The axillary lymph nodes are a group of approximately 20 to 30 encapsulated, bean-shaped structures located within the fatty axilla (armpit), serving as key components of the lymphatic system by draining lymph fluid from the upper limb, lateral aspects of the breast and chest wall, and the upper abdominal wall superior to the umbilicus.[1] These nodes filter interstitial fluid to remove pathogens, damaged cells, and foreign particles, while facilitating immune surveillance through the activation of B cells, T cells, and macrophages, ultimately returning cleansed lymph to the bloodstream via efferent vessels.[2] Clinically, they are of paramount importance in oncology, as they represent the primary site for metastasis in breast cancer, guiding diagnostic staging, prognostic assessment, and therapeutic interventions such as sentinel lymph node biopsy or complete axillary dissection.[1]Anatomically, the axillary lymph nodes are organized into five distinct groups within the axillary fat pad, based on their relations to adjacent muscles and vessels: the anterior (pectoral) group along the lower border of the pectoralis minor, the posterior (subscapular) group along the posterior axillary wall, the lateral (humeral) group adjacent to the humerus, the central group deep to the pectoralis minor, and the apical group superior to the muscle.[1] For surgical and radiological purposes, they are further subdivided into three levels relative to the pectoralis minor muscle: level I (lateral or inferior to the muscle, encompassing the lateral, anterior, and posterior groups), level II (behind or deep to the muscle, including the central group), and level III (medial or superior to the muscle, comprising the apical group).[1] Lymphatic inflow arrives via afferent vessels from the drained regions, passes through subcapsular and medullary sinuses for filtration, and exits through efferent vessels that converge on the apical nodes to form the subclavian lymphatic trunk, ultimately joining the thoracic duct or right lymphatic duct.[2]Embryologically, axillary lymph nodes originate from mesodermal hemangioblastic stem cells around the fifth gestational week, coalescing into primitive lymphatic sacs that differentiate into the node's cortical and medullary compartments.[1] Their vascular supply arises from branches of the axillary artery, with corresponding venous drainage into tributaries of the axillary vein, ensuring nutrient delivery and waste removal to support immune functions.[1] Beyond malignancy, axillary lymphadenopathy—enlargement or inflammation of these nodes—can signal systemic infections, autoimmune disorders like sarcoidosis, or hematologic cancers such as lymphoma, often prompting imaging or biopsy for differential diagnosis.[1] Surgical management, particularly in breast cancer, carries risks including lymphedema (affecting up to 25% of patients post-dissection), sensory disturbances, and chronic pain, underscoring the need for minimally invasive techniques like sentinel node procedures to preserve lymphatic integrity.[1]
Anatomy
Location and boundaries
The axilla is a pyramidal space located at the junction between the upper limb and the thorax, serving as a passageway for neurovascular structures between the upper arm and the thoracic wall.[3] It is bounded by four walls: the anterior wall formed by the pectoralis major, pectoralis minor, and subclavius muscles; the posterior wall comprising the subscapularis, teres major, and latissimus dorsi muscles; the medial wall consisting of the serratus anterior muscle and the upper thoracic wall (including ribs and intercostal muscles); and the lateral wall defined by the intertubercular groove of the humerus.[3]The apex of the axilla, also known as the cervico-axillary canal, is situated superiorly near the lateral border of the first rib, the superior border of the scapula, and the posterior border of the clavicle, providing continuity with the neck.[3] The base is formed inferiorly by the skin and superficial fascia of the armpit. The axillary lymph nodes, numbering approximately 20 to 30 (with up to 40 reported in some individuals), are situated within this space, extending from the lateral border of the pectoralis minor muscle inferiorly to the axillary vein superiorly and the latissimus dorsi muscle laterally.[4][3]These nodes are closely related to the axillary artery and vein, which traverse the central axis of the axilla and divide the region into anterior and posterior compartments, with the nodes distributed around these vessels in the surrounding adipose tissue.[4][5]
Levels and groups
The classification of axillary lymph nodes into levels is based on their anatomical relationship to the pectoralis minor muscle, a system originally proposed by pathologist John W. Berg in 1955 to facilitate the study of breast carcinoma spread.[6] This Bergclassification divides the nodes into three levels and has been widely adopted, with minor refinements for staging, by the American Joint Committee on Cancer (AJCC) in its guidelines for breast and other cancers.[7] The levels provide a standardized framework for surgical dissection, pathological examination, and prognostic assessment, emphasizing hierarchical lymphatic flow from peripheral to central nodes.Level I nodes, located lateral to the lateral border of the pectoralis minor muscle, represent the most peripheral group and include the following subgroups: the lateral (humeral) nodes along the axillary vein receiving drainage from the upper limb; the pectoral (anterior) nodes along the lateral thoracic artery and vein draining the breast and chest wall; the subscapular (posterior) nodes following the subscapular artery and vein from the posterior thoracic wall; and the interpectoral (Rotter's or Rotterdam) nodes situated between the pectoralis major and minor muscles.[1] These nodes are the first encountered in axillary clearance procedures and often harbor initial metastases.[8]Level II nodes lie posterior to the pectoralis minor muscle, encompassing the central group in the mid-axillary fat.[5] This level is accessed by dividing or retracting the muscle during surgery and is associated with intermediate prognostic risk when involved.Level III nodes, positioned medial to the medial border of the pectoralis minor muscle (also termed the apical or infraclavicular group), are situated near the axillary vein and its confluence with the subclavian vein, serving as the final axillary drainage point before supraclavicular nodes.[8] Involvement here indicates advanced disease and requires more extensive dissection.[7]Anatomical variability exists, with the total number of axillary nodes typically ranging from 20 to 30 (up to 40 in some individuals).[8]
Associated structures
The axillary lymph nodes are intimately related to the major vascular structures of the axilla, primarily surrounding the axillary artery and its accompanying vein. The axillary artery, which is the continuation of the subclavian artery distal to the lateral border of the first rib, courses through the center of the axilla, divided into three parts by the pectoralis minor muscle; the lymph nodes are distributed around these parts in a circumferential manner within the axillary fat pad.[1] Venous drainage of the nodes occurs via tributaries of the axillary vein, which parallels the artery and receives inputs from branches such as the cephalic vein.[1] Specific nodal groups maintain close associations with arterial branches supplying the region: the anterior (pectoral) nodes lie along the lateral thoracic artery, a branch of the second part of the axillary artery that runs along the lateral chest wall; the posterior (subscapular) nodes are positioned along the subscapular artery and its continuation, the thoracodorsal artery, which descend along the posterior axillary wall to supply the subscapularis and latissimus dorsi muscles.[9][1]Neural structures are also in close proximity to the axillary lymph nodes, increasing the complexity of their anatomical relationships. The cords of the brachial plexus (lateral, posterior, and medial) encircle the axillary artery and vein, with the nodes interspersed among their branches as they traverse the axilla toward the upper limb.[1] Additionally, the long thoracic nerve, arising from roots C5–C7 of the brachial plexus, courses along the medial wall of the axilla on the surface of the serratus anterior muscle, lying adjacent to the lateral and central nodal groups.[1]Muscular attachments further define the position of the axillary lymph nodes, which are embedded within the axillary fat pad bounded by key muscles of the shoulder girdle. Anteriorly, the nodes relate to the pectoralis major and minor muscles, with the latter serving as an anatomical landmark for subdividing the nodes into levels. Laterally, they are adjacent to the coracobrachialis and short head of the biceps brachii, while posteriorly, they border the teres major and latissimus dorsi muscles forming the posterior axillary fold.[1] The nodes' embedding in this fatty compartment positions them amid the muscular boundaries of the pyramidal-shaped axilla.The axillary lymph nodes are also associated with the clavipectoral fascia, a layer of connective tissue that extends from the clavicle to the pectoralis minor and invests the axillary artery, vein, and associated nerves. This fascia forms part of the anterior boundary of the axilla, with some nodal groups, particularly the apical ones, lying deep to or within extensions of this fascial sheath, facilitating lymphatic passage toward the subclavian trunk.[10]
Function
Lymphatic drainage pathways
The axillary lymph nodes primarily drain lymph from the upper limb, including the hand, forearm, and arm; the lateral quadrants of the breast; the anterior and posterior thoracic wall up to the level of the umbilicus; and portions of the upper abdominal wall.[1] These nodes receive afferent lymphatic vessels from the skin and muscles of these regions, serving as the main collection point for superficial and deep lymphatic flow in the upper body.[4] Specifically, the lateral (humeral) group drains the majority of the upper limb, excluding vessels along the cephalic vein; the anterior (pectoral) group collects from the breast and anterolateral chest wall; and the posterior (subscapular) group handles drainage from the scapular region, posterior thoracic wall, and upper back.[5]Lymphatic flow follows a structured sequence through the axillary node levels. Afferent vessels from peripheral tissues first enter the peripheral groups (lateral, anterior, and posterior, corresponding to Level I nodes inferior to the pectoralis minor muscle), then progress to the central group (Level II, embedded within the pectoralis minor), and finally to the apical group (Level III, superior to the pectoralis minor).[1] Efferent vessels from the apical nodes converge to form the subclavian lymphatic trunk, which on the left side joins the thoracic duct and on the right side connects to the right lymphatic duct, ultimately returning lymph to the venous system at the junction of the internal jugular and subclavian veins.[4]The axillary nodes handle a substantial volume of upper body lymph, receiving approximately 75% of the lymph from the breast and significant portions from the upper limb and thoracic wall, making them critical for regional lymphatic clearance.[11] In cases of obstruction, collateral pathways may redirect flow to the internal mammary (parasternal) nodes, supraclavicular nodes, or contralateral axillary nodes to maintain drainage.[5]
Immune surveillance role
Axillary lymph nodes function as key filters in the immune system, processing lymph fluid drained from the upper extremities, breast, and parts of the thoracic wall to trap and eliminate pathogens, cellular debris, and aberrant cells. Lymph enters the nodes via afferent vessels and flows into the subcapsular sinus, a peripheral compartment lined with macrophages and reticular cells that capture particulate matter, including bacteria, viruses, and potential tumor cells, preventing their dissemination. Further filtration occurs in the medullary sinuses and cords, where additional macrophages phagocytose trapped material, thereby maintaining tissue homeostasis and initiating local immune responses.[2][12][13]The internal architecture of axillary lymph nodes supports compartmentalized immune surveillance, with distinct zones housing specialized cell populations. The outer cortex features B-cell follicles, including germinal centers where B lymphocytes proliferate and differentiate during antigen-driven responses, while the paracortex is enriched with T lymphocytes, dendritic cells, and interdigitating cells for T-cell activation. Macrophages reside in the sinuses and medullary cords to aid in antigen clearance, and high endothelial venules within the paracortex express adhesion molecules that enable the transmigration of circulating naive lymphocytes from blood into the node for surveillance.[2][12][14]Central to their immune role, axillary lymph nodes orchestrate adaptive immunity through antigen presentation and lymphocyte activation. Dendritic cells and subcapsular macrophages transport filtered antigens to the paracortex, where they present processed peptides via major histocompatibility complex molecules to naive T cells, triggering clonal expansion and differentiation into effector T cells for cellular immunity. Concurrently, activated T cells provide helper signals to B cells in follicles, promoting germinal center formation, affinity maturation, and antibody production for humoral immunity, thus coordinating a targeted response against specific threats.[15][12][2]The lymphatic system, including axillary nodes, filters approximately 2-4 liters of lymph daily, representing interstitial fluid return to circulation after tissue exchange. During immune activation, such as in response to infection or inflammation, these nodes exhibit reactive hyperplasia, characterized by increased lymphocyteproliferation and influx, leading to visible enlargement that enhances filtration and response capacity.[16][17]
Clinical significance
Involvement in breast cancer
The axillary lymph nodes play a critical role in the metastatic progression of breast cancer, with tumors typically spreading sequentially from the primary site to the sentinel lymph node (SLN) in level I, followed by higher levels if progression occurs.[18] The SLN, often located in the lateral or pectoral group within level I, serves as the initial drainage site and is the first to show involvement in approximately 60-70% of cases with axillary metastasis.[18] This orderly pattern, observed through techniques like indocyanine green fluorescence imaging, supports the concept of predictable lymphatic flow, where level II and III nodes are involved only after level I positivity in the majority of patients without neoadjuvant therapy.[18]In breast cancer staging, the involvement of axillary lymph nodes is classified under the N category of the TNM system, which stratifies prognosis based on the number and extent of affected nodes.[19]N1 indicates metastasis to 1-3 axillary nodes or micrometastases (0.2-2 mm); N2 involves 4-9 nodes or clinically detectable internal mammary nodes; and N3 encompasses 10 or more nodes, infraclavicular involvement, or apical (level III) nodes.[19] Micrometastases are distinguished from macrometastases (>2 mm) due to their smaller size and potentially less aggressive behavior, with isolated tumor cells (<0.2 mm or <200 cells) classified as N0(i+) and carrying a more favorable outlook than macrometastases.[19]The presence of axillary node metastasis significantly worsens prognosis, with node-positive patients experiencing a 20-50% reduction in 5-year survival compared to node-negative cases, depending on the number of involved nodes and tumor biology.[20] For instance, 5-year survival rates drop from approximately 99% in node-negative disease to 85-93% in node-positive cases overall.[21] Isolated tumor cells or micrometastases confer better outcomes than macrometastases, with patients having isolated cells showing disease-free survival rates similar to node-negative individuals, while micrometastases increase recurrence risk by about 38%.[22]Historically, William Halsted's radical mastectomy, introduced in the late 1880s, emphasized en bloc removal of the breast, pectoral muscles, and axillary lymph nodes to address presumed contiguous spread, becoming the standard for over 80 years.[23] Modern approaches have shifted to selective axillary management, guided by sentinel lymph node biopsy to avoid unnecessary dissection in node-negative cases, improving quality of life while maintaining oncologic outcomes.[23]
Role in other cancers
Axillary lymph nodes play a significant role in the lymphatic drainage of the upper trunk and arm, making them a primary site for metastasis in cutaneous melanoma originating from these regions. In melanoma, involvement of these nodes is assessed through sentinel lymph node biopsy (SLNB), which identifies the first nodes to receive drainage from the tumor and is essential for accurate staging according to the American Joint Committee on Cancer (AJCC) system. The AJCC 8th edition classifies nodal involvement into levels I-III based on the number and location of affected nodes, with level I encompassing low axillary nodes, level II central nodes, and level III apical nodes; positive nodes in these levels indicate stage III disease and guide therapeutic decisions such as adjuvant therapy. SLNB positivity, particularly micrometastases, is a strong predictor of recurrence and survival, influencing the shift from stage I/II to stage III in up to 20% of intermediate-thickness melanomas.[24][25]In lung cancer, axillary lymph node metastasis is uncommon, occurring in less than 1% of cases, and typically signifies advanced disease classified as N3 in the TNM staging system, which includes contralateral or supraclavicular nodal involvement. Ipsilateral axillary metastases may arise from upper lobe tumors via direct lymphatic extension, while contralateral spread from lower lobe primaries can occur through crossover via the thoracic duct or intercostal lymphatics, often in the context of mediastinal involvement. Such distant nodal metastasis portends a poor prognosis, with median survival reduced to under 12 months, and it prompts systemic therapy over locoregional approaches.[26][27][28]Metastasis to axillary lymph nodes from gastrointestinal malignancies, such as colorectal or gastric cancer, is rare and usually represents hematogenous or distant lymphatic dissemination rather than regional drainage. In colorectal cancer, particularly BRAF-mutant subtypes, axillary involvement occurs in isolated cases as a non-regional site, often detected incidentally during staging and associated with widespread metastatic disease. Similarly, gastric cancer rarely metastasizes to axillary nodes, with reported instances linked to advanced stages and poor outcomes, potentially via retrograde lymphatic flow or systemic spread.[29][30]Lymphomas, including Hodgkin and non-Hodgkin types, frequently present with axillary adenopathy as a primary manifestation, reflecting the systemic nature of these hematologic malignancies. In non-Hodgkin lymphoma, painless enlargement of peripheral lymph nodes, including axillary nodes, is a common presentation, often involving B-cell subtypes and serving as an initial site for biopsy confirmation.[31] Hodgkin lymphoma frequently affects cervical and axillary nodes at presentation, with involvement indicating early favorable or advanced stages depending on the number of nodal regions.[32]Overall, axillary lymph node involvement in non-breast upper body cancers varies by primary site, with higher rates in melanomas draining to these nodes (up to 25% in trunk primaries) compared to rare occurrences in lung or gastrointestinal cancers (under 2%). Prognostically, nodal metastasis consistently worsens outcomes across these malignancies, akin to breast cancer, with multiple involved nodes correlating with reduced 5-year survival rates by 20-40%.[33]
Infections and lymphadenopathy
Axillary lymphadenopathy often arises as a reactive response to infections draining into the axillary region, reflecting the nodes' role in immune surveillance of the upper limb, chest wall, and breast.[34] Common infectious etiologies include bacterial, viral, and fungal agents, which trigger lymph node enlargement through inflammation and immune cell recruitment.[35]Bacterial infections frequently cause localized axillary lymphadenopathy, such as cat-scratch disease resulting from Bartonella henselae introduced via scratches or wounds on the arm or hand.[35] This condition typically presents with regional node tenderness and suppuration 1-3 weeks post-inoculation.[36] Viral infections like Epstein-Barr virus (EBV) causing infectious mononucleosis or human immunodeficiency virus (HIV) can lead to generalized or prominent axillary adenopathy as part of systemic immune activation.[34] Fungal pathogens, particularly Histoplasma capsulatum in endemic regions such as the Ohio and Mississippi River valleys, may disseminate to axillary nodes, resulting in granulomatous inflammation.[37]Lymphadenopathy in these contexts varies by acuity and pathogen. Acute forms are often tender and may progress to suppurative abscesses in bacterial cases like staphylococcal infections from skin wounds.[38] In contrast, chronic lymphadenopathy appears firm and nontender, as seen in tuberculous involvement where Mycobacterium tuberculosis forms caseating granulomas within nodes.[39] Pathologic enlargement is generally defined as nodes exceeding 1 cm in short-axis diameter, prompting further evaluation to distinguish reactive from malignant processes.[34]Breast-related non-malignant conditions also contribute to axillary involvement. Lactational mastitis, an inflammatory infection of breast tissue, commonly causes ipsilateral axillary node swelling due to contiguous lymphatic spread, accompanied by erythema and fever.[40] Similarly, breast abscesses lead to localized reactive lymphadenopathy. Granulomatous reactions to silicone from breast implants can mimic infection, with silicone droplets eliciting foreign-body inflammation in draining axillary nodes.[41]In outpatient settings, infectious and inflammatory causes are the most common etiologies of palpable axillary lymph nodes among benign conditions.[35] These reactive enlargements typically resolve with targeted antimicrobial treatment of the underlying infection, often within weeks, without residual nodal changes.[34]
Diagnosis and management
Imaging techniques
Ultrasound serves as the first-line imaging modality for evaluating axillary lymph nodes due to its accessibility, lack of radiation, and ability to guide biopsies. It assesses node size (typically >10 mm short axis suspicious), shape (round rather than oval), and cortical thickness, with values exceeding 3 mm indicating potential malignancy. Color Doppler ultrasonography further evaluates vascularity patterns, where peripheral or chaotic flow suggests metastasis compared to central hilar flow in benign nodes. The sensitivity of ultrasound for detecting metastatic axillary nodes is approximately 80%, with specificity up to 98% when combined with fine-needle aspiration.[42]Computed tomography (CT) and magnetic resonance imaging (MRI) are employed for regional staging, particularly in advanced breast cancer, to assess node involvement alongside tumor extension. On CT, suspicious features include nodal enlargement and increased density, with Hounsfield units greater than 50 in non-contrast images correlating with metastasis. MRI, often with gadolinium contrast, excels in delineating cortical thickening (>3 mm), loss of fatty hilum, and irregular borders, providing superior soft-tissue contrast for evaluating extracapsular extension. These modalities offer moderate accuracy for staging but are less specific for micrometastases.[43][42]Positron emission tomography-computed tomography (PET-CT) using 18F-fluorodeoxyglucose (FDG) is valuable preoperatively for identifying occult metastases, especially in clinically node-negative cases. It detects hypermetabolic activity, with standardized uptake values (SUV) exceeding 2.5 typically indicative of malignancy due to increased glucose metabolism in tumor cells. The modality demonstrates 75% sensitivity and 83% specificity for axillary nodemetastasis.[44][45]Despite their utility, these imaging techniques have limitations, including false positives from reactive lymphadenopathy due to inflammation or infection, which can mimic metastatic changes. Additionally, CT and PET-CT involve ionizing radiation exposure, necessitating judicious use, particularly in younger patients.[42]
Biopsy and surgical procedures
Sentinel lymph node biopsy (SLNB) is a minimally invasive procedure used to assess axillary lymph node involvement in early-stage breast cancer by identifying and removing the first (sentinel) node(s) that drain from the tumor site.[46] The technique typically involves peritumoral or intradermal injection of a radioactive colloid (radioisotope) and/or blue dye (such as isosulfan blue or methylene blue) around the tumor, which is then detected intraoperatively using a gamma probe for radioactivity or visual identification of the stained node, allowing targeted excision while sparing uninvolved nodes.[47] This approach has demonstrated high accuracy, with identification rates exceeding 95% and false-negative rates of 5-15% when using combined tracers, significantly reducing morbidity compared to complete dissection by avoiding unnecessary removal of healthy tissue.[48] Intraoperative frozen section analysis may be performed on excised sentinel nodes for real-time histopathological assessment to guide decisions on proceeding to further surgery.[49]Axillary lymph node dissection (ALND) involves the surgical removal of multiple lymph node levels in the axilla, primarily levels I and II (lateral to the pectoralis minor muscle and beneath it, respectively), with level III (medial to the pectoralis minor) included in cases of advanced disease or extensive involvement.[8] It is indicated for patients with positive sentinel nodes requiring further staging, clinically palpable axillary nodes, or those ineligible for radiation after neoadjuvant therapy, often performed via an open approach through an incision along the axillary skin crease.[8] Minimally invasive alternatives, such as video-assisted or endoscopic techniques, utilize small incisions and endoscopic tools to access and remove nodes, potentially reducing postoperative pain and recovery time while maintaining oncologic efficacy.[50] Common complications of ALND include lymphedema (affecting 10-25% of patients), seroma formation, nerve injury (e.g., to the intercostobrachial or long thoracic nerves leading to paresthesia or shoulder dysfunction), and wound infections.[51][8]Historically, routine ALND was standard for axillary staging in breast cancer prior to the 2000s, but the ACOSOG Z0011 trial in 2011 demonstrated that omitting ALND in women with T1-T2 tumors and 1-2 positive sentinel nodes—opting instead for whole-breast radiation—yielded equivalent 10-year overall survival rates (86.3% vs. 83.6%), and locoregional control without increased recurrence risk, shifting practice toward selective use of SLNB to minimize complications in early-stage disease. Subsequent guidelines, including the 2025 ASCO update, have further endorsed de-escalation by recommending omission of SLNB in select low-risk early-stage cases.[52][53]