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lymph node histology cortex medulla germinal center

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Lymph Nodes — Anatomy & Clinical Examination


1. Overview

There are approximately 600 lymph nodes throughout the body. They are small, bean-shaped, encapsulated organs distributed along lymphatic vessels, acting as biological filters and sites of immune activation. — Harrison's Principles of Internal Medicine 22E

2. Gross Anatomy

FeatureDescription
ShapeBean-shaped, 1–25 mm
CapsuleOuter collagenous fibrous capsule
TrabeculaeFibrous extensions from capsule that subdivide the node
HilusConcave indentation; entry of artery and vein, exit of efferent lymphatic
Afferent vesselsEnter through convex surface (multiple)
Efferent vesselExits at the hilus (single)

3. Microanatomy (Internal Structure)

The diagram below shows the full internal architecture:
Lymph node organization diagram showing cortex, paracortex, medulla, germinal centers, high endothelial venules, afferent and efferent lymphatics
Fig. Organization of the lymph node — Medical Microbiology 9e (Elsevier)

Zones and Their Cellular Composition

ZoneLocationCell TypeFunction
Subcapsular (marginal) sinusJust beneath capsulePhagocytic macrophagesFilters lymph from afferent vessels
CortexOuter zoneB cells in primary folliclesHumoral immunity; B-cell activation
Germinal centers (secondary follicles)Within cortexActivated B cells, follicular dendritic cellsSite of B-cell proliferation, somatic hypermutation, affinity maturation; plasma cell and memory B-cell development
ParacortexBetween cortex and medullaT cells, dendritic cellsCell-mediated immunity; antigen presentation
High endothelial venules (HEV)ParacortexSpecialized endotheliumEntry of naïve lymphocytes from blood into the node
MedullaCentral/inner zoneT cells, B cells, plasma cells in medullary cordsAntibody production and final lymph filtration
Medullary sinusesAround medullary cordsMacrophagesFurther phagocytic filtration before efferent exit
"The cortex contains B cells grouped in primary follicles and stimulated B cells in secondary follicles (germinal centers). The paracortex contains mainly T cells and dendritic cells. Lymphocytes enter the node from the circulation through the specialized high endothelial venules in the paracortex. Lymphocytes can leave the node only through the efferent lymphatic vessel." — Medical Microbiology 9e

Histology (H&E)

Lymph node histology showing germinal centers with pale centers surrounded by dense mantle zones — reactive follicular hyperplasia
Normal lymph node histology: pale germinal centers (B-cell zones) surrounded by dark mantle zones of small lymphocytes, with T-cell-rich interfollicular paracortex

4. Lymph Node Groups — Regional Anatomy

Head & Neck Nodes (Most Clinically Important)

The American Head and Neck Society classification uses 6 levels + additional regions:
Neck lymph node levels diagram — Levels IA, IB, IIA, IIB, III, IV, VA, VB, VI, P, R, S
Fig. Lymph node levels of the neck — Cummings Otolaryngology
LevelLocationKey NodesDrains
IASubmental triangleSubmental nodesFloor of mouth, tip of tongue, lower lip
IBSubmandibular triangleSubmandibular nodesOral cavity, anterior face
IIAUpper jugular (medial to CN XI)Jugulodigastric nodesTonsil, pharynx, oral cavity
IIBUpper jugular (lateral to CN XI)Upper spinal accessory chainPosterior scalp
IIIMiddle jugular (hyoid → cricoid)Mid-jugular nodesLarynx, hypopharynx
IVLower jugular (cricoid → clavicle)Lower jugular nodesThyroid, cervical esophagus
VAPosterior triangle superiorSpinal accessory nodesPosterior scalp, skin
VBPosterior triangle inferiorSupraclavicular, transverse cervical nodesThorax, abdomen (Virchow's node is in level IV)
VICentral compartmentPretracheal, paratracheal, Delphian nodeThyroid, larynx, cervical trachea
PParotid/preauricularAnterior scalp, face, ear
RRetroauricularPosterior scalp, pinna
SSuboccipitalPosterior scalp
"The Virchow node is not in the VB region but is located in level IV." — Cummings Otolaryngology

Other Major Node Groups

RegionKey Node GroupsDrains
AxillaryAnterior (pectoral), posterior (subscapular), lateral, central, apicalArm, breast, chest wall
Inguinal (superficial)Along inguinal ligament and great saphenous veinLower limb, perineum, external genitalia, anal canal below dentate line
Inguinal (deep)Along femoral vessels, Cloquet's nodeDeep structures of lower limb
EpitrochlearMedial arm above elbowUlnar forearm, hand (4th and 5th fingers)
PoplitealBehind kneeFoot, posterior lower leg
MesentericAlong superior/inferior mesenteric vesselsGI tract
MediastinalParatracheal, subcarinal, hilarLungs, trachea, esophagus
Para-aortic (lumbar)Alongside aortaTestes/ovaries, kidneys, uterus

5. Clinical Examination of Lymph Nodes

General Principles

A physical examination should assess lymph nodes in multiple regions — popliteal, inguinal, epitrochlear, axillary, and multiple cervical regions. For each palpable node, document: — Harrison's Principles of Internal Medicine 22E
ParameterWhat to Note
LocationWhich anatomical region
SizeNormal <1 cm in adults; <1.5 cm in children
TendernessPresent (suggests infection/inflammation) or absent
ConsistencySoft (reactive/infection), firm/rubbery (lymphoma), hard (metastatic carcinoma)
MobilityMobile (benign reactive) vs. fixed/matted (malignancy, TB, extranodal extension)
Overlying skinErythema, warmth, sinus tracts
NumberSingle vs. multiple
BordersDiscrete vs. matted (nodes connected and moving together)
"Nodes that are small and firm can also be described as 'shotty', referring to the size and consistency of buckshot pellets. Palpable epitrochlear nodes are always pathologic." — Harrison's 22E

Technique

  • Use pads of 2–3 fingers, applying gentle circular pressure
  • In the neck: examine systematically from Level I → VI, comparing both sides
  • Submandibular area: bimanual palpation (gloved finger in floor of mouth) distinguishes nodes from the submandibular gland
  • Carotid artery can be mistaken for a pulsatile node — auscultate for a bruit; pulsatility distinguishes it
"In the superior cervical chain, it is very common to have multiple, borderline, enlarged, indistinct, or slightly firm nodes that are often termed 'shoddy'." — Cummings Otolaryngology

Size Thresholds for Pathology

PopulationPathologic Threshold
Adults>1 cm in most regions
Children>1.5 cm in greatest diameter
All patientsAny palpable epitrochlear node
All patientsAny palpable supraclavicular node (always pathologic)

Characteristics That Suggest Malignancy vs. Benign

FeatureBenign/ReactiveMalignant
ConsistencySoft, rubberyHard, stony
MobilityMobileFixed to skin or deep structures
TendernessOften tenderUsually non-tender
GrowthFluctuatingProgressive
DurationAcute (<4–6 weeks)Subacute/chronic (>4–6 weeks)
SkinNormalDimpling, attachment, ulceration

6. Differential Diagnosis of Lymphadenopathy

Localised vs. Generalised

  • Localized lymphadenopathy: found in the head/neck (55% of cases), inguinal (14%), axillary (5%) — suggests regional infection, trauma, or local malignancy
  • Generalised (≥2 non-contiguous regions): suggests systemic disease — viral infection, lymphoma, HIV, autoimmune disorders, drugs

Key Clinical Framework (Cervical)

PresentationMost Likely Cause
Acute bilateral cervical nodesViral URTI
Acute unilateral cervical nodesBacterial (Staph, Strep)
Subacute/chronic (>4–6 weeks)Granulomatous infection (TB, atypical mycobacteria), malignancy
Progressive enlargementMalignancy
Fluctuating sizeInflammatory/infectious
— Tintinalli's Emergency Medicine

Causes by Category

CategoryExamples
InfectiousEBV (infectious mononucleosis), CMV, HIV, Toxoplasmosis, TB, cat-scratch disease (Bartonella), tularemia
Autoimmune/inflammatorySLE, rheumatoid arthritis, sarcoidosis
Malignant — primaryHodgkin lymphoma, non-Hodgkin lymphoma
Malignant — metastaticCarcinoma (squamous cell, thyroid, breast, lung, GI)
Drug-inducedPhenytoin, allopurinol, hydralazine
MiscellaneousKawasaki disease, Castleman disease

7. Special Clinical Notes

  • Virchow's node (left supraclavicular/level IV node): enlargement suggests metastatic intra-abdominal or thoracic malignancy (sentinel node of Troisier's sign)
  • Sister Mary Joseph node (periumbilical): intra-abdominal malignancy
  • Delphian node (precricoid, level VI): enlargement in thyroid carcinoma or subacute thyroiditis
  • Extranodal extension: nodes feel fixed and immobile on examination; diagnosed pathologically or when fixation is evident on palpation/imaging — Sabiston Textbook of Surgery
  • Adults >40 years with unexplained lymphadenopathy lasting >4 weeks should have biopsy considered to exclude lymphoma or metastatic disease

Sources: Medical Microbiology 9e, Harrison's Principles of Internal Medicine 22E, Cummings Otolaryngology: Head and Neck Surgery, Tintinalli's Emergency Medicine, Sabiston Textbook of Surgery
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