The lymphatic system is composed of lymphatic vessels and lymphoid organs such as the thymus, tonsils, lymph nodes, and the spleen. These assist in acquired and innate immunity, in filtering and draining the interstitial fluid and in recycling cells at the end of their life cycle. The fluid that leaks from end-stage capillaries returns to the vascular system via the superficial and deep lymphatic vessels, which in turn drain into the right lymphatic duct and the thoracic duct. The right lymphatic duct travels on the medial border of the scalenus anterior muscle and drains the lymph from the right upper quadrant of the body. The thoracic duct starts at the cisterna chyli and has a highly variable anatomy. The right lymphatic duct and the thoracic duct drain into the right and left subclavian arteries, respectively, at the jugulovenous angle.
Lymph nodes are found at the convergence of major blood vessels, and an adult will have approximately 800 nodes commonly sited in the neck, axilla, thorax, abdomen, and groin. These filter incoming lymph and play a role in infection as well as in malignancy. This paper will discuss the structure and function of lymph nodes, as well as the anatomical divisions of these.
Lymph nodes are kidney-shaped and receive lymph via multiple afferent vessels, and filtered lymph then leaves via one or two efferent vessels. Nodes typically have an associated artery and vein, which terminates into a high endothelial venule (HEV). The HEV is the site of trans-endothelial migration of circulating lymphocytes due to T and B-cell endothelial surface receptors.
Lymph nodes usually range in size from 1 to 2 cm and are enclosed in an adipose tissue capsule. They are considered pathological if they lose their oval shape, if there is a loss of the hilar fat, if there is an asymmetrical thickening of the cortex and if they are persistently enlarged.
Lymph Node Structure
The capsule of the lymph node is dense connective tissue stroma and collagenous fibers. The capsule sends trabeculae inside the lymph node, which pass inward radiating towards the center.
The subcapsular sinus is the space between the capsule and the cortex, which allows the transportation of the lymphatic fluid.; this is also called the lymph path, the lymph sinus, or the marginal sinus. The subcapsular sinus is present beneath the capsule and is traversed by both reticular fibers and cells. It receives the afferent vessels, continues with the trabecular sinuses, and joins the medullary sinus in the medulla of the lymph node.
The cortex of the lymph node is the layer beneath the subcapsular sinus. The cortex is formed of the outer cortex and the inner part known as the paracortex. The outer cortex layer is also named the B-cell layer, is rich in CXCR5 chemokines, and consists mainly of B-cells arranged into follicles. The immature B-cells develop into a germinal center when challenged with an antigen. Following this, resting B-cell and dendritic cells surround the germinal center to form a mantle zone. The paracortex layer, also called the T-cell layer, consists of T-cells which interact with the dendritic cells and is rich in CCR7 chemokines.
The medulla is the innermost layer of the lymph node and contains large blood vessels, sinuses, and medullary cords. The medullary cords contain antibody-secreting plasma cells, B-cells, and macrophages. The medullary sinuses (or sinusoids) are vessel-like spaces that separate the medullary cords. The medullary sinuses receive lymph from the trabecular sinuses and cortical sinuses and contain reticular cells and histocytes. The medullary sinus drains the lymph into the efferent lymphatic vessels.
Function of Lymph Node
The primary function of lymph nodes is filtering interstitial fluid collected from soft tissues and eventually returning it to the vascular system. Filtering this exudative fluid allows for exposure of T-cells and B-cells to a wide range of antigens. For antigen-specific B and T cells to activate, they must first suffer exposure to antigens with the aid of antigen-presenting cells, dendritic cells, and follicular dendritic cells. These form part of both the innate immune response and play a role in adaptive immunity.
Lymph nodes begin their development in utero as mesenchymal condensation, which later bulges to form a lymph sac. At the 13th gestational week, the T-cell region begins to develop, and by the 17th gestation week, the interdigitating reticulum cells (a subtype of T-cells) are found in the paracortical lymph node region, surrounded by lymphoid cells. B-cell regions within lymph nodes start their development at the 14th gestation week at the marginal sinus with a population of dendritic reticulum cell precursors, lymphoblasts, immunoblasts, and plasmablasts. By the 20th gestation week, incipient primary follicles are observable in the outer cortex containing lymphocytes. During the 12th and the 14th gestation weeks, lymph nodes undergo granulopoiesis and erythropoiesis to temporarily produce undifferentiated blast cells, monocytes, and macrophages.
Lymph Nodes of the Head and Neck
The lymph nodes in the head and neck are paired and broadly split into superficial and deep nodes.
In terms of anatomical dissection, these more easily split into levels of the neck.
These nodes, also called the upper internal jugular nodes, are found in an anatomical area bounded by the base of the skull superiorly, the hyoid bone inferiorly, the submandibular gland anteriorly, the posterior border of the sternocleidomastoid muscle laterally and the internal carotid artery medially. The spinal accessory nerve separates the level IIa and IIb nodes.
These nodes are also names the middle internal jugular nodes and are bound superiorly by the hyoid bone, the cricoid cartilage inferiorly, the anterior edge of the sternocleidomastoid muscle anteriorly, the posterior margin of the sternocleidomastoid muscle and the common carotid artery medially.
These nodes are also named the lower internal jugular nodes and include Virchow's node. The anatomical area in which they are found is bound superiorly by the cricoid cartilage, the clavicle inferiorly, the sternocleidomastoid muscle anteriorly, and the common carotid artery medially.
These are also named the posterior triangle nodes and are bounded by the convergence of the sternocleidomastoid and trapezius muscles superiorly, the clavicle inferiorly, the sternocleidomastoid muscle anteriorly and medially and the trapezius muscle posteriorly.
This level is also named the anterior compartment and contains the anterior jugular, pre-tracheal, para-tracheal, pre-cricoid, pre-laryngeal, and thyroid nodes. It is bound superiorly by the hyoid bone, inferiorly by the suprasternal notch, by the platysma muscle anteriorly and the common carotid artery laterally.
Lymph Nodes of the Upper Limb
The deep and superficial lymphatics in the upper limb eventually drain into the axillary nodes, although there are supratrochlear and cubital lymph nodes at the level of the elbow, brachial lymph nodes, and deltopectoral lymph nodes. The drainage of the upper limbs is particular due to the presence of sentry or sentinel lymph nodes. These are usually larger than the rest of the lymph nodes and are the first to filter the incoming lymph. However, it is not uncommon for multiple smaller sentry lymph nodes to also be present.
The apical nodes further form the subclavian lymphatic trunk, which then drains into the right lymphatic duct.
Lymph Nodes of the Lower Limb
The superficial and deep lymphatic vessels of the lower limb drain into the inguinal lymph nodes, which are in the femoral triangle. This anatomical region, also named Scarpa's triangle, is bounded by the inguinal ligament above, the medial border of the sartorius muscle laterally, and the medial border of the adductor longus muscle medially.
The inguinal lymph nodes split at the level (where the great saphenous vein becomes the deep femoral vein) into sub-inguinal lymph nodes below and superficial inguinal nodes above.
The lymphatic system is involved in infective, inflammatory, and malignant diseases, and as such, enlargement of lymph nodes can be attributed to multiple causes. In the case of lymphadenopathy of unclear origin, endoscopic ultrasound (EUS) with or without fine-needle aspiration (FNA) can aid in diagnosis. This diagnostic technique has been shown to have high accuracy with up to 85% sensitivity and 100% specificity and is key in detecting and staging malignancy. With lymph nodes that are out of the scope of fine-needle sampling, elastography plays an increasingly important role, similar to obtaining a virtual biopsy. Functional and anatomical data can be acquired using more traditional diagnostic methods such as positron emission tomography (PET) combined with computed tomography. However, this is commonly a whole-body imaging technique and therefore involves high doses of ionizing radiation. Despite the recent advancements in imaging modalities, the diagnosis still heavily relies on clinical correlation with symptoms.
|||Johnson OW,Chick JF,Chauhan NR,Fairchild AH,Fan CM,Stecker MS,Killoran TP,Suzuki-Han A, The thoracic duct: clinical importance, anatomic variation, imaging, and embolization. European radiology. 2016 Aug; [PubMed PMID: 26628065]|
|||Girard JP,Springer TA, High endothelial venules (HEVs): specialized endothelium for lymphocyte migration. Immunology today. 1995 Sep; [PubMed PMID: 7546210]|
|||Bontumasi N,Jacobson JA,Caoili E,Brandon C,Kim SM,Jamadar D, Inguinal lymph nodes: size, number, and other characteristics in asymptomatic patients by CT. Surgical and radiologic anatomy : SRA. 2014 Dec; [PubMed PMID: 24435023]|
|||Elmore SA, Histopathology of the lymph nodes. Toxicologic pathology. 2006; [PubMed PMID: 17067938]|
|||Baldazzi V,Paci P,Bernaschi M,Castiglione F, Modeling lymphocyte homing and encounters in lymph nodes. BMC bioinformatics. 2009 Nov 25 [PubMed PMID: 19939270]|
|||Liao S,von der Weid PY, Lymphatic system: an active pathway for immune protection. Seminars in cell [PubMed PMID: 25534659]|
|||Markgraf R,von Gaudecker B,Müller-Hermelink HK, The development of the human lymph node. Cell and tissue research. 1982; [PubMed PMID: 6980711]|
|||Cupedo T, Human lymph node development: An inflammatory interaction. Immunology letters. 2011 Jul; [PubMed PMID: 21333686]|
|||Grégoire V,Ang K,Budach W,Grau C,Hamoir M,Langendijk JA,Lee A,Le QT,Maingon P,Nutting C,O'Sullivan B,Porceddu SV,Lengele B, Delineation of the neck node levels for head and neck tumors: a 2013 update. DAHANCA, EORTC, HKNPCSG, NCIC CTG, NCRI, RTOG, TROG consensus guidelines. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2014 Jan; [PubMed PMID: 24183870]|
|||Suami H,Taylor GI,Pan WR, The lymphatic territories of the upper limb: anatomical study and clinical implications. Plastic and reconstructive surgery. 2007 May; [PubMed PMID: 17440362]|
|||Cuadrado GA,de Andrade MFC,Akamatsu FE,Jacomo AL, Lymph drainage of the upper limb and mammary region to the axilla: anatomical study in stillborns. Breast cancer research and treatment. 2018 Jun; [PubMed PMID: 29380209]|
|||Pan WR,Wang DG,Levy SM,Chen Y, Superficial lymphatic drainage of the lower extremity: anatomical study and clinical implications. Plastic and reconstructive surgery. 2013 Sep; [PubMed PMID: 23985641]|
|||Pan WR,Levy SM,Wang DG, Divergent lymphatic drainage routes from the heel to the inguinal region: anatomic study and clinical implications. Lymphatic research and biology. 2014 Sep; [PubMed PMID: 25229435]|
|||Hsu MC,Itkin M, Lymphatic Anatomy. Techniques in vascular and interventional radiology. 2016 Dec; [PubMed PMID: 27993319]|
|||Hocke M,Ignee A,Dietrich C, Role of contrast-enhanced endoscopic ultrasound in lymph nodes. Endoscopic ultrasound. 2017 Jan-Feb; [PubMed PMID: 28218194]|
|||Eloubeidi MA,Chen VK,Eltoum IA,Jhala D,Chhieng DC,Jhala N,Vickers SM,Wilcox CM, Endoscopic ultrasound-guided fine needle aspiration biopsy of patients with suspected pancreatic cancer: diagnostic accuracy and acute and 30-day complications. The American journal of gastroenterology. 2003 Dec; [PubMed PMID: 14687813]|
|||Popescu A,Săftoiu A, Can elastography replace fine needle aspiration? Endoscopic ultrasound. 2014 Apr; [PubMed PMID: 24955340]|