Cervical lymphadenopathy

Lymph Nodes

• Anatomy– Collection of lymphoid cells attached to both vascular and

lymphatic systems– Over 600 lymph nodes in the body

Anatomy• Are small bean-shaped

organs • Each node has fibrous

capsule & and has a hilum at one side.

• It receives many afferent vessels & gives efferent vessel from its hilum.

• The lymph node is divided into an outer cortex and an inner medulla. • Fibrous trabeculae extend from the deep surface of the capsule into

the cortex to divide it into compartments.• Fibrous trabeculae in the medulla are irregular & called medullary

Cords.• Lymphoid follicles form continuous row in the cortex and are absent

in the medulla.

Dr : Rabie Fahmy Zahran

Lymph

• Fluid similar in composition to blood plasma.• Derived from blood plasma by filtration

through capillary walls at the arterial end. • As soon as the interstitial fluid enters the

lymph capillaries, it is called lymph. • Returning the fluid to the blood helps to

maintain normal blood volume and pressure.

Function• To provide optimal sites for the concentration of free or cell-

associated antigens and recirculating lymphocytes – “sensitization of the immune response”

• To allow contact between B-cells, T-cells and macrophages• Lymph nodes and other lymphatic organs filter the lymph to

remove & destroy microorganisms and other foreign particles • It returns excess interstitial fluid to the blood to maintain

blood volume and blood pressure . • Absorption of fat and fat-soluble vitamins from the digestive

system by special lymph capillaries, called lacteals The lymph in the lacteals has a milky appearance due to its high fat content and is called chyle.

LYMPH NODES OF THE HEAD AND NECK

• CLASSIFICATION1. Upper horizontal chain of nodes(a) Submental(b) Submandibular(c) Parotid(d) Postauricular(e) Occipital(f) Facial

• 2. Lateral cervical nodes. They include nodes, superficial and deep to sternocleidomastoid muscle and in the posterior triangle.(a) Superficial external jugular group(b) Deep group

(i) Internal jugular chain (upper, middle and lowergroups)(ii) Spinal accessory chain(iii) Transverse cervical chain

• 3. Anterior cervical nodes(a) Anterior jugular chain(b) Juxtavisceral chain• (i) Prelaryngeal• (ii) Pretracheal• (iii) Paratracheal

Submental nodes• They lie on the mylohyoid muscle in

the submental triangle, 2–8 in number.Afferents come from the chin, middle part of lower lip, anterior gums, anterior floor of mouth and tip of tongue.Efferents go to submandibular nodes and internal jugularchain.

Submandibular nodes• They lie in submandibular triangle in

relation to submandibular gland and facial artery.Afferents come from lateral part of the lower lip, upper lip,cheek, nasal vestibule and anterior part of nasal cavity, gums,teeth, medial canthus, soft palate, anterior pillar, anterior part of tongue, submandibular and sublingual salivary glandsand floor of mouth. Efferents go to internal jugular chain.

• Parotid nodes• They lie in relation to the parotid salivary

gland and are extraglandular and intraglandular. Preauricular and infraauricular nodes are part of the extraglandular group.

• Afferents come from the scalp, pinna, external auditory canal, face, buccal mucosa.

• Efferents go to internal jugular or external jugular chain.

• Postauricular nodes (mastoid nodes)• They lie behindthe pinna over the mastoid.• Afferents come from the scalp, posterior

surface of pinna and skin of mastoid.• Efferents drain into infra-auricular nodes

and into internal jugular chain.

• Occipital nodes. They lie both superficial and deep to

splenius capitus at the apex of the posterior triangle.

Afferents come from scalp, skin of upper neck.

Efferents drain into upper accessory chain of nodes.

• Facial nodes. They lie along facial vessels and are grouped

according to their location. They are midmandibular, buccinator, infraorbital and malar (near outer canthus) nodes.

Afferents come from upper and lower lids, nose, lips and cheek.

Efferents drain into submandibular nodes.

LATERAL CERVICAL NODES

• Lateral Cervical Nodesa) Superficial group – it liesalong external jugular veinand drains into internaljugular and transversecervical nodes.

b.Deep Group• It consists of three chains,

1. the internal jugular chain2. spinal accessory and3. Transverse cervical

• Internal jugular chainLymph nodes of internal jugular chain lie anterior, lateral and posterior to internal jugular vein.Upper group (jugulodigastric node) – drains oral cavity, orpharynx, nasopharynx, hypopharynx, larynx and parotid.Middle group drains hypopharynx, larynx, throid, oral cavity, oropharynx.Lower jugular group drains larynx, thyroid and cervical oesophagus.

• Spinal accessory chainLies along the spinal accessory nerve. Spinal accessory chain drains the scalp, skin of the neck, the nasopharynx, occipital andpostauricular nodes.Efferents from this chain drain into transverse cervical chain

• Transverse cervical chain (supraclavicular nodes)It lies horizontally, along the trasverse cervical vessels, in the lower part of the posterior triangle. The medial nodes of the group called scalene nodes. Afferents to those nodes come from the accessory chain and also infraclavicular structures, e.d. breast, lung, stomach, colon, ovary and testis.

Anterior Cervical Nodes

Anterior Cervical NodesThey lie between the two carotids and below the level of hyoid bone andconsist of two chains:(a) Anterior jugular chian - It lies along anteriorjugular vein and drains the skin of anterior neck.(b) Juxtavisceral chain – It consists of

• prelaryngeal• pretracheal• and paratracheal nodes

(i) Prelaryngeal node (Delphian node) lies on cricothyroid membrane and drains subgotticregion of larynx and pyriform sinuses.

(ii) Pretracheal nodeslie in front of the trachea, and drainthyroid gland and the trachea. Efferents from thesenodes go to paratracheal, lower internal jugular andanterior mediastinal nodes.

(iii) Paratracheal Nodes drain the thyroid lobes, subglotticlarynx, tracha and cervical oesophagus

AJCC(American Joint Committee on Cancer) classification

• Level 1 –submental+ submandibular• Level 2 –upper deep cervical nodes• Level 3 –middle deep cervical nodes• Level 4 –lower deep cervical nodes• Level 5 –spinal accessory + transverse cervical• Level 6 –pretracheal, prelaryngeal, paratacheal• Level 7 –upper mediastinal nodes

Anatomic division• Deep lateral cervical group• Deep cervical chain• Spinal accessory chain• Transverse cervical chain• Anterior cervical group• Pretracheal• Prelaryngeal• Paratracheal• Submental-Submandibular group• Parotid group• Retropharngeal group

• Po st cer vical : scalp , n eck skin o f arms t ho r ax cer vical and axil lary n od es (lymph oma, h ead/neck ca)

What is lymphadenopathy

• Lymph nodes that are abnormal in size > 1cm, consistency or number

• Localized – one area involved• Generalized – two or more non-contiguous

areas

Why do lymph nodes enlarge?

• Increase in the number of benign lymphocytes and macrophages in response to antigens

• Infiltration of inflammatory cells in infection (lymphadenitis)

• In situ proliferation of malignant lymphocytes or macrophages

• Infiltration by metastatic malignant cells• Infiltration of lymph nodes by metabolite

laden macrophages (lipid storage diseases)

Epidemiology

• 0.6% annual incidence of unexplained adenopathy in the general population

• 10% were referred to a subspecialist and 3.2 % required a biopsy and 1.1% had a malignancy

When to worry?

• Age• Characteristics of the node• Location of the node• Clinical setting associated with

lymphadenopathy

Age

• Children/young adults – more likely to respond to minor stimuli with lymphoid hyperplasia– Lymph nodes in patients less than the age of 30 are

clinically benign in 80% of cases whereas in patients over the age of 50 only 40% are benign

– Biopsies done in patients less than 25 yrs have a incidence of malignancy of <20% vs the over-50 age group has an incidence of malignancy of 55-80%

Clinical examination

• Localized adenopathy should prompt a search for an adjacent precipitating lesion and an examination of other nodal areas to rule out generalized lymphadenopathy. In general, lymph nodes greater than 1 cm in diameter are considered to be abnormal. Supraclavicular nodes are the most worrisome for malignancy. A three- to four-week period of observation is prudent in patients with localized nodes and a benign clinical picture.

• The body has approximately 600 lymph nodes, but only those in the submandibular, axillary or inguinal regions may normally be palpable in healthy people.1 Lymphadenopathy refers to nodes that are abnormal in either size, consistency or number. There are various classifications of lymphadenopathy, but a simple and clinically useful system is to classify lymphadenopathy as “generalized” if lymph nodes are enlarged in two or more noncontiguous areas or “localized” if only one area is involved.

• First, are there localizing symptoms or signs to suggest infection or neoplasm in a specific site?

• Second, are there constitutional symptoms such as fever, weight loss, fatigue or night sweats to suggest disorders such as tuberculosis, lymphoma, collagen vascular diseases, unrecognized infection or malignancy?

• Third, are there epidemiologic clues such as occupational exposures, recent travel or high-risk behaviors that suggest specific disorders?

• Fourth, is the patient taking a medication that may cause lymphadenopathy? Some medications are known to specifically cause lymphadenopathy (e.g., phenytoin [Dilantin]), while others, such as cephalosporins, penicillins or sulfonamides, are more likely to cause a serum sickness-like syndrome with fever, arthralgias and rash in addition to lymphadenopathy

Characteristics of the node

• Nodes lasting less than 2 weeks or greater than one year with no progression of size have a low likelihood of being neoplastic – excludes low grade lymphoma

• Cervical nodes – up to 56% of young adults have adenopathy on clinical exam

• Inguinal adenopathy is common – up to 1-2 cm in size and often benign reactive nodes

Characteristics of the node

i. Consistency – Hard/Firm vs Soft/Shotty; Fluctuantii. Mobile vs Fixed/Mattediii. Tender vs Painlessiv. Clearly demarcatedv. Size

i. When to worry – 1.5-2cm in sizeii. Epitroclear nodes over 0.5cm; Inguinal over 1.5cm

vi. Duration and Rate of Growthvii. Mobile vs fixedviii. Symmetrical vs asymmetrical

Consistency• Stony hard: typical of cancer usually metastatic• Firm rubbery: can suggest lymphoma• Soft: infection or inflammation• Fluctuant : Suppurated nodes.• Matting : . A group of nodes that feels connected and

seems to move as a unit is said to be “matted.” Nodes that are matted can be either benign (e.g., tuberculosis, sarcoidosis or

lymphogranuloma venereum) or malignant (e.g., metastatic carcinoma or lymphomas).

Pain/Tenderness

• When a lymph node rapidly increases in size, its capsule stretches and causes pain. Pain is usually the result of an inflammatory process or suppuration, but pain may also result from hemorrhage into the necrotic center of a malignant node. The presence or absence of tenderness does not reliably differentiate benign from malignant nodes

size• in one series of 213 adults with unexplained lymphadenopathy,

no patient with a lymph node smaller than 1 cm2 (1 cm × 1 cm) had cancer,

while cancer was present in 8 percent of those with nodes from 1 cm2 to 2.25 cm2 (1 cm × 1 cm to 1.5 cm × 1.5 cm) in size, and

in 38 percent of those with nodes larger than 2.25 cm2 (1.5 cm × 1.5 cm).

• In children, lymph nodes larger than 2 cm in diameter (along with an abnormal chest radiograph and the absence of ear, nose and throat symptoms) were predictive of granulomatous diseases (i.e., tuberculosis, cat-scratch disease or sarcoidosis) or cancer (predominantly lymphomas).

Location of the node

• The anatomic location of localized adenopathy will sometimes be helpful in narrowing the differential diagnosis. For example, cat-scratch disease typically causes cervical or axillary adenopathy, infectious mononucleosis causes cervical adenopathy and a number of sexually transmitted diseases are associated with inguinal adenopathy .

Location of the node

• Supraclavicular lymphadenopathy Highest risk of malignancy – estimated as 90% in

patients older than 40 years vs 25% in those younger than 40 yrs

Right sided node – cancer in mediastinum, lungs, esophagus

Left sided node (Virchow’s) – testes, ovaries, kidneys, pancreas, stomach, gallbladder or prostate

• Paraumbilical node (Sister mary Joseph’s)– Abdominal or pelvic neoplasm

• Location helps guide differential dx• Lateral neck most common site for metastatic disease from UADT- upper neck anterior/deep to SCM• Midline neck masses likely related to thyroid, elevates with swallowingConcerning features:• any abnormality in other area of head and neck- skin/scalp/ear lesions, mucosal lesion of nasal cavity, oral cavity, pharynx, larynx• enlarging or hard mass• fixation to surrounding structures (skin, SCM, mandible)• single, asymmetric node/mass ~ > 2 cm• mass in supraclavicular fossa or parotid• neurologic abnormalities (cranial nerves)• multiple rapidly growing nodes may suggest lymphoma

Location of the node

• Epitroclear nodes– Unlikely to be reactive

• Isolated inguinal adenopathy– Less likely to be associated with malignancy

Generalized Lymphadenopathy• Malignancy – lymphoma, leukemia, Kaposi’s

sarcoma, metastases• Autoimmune – SLE, RA, Sjogren’s syndrome, Still’s

disease, Dermatomyositis• Infectious – Brucellosis, Cat-scratch disease, CMV,

HIV, EBV, Rubella, Tuberculosis, Tularemia, Typhoid Fever, Syphilis, viral hepatitis, Pharyngitis

• Other – Kawasaki’s disease, sarcoidosis, amyloidosis, lipid storage diseases, hyperthyroidism, necrotizing lymphadenitis, histiocytosis X, Castlemen’s disease

Unexplained Generalized lymphadenopathy

• Always requires an evaluation• Start with CXR and CBC• Review Medications • PPD (TB test), RPR(Rapid plasma reagin , a

blood test for syphilis) , Hepatitis screen, ANA, HIV

• No yield on above test: Biopsy from most abnormal node.

persistent generalized lymphadenopathy

• Enlargement of the lymph nodes that persists for at least three months in at least two extrainguinal sites is defined as persistent generalized lymphadenopathy and is common in patients in the early stages of HIV infection. Other causes of generalized lymphadenopathy in HIV-infected patients include Kaposi's sarcoma, cytomegalovirus infection, toxoplasmosis, tuberculosis, cryptococcosis, syphilis and lymphoma

Clinical Setting

• symptoms – fever, night sweats, weight loss, Fatigue, Pruritis

• Evidence of other medical conditions – connective tissue disease

• Young patient – mononucleosis type of syndrome

History

• Identifiable cause for the lymphadenopathy?– Localizing symptoms or signs to suggest

infection/neoplasm/trauma at a particular site• URTI, pharyngitis, periodontal disease, conjunctivitis, insect bites,

recent immunization etc

• Constitutional symptoms(fever, night sweats, weight loss, Fatigue, Pruritis)

• Epidemiological clues– Occupational exposures, recent travel, high-risk behaviour

• Medications – serum-sickness syndrome

Physical Exam

• Full nodal examination – nodal characteristics• Organomegaly• Localized – examine area drained by the nodes

for evidence of infection, skin lesions or tumours

Drugs

• Allopurinol• Atenolol• Captopril• Carbamazepine• Gold• Hydralazine• Penicillins

• Phenytoin• Primidone• Pyrimethamine• Quinidine• Trimethoprim/Sulfamethozole• Suldinac

Management

• Identify underlying cause and treat as appropriate – confirmatory tests

• Generalized adenopathy – usually has identifiable cause

• Localized adenopathy– 3-4 week observation period for resolution if not

high clinical suspicion for malignancy– Biopsy if risk for malignancy - excisional

Radiographic Investigation of the Head and Neck Masses

• MRI – Magnetic Resonance Imaging can clearly highlight soft tissue pathologies better than the C.T. Scan.– It uses a magnetic field rather than x-rays (radiation).

• CT SCAN – Computed tomography is less accurate than M.R.I for the soft tissue examination, but is very useful to locate bony tumors and their dimensions and extensions.– C.T with contrast is used to enhance the visibility of abnormal tissue during

examination.• PET (Positron Emission Tomography) and SPECT (Single Photon Emission

Tomography) are useful after diagnosis to help determine the grade of a tumor or to distinguish between cancerous and dead or scar tissue.– They involve injection with a radioactive tracer.

• Gallium scanning

Fine Needle Aspirate• Safe Convenient, less invasive, quicker turn-around time• especially beneficial for verification of lymphoid

origin of the enlarged growth and in differentiatingbetween metastatic, infectious, reactive andlymphomatous causes of lymphadenopathy. It alsohelps in the determination of the extent of tumor;detection of recurrence; monitoring of the course ofdisease; obtaining of material for special studies suchas microbiological cultures, immunological or genetic studies as well as electron microscopy. Furthermore

• Most patients with a benign diagnosis on FNA biopsy do not undergo a surgical biopsy

• overall sensitivity was 92.7%, specificity 98.5%

• If the LN arenot palpable, endoscopic ultrasound-guided fineneedle aspiration (EUS-FNA) has been shown to accurately diagnose mediastinal lymph nodepathology with diagnostic accuracy of 84%

• endobronchial ultrasound guided transbronchialneedle aspiration (EBUS-TBNA) have been shown tobe highly sensitive and specific in the diagnosis ofmediastinal and hilar lesions

• Limitations of FNA:– the lack of proper

tissue sample to run special studies including cytogenetics, flow cytometry, electron microscopy,

– the potential risk of seeding a tract with malignancy as a result of FNA

BIOPSY• Can be done by bedside, open surgery, mediastinoscopy FNA cannot

distinguish between lymphomas (nodal architecture needs to be intact) The preservation of nodal architecture is critical to theproper diagnosis of lymphadenopathy, particularly when differentiating lymphoma from benign reactive hyperplasia

• Biopsy should be avoided in patients with probable viral illness because lymph node pathology in these patients may sometimes simulate lymphoma and lead to a false-positive diagnosis of malignancy.

• The diagnostic yield of the biopsy can be maximized by obtaining an excisional biopsy of the largest and most abnormal node (which is not necessarily the most accessible node). If possible, the physician should not select inguinal and axillary nodes for biopsy, since they frequently show only reactive hyperplasia.

• Patients should be cautioned to remain alert for the reappearance of the nodes because lymphomatous nodes have been known to temporarily regress.

TB abscess

Treatment should be

started following the

national TB Guidelines.

Thank you

Creating a Differential

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Cancer

• Heme. malignancies: Hodgkin, NHL, acute and chronic

leukemia , waldenstroms , multiple myeloma ( plastmocytomas)• Metastatic: solid tumor breast, lung,

renal, cell ovarian.

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Hypersensitivity syndromes

• Serum sickness.• Serum sickness like illness.• Drugs• Silicone• Vaccination• Graft vs Host

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Infections

• Viral• Bacterial• Protozoan• Mycotic• Rickettsial (typhus)• Helminthic (filariasis)

VIRAL• EBV…mono spot test• CMV….cmv titers, immunsuppresed, transplant

recipient, recent blood transfusion• HIV…IV drug use, high risk sexual behavior• Hepatitis….IV drug use• Herpes Zoster….superficial cutaneous nodules

Bacterial

• Staph/strep: cutaneous source, lymphadenitis

• Cat scratch: bartonella hensalae, two weeks after inoculation

• Mycobacterium: TB and non-tb, host characteristics (HIV, foreign born, low socioeconomic status, homo….)

Spirochete

• Syphilis: Treponema pallidum Primary localized inguinal lymph nodes and secondary, non-treponemal, treponemal• Lyme disease( the most common tick-borne

disease caused by Borrelia )

Protozoan

• Toxoplasmosis: ELISA assay, intracellular protozoan toxoplasmosis gondii….bilateral, symmetrical, non-tender cervical adenopathy

…consider undercooked meat, reactivation in immun-compromised host

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Connective Tissue Disease

• Rheumatoid Arthritis• SLE• Dermato-myositis• Mixed connective tissue disease• Sjogren

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Atypical lymphoproliferative disorders

• Castleman’s disease.• Wegener's granulomatosis ( a form of

vasculitis that affects the lungs, kidneys and other organs..)

• Angio-immuonplastic lymph-adenopathy with dysproteinemia.

chicaGo

Granulomatous

• Histoplasmosis.• Mycobacterial infections.• Cryptococcus.• Silicosis: coal, foundry, ceramics, glass.• Berylliosis: metal, alloys.• Cat Scratch .

chicagO OTHER…….

• RARE • Kikuchi (histiocytic necrotizing

lymphadenitis ( non-cancerous enlargement of the lymph nodes)

• Rosi Dorfman disease (sinus histiocytosis with massive lymphadenopathy, is a rare, benign disorder of unknown etiology )

• Kawasaki disease.