The lymph vessels and their nodes are part of a discontinuous circulation whose efferent loop is the arteries, arterioles, and capillaries of the vascular system, and whose afferent loop is the network of lymphatic vessels that drain centrally through the regional lymph nodes to the thoracic duct, which empties into the left subclavian vein. The lymphatic system plays a major role in the recognition and response to foreign antigens. Macrophages and Langerhans cells from the periphery (antigen-presenting cells) migrate from peripheral sites with processed antigen, which they present to T cells and B cells in the lymph nodes. T cells circulate from the capillary circulation to the lymphatics and nodes and back into the circulation until they are presented with an antigen specific to their T-cell receptor; recognition leads to activation and proliferation, generating an immune response. Disorders of the lymphatics produce only three physical signs: palpable lymph nodes, red streaks in the skin from superficial lymphangitis, and lymphedema. Palpable lymph nodes indicate lymphadenopathy.
Examination of the Lymph Nodes
Enlarged nodes may be visible by inspection, especially with oblique light. Examination is primarily by palpation. The following characteristics of palpable lymph nodes should be noted: number, size, consistency, mobility, tenderness, warmth, and whether they are discrete or matted together. Procedures for examining the major lymph node beds are described below, but all lymph node-bearing areas should be palpated when searching for generalized lymphadenopathy. The spleen should always be examined as part of the examination of the lymphatic system.
Palpation of the cervical lymph nodes
Seat the patient in a chair, stand behind the patient to palpate the neck with your fingertips. Examine, in sequence, these lymph node sites: (1) submental, under the chin in the midline and on either side; (2) submandibular, under the jaw near its angle; (3) jugular (anterior triangle), along the anterior border of the sternocleidomastoid; (4) supraclavicular, behind the midportion of the clavicle; (5) poststernocleidomastoid (posterior triangle), behind the posterior border of the upper half of the sternocleidomastoid; (6) postauricular, behind the pinna on the mastoid process; (7) preauricular, slightly in front of the tragus of the pinna; (8) suboccipital, in the midline under the occiput and to either side; and (9) pre-trapezius, in front of the upper border of the trapezius (Fig. 5-1). When an enlarged lymph node is found, carefully examine the drainage region from a primary lesion: anterior cervical triangle—the anterior third of the scalp and face, posterior cervical triangle and occiput—the posterior two-thirds of the scalp.
Superficial Lymph Nodes of the Neck
Palpation of the neck for lymphadenopathy is accurate when the region of each group of nodes is examined in systematic fashion. The drawing contains a numbered scheme for examining nine groups of nodes in sequence.
Palpation of axillary, infraclavicular and supraclavicular lymph nodes
Examine the sitting patient by palpating the left axilla with your right hand and vise versa (Fig. 5-2A). Relax the patient’s left arm and axillary muscles by holding the left wrist with your left hand and elevating the upper arm toward the chest wall. Place your hand in the axilla with the fingers together and the palm toward the chest wall. Point your fingers obliquely toward the apex of the axilla. Now have the patient rest their left hand on your examining right arm, while your left hand supports the shoulder. Gently, but firmly, rake the pulps of your examining fingers along the thoracic cage to feel for enlarged lymph nodes. The central group of nodes occurs near the middle of the thoracic wall of the axilla (Fig. 5-3). The lateral axillary group is located near the upper part of the humerus and is best demonstrated by having the patient’s arm elevated so that you can feel along the axillary vein. With the patient’s arm still elevated, feel along beneath the lateral edge of the pectoralis major muscle for the pectoral group. Palpate the subscapular nodes from behind the patient with the arm raised, palpating with the left hand under the anterior edge of the latissimus dorsi muscle. Palpate under the clavicle for the infraclavicular group. Enlargement in the supraclavicular group is sought by feeling the soft tissues above and behind the clavicle (Fig. 5-2B).
Palpation of Axillary and Supraclavicular Lymph Nodes
A. Axilla: In palpation of the left axilla, the examiner slides his right hand toward the axillary apex, with palm toward the chest wall and approximated fingers extended so the pulps feel the structures on the thoracic cage. With his left hand, he directs the patient’s upper arm close to the chest to relax the axillary muscles. He asks the patient to rest her arm on his examining arm and he supports her shoulder with his left hand. The positions are reversed to examine the right side. B. Supraclavicular fossa.
Axillary Lymph Node Groups
Note that the lateral axillary group is on the inner aspect of the upper arm, near the axillary vein. The subscapular group lies deep to the anterior edge of the latissimus dorsi muscle. The pectoral group is behind the lateral edge of the pectoralis major muscle.
Palpation of the inguinal nodes
Palpate at and just below the inguinal ligament then distally along the course of the greater saphenous vein.
Lymph node enlargement results from a stimulated regional or systemic immune response, direct infection of the node, which can lead to suppuration, deposition of intracellular or extracellular material, or infiltration with neoplastic cells. Physical examination of the nodes should describe their distribution, number in each location, size, mobility, consistency (fluctuant, soft, firm, hard), surface (smooth, irregular), and the presence of tenderness, warmth, and/or sinus tracts draining to the skin. A meticulous examination of the skin and soft tissues of the involved region is mandatory when looking for signs of regional inflammation, infection, or neoplasm. Pain and tenderness suggests inflammation and/or infection, whereas painless lymphadenopathy is more likely to be neoplastic. Fluctuant nodes suggest suppuration from bacterial, mycobacterial, or fungal infection. Fixation of the nodes to underlying tissue is most common with metastatic carcinoma, but may occur with chronic inflammation. Matting together of nodes suggests lymphoma or chronic inflammation. Lymph node enlargement may be the presenting sign in many diseases. Lymphadenopathy, which is widespread, involving several lymph node regions both above and below the diaphragm, suggests a systemic disease.
Lymphadenopathy occurring simultaneously in multiple lymphatic beds, especially above and below the diaphragm, suggests a systemic process, usually infectious, inflammatory or neoplastic. CLINICAL OCCURRENCE: Congenital: Niemann–Pick disease, Gaucher disease; Idiopathic: Sarcoidosis, sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease); Inflammatory/Immune: RA, Still disease, dermatomyositis, SLE, amyloidosis, serum sickness, drug allergy, graft-vs-host disease, hyper IgM syndrome; Infectious: bacterial scarlet fever, brucellosis, Lyme disease, secondary syphilis, tularemia, bubonic plague, cat-scratch fever, Whipple disease, melioidosis, scrub typhus; mycobacterial tuberculosis, atypical mycobacteria; viral rubella, rubeola, infectious mononucleosis, HIV; protozoal African trypanosomiasis, Chagas disease, kala-azar, toxoplasmosis; fungal sporotrichosis; helminths filariasis; ectoparasites scabies; Metabolic/Toxic: Drugs (e.g., diphenylhydantoin), berylliosis, silicosis; Neoplastic: Hodgkin disease, non-Hodgkin lymphoma, chronic lymphocytic leukemia, systemic mastocytosis, metastatic carcinomas.
Lymph Node Diseases and Syndromes
These disorders are clonal proliferation, usually of B-lymphocytes at a specific stage of maturation and with specific surface markers. Patients may present with systemic symptoms of fever, weight loss, and night sweats, with abdominal pain or fullness, or with palpable lymphadenopathy. These diseases involve multiple sites and may arise in nonlymphoid tissue such as the lung, stomach, intestine, and central nervous system. Clinically, they are separated into high-grade disease that tends to be rapidly progressive, but potentially curable and low-grade disease for which curative therapy is not generally available.
This is a malignant disease of B cells of unknown etiology that spreads to contiguous lymph node beds, the spleen, liver, and bone marrow. There are two age peaks, in the third and eighth decades. Symptoms include pruritus, painless enlargement of lymph nodes, abdominal pain, and occasionally periodic or continuous fever (Pel–Epstein fever) and cachexia. Although the disease may involve any lymph nodes in the body, only a single group is affected frequently, most often in the neck (Fig. 5-4A). The lymph nodes may enlarge rapidly over 1 to 3 weeks, or slowly over a few months. The nodes are resilient or rubbery and larger than acute adenitis. Hepatomegaly and splenomegaly may be present. Nephrotic syndrome may accompany or precede the diagnosis. A thorough examination of all accessible nodes is required. DDX: The ingestion of alcohol may rarely produce severe pain in the nodes so severe and predictable that patients voluntarily abstain from alcohol. Lymphadenopathy in non-Hodgkin lymphoma is usually generalized and rarely confined to the neck.
A. Hodgkin disease: there is no specific pattern of involvement of the nodes. The neck is frequently affected first, often unilaterally. The nodes are large, firm, discrete, nontender, and nonsuppurative. B. Tuberculosis: one finds a matted mass of nontender lymph nodes. The nodes are firm, but some have suppurated and formed draining sinuses.
Chronic lymphocytic leukemia
A clonal proliferation of mature lymphocytes (90% B cell, 10% T cell) leads to infiltration of the lymph nodes and bone marrow with progressive cytopenias and impaired humoral or cellular immunity. Patients are often asymptomatic until relatively late in the disease. They present with lymphadenopathy and progress to anemia, neutropenia, and thrombocytopenia with recurrent infections. Death usually results from infection or hemorrhage.
Obstruction of lymphatic drainage by whatever cause leads to the accumulation of interstitial fluid with a high protein content. Massive enlargement of the part may occur and fibrosis develops over time. Patients present with progressive painless swelling of a body part. Common causes are surgical, irradiation or traumatic injury to lymphatics, and neoplastic obstruction. Longstanding lymphedema is associated with an increased risk for lymphangiosarcoma. DDX: The edema may pit at first, but characteristically is not pitting.
Lymphatic infestation with larvae of Wuchereria bancrofti or Brugia malayi follows the bite of an infected mosquito. There is inflammation and later scarring with lymphatic obstruction, and lymphedema. Headache, photophobia, vertigo, fatigue, low-grade fever, and myalgia are common symptoms. Signs include conjunctivitis, orchitis, lymphangitis, and lymphadenopathy acutely; later, obstruction of lymphatic and venous drainage with edema, hydrocele, elephantiasis of breasts, scrotum, vulva, or legs.
Inoculation lesion with regional lymphadenopathy
Cutaneous inoculation of infectious agents is followed by spread through the subcutaneous lymphatics, with varying degrees of inflammation and induration, to regional lymph nodes. The cutaneous inoculation site may show minimal signs, or may be marked by local inflammation, ulceration, and/or necrosis with eschar formation. A careful history, including the time of year and occupational or avocational exposures, is essential to an accurate and timely diagnosis. CLINICAL OCCURRENCE: Infectious: Bacterial streptococcal infections, syphilitic chancre, anthrax, erysipeloid, tularemia (ulceroglandular type), bubonic plague, rat-bite fever, cat-scratch disease, nocardia, actinomycosis, glanders; Mycobacterial inoculation tuberculosis, atypical mycobacteria; Fungal sporotrichosis; Rickettsial scrub typhus, boutonneuse fever, South African tick fever, Kenya typhus, rickettsialpox; Viral herpes simplex; Helminths filariasis, trypanosomiasis, leishmaniasis; Neoplastic: Melanoma, squamous cell carcinoma, lymphangioleiomyomas.
The following diseases commonly cause suppuration of lymph nodes: streptococcal infections, staphylococcal infections, tuberculosis (bovine type) actinomyces lymphogranuloma venereum, coccidioidomycosis, anthrax, cat-scratch fever, sporotrichosis, plague, and tularemia.
Diseases and Syndromes of Specific Regional Lymph Nodes
Infectious, inflammatory, or neoplastic lesions within the regional drainage give rise to regional lymphadenopathy. Since each of the causes of generalized lymphadenopathy may cause regional adenopathy, we will avoid repetition by only mentioning singular or unusual entities specific to a given region as etiology in this section.
Location: Midway between the external occipital protuberance and the mastoid process (Fig. 5-1), near the great occipital nerve. Drainage: Afferents from back of scalp and head; efferents to deep cervical nodes. Symptoms: Impingement of the enlarged nodes on the great occipital nerve may produce headache. CLINICAL OCCURRENCE: Ringworm of the scalp, pediculosis capitis, seborrheic dermatis, secondary syphilis and metastatic cancer.
Location: On mastoid process and at insertion of stern-ocleidomastoid muscle, behind pinna (Fig. 5-1). Drainage: Afferents from external acoustic meatus, back of pinna, temporal scalp, efferents to superior cervical nodes. Symptoms: Mastoid tenderness simulating mastoiditis. CLINICAL OCCURRENCE: Bacterial or herpetic infection of the acoustic meatus, rubella (not rubeola), leishmaniasis.
Location: In front of the tragus of the external ear (see Fig. 5-1). Drainage: Afferents from lateral portions of eyelids and their palpebral conjunctivae, skin of temporal region, external acoustic meatus, and anterior surface of pinna. CLINICAL OCCURRENCE: Ulcerating basal cell carcinoma, epithelioma, chancre of face, erysipelas, ophthalmic herpes zoster, rubella, trachoma. Ocular-glandular syndromes, gonorrheal ophthalmia, tuberculosis, syphilis, sporotrichosis, glanders, chancroid, epidemic keratoconjunctivitis, adenoidal-pharyngeal-conjunctival virus, Leptothrix infection, lymphogranuloma venereum, tularemia, cat-scratch fever, Chagas disease.
Location: Under the mandible (Fig. 5-1). Drainage: Afferents from tongue, submandibular gland, submental nodes, medial conjunctivae, mucosa of lips and mouth; efferents to superficial and deep jugular nodes.
Location: In midline under apex of mandibular junction (Fig. 5-1). Drainage: Afferents from central lower lip, floor of mouth, tip of tongue, skin of cheek; efferents to mandibular nodes, deep jugular nodes.
Location: Along anterior border of the sternocleidomastoid, from angle of mandible to clavicle (Fig. 5-1). Drainage: Afferents from tongue except apex, tonsil, pinna, parotid gland; efferents to deep jugular nodes. CLINICAL OCCURRENCE: Infection or neoplasm of the tonsils and oral cavity; thyroid cancer.
Posterior sternocleidomastoid nodes
Location: Along the posterior border of the sternocleidomastoid muscle are the posterior cervical and inferior deep cervical nodes which are not readily separated clinically (Fig. 5-1). Drainage: Afferents from the scalp and neck, upper cervical nodes, axillary nodes, skin of arms and pectoral region, surface of the thorax. CLINICAL OCCURRENCE: Trypanosomiasis (Winterbottom sign).
Location: These are part of the inferior deep cervical nodes that lie deep in the supraclavicular fossa behind the sternocleidomastoid muscle. Drainage: Afferents from the thorax. Although not palpable, they are easily biopsied. CLINICAL OCCURRENCE: Intrathoracic granulomatous disease and neoplasms.
Acute cervical lymphadenopathy—localized lymphadenitis
Infections of the scalp, face, mouth, teeth, pharynx, or ear cause localized lymphadenitis of the neck in the particular group of nodes draining the involved region. Included in localized lesions is chancre of the face with its regional lymphadenitis. Cervical adenopathy is also common in erythema nodosum, although the subcutaneous lesions are almost always limited to the legs. If the patient is toxic and tenderness is severe, consider Lemmiere syndrome (Septic thrombophlebitis of the internal jugular vein (Lemmiere syndrome)).
Subacute localized cervical lymphadenopathy: metastatic carcinoma
Asymptomatic cancers of the head and neck frequently present as metastases in a cervical lymph node. The nodes are usually stony hard, nontender, and nonsuppurative. Epidermoid carcinoma predominates. With anterior triangle involvement, primary malignancies are found in the upper aerodigestive tract, including the maxillary sinus, oral cavity, tongue, tonsil, hypopharynx, and larynx. In the submental region, metastases occur from primary neoplasms in the lower lip, anterior tongue, and floor of the mouth. In the posterior triangle, the nasopharynx and scalp are common sites of origin. Carefully examine suspicious areas and the remainder of the upper aerodigestive tract. Never surgically biopsy a solitary cervical lymph node suspicious for metastatic cancer. Violation of the tissue planes of the neck may preclude surgical cure. Always refer such a patient for direct examination of the aerodigestive tract by an experienced observer to search for the primary tumor.
Sentinel node (Virchow node)
The node is the site of metastasis via the thoracic duct from a primary carcinoma in the upper abdomen. There is enlargement of a single lymph node, usually in the left supraclavicular group and frequently behind the clavicular head of the left sternocleidomastoid. It is often so deep that it escapes casual examination. A purposeful search requires the patient to be erect; examine behind the muscle head while facing the patient. The node may be better appreciated as the patient performs a Valsalva. When a primary carcinoma is found in the abdomen, demonstration of the sentinel node is the proof of distant metastasis. Breast and lung cancers spread to the supraclavicular nodes, usually more laterally in the supraclavicular fossa.
Chronic localized cervical lymphadenopathy: tuberculosis (scrofula)
Usually the disease is caused by the bovine strain of tubercle bacilli, although human strains have been implicated. The disease has a predilection for the cervical lymph nodes. The nodes are large, multiple, and nontender. Classically, they are matted together, but this is often difficult to determine by palpation (Fig. 5-4B). Frequently the nodes suppurate and form indolent sinus tracts. Extensive scarring of the neck often results.
This unusual syndrome affects young women who present with cervical lymphadenopathy. It is benign, but often confused with other entities [Dorfman RF, Berry GJ. Kikuchi’s histiocytic necrotizing lymphadenitis: an analysis of 108 cases with emphasis on differential diagnosis. Semin Diagn Pathol. 1988;5:329–345].
Infection by bacteria of the genus Actinomyces from the oral flora involves the mouth, face, and cervical lymph nodes. The infection crosses tissue planes. The nodes are prone to suppurate, forming sinuses with a bright-red hue. The pus contains sulfur granules, 1 to 2 mm in diameter.
The chest, axilla, and arms
Location: Part of the inferior deep cervical chain, behind the origin of the sternocleidomastoid muscle (Fig. 5-1). Drainage: Afferents from head, arm, chest wall, breast. CLINICAL OCCURRENCE: Granulomas and neoplasms of the lung and esophagus on the right and left; in addition on the left, neoplasms in the abdomen.
Location: Five groups lie on the medial aspect of the humerus, the axillary border of the scapula, and the lateral border of the pectoralis major (Fig. 5-3). Drainage: Afferents from the upper limb, the thoracic wall, and the breast. In women, enlarged axillary nodes on the thoracic wall must be distinguished from axillary tail of the breast. CLINICAL OCCURRENCE: Small mobile axillary nodes are common in normal individuals.
Location: Approximately 3 cm proximal to the medial humeral epicondyle, in the groove between the biceps and triceps brachii. Drainage: Afferents from ulnar aspect of forearm and hand, and entire little and ring fingers, the ulnar half of the long finger. CLINICAL OCCURRENCE: Cat-scratch disease, secondary syphilis (father-in-law sign); a common inoculation site of systemic infections.
Location: These are not accessible to palpation. Chest radiographs show widening of the mediastinum, a mass in the anterior mediastinum, and masses in the hilar regions. CLINICAL OCCURRENCE: Tuberculosis, coccidioidomycosis, histoplasmosis, anthrax, sarcoidosis, silicosis, beryllium poisoning, erythema nodosum, Hodgkin disease, non-Hodgkin lymphoma (lymphoblastic lymphoma), chronic lymphocytic leukemia, testicular cancer.
The abdominal and inguinal nodes
Location: Distinction between intraabdominal and retroperitoneal nodes cannot be made clinically. Occasionally, large nodes may be palpated as vague masses in the abdomen. Calcified nodes may be seen in the X-ray films. CLINICAL OCCURRENCE: Lymphoma and testicular carcinoma.
Location: A horizontal group lies along the inguinal ligament and a vertical group is beside the great saphenous vein in the proximal thigh. Drainage: Afferents of the horizontal group come from the skin of the lower anterior abdominal wall, retroperitoneal region, penis, scrotum, vulva, vagina, perineum, gluteal region, and lower anal canal; afferents of the vertical group come from the lower limb, along the great saphenous vein, penis, scrotum, and gluteal region. CLINICAL OCCURRENCE: Many persons have moderately enlarged nodes from recurrent infections or trauma. Remember that tumors of the testis metastasize directly to the paraaortic nodes and do not involve the inguinal nodes; scrotal cancer spreads to inguinal nodes.
Genital lesion with satellite nodes
Syphilis, gonorrhea, chancroid, herpes simplex, lymphogranuloma venereum, tuberculosis, and cancer of penis need to be considered.
Disorders of B Cells/Plasma Cells
Proliferation and infiltration of the bone marrow, spleen, and liver by plasmacytoid lymphocytes producing excessive monoclonal IgM (macroglobulin) leads to hemolytic anemia, immune thrombocytopenia, and increased blood viscosity. Symptoms are insidious in onset with anorexia, malaise, and weakness, nasal and gingival bleeding, and exertional dyspnea. Signs include any combination of pallor, petechiae, ecchymoses, retinal hemorrhages, lymphadenopathy, hepatosplenomegaly, edema, and signs of heart failure. The disease runs a very prolonged course.
A clonal proliferation of plasma cells produces intact immunoglobulins and/or light chains that are detected in the serum and urine. Humoral activation of osteoclasts leads to bone resorption without healing, hypercalcemia, and pathologic fractures. Symptoms include bone and muscle pain, backache, weakness, weight loss, and fatigue. There are no specific signs; bone pain may indicate pathologic fractures [Weinstein R, Mahmood M. Case 6-2002—A 54-year-old woman with left, then right, central-retinal-vein occlusion. N Engl J Med. 2002; 346:603–610].
Deposition of the fibrillar amyloid proteins leads to organ enlargement and dysfunction. Several specific types exist, identified by the specific protein in the deposits. AL amyloidosis results from deposition of immunoglobulin light chains. AA amyloidosis occurs in chronic inflammatory diseases. The hereditary amyloidoses have specific fibrillar proteins depending upon the specific familial syndrome. Deposition of amyloid proteins, either generally or locally, can be asymptomatic or can cause organ dysfunction. Symptoms are nonspecific with constitutional complaints of weakness and fatigue. Specific complaints are referable to the organ system involved: diarrhea, dysphagia, and weight loss (GI involvement); paresthesias (peripheral nerves); dyspnea, orthopnea, and pleural effusions (restrictive cardiomyopathy). The signs depend upon the organs involved: macroglossia, eyelid plaques, hypertension, lymphadenopathy, hepatomegaly, splenomegaly, purpura, nephrotic syndrome, edema, shoulder-pad sign, joint and muscle pain, neuropathy, and fluid in serous cavities [Dember LM, Shepard J-A, Nesta F, et al. Case 15–2005: an 80-year-old man with shortness of breath, edema, and proteinuria. N Engl J Med. 2005;352:2111–2119]. CLINICAL OCCURRENCE: AL Amyloidosis—multiple myeloma, monoclonal gammopathies, primary idiopathic amyloidosis; AA amyloidosis—chronic inflammatory diseases (e.g., osteomyelitis, tuberculosis, leprosy), familial Mediterranean fever, other familial periodic fevers.
Chronic lymphocytic leukemia