomen. The
removed spleen should be sectioned in 0.3cm slices. If disease is identified in
spleen total number of nodules should be enumerated. Examination of liver
should include a wedge biopsy of the right lobe, three needle biopsies of the
right and left lobes and a biopsy of any grossly abnormal hepatic lesions. After
inspection and palpation of the nodal groups, a biopsy should be taken from
the right and left para aortic and iliac nodes. Lymph nodes should be removed
from splenic hilar, porta, hepatic and mesenteric regions. Iliac bone marrow
biopsy should be performed at the time of operation.
1. LYMPH NODE PATHOLOGY, Second Edition, Harry L. loachim. J.B. Olippincott Company,
2. Slevens A, Lowe J. Histology. London: Gower Medical Publishing 1992
3. Ehrich, W.E.: The role of the lymphocyte in the circulation of lymph . Ann. NY Acad Sci, 46:823,
4. Arno J 91980) Atlas of lymph node Pathology M.T.P. Press, Lancaster.
5. GAG Decker, D.J. Dee Plessis: Lee Mc Gregor’s Synopsis of SURGICAL ANATOMY
12th Ed. (1986)
6. Suen J.Y., Goeptent H: Editorial standerization of neck dissection nomenclature., Head Neck
Surg 11:25, 1981
7. Shah J.P., Strong E, Spiro RH, Vikram B: Neck dissection: current status and future
possibilities. Clin Bull 11:25, 1981
8. Turner – warwick RT. The lymphatics of the breast Br J Surg. 1959, 46: 574-82
9. Butcher E., Weissman I, Lymphoid tissues and organs in WE Paul (ed). New York, Raven 1984
10. Na DG, Lim HG, Byun HS, Kim HD, K.YH: Differential diagnosis of cervical
lymphadenopathy. Usefulness of color Doppller Sonography. Am J Roentgenol 1998
Mar, 170(3): 715-718
11. Yang 2, Sone S, Min P, etal. Distribution of contrast enhanced CT appearance of abdominal
tuberculosis lymphadenopathy. Orv Hetil 1996 Decl: 137 (48): 2683-2685
12. Bergsagel. D.E. etal (1982) Results of treating Hodgkin’s disease without a policy of
laparotomy staging. Cancer Treatment Reports 66, 717-731.
13. Carbone P.B., Kaplan H.S. Musshof K. Smithers D.W. and Tubiana M. (1921). Report on the
committee on Hodgkin’s disease staging classification. Cancer Research, 31, 1860-1