CERVICO‐FACIAL ADENOPATHIES

Cervical lymphadenopathy has multiple causes. It is often caused by infectious diseases in children and young adults, but it raises concerns about cancerous pathologies, which often have a poor prognosis after the age of 40. Tuberculosis remains a common problem at any age.

A rigorous interview and a careful clinical examination often provide a diagnostic orientation. Additional tests are performed to support this and help establish an appropriate therapeutic strategy. The use of lymph node sampling for histological purposes is often necessary to confirm a precise diagnosis.

GENERAL INFORMATION:

Definition :

Lymph node

Immune organ, kidney-shaped, variable in size (major axis ≤ 10 mm), ovoid in structure, it is located along the lymphatic pathways

Lymphadenopathy

Adenopathy is an increase in the volume of one (or more) lymph node(s) (hypertrophy) which corresponds to the stimulation of the lymph node tissue by an infectious or non-infectious process, or to the invasion of the node by a tumor population

HISTOLOGICAL REMINDER

Lymph node:
- Clusters of lymphocytes grouped into encapsulated and organized structures
- kidney-shaped organs of variable size
- located on the path of the large lymphatic vessels
- It contains T and B lymphocytes => Afferent blood and lymphatic Vx
- It reflects local antigenic stimulation and immunological status

Lymphatic vascular system
- Lymph Biological fluid resulting from extravasation of extracellular fluid
- The lymphatic system is made up of afferent and efferent vessels which drain the entire body, ensuring the transport of lymph rich in defense cells.

Pathophysiology:
- Function of the Ganglia:
  - non-specific filtration of lymph by phagocytic activity of macrophages
  - sequestration and production of B and T lymphocytes
Increased volume of the lymph nodes:
- Intrinsic cell multiplication
- Extrinsic cell multiplication
- Association of the two

In response to antigenic stimulation : lymphocytes transform into large blast cells or plasma cells and secrete lymphokines amplifying the local response; the lymph node may remain enlarged if the antigen persists;
Infiltration of inflammatory cells (polymorphonuclear cells, monocytes) of blood origin in response to an infectious agent;
Local proliferation of malignant lymphocytes or macrophages, or colonization by metastatic malignant cells;
Macrophage overload in certain dyslipidemias, lymphatic stasis, vascular congestion

ANATOMY OF LYMPHATIC DRAINAGE

2 major systems:

*Horizontal system: Lymph node circle or the pericervical lymphatic chain of Cuneo. (lymphocenter of the head).

*Vertical system : Lymphonodeuds are located along the venous axes (superficial) or in contact with the cervical visceral axes (deep) lymphocenter of the neck.

POSITIVE DIAGNOSIS

Clinical diagnosis

Examination
- age
- general condition of the patient (asthenia, fever, weight loss, lack of appetite, insomnia)
- date and circumstances of appearance of the adenopathy
- asymptomatic or associated with signs
  - local (pain provoked or spontaneous, in favor of adenitis, cutaneous appearance, discharge through a fistula, etc.)
  - locoregional (irradiated neck pain, earache, pharyngeal discomfort or dysphagia)
- are sought for tuberculosis, thyroid cancer or cancer of the upper aerodigestive tract, a systemic disease, cervical radiotherapy, blood transfusion
- are specified (profession, tobacco and alcohol consumption, drug addiction, contact

with pets, unprotected sex, stays abroad, recent medication intake: antiepileptics, phenylbutazone, etc.)

Clinical examination:
- Local examination (inspection + palpation)
  - the number of lymph nodes perceived
  - their unilateral or bilateral character
  - their original location (orientation towards a primary lesion)
  - their volume, measured with a tape measure, assessing their speed of evolution
  - their painful characteristic (when they are inflammatory) or not
  - their mobility in relation to the superficial cutaneous plane and to the deep planes (muscular or vascular)
  - the appearance of the skin opposite (inflammatory, fistulization, ulceration, “orange peel”)
  - their firm, even hard and woody, elastic or soft consistency, with a fluctuating collected appearance

Palpation of the lymph node areas:

Locoregional examination
- look for a potential cutaneous-mucosal microbial entry point (skin redness, ulceration, impetigo, folliculitis, trace of an insect or needle bite, cat scratch, erysipelas or angina, etc.)
- any lesion suggesting a primary tumor: (cervico-facial skin or mucosa of the oropharyngeal cavity)
- the skin of the face, neck and scalp is carefully examined
- indirect mirror laryngoscopy should be systematic, in phonation and in respiration (after 40 years)
- ENT advice (larynx, pharynx, nasal passages)
General examination
- careful examination of the integuments
- palpation of all lymph node areas (axillary, inguinal, etc.)
- abdominal palpation for hepatosplenomegaly
- chest x-ray (mediastinal lymphadenopathy)
- signs of hemostasis disorders should be sought

Additional examinations:

Biological examination
- NFS and VS : screening for an infectious process (mononucleosis, bacterial hyperleukocytosis or viral neutropenia) or a blood disease
- Tuberculin intradermal test (IDR) : tuberculosis
- Serological tests : infectious mononucleosis, toxoplasmosis, human immunodeficiency virus (HIV), syphilis
Bacteriological examinations
- lymph node puncture of pus, direct examination and culture can be performed (*proc GS)
- specify to the laboratory the diagnostic guidelines for the choice of possible special culture media or the search for parasites
Histological examinations
- fine needle aspiration cytology (Dc imprecise or false negative, orientation value)
- histological examination of a fresh surgical adenectomy, taken under general anesthesia:
  - never an “orange segment” biopsy (capsular rupture)
  - excision of the largest lymphadenopathy in its entirety (immunohistochemistry)
  - sentinel lymph node biopsy
Radiological explorations:

High-frequency ultrasound : as a first-line treatment, it can detect subclinical adenopathies and can assess their malignant or benign nature.
Chest X-ray : as part of an infectious assessment (tuberculosis), desarcoidosis or carcinological assessment
Computed tomography (CT) with injection: ratio of large adenopathies with adjacent structures, operability)
Magnetic resonance imaging (MRI) : More reliable than CT for exploring relationships with adjacent structures

ETIOLOGICAL DIAGNOSIS
ADENOPATHIES OF INFECTIOUS ORIGIN
- Origin :
  - local or general
- related to an infection
  - bacterial
  - viral
  - parasitic
  - mycotic

– Clinical forms of INFECTIOUS ADENOPATHIES

Acute lymphadenitis
- first congestive or serous stage
- rapid increase in lymph node volume
- spontaneously painful and covered with hot, erythematous skin.
- extra-lymph node inflammatory zone

Periadenitis = induration on palpation and fixation of the lymph node to the skin

in the next stage, the adenitis becomes suppurative
pain, skin adhesions and fluctuation +++
fluctuation (under TRT) = drainage
evolution = fistulization or adenophlegmon
The evolution of acute adenitis is favorable under appropriate treatment, but the adenopathy may remain palpable for several weeks after healing.
etiology is most often common bacterial (streptococcus or staphylococcus depending on the entry point)

Adenophlegmon
- the inflammatory process extends beyond the lymph node capsule
- worsening of local and general signs.
- primary or consecutive to acute suppurative adenitis
- preferentially located in the jugulocarotid region
- exposes the patient to serious local (vascular thrombosis) or regional (mediastinal diffusion, suprahyoid location) complications
Childhood lymphadenopathy
- more significant and rapid lymph node hyperplasia, in response to antigenic stimulation
- The lymph nodes are not palpable at birth
- The development of the lymphatic system is maximal between 4 and 8 years of age, then gradually regresses after puberty

Etiological forms of infectious adenopathy

Adenopathies of local cause:
- inflammatory and painful nature of the adenopathy + infectious or inflammatory focus in the drainage area.
- They are due either to:
  - Cutaneous and mucosal infections located in the drainage area of the adenopathy, which are inflammatory and painful, representing the gateway.
  - At the skin level , we will look for impetigo, a boil, folliculitis,
  - in the oral cavity , pericoronitis, gingivostomatitis or periodontitis.
  - ENT infections , discreet, gone unnoticed: tonsillitis, pharyngitis.
Adenopathies of general infectious cause:

TUBERCULOSIS

Definition :
- Infection with Mycobacterium tuberculosis hominis especially and sometimes Mycobacterium tuberculosis bovis
- It is transmitted by air (patient with pulmonary tuberculosis)
- elderly or immunocompromised people (immunosuppressive treatment, HIV)
Questioning:
- lifestyle
- research into the concept of counting +++
- the subject’s vaccination status (BCG)
- screening of relatives for the disease
Clinic:
- Tuberculous adenopathies have several clinical forms:
  - Chronic lymphadenopathy is the most common presentation;
  - The lymph nodes are multiple, firm, painless, of unequal size and without periadenitis at the level of the spinal and upper cervical chains, gradually increasing in volume, then evolving into a cold abscess with softening then fistulization allowing the drainage of a lumpy pus, the caseum;
  - Adenopathies may accompany an inoculation chancre: on the tonsil or mandibular gum;
Positive diagnosis
- IDR : positive test (papule greater than or equal to 6 mm at the 72nd hour), or even phlyctenular; in the acute period (tuberculous miliary), the IDR may be negative or even positive, reflecting an old infection
- Direct examination of samples ; lymph node puncture, sputum,

gastric intubation

Systematic frontal and lateral chest X-rays are normal in almost 50% of cases.
Histological examination of an adenectomy specimen notes follicles of epithelioid (histiocytic) cells and giant cells without initial caseous necrosis. Secondary caseum formation is a major argument in favor of tuberculosis
Treatment
- anti-tuberculosis drugs over a period of several months (6 to 12 months)
  - isoniazid, rifampicin, ethambutol, pyrazinamide.
- conservative cervical lymph node dissection (ADP which regresses poorly, softening, fistula). *

SYPHILIS:

Definition
- sexually transmitted infection caused by the spirochete Treponema pallidum
- epidemiological investigation is essential to the interrogation
Clinic:
- Primary syphilis:
  - 20-day incubation
  - primary chancre, mucosal exulceration with hardened base
  - chancre precedes grouped submandibular adenopathies by 8 days, one of which is larger, hard, painless, and mobile without periadenitis
  - These polyadenopathies persist after healing of the chancre: 2 to 4 months after treatment and 1 to 2 years in its absence
- Secondary syphilis
  - generalized micropolyadenopathy with firm, non-inflammatory, mobile and painless lymph nodes, disseminated in the posterior cervical areas (occipital, mastoid and epitrochlear)
Positive diagnosis is based on:
- serological tests by TPHA, VDRL, FTA and the Nelson test
- samples taken by puncture of the lymph node or scraping of the chancre (without making it bleed) for direct examination under a dark-field microscope and culture
Treatment :
- It is based on penicillotherapy (Benzathine penicillin G) or, in case of allergy, on erythromycin or cycline.

TULAREMIA

Definition
- rare infection due to the germ Francisella (Pasteurella) tularensis
- bite from a vector insect, through direct skin contact or through ingestion of contaminated hare meat.
- exposed professions = butchers, cooks and hunters

Clinic:
- Multiplication of the germ + bacteremia after lymph node swarming
- visceral damage (lung and lymphatic system)
- 1 to 14 days of incubation => flu-like syndrome
- large and painful inflammatory adenopathies in the drainage area
- inoculation chancre = slightly congestive ulceration covered with a crust
- oropharyngeal involvement
  - severe tonsillitis, unilateral erythematopultaceous
  - large and painful jugulo-carotid or submandibular satellite inflammatory adenopathies
- the most common complication = lymph node suppuration, even after antibiotic therapy
The diagnosis is confirmed by bacteriology:
- Search for the germ by puncturing a lymph node, scraping a skin lesion, blood culture or stool examination;
- Serology (cross-reactions with brucellosis serologies)
- Tularin IDR, positive from the second week; it triggers an erythematopultaceous, even phlyctenular, reaction in 48 hours.
Treatment:
- Preventive:
  - vaccine that reduces the severity of the symptoms
- Curative:
  - Aminoglycosides for 7 days by parenteral route as monotherapy (gentamicin)
  - In the presence of suppurative adenitis, drainage is necessary

CAT SCRATCH DISEASE

Definition :
- benign inoculation lymphoreticulosis
- inoculation of chlamydia by the claw (cat + dog)
- several germs were suspected: Chlamydiae, mycobacteria, viruses and a Gram-negative bacillus of the genus Rothia
- Currently, the germ incriminated is Rochalimaea henselae
Clinic:
- occurs before age 18
- After two to three weeks, one or more large adenopathies appear, satellites of the inoculation point, in the form of a red, indolent papule or a vesiculopustule.

spontaneously favorable evolution (sometimes after fistulization of the adenopathy)
the pus is greenish yellow and apparently sterile when cultured on standard media

Additional examinations:
- IDR: Positive for Reilly-specific antigen, but it may correspond to an old, undetected cat scratch disease
- histologically, the adenopathy is suppurative tuberculoid
Treatment :
- relies on cyclins

ATYPICAL MYCOBACTERIAL ADENITIS

Definition
- Often due to Mycobacterium scrofulaceum
- very young child (65% before 3 years old)
- entry point would be cutaneous (scalp, external ear or face) and mucous membrane (upper airways)
Clinical:
- cold, isolated, firm and mobile cervical adenopathy, with rapid initial growth; it progresses in 1 to 2 months to suppuration and fistulization, with preservation of the general condition
- pretragic and submental, even subangulomandibular and upper cervical seat
- Benign evolution
  - remains localized
  - but can last several months with healing then reappearance of the fistulas. (aesthetic after-effects)
- Differential diagnosis:
  - Tuberculosis sometimes difficult to eliminate
  - Serologies rule out tularemia and cat scratch disease
Positive diagnosis made thanks to:
- At IDR with atypical mycobacteria sensitins positive from the 4th day
- On direct examination of the lymph node puncture which brings back frank pus: presence of numerous acid-fast bacilli and absence of common germs
- When culturing samples on Löwenstein-Jensen and Colestos medium
- Waiting for results = anti-tuberculosis treatment*

ACTINOMYCOSIS

Definition :
- Germ involved Actinomyces israelli, Gram-positive bacillus, strict anaerobe
- cervicofacial involvement +++ (50 to 60% of cases)
Clinic:
- The entry point is intraoral: dental care, oral trauma, poor oral hygiene
- After a few weeks, adenopathy appears, subangulomandibular, woody, adherent, evolving towards abscessation,
- Fistulization => thick pus containing characteristic yellow actinomycotic grains, called “sulfide grains”
- Dc = cultures in special medium enriched in strict anaerobiosis. On direct examination of the pus, yellow grains and palisade filaments are characteristic
Treatment:
- Relies on prolonged parenteral penicillin

VIRAL ADENOPATHIES

INFECTIOUS MONONUCLEOSIS

Epstein-Barr virus disorder
Clinic:
- adolescent or young adult (between 15 and 25 years old)
- salivary contamination
- erythematopultaceous or ulceronecrotic, or even pseudomembranous, angina
- general signs: fever, malaise, splenomegaly
- polyadenopathy + major and early infection
- They are firm, mobile, sensitive to palpation, submandibular and spinal
- sometimes very large volume, never progressing to suppuration
Diagnosis is based on:
- NFS: hyperleukocytosis and monocytosis
- The MNI-test (8% false positives) to be confirmed by the positive Paul-Bunnell-Davidsohn reaction around the 7th day
Treatment:
- symptomatic
- bed rest
- spontaneous healing in 3 to 6 weeks

Acquired immunodeficiency virus HIV:

Clinic:
- firm, painless, mobile lymphadenopathy, persisting in at least two lymph node areas, often with a diameter greater than 1 cm
- at the stage of proven AIDS, the adenopathies disappear due to lymphocyte depletion
- their reappearance should raise suspicion of lymphoma, lymphonodal Kaposi’s sarcoma or an opportunistic mycobacterial infection
- other parasites or mycoses (toxoplasmosis, Pneumocystis carinii, cryptococcosis,

histoplasmosis…) can be responsible for cervical swelling in patients with HIV

Additional examinations:
- Serologies: ELISA and Western blot tests
- a lymph node sample for histological and bacteriological study is essential

HERPES virus

Herpes simplex hominis virus type 1
gingivostomatitis in primary infection
bilateral upper cervical lymphadenopathy
fever
dysphagia related to erosive mucosal lesions
evolution is spontaneously favorable in 10 to 15 days
during herpetic recurrences, adenopathies are classically absent, except in the presence of superinfection

RUBELLA

Togavirus
retroauricular or suboccipital cervical polyadenopathy
occurs one week before the rash and may persist for 2 to 3 months
adenopathies are small, easily mobile and not very tender, associated with arthralgia and fever
NFS: leukopenia with plasmacytosis, and sometimes mononucleosis
Dc confirmed by antibody testing at 15-day intervals
treatment is symptomatic
in non-immune pregnant women, serotherapy is necessary

MEASLES

paramyxovirus infection
small and mobile lymph nodes
coexisting with Koplik’s sign at the ostium of the Steno canals

PARASITIC ADENOPATHIES

TOXOPLASMOSIS

very common infection
often goes unnoticed
- special attention for pregnant women, since 90% of the population has a positive serology at 30 years of age
Toxoplasma gondii
- contagion = contact with cat droppings or consumption of contaminated, undercooked meat or contaminated raw or uncooked vegetables
primary infection
- occipital and spinal adenopathies (multiple, painless and mobile), persist for 6 to 12 months, mobile, firm, and painless
- inconsistent flu syndrome
the diagnosis is based mainly on the context and serology with dosage of immunoglobulinsM present from the first week and for several months

ADENOPATHIES OF MYCOTIC ORIGIN

Histoplasmosis
- granulomatous lesions
- cutaneous and mucosal manifestations
- cold abscessed lymphadenopathy
- by inhalation of spores, fungus Histoplasma capsulatum
- the manifestations are pulmonary
- Dc = direct examination of samples, culture on Sabouraud medium and histoplasmin IDR.
Other forms: Sporotrichosis, Coccidioidomycosis, Paracoccidioidomycosis.

ADENOPATHIES OF INFLAMMATORY IMMUNOALLERGIC ORIGIN SARCOIDOSIS
- Cervical lymphadenopathy
  - supraclavicular, firm, mobile, painless and small
  - never passing into the stage of suppuration
  - generally evolving towards spontaneous regression or which may persist for several years
- histology is tuberculoid type with absence of any suppurative or caseous necrosis
- Differential DC = tuberculosis.
- serum angiotensin converting enzyme levels, which are elevated in 90% of active sarcoidosis, are diagnostic elements
- depending on the stage of the disease, corticosteroid therapy is proposed

CONNECTIVITY AND AUTOIMMUNE DISEASES

Nearly half of cases of systemic lupus erythematosus have diffuse and discrete cervical lymphadenopathy
One third of cases of rheumatoid arthritis have axillary and epitrochlear adenopathies; the cervical site is less frequent

Drug Reaction Adverse Drug Reactions

Appears 9th day – 4th month
precede the appearance of cutaneous signs (morbilliform rash, pruritus),
Can affect all cervical chains
Regress after stopping the medication.
Usually firm, painless, without periadenitis
Drugs incriminated: Diphenylhydantoin, iodine products, phenylbutazone, penicillin, L-dopa, antiparkinsonian drugs, carbamazepine, retinoids, captopril and methyldopa

ADENOPATHIES OF TUMOR ORIGIN
- Given the seriousness of the prognosis, in case of suspicion of tumor adenopathy, the definitive diagnosis must be made as quickly as possible in order to establish an appropriate and early therapeutic strategy.

ADP HEMATOLOGICAL MALIGNANCIES

They are generally mobile, firm or elastic, painless and inflammatory in appearance.

HODGKIN’S LYMPHOMA

Child + young adult (20 to 30 years old)
often begins with one or more low and superficial cervical adenopathies
- Unilateral ADP, more or less firm, painless, without periadenitis and without accompanying signs
evolution = cervical bilateralization + general dissemination

• + later = general signs: fever, splenomegaly, pruritus, mediastinal adenopathies

The clinical picture can be summarized as a single adenopathy rapidly increasing in volume
lymph node puncture = Sternberg cells
- only surgical adenectomy allows a reliable and precise histological diagnosiscertain prognostic factors
- An extension assessment allows the disease to be classified into four stages, depending on the extent and number of areas affected.

NON-HODGKIN’S LYMPHOMA

man aged 50 to 70
extra-lymph node manifestations in 20 to 40% of cases
lymphadenopathy is an early clinical sign
most often supraclavicular
elastic, mobile, multiple
sometimes general signs: asthenia, weight loss, etc.
in 20% of cases a location at the level of Waldeyer’s ring
smooth, firm swelling covered with normal or purplish mucosa
the histological type and the extension assessment => prognosis + therapeutic strategy

LEUKEMIA

Bleeding disorders + infections + asthenia + fever
Chronic lymphocytic leukemia:
- subjects over 50 years old
- frequent adenopathies, often large, firm, elastic and mobile, bilateral and symmetrical, located in the cervical and supraclavicular region
- Dc = hemogram = mature hyperlymphocytosis
Chronic myeloid leukemia:
- non-lymphoid blood disease
- adenopathy appears during an acute transformation of the disease
Acute leukemia:
- rarer, moderately sized, painless, firm, mobile, diffuse and less symmetrical adenopathies
- more frequent during acute lymphoblastic leukemia (75%) than myeloid leukemia
Treatment: it is based on chemotherapy and radiotherapy protocols.

METASTATIC MALIGNANT ADENOPATHIES

METASTATIC ADP OF SQUARED CARCINOMA

squamous cell carcinoma VADS
- This should be systematically considered when adenopathy occurs in a man in his fifties who is alcoholic and/or smokes.
- *The capital lymphadenopathy, the crossroads of facial lymphatic drainage, is the subdigastric node known as Kuttner’s lymph node
it is therefore the most frequently invaded
Circumstances of discovery:
- sometimes reason for consultation = ADP
- oral cavity lesion
- clinical examination highlights cervical adenopathies, which are detrimental to the prognosis
Clinical examination:
- the oral cavity is carefully inspected and palpated, site by site, looking for a lesion and its underlying induration
- sometimes we speak of malignant cervical adenopathy of primitive appearance, without an entry point
- adenopathies suspected of invasion are:
  - hard, woody, painless and initially mobile
  - they become fixed to the superficial and deep planes
  - may take on an inflammatory aspect in the event of a sudden progressive flare-up, or progress to fluctuation and then fistulization
N0: absence of clinical adenopathy
N1: single, homolateral adenopathy, less than or equal to 3 cm
N2a: single, ipsilateral adenopathy, between 3 and 6 cm
N2b: multiple ipsilateral adenopathies, all less than 6 cm
N2c: single or bilateral contralateral adenopathy(s), less than 6 cm
N3: adenopathy measuring more than 6 cm
EXTENSION REPORT

METASTATIC ADP FROM OTHER TUMORS

adenocarcinoma = metastases more likely supraclavicular
supraclavicular lymphadenopathy
- primary thoracic lesion
- subdiaphragmatic (digestive tract, kidney, prostate)
Malignant melanoma can cause cervical lymph node metastases
cervical lymphadenopathy may be indicative of thyroid cancer

ADP AFTER IRRADIATION
- Cervical radiotherapy modifies lymph node architecture
- Histologically
  - first stage of cellular destruction, with necrosis and lymphocytic degeneration, and disappearance of follicles
  - in the second stage, after 24 hours, there is a rapid repopulation with reappearance of germinal centers, and after 8 weeks, presence of mast cells
  - the third stage continues for 9 to 12 months, with secondary depletion and fibrous proliferation
What to do when faced with cervicofacial adenopathy:

Questioning: marital status, history, tobacco, alcohol, mode of appearance of ADP, associated signs
Clinical examination
Paraclinical examinations
ADP balance sheet: number, location, size, consistency, mobility, sensitivity, relationships with neighboring structures to be mentioned according to a dated diagram.
Etiological diagnosis which consists of looking for the cause.
Fine needle aspiration or biopsy or even surgical adenectomy.

DECISION TREE

CONCLUSION

Cervicofacial lymphadenopathy is a fairly common reason for consultation. Although most etiologies are benign, the possibility of a malignant tumor etiology should never be neglected .

In this perspective, the interview and clinical examination must be as complete as possible in search of a primary lesion, supplemented by investigations chosen according to the context, without delaying the lymph node biopsy, when this is essential.

TO REMEMBER

– Any cervical adenopathy persisting for more than one month should be considered suspicious.

– A large, painless, fixed and indurated cervical adenopathy is in favor of a tumor etiology; it will be all the more suspicious the lower it is located.

– Cervical lymphadenopathy that may soften and fistulize is secondary to tuberculosis, cat scratch disease, or tularemia.

– In case of diagnostic doubt, a cervicotomy with extemporaneous anatomopathological analysis is necessary.

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