Lymphatic system — Medicine Library

Summary

The lymphatic system is part of the adaptive immune system as well as the circulatory system and comprises the thymus and bone marrow (primary lymph organs); mucosa-associated lymphatic tissue (MALT), the spleen, and the lymph nodes (secondary lymphatic organs); the lymphatic vessels and capillaries; and the lymph fluid. The primary function of the lymphatic system is to return excess interstitial fluid and waste products, such as proteins and cellular debris, to the bloodstream. The interstitial fluid is absorbed by lymphatic capillaries throughout the body via diffusion. The lymph fluid is then transported through the network of lymphatic vessels and lymph nodes to the right lymphatic duct, which drains into the right subclavian vein, and the thoracic duct, which drains into the left subclavian vein. Its secondary function is immune defense, which mainly involves the transport of leukocytes (esp. lymphocytes) between the bone marrow and the lymph nodes and the stimulation of immune response through the transport of antigen-presenting cells to the lymph nodes. Another function is the transport of fats as chyle from the digestive system to the bloodstream. Accordingly, lymph fluid is transparent when initially formed from the interstitial fluid but adopts a milky appearance as it accumulates proteins, fats, cellular debris, and leukocytes.
The lymph nodes are the main sites for lymph filtration and the storage of lymphocytes, including B cells, which mature and differentiate in the bone marrow, and T cells, which likewise form in the bone marrow but migrate to the thymus for maturation. Antigen presentation induces the differentiation and proliferation of B lymphocytes and the activation of T lymphocytes. Following antigen presentation, mature lymphocytes differentiate into effector cells in the secondary lymph organs. Lymph node clusters exist throughout the body, some of which are palpable (e.g., cervical lymph nodes) while others are not (e.g., mediastinal lymph nodes). They may become enlarged in response to inflammatory processes due to local infection, malignancy, or granulomatous disease.

Primary lymphatic organs

Lymphocytes form and mature in the primary lymphatic organs (the bone marrow and thymus). Both B lymphocytes and T lymphocytes arise from hematopoietic stem cells in the bone marrow. While B lymphocytes remain within the bone marrow during the process of maturation, T lymphocytes migrate to the thymus to mature and differentiate.

Bone marrow

B lymphocytes and
T lymphocytes originate from pluripotent stem cells in the bone marrow.

T lymphocytes migrate to the thymus to mature and differentiate.

B lymphocytes mature in the marrow and migrate to secondary lymphatic organs to form follicles and proliferate.

Bone marrow: B cell maturation; Thymus: T cell maturation

Normal bone marrow smear

Thymus

Function: maturation and differentiation of T lymphocytes
Location
- Superior anterior mediastinum
- Retrosternal, precordial
Structure: bilobar organ
surrounded by a fibrous capsule
- Neonates and infants
  
  The largest and most active thymus
  
  A prominent thymic shadow can be seen on chest x-ray (thymic sail sign).
  
  Involution begins at 1 year of age. [1]
- Adults
  
  Atrophic, mostly replaced by fatty tissue
  
  Thymus undergoes age-related thymic involution.
Histology
Thymic epithelial cells, dendritic cells, and macrophages

Thymic cortex

Peripheral region

Dark

Densely packed, immature T lymphocytes (thymocytes)

Thymic medulla

Central region

Light

Fewer cells: mature T lymphocytes and Hassall corpuscles that consist of concentrically arranged eosinophilic reticular cells (onion-like appearance)
Embryology
- Thymus epithelium arises from the 3^rd pharyngeal pouch (endoderm).
- Thymic lymphocytes originate from the mesoderm.
Clinical significance
- Thymic hypoplasia or aplasia: DiGeorge syndrome, SCID
- True thymic hyperplasia : secondary to steroid therapy, chemotherapy
- Thymic lymphoid hyperplasia : certain autoimmune diseases (e.g., myasthenia gravis, SLE, and rheumatoid arthritis)
- Thymoma: tumor of thymic epithelial cells
  
  Seen in the context of myasthenia gravis, pure red cell aplasia, immunodeficiency with thymoma
  
  An asymptomatic thymoma is usually detected as an incidental finding on a chest x-ray, where it appears as an anterior mediastinal mass.
  
  Symptomatic thymomas typically manifest in individuals 40–60 years of age with thoracic symptoms (e.g., chest pain, cough, dyspnea, SVC syndrome) or paraneoplastic syndromes.
  
  Treatment: options include surgery, chemotherapy, and/or radiotherapy.
- Thymic carcinoma: more aggressive than thymoma (mediastinal invasion and extrathoracic metastasis)

The Thymus arises from the Third pharyngeal pouch.

DiGeorge syndrome is caused by abnormal development of the 3^rd and 4^th pharyngeal pouches, which prevents the formation of thymus and parathyroid glands. As a result, patients with DiGeorge syndrome have an increased susceptibility to hypocalcemia and viral and fungal infections.

**Normal bone marrow smear**
Photomicrograph of a bone marrow smear (H&E stain; high magnification)
Numerous, darkly stained granulocytes can be seen within a sea of red blood cells at various stages of development. Several eosinophils (red-stained cells), basophils (dark blue-stained cells), and two large megakaryocyte cells are also visible (center right; center left).
Click on the Smartzoom button to view the entire specimen through a virtual microscope.

Source: © Smart Zoom, Smart In Media. Image and annotations in digital microscopy: Prof. Dr. Karl-Anton Kreuzer, Facharzt für Innere Medizin, Hämatologie und Onkologie

**Thymus (child)**
Microscopic image of the thymus (H&E stain, 25x magnification)
The thymus retains its characteristic two-layered structure until puberty. The lymphocyte-rich cortex (dark purple) is clearly distinguishable from medulla with its lower density of lymphocytes and presence of thymic corpuscles (red).
Click on the Smartzoom button to view the entire specimen through a virtual microscope.

Source: © Smart Zoom, Smart In Media. Image and annotations in digital microscopy: PD Dr. Alberto Perez Bouza

**Thymic sail sign**
X-ray chest (AP view) of an infant
A homogeneous soft tissue opacity representing normal thymic tissue extends laterally from the right side of the superior mediastinum into the right upper hemithorax. Its lateral border is convex while its inferior border is straight (green overlay) producing a sail-like appearance (illustration) that has been termed the thymic sail sign.

Source: “Radiology 1300566 Nevit” by Nevit Dilmen, Wikimedia Commons, licensed under CC BY-SA 3.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 3.0.

**Thymus (adult)**
Microscopic image of the thymus (H&E stain, 25x magnification)
Age-related thymic involution occurs after puberty. The parenchyma of the thymus (purple) loses mass and is replaced by adipose tissue (pale pink). The thymic cortex (dark purple) is affected to a greater degree by this process than the medulla (light purple), which contains thymic corpuscles (red) are visible.
Click on the Smartzoom button to view the entire specimen through a virtual microscope.

Source: © Smart Zoom, Smart In Media. Image and annotations in digital microscopy: PD Dr. Alberto Perez Bouza

**Thymus**
Photomicrograph of thymus tissue
The cortex (e.g., red overlay) is rich in lymphocytes and divided into lobules by strands of connective tissue (e.g., yellow overlay).
The medulla (green overlay) contains the eosinophilic Hassall corpuscles (white arrowheads), which are composed of epithelial reticular cells (the cells in the center of those corpuscles are degenerated and keratinized). Hassall corpuscules are characteristic of thymus tissue.

Source: © IMPP

**Hassal corpuscle (thymic corpuscle)**
Photomicrograph of thymic biopsy depicting the thymic medulla (H&E stain)
Concentric eosinophilic whorls (green overlay) composed of elongated eosinophilic epithelial cells (blue overlay) of the thymus with pale nuclei are seen in the center of the image.
This is the characteristic appearance of Hassal corpuscles that are normally present in the thymic medulla.
Numerous mature T lymphocytes (black arrowhead) and thymic epithelial cells (yellow overlay) surround the corpuscles.

Source: “Thymic corpuscle” by Nephron, Wikimedia Commons, licensed under CC BY-SA 3.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 3.0.

Secondary lymphatic organs

The secondary lymphatic organs are the spleen, lymph nodes, and mucosa-associated lymphatic tissue (e.g., the Peyer patches and tonsils). It is in the secondary lymphatic organs that antigen presentation occurs. They are also the site of differentiation of mature, naive lymphocytes into effector cells.

Spleen

Function
- Filtration of old or misshapen RBCs and platelets
- Vital role in forming and initiating a humoral immune response through B and T lymphocytes
- See “Spleen” for more information.
Location
- Underneath the left part of the diaphragm
- Close to the left kidney (anterolateral)
- Behind the ninth, tenth, and eleventh ribs
Structure
- White pulp is responsible for antigen filtration and presentation, and contains the following structures:
  
  Lymphoid follicles: house large numbers of B lymphocytes
  
  Periarteriolar lymphatic sheath: contains T lymphocytes
- Red pulp: responsible for blood filtration

Lymph nodes

Function

Nonspecific lymph filtration: macrophages within lymph node
Storage and circulation of B cells and T cells
Immune system activation: Antigen presentation induces differentiation and proliferation of B lymphocytes and activation of T lymphocytes.

Location

Throughout the body in close proximity to organs and large vessels
See “Lymph nodes clusters” below.

Structure

Bean-shaped organ; surrounded by fibrous capsule with trabeculae
The trabecular sinus leads lymph from the subcapsular sinus to the medullary sinus.
The hilus
- Allows blood vessels and efferent lymphatic vessels to enter or leave the lymph node
- Typically, only one or a small number of efferent lymphatic vessels leave the lymph node, compared to the larger number of afferent lymphatic vessels that enter the lymph node through the cortex.
The entering artery and vein branch into a large capillary network, which forms the post-capillary high endothelial venules.

Anatomy of the lymph node

Histology

Cortex (
B-cell zone): contains lymphoid follicles, which is the site of B lymphocyte storage, differentiation, and proliferation

Secondary lymphoid follicle (active): dense mantle zone; surrounding a pale germinal center

Primary lymphoid follicle (inactive): dense aggregates of naive B lymphocytes
Paracortex (
T-cell zone)

Region between the cortex and medulla

Contains T lymphocytes and high endothelial venules, which allows circulating B and T lymphocytes to enter or leave the bloodstream

Site of T-cell activation
Medulla
- Medullary cords: tightly packed with plasma cells and lymphocytes
- Medullary sinus of the lymph node
  
  Composed of macrophages, reticular cells
  
  Connected to the efferent lymphatic structures

Fine structure of a lymph node Germinal center Microstructure of a lymph node High endothelial venule

Clinical significance

Inflammatory or immune reactions (e.g., due to EBV infection) → reactive paracortical hyperplasia → clinically apparent lymphadenopathy (see “Lymphadenopathy”)
Depletion of paracortical lymphocytes: DiGeorge syndrome

Cervical lymphadenopathy

Mucosa-associated lymphoid tissues (MALT)

MALT include the tonsils, Peyer patches, and solitary lymphoid follicles of the mucosa; . The structure of MALT resembles that of other secondary lymphatic organs but it is also composed of a specialized reticular epithelium (follicle-associated epithelium) with a humoral defense mechanism . The follicle-associated epithelium of the gut-associated lymphatic tissue (GALT) contains M cells, which allow transcytosis of antigens into the lamina propria.

Peyer patches

Function
- Immune system activation in response to ingested pathogens
- M cells transport antigens from the intestinal lumen to antigen-presenting cells (e.g., macrophages) → B cells within the germinal center detect antigens and differentiate to plasma cells that secrete IgA → IgA acquires a secretory component and becomes secretory IgA → secretory IgA is transported across the intestinal epithelium and secreted on the luminal surface of the gut
Location: ileum (lamina propria and submucosa)
Histology
Aggregates of lymphoid follicles: contain numerous lymphocytes and dendritic cells

Follicle-associated epithelium : site of specialized M cells

Peyer patches

Tonsils

Function: Waldeyer tonsillar ring (first line of defense against inhaled or ingested pathogens)
Structure: similar to other secondary lymphatic organs
Location and histology

Characteristics of tonsils
Characteristic	Pharyngeal tonsils (adenoids)	Palatine tonsils	Lingual tonsils	Tubal tonsils
Location	Roof and posterior wall of the nasopharynx	Tonsillar fossa on both sides of the oropharynx	Base of the tongue	Lateral wall of the nasopharynx
Histology	Respiratory epithelium Small folds, no crypts	Fibrous capsule Non-keratinized stratified squamous epithelium 10–20 deep, branched crypts	Non-keratinized stratified squamous epithelium Shallow crypts In close proximity to skeletal muscle fibers of the tongue	Respiratory epithelium

Location of tonsils Vascular supply of the palatine tonsils Adenoid

Inducible bronchus associated lymphoid tissue (iBALT) [2][3][4]

Location: walls of the upper and lower respiratory tracts (in the perivascular spaces)
Function: immune system activation in response to antigens encountered in the upper and lower respiratory tracts following inflammation or infection
Structure and
histology
- Central, large B-cell follicles with or without adjacent T-cell areas
- Numerous follicular dendritic cells
- Contains specialized stromal cells, lymphatics, and high endothelial venules
- Lacks an M cell-containing dome epithelium

**Anatomy of the lymph node**
The parenchyma of the lymph node is divided into a B-cell zone (cortex), a T-cell zone (paracortex), and the marrow. The cortex contains primary and secondary lymph follicles with germinal centers, which allow affinity maturation of B cells. At the hilum (concave side), blood vessels enter and efferent lymphatic vessels leave the node. The entering artery and vein branch into a large capillary network. Special high endothelial venules in the paracortex allow for lymphocyte extravasation.
Afferent lymphatic vessels enter through the capsule at many points in the periphery and open into the subcapsular sinus. The cortical sinus runs from the cortex via the paracortex to the medullary sinus, which then drains into the efferent lymphatic vessel.

© AMBOSS

**Fine structure of a lymph node**
Photomicrograph of a lymph node tissue specimen (H&E stain, low magnification)
The cortex of a lymph node consists of numerous round lymph follicles (examples indicated by green overlay), in whose pale germinal centers B cells differentiate. The interfollicular areas are rich in T cells. The light areas represent the lymph sinuses (examples indicated by yellow overlay), which are rich in histiocytes.
Click on the Smartzoom button to view the entire specimen through a virtual microscope.

Source: © Smart Zoom, Smart In Media. Image and annotations in digital microscopy: PD Dr. Alberto Perez Bouza

**Germinal center**
Microscopic image of a lymph node (H&E stain, 200x magnification)
The pale germinal center contains centroblasts and centrocytes. The darker mantle zone is composed of mature, naive B cells.

Source: © Smart Zoom, Smart In Media. Image and annotations in digital microscopy: PD Dr. Alberto Perez Bouza

**Microstructure of a lymph node**
Photomicrograph of lymph node tissue (toluidine blue stain)
Left image (overview, low magnification): The B-cell zone (B) consists of several lymphoid follicles (here, three secondary follicles can be seen) with a light germinal center (yellow overlay) and a darker margin (red overlay).
The T-cell zone (T) is homogeneous and mainly contains naive T lymphocytes and high endothelial venules (HEV; black box).
Right image (cross section of an HEV; high magnification detail of black box): HEV (lumen: asterisk) enable lymphocytes in the circulation to enter lymph nodes. The endothelium of HEV is characteristically cobble-shaped with round cell nuclei.

Source: © IMPP

**High endothelial venule**
Microscopic image of a lymph node (azan stain, 550x magnification)
The asterisk indicates a high endothelial venule (HEV), sectioned longitudinally. HEVs are lined by cuboidal endothelium with prominent nuclei (black outlines). Additional transverse sections of HEV are marked by arrowheads.
The endothelium is situated on a blue-stained, discontinuous basement membrane. HEVs are located in the parafollicular T zone (green overlay highlights numerous round T cell nuclei) in secondary lymphatic organs (apart from the spleen) and permit recirculation of lymphocytes (white outline).

Source: © IMPP

**Peyer patches**
Photomicrograph of ileal tissue (Masson trichrome stain; low magnification)
Peyer patches (example indicated by green overlay) are large, secondary lymphoid follicles within the ileal mucosa and submucosa. They are covered by the ileal epithelium, which is composed of villi and crypts.
Click on the Smartzoom button to view the entire specimen through a virtual microscope.

Source: © Smart Zoom, Smart In Media. Image and annotations in digital microscopy: PD Dr. Alberto Perez Bouza

**Location of tonsils**
The tonsils are lymphatic organs located between the oral and nasal cavity and the pharynx. The tonsils are part of the immune system's mucosa-associated lymphoid tissue (MALT).
The pharyngeal tonsil is located at the roof of the nasopharynx. The paired tubal tonsils are located in proximity of the opening of the eustachian tube. In the oropharynx, the paired palatine tonsils are based in the tonsillar fossa, and the unpaired lingual tonsil is situated at the root of the tongue.

© AMBOSS

**Adenoid**
Microscopic image of adenoid tissue (H&E stain, 50x magnification)
The surface of the adenoid is lined with a pseudostratified ciliated columnar epithelium that allows for clear distinction from the tonsils, which are lined with a nonkeratinized stratified squamous epithelium. Beneath the epithelial lining, lymphatic nodules (purple, round) with germinal centers and seromucous glands with ducts extending to the surface (pink, left of center) are visible.
Click on the Smartzoom button to view the entire specimen through a virtual microscope.

Source: © Smart Zoom, Smart In Media. Image and annotations in digital microscopy: PD Dr. Alberto Perez Bouza

**Palatine tonsil**
Photomicrograph of a palatine tonsil tissue sample (H&E stain; 400x magnification)
The characteristic stratified nonkeratinized squamous epithelium lining the palatine tonsil can be seen at the top. There are single lymphocytes infiltrating the epithelium between the keratinocytes (examples indicated by arrows; white arrowheads indicate examples of keratinocyte nuclei), features that are physiological in the tonsils and other lymphoepithelial tissues. Mucosa-associated lymphatic tissue can be seen in the underlying tissue in the lower part of the image.

Source: © IMPP

**Palatine tonsils**
Microscopic image of palatine tonsillar tissue (H&E stain, 25x magnification)
The palatine tonsil is lined with nonkeratinized stratified squamous epithelium and is characterized by the round lymphoid follicles (light purple lined with dark purple) and deep branched tonsillar crypts (white, top center of image).
Click on the Smartzoom button to view the entire specimen through a virtual microscope.

Source: © Smart Zoom, Smart In Media. Image and annotations in digital microscopy: PD Dr. Alberto Perez Bouza

**Vascular supply of the palatine tonsils**
Sagittal section of the mouth, larynx, and pharynx
The palatine tonsils are supplied by branches of the lingual artery, ascending palatine artery, ascending pharyngeal artery, and descending palatine artery, all of which arise from the external carotid artery.

© AMBOSS

Lymphatic drainage

Overview

Lymph
- Drained by the lymph capillaries from body tissues, then circulates through lymphatic vessels and secondary lymphatic organs
- Lymph reenters blood circulation via the thoracic duct and right lymphatic duct.
Chyle (lymph and triglycerides) is taken up from the intestine during digestion and conveyed by the thoracic duct to empty into the venous system.

Thoracic duct

Drains lymph fluid from all body sections except for the right arm, the right side of the thorax, and the right head and neck region (including the left side of the thorax and upper limb)

Cisterna chyli; : a dilated lymphatic sac that lies near the left crus of the diaphragm, from which the thoracic duct arises [5]

The thoracic duct continues from the cisterna chyli, ascends the posterior mediastinum (thoracic aorta to its left), and empties into the left venous arch (junction of the left subclavian vein and left internal jugular vein).

Drains up to 4 liters of lymph per day

Injury to the thoracic duct may result in chylothorax.

Right lymphatic duct

Drains lymph fluid from the right arm, the right side of the thorax, and the right head and neck region.

Originates from the junction of the right subclavian trunk, the right bronchomediastinal trunk, and the right jugular trunk

Empties into the right venous arch (junction of the right subclavian vein and right internal jugular vein)

Lymph node clusters

Palpable lymph nodes

Head and neck

Lymph nodes of the head and neck
Cluster	Location	Drainage area	Differential diagnoses
Parotid lymph nodes	On and within parotid glands	Skin of the ear, cheek, and forehead	Bacterial, viral, or fungal infections
Preauricular lymph nodes	In front of the tragus	Parotid gland, nose, eyelids	Herpes zoster, conjunctivitis, other localized infections in the drainage area
Retroauricular lymph nodes	Area surrounding the mastoid process	Back of the head, crown, outer ear	Rubella
Submandibular lymph nodes	Area surrounding the mandibular angle, and between the chin and mandibular angle	Tongue, gum, cheek, lips	Tumors of and metastasis to the oral cavity, tonsillitis
Submental lymph nodes	Below the chin	Base of the mouth, tongue, lower lip	Tumors of and metastasis to the oral cavity, localized infections in the drainage area
Occipital lymph nodes	Area surrounding the neck and back of the head	Back of the head, neck	Localized infections of the scalp (e.g., lice, fungal), rubella, measles
Deep cervical lymph nodes	Ventral and dorsal to the sternocleidomastoid muscle Accompany the internal jugular vein in the carotid triangle	Lymph fluid drainage of all superficial lymph node groups of the head and neck Drain into the right lymphatic duct and thoracic duct	Upper respiratory tract infections Infectious mononucleosis Kawasaki disease Malignancy of the head, neck, and oropharynx
Posterior triangle lymph nodes	Triangle between sternocleidomastoid muscle, trapezius muscle, and the clavicle	Neck and lateral cervical region	Localized infections in the drainage area
Supraclavicular lymph nodes	Supraclavicular fossa, closer to the sternal end of the clavicle	Right supraclavicular nodes drain into the right lymphatic duct and collect Neck Right thorax Right upper extremity Right mediastinum Lungs Esophagus Left supraclavicular nodes (Virchow nodes) drain into the thoracic duct Left thorax Lungs Left upper extremity Abdomen Pelvis	Lung carcinoma Sarcoidosis Left supraclavicular lymphadenopathy (Troisier sign) is usually indicative of a possible abdominopelvic malignancy (especially metastatic gastric or pancreatic carcinoma).

Lymph nodes of the head and neck Cervical lymph node levels Lymphadenopathy in a patient with mononucleosis Neck swelling in mumps

Upper extremity

Lymph nodes of the upper extremity
Cluster		Location	Drainage area	Differential diagnoses
Axillary lymph nodes	Central lymph nodes	Lie in axillary fat	Lymph from the anterior, posterior, and lateral axillary lymph nodes Drain into the apical lymph nodes	Localized infection in the drainage area (e.g., mastitis) Breast cancer or metastasis
	Anterior (pectoral) lymph nodes	Anterior axillary fold	Mammary and pectoral regions Skin region located above the umbilicus
	Posterior (subscapular) lymph nodes	Posterior axillary fold	Upper back and posterior neck	Localized infection of the upper extremities/chest wall
	Lateral (brachial) lymph nodes	Medial, proximal upper arm	Majority of the upper limb	Localized infections of the upper extremities
	Apical (subclavicular) lymph nodes	Infraclavicular	Lymph from the central lymph node group Upper outer quadrant of the breast Drain into the right lymphatic duct and thoracic duct	Localized infection in the drainage area (e.g., mastitis) Breast cancer or metastasis
Supratrochlear/epitrochlear lymph nodes		Subcutaneous fat above medial epicondyle of humerus (∼ 3 cm from elbow)	Ulnar forearm and hand Drain into the axillary lymph nodes	Melanoma Lymphoproliferative disorders Secondary syphilis Infections of hand and forearm Tularemia

Palpable lymph nodes of the axillary region Lymph nodes of the breast Axillary lymph node swelling due to plague

Abdomen and lower extremity

Lymph nodes of the lower extremity
Cluster		Location	Drainage area	Differential diagnoses
Periumbilical [6]		Grouped around the umbilicus	Abdomen and pelvis (umbilical area) Drain into axillary, inguinal, and para-aortic lymph nodes	Sister Mary Joseph nodule: metastasis of malignant cancer in the abdominopelvic region (e.g., gastric cancer, pancreatic cancer, ovarian cancer)
Inguinal lymph nodes	Superficial inguinal lymph nodes	Superficial fascia of the thigh in the region of the femoral triangle Arranged in the shape of “T” The upper horizontal group lies along the inguinal ligament. The lower vertical group lies along the terminal part of the long saphenous vein.	Horizontal group Inguinal region Inferior abdominal wall (below the umbilicus) Gluteal region Scrotum, vulva, distal vagina, penis except for the glans Distal anal canal (below the pectinate line) Vertical group: lower limb with the exception of the gluteal region, popliteal area, and the lateral surface of the lower leg Drain into the deep inguinal lymph nodes	STDs (e.g., lymphogranuloma venereum, genital herpes, chancroid, syphilis) Pelvic malignancy (e.g., anal or vulvar cancer) Infection of the lower extremity Melanoma of the lower extremity Medial foot and leg cellulitis
Inguinal lymph nodes	Deep inguinal lymph nodes	Medial thigh (femoral triangle), parallel to the junction of the great saphenous vein and the femoral vein	Lower limbs Glans penis or clitoris Lymph from the superficial inguinal and popliteal lymph nodes Drain into the external iliac lymph nodes	STDs Infections of the leg or foot (e.g., cellulitis) Melanoma
Popliteal lymph nodes		Popliteal fossa	Dorsolateral aspect of the foot and the posterior calf Drain into the deep inguinal lymph nodes	Infections of the lateral leg or foot (e.g., cellulitis) Melanoma

The testicles, epididymis, and seminal ducts are drained by the deep, iliac, and lumbar lymph nodes.

Nonpalpable lymph nodes [7][8]

Deep lymph nodes

Thoracic

Thoracic lymph nodes
Cluster	Location	Drainage area	Drain into	Differential diagnoses
Mediastinal lymph nodes (paratracheal)	In the anterior mediastinum	Structures within the mediastinum (trachea, esophagus, hila of the lungs, heart and pericardium, thymus)	Thoracic duct	Mediastinal malignancies Lung carcinoma Esophageal carcinoma Hodgkin lymphoma Metastatic malignancies (e.g., breast carcinoma, thyroid carcinoma) Granulomatous pulmonary diseases e.g., tuberculosis (unilateral), sarcoidosis (bilateral), histoplasmosis, pneumoconiosis, mycoplasma
Hilar lymph nodes	Adjacent to main stem bronchus (hila of the lungs)	Lungs	Thoracic duct	Lung carcinoma Granulomatous pulmonary diseases e.g., tuberculosis (unilateral), sarcoidosis (bilateral), histoplasmosis, pneumoconiosis, mycoplasma

Anterior mediastinal mass in Hodgkin lymphoma Bilateral hilar and right paratracheal lymphadenopathy

Abdominal

Abdominal lymph nodes
Cluster		Location	Drainage area	Drain into	Differential diagnoses
Pre-aortic lymph nodes	Celiac lymph nodes	Around the origin of the celiac trunk	Stomach, upper duodenum, pancreas, spleen, liver and biliary tract (foregut)	Cisterna chyli (via intestinal lymphatic trunk)	Infectious focus in the bowel (e.g., appendicitis, colitis, typhoid fever) Mesenteric lymphadenitis Inflammatory bowel disease (e.g., ulcerative colitis) Celiac disease Colon cancer
	Superior mesenteric lymph nodes	Around the origin of the superior mesenteric artery	Lower duodenum, small intestine and colon to the splenic flexure (midgut)
	Inferior mesenteric lymph nodes	Around the origin of the inferior mesenteric artery	Colon from splenic flexure to the uppermost part of the rectum (hindgut)
Paraaortic lymph nodes (lumbar)		In front of the lumbar vertebrae near the aorta, around the renal vein	Kidneys and suprarenal glands Females: ovaries, uterus, fallopian tubes Males: testes Receive lymph from the common iliac nodes	Cisterna chyli (via lumbar lymphatic trunk)	Endometrial cancer Ovarian cancer Testicular cancer Metastasis

Pelvic

Pelvic lymph nodes
Cluster	Location	Drainage area	Drain into	Differential diagnoses
Internal iliac lymph nodes	Surrounding the internal iliac arteries	Lower rectum and anal canal (above the dentate line) Bladder (except the fundus) Cervix, lower uterus, and proximal vagina Prostate and corpora cavernosum	Common iliac lymph nodes	Bladder cancer Cervical cancer Prostate cancer Sexually transmitted infections
External iliac lymph nodes	Around the external iliac arteries	Body of the uterus Fundus of the bladder Cervix Upper part of the vagina Lymph from the deep inguinal nodes	Common iliac lymph nodes	Sexually transmitted infections Metastasis
Common iliac lymph nodes	Around the common iliac vessels	Lymph from the internal and external iliac nodes	Paraaortic lymph nodes	Metastasis

Blood supply and lymphatic drainage of the anal canal

**Overview of the systemic, pulmonary, and lymphatic circulation**
The systemic circulation carries blood from the left ventricle via the upper and lower circulation to the capillaries of the organs, and back to the right atrium of the heart. From there, the pulmonary circulation carries blood to the lungs and back to the left atrium of the heart.
The lymphatic system, shown in green, starts with blind-ended tubes in tissues that collect interstitial fluid. It drains into the upper circulation of the systemic circulation near the junction of internal jugular vein and subclavian vein.
Portal circulation is particular to the systemic circulation and is present in the liver and pituitary gland; there, the blood passes through the consecutive capillary beds of two different structures before returning to the heart.

© AMBOSS

**Palpable lymph nodes**
Lymph is drained into the systemic circulation via the subclavian veins. The right lymphatic duct primarily drains the upper right side of the body (green overlay). The thoracic duct is responsible for draining the rest of the body.
Testicular tumors do not typically disseminate to scrotal lymph nodes, because the two organs have separate lymphatic systems: testes drain to the para-aortic nodes and the scrotum drains to superficial inguinal nodes.

© AMBOSS

**Lymph nodes of the head and neck**
Palpable superficial and deep lymph nodes.

© AMBOSS

**Cervical lymph node levels**
– Level I (submental and submandibular lymph nodes): extends from the inferior border of the mandible to the upper border of the hyoid
– Level II (upper jugular lymph nodes): extends from the base of the skull to the hyoid
– Level III (middle jugular lymph nodes): extends from the hyoid to the cricoid
– Level IV (lower jugular lymph nodes): extends from the cricoid to the clavicle
– Level V (posterior triangle): posterior to the posterior edge of the sternocleidomastoid muscle and anterior to the anterior border of the trapezius muscle
– Level VI (prelaryngeal, pretracheal, and paratracheal lymph nodes): extends from the suprasternal notch to the innominate artery

© AMBOSS

**Lymphadenopathy in a patient with mononucleosis**
Bilaterally enlarged cervical lymph nodes (black arrows) and submandibular lymph nodes are seen in the neck region of a patient with infectious mononucleosis.
Additionally, there is a pale, macular rash on the neck and upper chest. A rash seen in infectious mononucleosis may be caused by the infection itself but is more commonly due to antibiotic use.

Source: “Lymphadenopathy” by James Heilman, MD, Wikimedia Commons, licensed under CC BY-SA 3.0.

**Neck swelling in mumps**
There is significant symmetrical neck swelling due to swelling of the salivary glands and lymph nodes.

Source: "ID#: 3168", CDC/ Heinz F. Eichenwald, MD, Centers for Disease Control and Prevention (CDC) licensed under Public Domain

**Palpable lymph nodes of the axillary region**
The lateral nodes drain most of the arm and shoulder and are palpable near the proximal humerus. The pectoral or anterior nodes drain the thoracic wall and parts of the thorax and are palpable in the anterior axillary line. The subscapular or posterior nodes drain the posterior thoracic wall and parts of the arm and are palpable in the posterior axillary line.
All these lymph nodes drain into the central nodes, which are palpable at the base of the axilla. Before entering the venous system, lymph from the central nodes passes through the subclavicular or apical nodes before entering the venous system. Therefore, these nodes should also be palpated in the examination.
For educational purposes, the lymph nodes are depicted enlarged.

© AMBOSS

**Lymph nodes of the breast**
Lymphatics of the breast drain into three groups:
1. Axillary group, further divided into three levels
– Level I: lateral to the lateral border of the pectoralis minor
– Level II: behind the pectoralis minor
– Level III: medial to the medial border of the pectoralis minor
2. Parasternal (internal thoracic) group
3. Posterior intercostal group (not shown here)

Efferent lymphatics travel to the supraclavicular nodes and terminate in the thoracic duct (on the left; not shown here) or the right lymphatic duct.

© AMBOSS

**Axillary lymph node swelling due to plague**
Right axilla of a male patient diagnosed with plague
The axilla appears swollen secondary to underlying lymph node enlargement due to infection with Yersinia pestis.
This disease is rare but if diagnosed requires immediate antibiotic treatment.

Source: "ID #2045", CDC, Centers for Disease Control and Prevention, Atlanta, USA licensed under Public Domain

**Superficial inguinal lymph nodes**
The superficial inguinal lymph nodes are divided into a horizontal group, which can be palpated directly underneath the inguinal ligament, and a vertical group, which can be palpated in the region where the great saphenous vein drains into the femoral vein.

© AMBOSS

**Blood supply and lymphatic drainage of the anal canal**
Illustration depicting the dual lymphovascular supply of the anal canal
The anal valves form the pectinate line (seen as a longitudinal scalloped line), which divides the anal canal into upper and lower parts.
Arterial supply
Above the pectinate line:
- Superior rectal artery (a branch of the inferior mesenteric artery)
- Middle rectal artery (a branch of the internal iliac artery)
Below the pectinate line: inferior rectal artery (a branch of the internal pudendal artery)
Venous drainage (site of porto-systemic anastomosis)
Above the pectinate line:
- Superior rectal vein (drains into the inferior mesenteric vein, which drains into the portal vein)
- Middle rectal vein (drains into the internal iliac vein, a systemic vein)
Below the pectinate line: inferior rectal vein (drains into the internal pudendal vein, a systemic vein)
Lymphatic drainage
Above the pectinate line: into the internal iliac and inferior mesenteric lymph nodes
Below the pectinate line: into the superficial inguinal lymph nodes

© AMBOSS

**Bubonic plague**
Photograph of the right upper leg of a patient diagnosed with plague
Enlarged lymph nodes secondary to an infection with Yersinia pestis, the causative bacterium for plague, are visible.

Source: "ID #2047", CDC, Centers for Disease Control and Prevention, Atlanta, USA licensed under Public Domain

**Deep lymph nodes**
Lymph is ultimately drained into the systemic circulation via the subclavian veins. The right lymphatic duct only drains roughly the upper right area of the body (green), whereas the thoracic duct is responsible for the rest of the body. The deep lymph nodes are not palpable.

© AMBOSS

**Anterior mediastinal mass in Hodgkin lymphoma**
X-ray chest (a: PA view; b: left lateral view) and CT chest (c: with contrast; coronal plane) of a patient with nodular sclerosing Hodgkin lymphoma
The PA radiograph shows an abnormal superior mediastinum that is dense, markedly widened, and lobulated (green overlay). On the lateral radiograph, there is opacification of the retrosternal space, which should normally be a clear area. CT confirms the presence of a large anterior locally invasive mediastinal soft tissue mass (arrows).
Li: liver; LV: left ventricle

Source: “Fig. 1.3, in: A Systematic Approach to Chest Radiographic Analysis” by Jeffrey S. Klein, Melissa L. Rosado-de-Christenson, Springer Link, licensed under CC BY 4.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above (© AMBOSS).

**Bilateral hilar and right paratracheal lymphadenopathy**
Chest x-ray (PA view) of a patient with sarcoidosis
The pulmonary hila (green overlay) are enlarged and lobulated. Additionally, the right superior mediastinum (red overlay) is widened and dense. A normal thin right paratracheal stripe is not seen.
Relatively symmetric bilateral hilar and right paratracheal lymph node enlargement on a chest radiograph in sarcoidosis is termed the “1-2-3 sign” or “Garland triad.” Examples of other causes of hilar and mediastinal lymphadenopathy include lymphoma, metastatic disease, granulomatous infections, and inorganic dust disease.

Our great thanks to Dr. Kissig (Center for Diagnostic and Interventional Radiology, Hedwigshöhe, St. Hedwig, Berlin, and St. Josefs Hospital, Potsdam) for kindly providing this image.

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