CLINICAL WORK UP OF A PATIENT WITH

LYMPH NODE ENLARGEMENT

 

Dr.Anil Haripriya

 

          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 GROUPS

DEEP LYMPH NODE GROUPS

1.Superficial Cervical lymph nodes:

1.  Deep Cervical lymph nodes

2. Supra clavicular lymph nodes 2. Intra thoracic lymph nodes    (Mediastinal)

3.  Extra thoracic lymph nodes (axillary group)

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 inferior mesenteric)

  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

facial artery.

These nodes receive lymph from conjunctiva and eyelids, nose and the

neck.

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 the neck.

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 supraclavicular nodes.

 

    

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 thoracic duct.

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

(submandibular nodes).

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

the triangle).

 

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 muscle.

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

omohyoid muscle.

 

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

vessels.

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 from above.

          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

carcinoma etc.

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 thin subjects.

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

erythematous.

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 direction.

              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:

Infection:

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

NEOPLASTIC

A.       HEMATOLOGIC – Hodgkin’s disease, lymphomas, malignant

histiocytosis & leukemias.

B.  METASTATIC TUMORS OF LYMPH NODES: Breast, Melanoma,

Seminoma, tumors of lung, prostate, kidney, head and neck, gastrointestinal

tract, Kapsoi’s sarcoma Neuroblastoma.

C.      IMMUNOLOGICAL DISEASES

a)      Rheumatoid arthritis

b)     Systemic lypus erythematosis

c)     Dermatomyositis

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

F.      MISCELLANEOUS

a)      Giant follicular lymph node hyperplasia

b)     Sinus histiocytosis

c)     Dermatopathic lymphadenitis

d)     Sarcoidosis

e)     Amyloidosis

f)      Muco cutaneous lymph node syndrome.

 

INVESTIGATION  

     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

dependent. 

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

enlargement.

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

lymphadenopathy.

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 uninterpretable.

          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 lymphangiogram.

          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

immunochemical studies. 

LYMPHANGIOGRAPHY:  

          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

AdvantagesMesentric and high para-aortic lymphnodes can be delineated.

Internal node structure can be seen. Images persist for month or

Thin patients especially good for nodes in the hilum of liver and spleen and mesentric

years

lymph nodes

useful for guidance of FNAC 

Disadvantages

Needs fat for resolution thus not good in thin patients

Cannot determine internal node structure

Of little value for diagnosis of malignancy in normal size nodes

Does not image nodes in hilum of liver and spleen or in mesentry. May have reaction to contrast dye.

Poor for low para-aortic and illiac nodes due to interface from intestinal gas.

 

LYMPHOMAS:  

          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 cell phenotype.

          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-

Hodgkin’s lymphoma.

          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. 

PATHOLOGY:  

          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,

                                    rare RS.Cells

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

NON-HODGKIN’S LYMPHOMA: 

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

          Histiocytic

Diffuse sub types

          Lymphocytic well differentiated

          Lymphocytic poorly differentiated

          Mixed, lymphocytic and histiocytic

          Lymphoblastic Lymphoma

          Histiocytic

          Undifferentiated (Burkitt’s or non-Burkitt’s types)

 

STAGING

          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

diaphragm (IIE)

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

disease.

(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. 

 

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