DISEASES OF LYMPHATIC SYSTEM

CONTENTS

▪ Introduction

▪ Lymphadenopathy

i. Cervical

ii. Generalized

▪ Lymphadenitis

▪ Lymphangioma

▪ Lymphoid neoplasms

▪ Investigations

▪ Conclusion

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 INTRODUCTION

Lymph node enlargement may be an incidental finding on examination, or may be

associated with a patient complaint. It is likely that over half of all patients examined each
day may have enlarged lymph nodes in the head and neck region. Although most cervical
lymphadenopathy is the result of a benign / infectious etiology, clinicians should search for a
precipitating cause and examine other nodal locations to exclude generalized
lymphadenopathy.With such a high frequency of occurrence, oral health care providers need
to be able to determine when lymphadenopathy should be investigated further?

Lymph nodes in the axillary and cervical regions up to 1 cm in diameter, those in the
inguinal region up to 1.5 cm in diameter, and those in the epitrochlear region up to 0.5 cm in
diameter are considered normal. Because younger children are being exposed constantly to
newer antigens and inciting immune responses, lymph nodes in children usually are larger
than those found in adults

Lymph nodes may be palpable in normal people, especially in the submandibular,

axilla and groin regions. Lymph nodes larger than 1 cm in diameter are generally
considered abnormal.

Lymph node enlargement is part of our body’s normal immune response. Lymph
nodes are distributed along the lymphatic system and found throughout the human body; they
are centres for antigen presentation, antigen processing, and antigen recognition.

The cell population within a lymph node consists mainly of macrophages, dendritic
cells, B- lymphocytes, and T-lymphocytes. These cells function to coordinate an antigenic
response. Upon detection of foreign proteins and microorganisms, the macrophages and
dendritic cells, or antigen presenting cells, are carried through lymphatic channels to the
nearest lymph node. These antigen-presenting cells travel through the lymph node, presenting
antigens to lymphocytes found within the node. B-cells are found within the lymphoid
follicles of the cortex, and T-cells reside in the paracortical regions.

When antigen recognition occurs, B-cell surface immunoglobulin binds with the
antigen and forms a germinal centre within the lymph node. Next, an immunoglobulin gene
with higher affinity for the antigen is produced. Migration of the B-cell to the medullary
region occurs, followed by differentiation of the B-cell to a plasma cell, which then secretes
modified immunoglobulin.

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 When T-cells encounter antigen and recognition occurs, the T-cell proliferates and
produces T-cells specific for the inciting antigen. Consequently, this humoral and cell-

HUMORAL CELL MEDIATED

Surface Ig
B-cell T-cell
Binds with antigen

Germinal centre in
Lymph node Proliferation

Medullary region
Differentiation Antigen specific t-cells

Plasma cell

secretes

Modified Ig

mediated response results in expansion of the lymph node. Antibodies and specified T-cells
spill from the node, entering the lymphatic circulation and eventually travel into the blood
stream, where they will be able to localize to the site of infection.

Normal Lymph Nodes

It is important to know the normal sizes of lymph nodes at different sites in healthy
children. A number of studies have demonstrated enlarged and palpable lymph nodes in up to
one-half of healthy neonates, infants, and older children. Because younger children are being
exposed constantly to newer antigens and inciting immune responses, lymph nodes in
children usually are larger than those found in adults. Older children and adolescents have
smaller lymph nodes than do younger children. Lymph nodes in the axillary and cervical
regions up to 1 cm in diameter, those in the inguinal region up to 1.5 cm in diameter, and
those in the epitrochlear region up to 0.5 cm in diameter are considered normal.

Examination of Lymph Node and Lymphatic Organs:

The size of the enlarged lymph node aids in determining the need for further
evaluation. Lymph nodes larger than 2 cm are more likely to harbour a more serious disease
process. The number of lymph nodes and the consistency, fluctuance, tenderness, mobility,
and presence of matting should be noted. Lymphadenitis is characterized by swelling of
lymph nodes in conjunction with pain, skin changes in the form of erythema and edema, and

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tenderness. All other areas of potential lymph node enlargement should be examined. The
presence of liver and spleen enlargement should be evaluated. It is important to examine the
drainage area in cases of localized lymphadenopathy. A careful head, neck, and
oropharyngeal examination may reveal a primary focus of infection. The presence of rash and
petechiae may help to make the diagnosis. Conjunctival injection without exudates may be
present in patients with Kawasaki disease. Exudative conjunctivitis is present in infection
with Bartonella, adenovirus, and Francisella tularensis (tularemia). Bone and joint tenderness
should be looked for.

LYMPHADENOPATHY

DEFINITION:

Lymphadenopathy is defined as an abnormality in size and consistency of lymph

nodes.It is a clinical manifestation of regional or systemic disease and serves as an excellent
clue to the underlying disease.

LYMPHADENOPATHY

Hyperplasia Infiltration
Tissue oedema

Immunologic/Infectious Cancer Cells, lipid cells,

Glycoprotein laden
macrophages

CAUSES OF LYMPHADENOPATHY

Infectious Diseases

a. Viral—Infectious mononucleosis (EBV, CMV), Infectious hepatitis, Herpes simplex,

HHV6, VZV, Rubella, Measles, Adenovirus, HIV

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b. Bacterial—Streptococcus, Staphylococcus, Cat-scratch disease, Brucellosis, Tularaemia,
Chancroid, Tuberculosis, Atypical mycobacterial infection, Primary and Secondary syphilis,
Diphtheria, Leprosy.

c. Fungal—Histoplasmosis, Coccidioidomycosis, Paracoccidioidomycosis

d. Chlamydial—Lymphogranuloma venereum, Trachoma

e. Parasitic—Toxoplasmosis, Leishmaniasis, Trypanosomiasis, Filariasis

f. Rickettsial—Scrub typhus, Rickettsial pox

II. Immunologic diseases

a. Rheumatoid arthritis

b. Mixed connective tissue disease

c. Systemic lupus erythematosus

d. Dermatomyositis

e. Sjogren’s syndrome

f. Serum sickness

g. Drug hypersensitivity

h. Primary biliary cirrhosis

i. Graft-vs-host disease

j. Silicone-associated

III. Malignant diseases

a. Hematologic - Hodgkin’s, non-Hodgkin’s, ALL, CLL, Hairy cell Leukaemia, Malignant

Histocytosis, T-cell lymphoma, multiple myeloma with amyloidosis.

b. Metastatic—from primary sites

IV. Lipid storage disease—Gaucher’s disease, Niemann-Pick, Tangier

V. Endocrine disease—Hyperthyroid, Adrenal insufficiency, Thyroiditis

VI. Other disorders

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a. Castleman’s disease (giant lymph node hyperplasia)

b. Sarcoidosis

c. Dermatopathic lymphadenitis

d. Lymphomatoid granulomatosis

e. Kikuchi’s disease (histiocytic necrotizing lymphadenitis)

f. Kawasaki’s disease (mucocutaneous lymph node syndrome)

g. Histocytosis X

h. Severe hypertriglyceridemia

INFECTIONS

UPPER RESPIRATORY INFECTIONS

Acute bilateral cervical lymphadenopathy is commonly caused by viruses and bacteria

that infect the upper respiratory tract in both adults and children. Symptoms suggestive of
upper respiratory infections include cough, sinus congestion, rhinorrhea, and occasionally
fever and malaise.

Cervical lymph nodes may be bilateral, acutely swollen and tender, and may persist
for weeks after the resolution of other symptoms. Nodes may be palpable in the anterior
triangle of the neck. Diagnosis is often based on symptomatology.

Viruses

 Adenovirus

 Influenza virus

 Respiratory syncytial virus

Bacteria

 Group A beta hemolytic Streptococcus

 Groups B, C, and G hemolytic Streptococci,

 Cornybacteria, and

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  Several anaerobes.

LOCAL INFECTION

Cervical lymphadenopathy is a common feature of localized infection. Local bacterial

infections of the head and neck often cause cervical adenopathy when draining nodes respond
to local infection, or when the infection localizes within the node itself.Bacterial infections
often result in acutely enlarged lymph nodes that are warm, erythematous, and tender. The
infection can cause cervical lymphadenopathy, which begins as enlarged, tender nodes that
may become fluctuant.

Cervical lymphadenopathy from local infection may also be of viral origin, commonly
herpes simplex virus or Coxsackie virus. Common clinical findings include acute painful
ulcers of the oral cavity or oropharynx, enlarged bilateral tender lymph nodes in the anterior
triangle of the neck, impressive submandibular and submental adenopathy, and occasionally
fever and malaise.

Local Infections:

 Tonsillar abscesses

 Salivary adenitis

 Dental abscesses

Viruses- Herpes simplex virus, Coxsackie virus

Bacteria – Staphylococcus aureus, Streptococcus pyogenes

LYMPH NODES

Bacterial Infections

 Acutely enlarged lymph nodes

 Soft

 Warm

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  Erythematous

 Tender

Viral Infections

 Enlarged

 Soft

 Bilateral

 Tender

Tuberculosis: Usually firm in consistency, discrete or matted.

Lymphomas: Usually rubbery in consistency

Malignancy: Typically hard in consistency, fixed.

Systemic Infection:

Cervical adenopathy is a common feature of many viral infections. Enlarged lymph

nodes resulting from these viral infections are firm and tender, and characteristically not
warm or erythematous.

Infectious Mononucleosis often presents with posterior and anterior cervical adenopathy

Human Immunodeficiency Virus Infection: Fever, Malaise, Failure to thrive, Non-tender

lymphadenopathy, Hepatosplenomegaly, and chronic diarrhoea.

Cat-Scratch Disease –Warm, tender, erythematous, and may be indurated or suppurative

lymph nodes.

Toxoplasmosis – enlargement of cervical nodes, firm, discrete, tender,

Primary Form of Syphilis– Oral canchre + cervical lymphadenopathy

Lyme disease– Adenopathy, fever, malaise, rash and multiple systemic findings

Rubella – Maculopapular rash + lymphadenopathy in posterior triangle of neck

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 GENERALIZED LYMPHADENOPATHY

The presence of two or more non-contiguous sites of lymph node enlargement represents a
generalized lymphadenopathy.

DIFFERENTIAL DIAGNOSIS OF SYSTEMIC GENERALIZED LYMPHADENOPATHY

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 DIAGNOSTIC ALGORITHM

LYMPHADENITIS

DEFINITION:

The term lymphadenitis refers to lymphadenopathy that occurs from infectious and
other inflammatory processes.

PATHOGENESIS:

Microorganisms reach the infected lymph node via lymphatic flow from an
inoculation site, by lymphatic flow from adjacent lymph nodes, or by hematogenous spread

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of systemic infection. Local cytokine release results in neutrophil recruitment, vascular
engorgement, and nodal edema.

Involvement of the soft tissues adjacent to the node can result in cellulitis and abscess
formation. Eventually, the node heals with fibrosis. Microorganisms that cause subacute or
chronic inflammatory changes generally produce less of an inflammatory response.

Acute Unilateral Cervical Lymphadenitis

Acute unilateral cervical lymphadenitis is usually caused by Staphylococcus aureus or

Streptococcus pyogenes (group A) in over 80% of cases. Submandibular and cervical nodes
are most frequently involved and occur most commonly in children between 1 and 4 years of
age.

Patients may have a history of recent upper respiratory tract infection or impetigo. Nodes
may be very large (up to 6 cm) and infected children may suffer overlying cellulitis and high
fever. Nodes infected with Staph aureus are more likely to suppurate

Acute Bilateral Cervical Lymphadenitis

Acute bilateral cervical lymphadenitis is the most common clinical presentation. It is

usually caused by benign, self-limited viral upper respiratory infection (eg, adenovirus,
influenza virus, enterovirus, RSV).

Symptoms of cough, rhinorrhea, and nasal congestion may suggest these etiologies. The
lymph nodes are small, rubbery, mobile, discrete, minimally tender, and without erythema or
warmth.

They are often referred to as “reactive” or “shotty” lymphadenopathy. Although the

clinical course is self-limited, the lymph node enlargement may persist for weeks.

Subacute/Chronic Bilateral Cervical Lymphadenitis

Subacute or chronic bilateral lymphadenitis is most often caused by EBV or CMV

infection. EBV causes infectious mononucleosis that can present with fever, exudative
pharyngitis, lymphadenopathy, and hepatosplenomagaly.

CMV also causes a mononucleosis-like illness. Both infections are more likely in
school-aged children and adolescents.

Subacute/Chronic Unilateral Cervical Lymphadenitis

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 Subacute or chronic cervical lymphadenitis is usually caused by Non-tuberculous
mycobacterium (NTM - Mycobacterium avium-intracellulare and Mycobacterium
scrofulaceum most commonly).

Most NTM infections occur in immunocompetent children younger than 5 years of age.
The organisms are ubiquitous in the environment. Infection usually is insidious, with node
enlargement occurring over weeks or months, although onset may be very rapid and the
clinical course indistinguishable from acute unilateral cervical lymphadenitis.

Infected lymph nodes progress to fluctuance, and the overlying skin often becomes
violaceous and thin. Fever and marked tenderness are unusual. Untreated lymphadenitis
caused by NTM may resolve, but often it progresses to spontaneous drainage with sinus tract
formation and scarring.

TUBERCULOUS LYMPHADENITIS

Lymphadenitis is the most common extra pulmonary manifestation of Tuberculosis.

Cervical lymph nodes are the most common site of involvement and reported in 60% to 90%
patients. Cervical lymphadenitis is also referred to as SCROFULA, derived from the Latin
word “glandular swelling”.

CLINICAL PRESENTATION:

It may present as a unilateral single or multiple painless slow growing mass or masses
developing over weeks to months, mostly located in the posterior cervical and less
commonly in supraclavicular region. Low grade fever, weight loss, fatigue and night sweats.

Lymph nodes are usually not tender unless (i) secondary bacterial infection, (ii)
rapidly enlarging nodes or (iii) coexisting HIV infection are evident.

PATHOGENESIS:

Tuberculous lymphadenitis is a local manifestation of the systemic disease. Primary

infection occurs on initial exposure to tubercle bacilli. Inhaled droplet nuclei are small
enough to pass mucociliary defences of bronchi and lodge in terminal alveoli of lungs.

The bacilli multiply in the lung which is called ghon focus. The lymphatics drain the
bacilli to the hilar lymph nodes. The ghon focus and related hilar lymphadenopathy form the
primary complex.

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 The infection may spread from primary focus to regional lymph nodes. From the
regional nodes, organism may continue to spread via the lymphatic system to other nodes or
may pass through the nodes to reach blood stream, from where it can spread to virtually all
organ of the body.

Hilar, mediastinal and paratracheal lymph nodes are the first site of spread of infection
from the lung parenchyma. Supraclavicular lymph node involvement may reflect the
lymphatic drainage routes for the lung parenchyma. Cervical tuberculous lymphadenitis may
represent a spread from the primary focus of infection in the tonsils, adenoids, sinonasal or
osteomyelitis of the ethmoid bone.

In untreated primary tuberculosis of children, enlargement of hilar and paratracheal

lymph nodes (or both), become apparent on chest radiographs. In initial stage of superficial
lymph node involvement progressive multiplication of the M. tuberculosis occurs, the onset
of delayed hypersensitivity is accompanied by marked hyperaemia, swelling, necrosis and
caseation of the centre of the nodes.

This can be followed by inflammation, progressive swelling and matting with other
nodes within a group. Adhesion to the adjacent skin may result in induration and purplish
discolouration. The centre of the enlarging gland becomes soft and caseous material may
rupture into surrounding tissue or through skin with sinus formation.

Jones and Campbell classified peripheral tuberculous lymph nodes into following five stages.

1. STAGE 1: Enlarged, firm, mobile, discrete nodes showing

non-specific reactive hyperplasia

2. STAGE 2: Large rubbery nodes fixed to surrounding tissue owing to Periadenitis

3. STAGE 3: Central softening due to abscess formation

4. STAGE 4: Collar-stud abscess formation and

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5. STAGE 5: Sinus tract formation.

DIAGNOSIS

The presence of 2 of the following 3 criteria has 92% sensitivity in identifying

Tuberculous lymphadenitis. The criteria are:

(1) Positive PPD skin test result,

(2) Abnormal chest radiograph, and

(3) Contact with a person who has infectious TB.

Smears

Smears can be obtained either from a draining sinus or by FNA. Ziehl-Neelsen staining of the
smears may reveal mycobacteria in the fresh specimens.

Chance of finding AFB is higher in patients with cold abscess. The sensitivity and
specificity of FNA cytology in the diagnosis of tuberculous lymphadenitis are 88% and 96%,
respectively.

Combination of FNA with culture or a Mantoux test further increases the diagnostic yield in
mycobacterial cervical lymphadenitis. If cytological findings are inconclusive repeatedly,
tissue biopsy by surgery is advisable.

Culture

Culture of mycobacterium is diagnostic for mycobacterial cervical lymphadenitis. However, a

negative culture result should not exclude the diagnosis of mycobacterial cervical
lymphadenitis.

However, several weeks are needed to obtain the culture result, which may prolong the
initiation of treatment.

Tuberculin Test

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 This intradermal test (Mantoux test) is used to show delayed type hypersensitivity
reactions against mycobacterial antigen, in which the reagent is mostly protein purified
derivative (PPD).the test becomes positive 2–10 weeks after the mycobacterial infection.

Positive reactions (>10-mm induration) can occur in M. tuberculosis infections.

Intermediate reactions (5- to 9-mm induration) can occur after BCG vaccination, M.
tuberculosis infection or Non-tuberculous mycobacterial infections. Negative reactions (< 4-
mm induration) represent a lack of tuberculin sensitization.

False-negative reactions can occur in about 20% of all persons with active tuberculosis.

Histopathology

Histopathologic examination is diagnostic of mycobacterial cervical

lymphadenitis. Langerhans giant cells, caseating necrosis, granulomatous inflammation and
calcification can be seen.

The presence of microabscesses, ill-defined granulomas, noncaseating granulomas and a

small number of giant cells is more prominent in nontuberculous adenitis when compared
with tuberculous adenitis

Radiology and imaging

Associated chest lesions as seen on chest radiography are very common in children but
less common in adults. Ultrasound of the neck can demonstrate singular or multiple
hypoechoic and multiloculated cystic lesions that are surrounded with thick capsule.

On CT, the presence of conglomerated nodal masses with central lucency, a thick irregular
rim of contrast enhancement and inner nodularity, a varying degree of homogeneous
enhancement in smaller nodes, dermal and subcutaneous manifestations of inflammation,
such as thickening of the overlying skin, engorgement of the lymphatics and thickening of the
adjacent muscles, and a diffusely effaced fascial plane may suggest mycobacterial cervical
lymphadenitis.

MRI may reveal discrete, matted and confluent masses. Necrotic foci, when present, are more
frequently peripheral rather than central, and this together with the soft tissue edema may be
of value in differentiating mycobacterial cervical lymphadenitis from metastatic nodes.

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 LYMPHANGITIS

Lymphangitis is defined as an inflammation of the lymphatic channels that occurs as a

result of infection at a site distal to the channel. Pathogen enter the lymphatic channels,
invading directly through an abrasion or wound or as a complication of infection, local
inflammation and subsequent infection ensue, manifesting as red streaks on the skin.

Group A beta-hemolytic streptococci (GABHS) are the most common causes of

lymphangitis. These organisms elaborate fibrinolysins and hyaluronidase, which aid their
invasion of lymphatic channels. Patients often have a history of a recent cut or abrasion of an
area of skin that appears infected and spreading. Lymphangitis can progress rapidly
to bacteremia and disseminated infection and sepsis, particularly when caused by group A
streptococci.

LYMPHOEDEMA

Lymphedema describes a progressive pathologic condition of the lymphatic system in

which there is interstitial accumulation of protein-rich fluid and subsequent inflammation,
adipose tissue hypertrophy, and fibrosis. The swelling and subsequent induration of the
affected region can cause disfigurement, as well as decreased mobility and function.

The underlying etiology in lymphedema is one of lymphatic transport dysfunction.

Two types:

1. Primary – lymphatic agenesis or hypoplasia

Primary lymphedema is subdivided into categories based on the age of onset of the
patient’s symptoms. The diagnosis of congenital hereditary lymphedema, or Milroy disease,
is made in patients presenting at birth or within the first 2 years of life. Milroy disease
demonstrates an autosomal-dominant pattern of inheritance and is seen to frequently affect
the entire lower extremity and cause bilateral lymphedema of the legs, as well as intestinal
lymphangiectasia and cholestasis.

2. Secondary or Obstructive – Malignant tumors,Surgical procedures, Filariasis, Post

irradiation fibrosis.

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 Worldwide, the most prevalent etiology of secondary lymphedema is filariasis secondary
to infection with the nematode Wuscheria banrofti, which has been estimated to affect more
than 90 million people. Adult filarial worms lodge in the lymphatic systems, thus obstructing
lymphatic vessels and disrupting lymphatic transport.

PATHOGENESIS:

The underlying etiology in lymphedema is one of lymphatic transport dysfunction.

Lymphatic vessels normally function to remove the net fluid efflux from capillaries that
accumulates in the interstitium, thus maintaining steady interstitial pressure. Venous
capillaries reabsorb 90% of the fluid in the interstitium, while the remaining fluid is
transported to the blood by the lymphatics as lymph.

Under normal conditions, the same amount is transported to the interstitium as is

transported from it, a balance that is disrupted in lymphedema due to reduced lymph transport
capacity, thus leading to fluid accumulation and swelling. Lymph vessels also serve to
remove macromolecules such as protein from the interstitium. As protein diffuses through
arterial capillary walls, it is typically degraded by macrophages, thus allowing it to reenter the
circulation through venous capillaries, or to be reabsorbed through lymphatic vessels.

In cases of absent, dysfunctional, or obstructed lymphatic systems, lymphatic stasis

occurs, thus allowing for the buildup of protein and fluid within the interstitium. Classic
theory posits that this increased protein concentration leads to increased tissue colloid
osmotic pressure, which drives fluid into the interstitium and causes edema and the clinical
manifestations of lymphedema.

Clinical Presentation:

The clinical manifestations of lymphedema occur secondarily to the subcutaneous

accumulation of edematous fluid and adipose tissue. An inflammatory response develops with
chronic interstitial fluid accumulation. In addition to inflammation, slowed lymphatic flow
has also been shown to incite lipogenesis and fat deposition and later leads to increased
fibrocyte activation and connective tissue overgrowth. Affected patients thus develop
progressively firmer subcutaneous tissue as fibrosis ensues, in addition to hypertrophy of their
adipose tissue. These pathologic changes manifest initially as swelling of the affected limb or
region, described as soft and pitting, but later progress to a more indurated state.

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Clinical classification of lymphedematous swelling has been defined by the International
Society of Lymphology using the following parameters:

Stage 0: Latent or subclinical condition where swelling is not evident despite impaired lymph
transport. It may exist months or years before overt edema occurs (stages I–III).

Stage I: Early accumulation of fluid relatively high in protein content (eg, in comparison with
“venous” edema) that subsides with limb elevation. Pitting may occur.

Stage II: Pitting may or may not occur as tissue fibrosis develops. Limb elevation alone
rarely reduces tissue swelling.

Stage III: Lymphostatic elephantiasis where pitting is absent. Trophic skin changes, such as
acanthosis, fat deposits, and warty overgrowths, often develop.

Diagnosis:

Diagnosis of lymphedema, particularly in more advanced stages, is typically made

through clinical presentation and history. Earlier stages, however, can be more difficult to
differentiate from other common causes of limb edema.

The differential diagnosis for lymphedema includes systemic causes of edema, such
as cardiac failure, renal failure, and protein-losing conditions, and local etiologies, including
lipedema, deep vein thrombosis, chronic venous insufficiency, myxedema, and cyclical or
idiopathic edema.

Treatment algorithm:

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 LYMPHANGIOMA

Lymphangioma is a benign hamartomatous tumor of lymphatic channels, with a

marked predilection for the head and neck region. Lymphangiomas are rare congenital benign
lesions occurring mainly in the head, neck and oral cavity. They consist in localized centres
of abnormal development of the lymphatic system.

Classification:

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 Lymphangiomas are classified as :( according to the size of the lymphatic vessels
incorporated)

Ψ Microcystic (capillary lymphangiomas),

Ψ Macrocystic (cavernous lymphangiomas) and

Ψ Cystic hygromas

A commonly used classification classifies these lesions into capillary lymphangioma or

lymphangioma simplex, cavernous lymphangioma, and cystic lymphangioma or cystic
hygroma. When a lymphangioma is confined to fairly dense tissue, such as the tongue, it
presents as a cavernous lymphangioma, but when it develops in the relatively loose fascia of
the neck, a cystic lesion occurs.

Cystic hygromas, however, account for approximately 90% of the lymphangiomas in the
head and neck region. Other common sites, outside the head and neck, include the axilla,
shoulder, chest wall, mediastinum, abdominal wall, and thigh.

Clinical features:

The incidence of lymphangiomas has been reported to range from 1.2 to 2.8 per 1000
newborns. The most prominent sign or symptom of all lymphangiomas is the presence of a
mass. The mass may be small and unnoticed at birth only to present later with an upper
respiratory tract disorder or incidental trauma at the site. most lesions, however, are
recognized early on account of their size and associated symptoms of respiratory obstruction
and problems with feeding which are the second and third most common presenting
symptoms.

Difficulty in swallowing results from lymphangiomas extending to involve the oral

cavity, oropharynx, and/or the hypopharynx. Isolated tongue involvement can lead to
macroglossia with dysphagia and airway obstruction. airway and swallowing problems may
persist after surgery in the neck on account of mucosal oedema, enlargement of internal
lymphangiomas, and loss of neural innervation to the pharynx or tongue. In adult patients,
neoplasm can switch to squamous cell carcinoma

Pathogenesis:

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 Three theories have been proposed to explain the origin of this abnormality. The first
suggests that a blockage or arrest of normal growth of the primitive lymph channels occurs
during embryogenesis, the second that the primitive lymphatic sac does not reach the venous
system, while the third advances the hypothesis that, during embryogenesis, lymphatic tissue
lays in the wrong area

3 Theories:

1. Blockage or arrest of normal growth of lymphatic channels during embryogenesis

2. Primitive lymph sac does not reach venous system

3. Lymphatic tissue lays in wrong area

Diagnosis:

Diagnosis is not difficult in most cases. The neoplasms are usually characterized by
the presence of a soft, compressible, loculated and ill-defined mass, which is usually located
in the posterior cervical triangle. The lesions are not attached to the skin or movable across
deeper tissues, and readily transilluminate.

The anterior triangle of the neck has been indicated as the most common site. Cystic
hygroma may be localized in the parotid area, and is the second most common congenital
mass of the parotid area. CT and MRI can be used to define the relationship of the lesion with
the neighbouring structures and to help plan surgical strategies which provides size and
extension of the lesion, should be performed routinely.

Treatment:

Although various methods have been described, surgical removal of the neoplasm still
appears to be the best choice in the treatment of lymphangiomas. Nevertheless, in the neck,
the close relationship of the tumour to vital structures requires softer approaches in order to
avoid fatal consequences. On the other hand, total removal of the mass is necessary to
eliminate the risk of recurrence.

To this end, many authors have described various techniques, including serial
aspiration, radiotherapy, sclerosing therapy with steroids, alcohol, bleomycin sulphate,
tetracycline, and, more recently, OK-432. The main advantage of OK-432 with respect to
other sclerosing agents is the absence of perilesional fibrosis, and intralesional injection of
OK-432 has been proposed as the first-line treatment for lymphangioma, for the past decade

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 CYSTIC HYGROMA

Cystic hygromas are fluid-filled sacs that result from a blockage in the lymphatic
system. The lymphatic system is a network of vessels that maintains fluids in the blood, as
well as transports fats and immune system cells. Cystic hygromas are single or multiple cysts
found mostly in the neck region.

A cystic hygroma can be present as a birth defect (congenital) or develop at any time
during a person’s life. A cystic hygroma in a developing baby can progress to hydrops (an
excess amount of fluid in the body) and eventually fetal death. Some cases of congenital
cystic hygromas resolve leading to webbed neck, edema (swelling), and a lymphangioma (a
benign yellowish-tan tumor on the skin composed of swollen lymph vessels). In other
instances the hygroma can progress in size to become larger than the fetus.

Cystic hygromas occur in approximately 1% of fetuses between weeks 9 and 16 of

pregnancy.

Causes:

Cystic hygromas can occur as an isolated finding or in association with other birth
defect as part of a syndrome. They result from environmental factors, genetic factors, or
unknown factors.

Environmental causes for cystic hygroma include:

• Maternal viral infections, such as Parvovirus of Fifth’s disease

• Maternal substance abuse, such as abuse of alcohol

Genetic syndromes with cystic hygroma as a clinical feature:

• The majority of prenatally diagnosed cystic hygromas are associated with Turner syndrome,
a chromosome abnormality in which a female has only one X chromosome instead of two.

• Chromosome abnormalities such as trisomies 13, 18, and 21

• Noonan syndrome

The pattern of inheritance for these syndromes varies depending upon the specific
syndrome. Isolated cystic hygroma can be inherited as an autosomal recessive disorder for

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which parents are “silent” carriers. Finally, a cystic hygroma can occur from an unknown
cause.

Treatment:

A baby with a prenatally diagnosed cystic hygroma should be delivered in a major

medical center equipped to deal with neonatal complications. An obstetrician usually decides
the method of delivery. If the cystic hygroma is large, a cesarean section may be performed.
After birth, infants with persistent cystic hygroma must be monitored for airway obstruction.
A thin needle may be used to reduce the volume of the cystic hygroma to prevent facial
deformities and airway obstruction. Close observation of the baby by a neonatalogist after
birth is recommended. If resolution of the cystic hygroma does not occur before birth, a
pediatric surgeon should be consulted.

Cystic hygromas that develop in the third trimester (after thirty weeks gestation) or in
the postnatal period are usually not associated with chromosome abnormalities. There is a
chance of recurrence after surgical removal of the cystic hygroma. The chance of recurrence
depends on the extent of the cystic hygroma and whether the wall of the cyst was able to be
completely removed.

LYMPHOID NEOPLASMS

Lymphoma is a general name for a group of cancers that affect the lymphatic system.
The two major types of lymphoma are Hodgkin lymphoma (HL) and Non-Hodgkin
lymphoma (NHL).

HODGKIN LYMPHOMA

Hodgkin lymphoma (HL), one of the most curable forms of cancer, was named for
Thomas Hodgkin, a British pathologist.

Incidence:

▪ Age: 20s or early 30s.

▪ It is less common in middle age but becomes more common again after age 65

Etiology:

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 ▪ The altered DNA in the lymphocyte produces a cancerous change that if untreated —
results in the uncontrolled growth of the cancerous lymphocytes.

▪ The accumulation of the cancerous lymphocytes results in the tumor masses that are
found in the lymph nodes and other sites in the body.

Subtypes Of Hodgkin Lymphoma:

1. Classical Hodgkin lymphoma

▪ Nodular sclerosis Hodgkin lymphoma

▪ Mixed cellularity Hodgkin lymphoma

▪ Lymphocyte-depleted Hodgkin lymphoma

▪ Lymphocyte-rich classical Hodgkin lymphoma

2. Nodular lymphocyte-predominant Hodgkin lymphoma

Signs and symptoms:

Ψ The most common early sign of HL is a painless swelling (enlargement) of one or

more lymph nodes.

Ψ Usually in the neck or upper chest.

Ψ The lymphadenopathy usually develops over weeks and months.

Ψ The nodes are non-tender, discrete, firm, mobile, large, and rubbery.

Diagnosis:

1. Imaging tests include:

 Chest x-ray

 Computed tomography (CT) scan of the chest, abdomen and pelvis

 Magnetic resonance imaging (MRI) in select cases

 Fluorodeoxyglucose positron emission tomography (FDG-PET)

2. Lymph node biopsy.

3. Immunophenotyping.

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Treatment:

1. Chemotherapy combinations

 ABVD (Adriamycin® [doxorubicin], bleomycin, vinblastine and dacarbazine)

 BEACOPP (bleomycin, etoposide, Adriamycin® [doxorubicin], cyclophosphamide,

Oncovin® [vincristine], procarbazine and prednisone)

 Stanford V (mechlorethamine [Mustargen®], doxorubicin, vinblastine, vincristine,

bleomycin, etoposide and prednisone)

2. Combination chemotherapy with or without involved field radiation

3. High-dose chemotherapy with stem cell transplantation.

NON-HODGKIN LYMPHOMAS

The NON-HODGKIN LYMPHOMAS (NHL) are a heterogeneous group of

malignancies arising from lymphoid tissue, with varied clinical and biological features. The
two most common subtypes of NHL, diffuse large B-cell lymphoma and follicular
lymphoma. Non-Hodgkin lymphoma occurs in individuals at virtually all ages, but it is
uncommon in children.

Etiopathogenesis:

The etiology is unknown. However, there is a striking increase in the frequency of

aggressive NHL in patients who are taking long-term immunosuppressive agents.
Overexpression of BCL2 gene prevents apoptosis, or programmed cell death. The BCL1 gene
is overexpressed in patients with mantle cell lymphoma, with overproduction of cyclin D1.

NHL SUBTYPES (WHO):

 T-Cell and Natural Killer (NK)-Cell Lymphoma (about 12%)

▪ Peripheral T-Cell Lymphoma

▪ Cutaneous T-Cell Lymphoma

▪ Anaplastic Large Cell Lymphoma

▪ Angioimmunoblastic T-Cell Lymphoma

▪ NK-Cell Lymphoma

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 Immunodeficiency-Associated Lymphoproliferative Disorders

Signs and symptoms:

Ψ An enlarged lymph node in the neck, armpit or groin

Ψ Fever

Ψ Excessive sweating (especially noticeable at night),

Ψ Unexplained fatigue,

Ψ Loss of appetite

Ψ Weight loss.

Ψ Enlarged spleen

Investigations:

Ψ Lymph Node Biopsy

Ψ Imaging tests

Ψ Blood and Marrow Tests

ANN ARBOR STAGING SYSTEM

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Treatment:

 Chemotherapy
 Radiation therapy
 Stem cell transplantation

DRUG COMBINATIONS:

 R-CHOP: Rituximab plus Cyclophosphamide, doxorubicin (hydroxydoxorubicin),

Oncovin® (vincristine), Prednisone
 R- or F-CVP: Rituxan or Fludarabine, plus Cyclophosphamide, Vincristine, Prednisone
 R-HCVAD: Rituxan, Cyclophosphamide, Vincristine, Adriamycin® (doxorubicin),
Dexamethasone, alternating with R-MTXARAC: Rituxan, methotrexate-cytarabine
 B-R: Bendamustine, Rituximab
 DHAP: Dexamethasone, High-dose Cytarabine, Cisplatin
 ICE: Ifosfamide, Carboplatin, Etoposide

BURKITT’S LYMPHOMA

Burkitt lymphoma is an uncommon form of non-Hodgkin lymphoma. BURKITT’S

NON-HODGKIN’S lymphoma comprises a heterogeneous group of highly aggressive B-cell
malignancies.

World Health Organization classification maintains BL as a distinct category of

peripheral B-cell lymphoma. The World Health Organization classification reports three
subcategories of Burkitt’s lymphoma (BL)—endemic, non-endemic, and immunodeficiency
associated.

Pathogenesis:

BL is invariably associated with chromosomal translocations that dysregulate the

expression of c-myc gene.c-myc normally plays a central role in the transcriptional regulation
of an emerging set of downstream genes that control diverse cellular processes, including cell
cycle progression and programmed cell death (apoptosis).BL is a malignancy of
intermediately sized B cells that infiltrate nodal or extranodal tissues in a diffuse pattern.

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Clincal features:

Ψ Bulky abdominal mass

Ψ Bone marrow involvement

Ψ Leptomeningeal involvement

Ψ Extranodal involvement in other sites

Ψ Burkitt lymphoma should be considered over DLBCL in cases when numerous

extranodal sites are involved with disease

MURPHY STAGING SYSTEM FOR BURKITT LYMPHOMA.

Stage I: Single nodal or extranodal site excluding mediastinum or abdomen

Stage II: Single extranodal tumour with regional nodal involvement

Stage IIR: Completely resected intra-abdominal disease

Stage III: Two single extranodal tumours on opposite sides of diaphragm

Stage IIIA: Localized, non-resectable abdominal disease

Stage IIIB: Widespread multiorgan abdominal disease

Stage IV: Initial CNS or bone marrow involvement (< 25%)

Treatment:

Principles of therapy include

Ψ High doses of alkylating agents,

Ψ Frequent administration of chemotherapy,

Ψ Attention to CNS prophylaxis with high doses of systemic chemotherapy, Intrathecal

therapy, or both.

TNM STAGING

▪ Nx Regional lymph nodes cannot be assessed

▪ No No regional lymph node metastasis

▪ N1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension

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 ▪ N2 Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6
cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm
in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6
cm in greatest dimension

▪ N2a Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6
cm in greatest dimension

▪ N2b Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest
dimension

▪ N2c Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in

greatest dimension.

▪ N3 Metastasis in a lymph node more than 6 cm in greatest dimension

INVESTIGATIONS

FINE NEEDLE ASPIRATION CYTOLOGY (FNAC)

Easy, quick, reliable and cost-effective diagnostic tool for lymphadenopathies.

Differentiate between malignancy and reactive conditions as well as lymphomas and
metastases. Preliminary diagnosis.

REACTIVE LYMPHADENOPATHY: Mixture of small and large lymphocytes, tangible

body macrophages, histiocytes and polymorphonuclear cells with typical reactive cytologic
changes or hyperplasia.

GRANULOMATOUS INFLAMMATION: clusters of epithelioid cells with or without the

presence of Langhans' giant cells and necrotic materials.

METASTATIC MALIGNANCIES: high cellularity of atypical foreign cells accompany by

lymphoid cells in the background.

Reed-Sternberg cells in a background of polymorphous lymphoid cells are diagnostic of

HODGKIN'S lymphoma.

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 Predominance of monomorphic population of atypical lymphoid cells are suggestive of
NON-HODGKIN'S lymphoma

ULTRASONOGRAPHY

Ultrasonography (US) is a non-invasive and non-irradiating imaging

procedure that may be helpful in looking for a hypoechoic, suppurative center of a lymph
node.US is more specific but less sensitive than contrast computed tomography (CT) for
diagnosis of an abscess. In Kawasaki disease, the lymph nodes may show a “cluster of
grapes” pattern. High-resolution sonography has been commonly used to evaluate cervical
lymphadenopathy. The role of grey scale sonography in the assessment of cervical lymph
nodes is well established.

With the advent of power Doppler sonography (PDS), the distribution of intranodal
vessels and perfusion of the cervical nodes can be evaluated, and the blood flow velocity and
vascular resistance of the intranodal vessels can also be measured.

ULTRASOUND GUIDED FNAC

In some non-palpable area, ultrasound guidance is very useful for correct targeting of
the lesion. Ultrasound with fine needle aspiration cytology (FNAC) has been well described
for cancer of the head and neck with sensitivity and specificity for malignancy of over
90%.The sensitivity of ultrasound for detecting nodes of more than 1 cm is 16.7% higher than
clinical examination.

On colour or power Doppler these nodes lose their normal central (hilar) vasculature
and develop a predominantly peripheral (capsular) flow pattern. Ultrasound guided FNAC is
an effective way of identifying and sampling non-palpable malignant supraclavicular nodes
in patients with suspected lung cancer.

Ultrasound-guided FNAC is more accurate than the conventional or blinded FNAC in

differentiating metastatic and non-metastatic cervical nodes.

FINE-NEEDLE ASPIRATION BIOPSY

FNA biopsy can be defined as the removal of a sample of cells, using a fine needle,
from a suspicious mass for diagnostic purposes. Safe and minimally invasive procedure, with
an excellent diagnostic yield. It should preferably be confined to those cases with a strong

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clinical suspicion of a specific infection such as TB or neoplasia, unless the alternative is
surgical biopsy.

LYMPHANGIOGRAPHY

Lymphangiography is the preoperative imaging procedure of choice and the most

powerful diagnostic tool as it demonstrates the site, the caliber and the number of the
fistulous communications. It can also diagnose vascular dysplasias of the lymphatic vessels.
Findings generally include lymphatico-urinary fistulae at level of kidney, ureter or bladder;
tortuous dilated lymphatics around hilar region (lymphangiectasia) communicating with
paravertebral lymphatics; contrast outlining major/minor calyces.

Other findings that may be seen include tortuosity and beading of thoracic duct, round
granular enlarged nodes in paraortic area, skipping of lymphatic chain, dilated cisterna chylii
and abnormal lymphatics coursing down along the ureters. In 40% cases contrast may enter
PCS and drain via bladder. It is not routinely done as it is time consuming, technically
demanding and invasive.

Unilateral pedal lymphangiography can detect lymphaticorenal fistulae via lymphatic

crossover even when it is on the side opposite from which contrast agent has been injected.
The advantages of unilateral lymphangiography over bilateral procedures are that it is easy to
identify crossover channels, and the discomfort for the patient is reduced because there are
fewer incisions and it is quicker. It demonstrates the site, the caliber and the number of the
fistulous communications. It can also diagnose vascular dysplasias of the lymphatic vessels.
It is not routinely done as it is time consuming, technically demanding and invasive.

MRI

MRI is one of the imaging techniques that is used to guide treatment decisions. The
ability of MRI to discriminate between lymph nodes with and without metastasis is still poor.
High-resolution MRI with lymphotropic contrast agent, are used to overcome the limitation
of morphologic evaluation of nodes.

CT SCAN

When more anatomic detail is required, CT may be necessary and might be advisable
before undertaking a surgical procedure. Contrast-enhanced CT is a highly sensitive modality
for detecting an infection in a deep neck space but it is not very specific for identifying frank

31
pus. A short axis-diameter (> 5.3 mm), irregular margin, and presence of central necrosis are
the suggestive morphologic features of metastatic paraaortic nodes.

EXCISIONAL BIOPSY

An excisional biopsy will confirm the presence of malignancy or disclose the

granulomatous lesions of TB or sarcoid. It is important to consider an early excisional biopsy
when there is a high suspicion for malignancy. The largest accessible node should be
biopsied. A pathologic process may be found on a repeat biopsy even in the presence of an
initial normal biopsy.

INDICATIONS FOR LYMPH NODE BIOPSY

Size

Ψ Greater than 2 cm

Ψ Increasing over 2 weeks

Ψ No decrease in size of node after 4 weeks

Location

Ψ Supraclavicular lymph node

Consistency

Ψ Hard

Ψ Matted

Ψ Rubbery

Associated Features

Ψ Abnormal chest radiograph suggestive of lymphoma

Ψ Fever

Ψ Weight loss

Ψ Hepatosplenomegaly

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 REFERENCES

1. Cervical lymphadenopathy in the dental patient:A review of clinical approach.Ernesta

Parisi, DMD/Michael Glick, DMD.

2. Review Article: Tuberculous Lymphadenitis.Prasanta Raghab Mohapatra, Ashok Kumar

Janmeja.

3. Sonography of Neck Lymph Nodes. Part II: Abnormal Lymph Nodes A. AHUJA*, M.

YING†

4. Comparison of CT and MRI for presurgical characterization of paraaortic lymph nodes in

patients with pancreatico-biliary carcinoma World J Gastroenterol 2008 April 14; 14(14):

2208-2212.

5. Pediatrics in Review Vol.34 No.5 May 2013

6. Chyluria - An Overview Sachit Sharma, Ashok Kumar Hemal. Int J Nephrol Urol, 2009;

1(1): 14 – 26

7. World J Gastroenterol 2008 April 14; 14(14): 2208-2212

8. Eur Radiol (2009) 19: 626–633

9. Int J Nephrol Urol, 2009; 1(1): 14 – 26

10. Clinical Radiology (2003) 58: 351–358

11. Sonography of Neck Lymph Nodes Clinical Radiology (2003) 58: 351–3

12. Burkitt Lymphoma in Adults American Society of Haematology

13. Ann Saudi Med 2012; 32(3): 296-305

14. Int. J. Cancer: 120, 1–39 (2007)

15. Annals of Plastic Surgery • Volume 59, Number 4, October 2007

16. ACTA Otorhinolaryngology Italica2008;28:17-20

17. FNAC OF SLN IN HEAD AND NECK CANCER Ho ¨ftetal

18. CA Cancer J Clin 2005;55:242–258

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