Evaluation of Lymphadenopathy
Of the nearly 600 lymph nodes throughout the body, only a few are normally palpable, including small nodes in the submandibular, axillary, and inguinal regions. Nevertheless, lymphadenopathy is a very common presenting symptom. Most often, adenopathy indicates benign, self-limited disease; this is particularly true in children and young adults, who are more prone to reactive lymphatic hyperplasia. Despite this, patient concern is often substantial because of worry about serious infectious processes (e.g., AIDS) on one hand and neoplastic diseases on the other. A systematic evaluation of lymphadenopathy will provide both reassurance and a correct diagnosis. A critical decision for the primary physician is when to refer the patient for a lymph node biopsy.
Pathophysiology
As part of the lymphoreticular system, normal lymph nodes play an essential role in host defense, often reacting to threat with a hyperplastic response that usually resolves within 1 month of resolution of the underlying stimulus. Sometimes, a degree of hyperplasia may persist leaving some residual enlargement, especially if the nodal response was marked or the stimulus was severe or prolonged. Pathologic enlargement ensues when inflammation or infiltration overtakes the node. If the underlying disease is well localized, the accompanying adenopathy tends to be focal and limited to the area of involvement. If the illness is widespread or systemic, generalized adenopathy may ensue.
Clinical Presentation
Size and Quality
Most nodes are not normally palpable in healthy individuals, except for the small lymph nodes in the neck, axilla, and groin. Palpable nodes in other regions or any node greater than 1 cm in size should be regarded as potentially abnormal, especially if they persist for more than 1 month in the absence of an obvious explanation. Size alone is not itself diagnostic of the underlying pathology, but nodes greater than 3 cm suggest neoplastic disease. The presentation of pathologic nodal enlargement can range from painless to tender, soft to hard, and mobile to fixed. Although soft, freely moveable nodes are more characteristic of nonmalignant nodal disease, early malignant involvement may present in similar fashion. Tenderness is not unique to adenopathy due to inflammation; rapidly expanding malignant nodes and those with intranodal hemorrhage may also be painful, as may the nodes of Hodgkin disease after intake of alcohol.
Accompanying Symptoms
“B” symptoms (recurrent fevers >38°C, night sweats, weight loss) are characteristic of the lymphomas, especially Hodgkin disease, and carry a worse prognosis (see Chapter 84). Such symptoms may also occur in systemic infections. Fever alone can occur
across the full spectrum of etiologies of lymphadenopathy. Lymphangitic streaking is a hallmark of infection in the area of drainage. Accompanying splenomegaly is limited to infectious mononucleosis, lymphomas, and lymphocytic leukemias.
across the full spectrum of etiologies of lymphadenopathy. Lymphangitic streaking is a hallmark of infection in the area of drainage. Accompanying splenomegaly is limited to infectious mononucleosis, lymphomas, and lymphocytic leukemias.
Distribution
The location of the adenopathy is directly related to etiology.
Generalized.
Widespread lymph node enlargement results from systemic processes, such as infection, malignancy, hypersensitivity, and sometimes even metabolic disease with node infiltration. The adenopathy associated with infection may be caused by the disease itself (e.g., HIV infection) or to secondary infection (e.g., with cytomegalovirus). It may result from an illness that first produces localized adenopathy (e.g., catscratch disease). At the intersection of neoplastic and reactive lymphadenopathy is Castleman disease, a rare, idiopathic, atypical lymphoproliferative disease that can be localized or multicentric. Its clinical presentation can mimic that of lymphoma and HIV disease. Localized disease has a benign clinical course, but multicentric disease produces disseminated lymphadenopathy, systemic symptoms, and an increased risk for infection and cancer.
Cervical.
Most cervical adenopathy is a consequence of head or neck infection, but lymphomas (especially Hodgkin disease) have a predilection for beginning in the cervical or supraclavicular nodes. Submandibular nodal enlargement, perhaps the most common type of adenopathy, typically results from pharyngitis (viral, streptococcal, gonococcal) or oral cavity infection. Preauricular adenopathy may be a component of “oculoglandular fevers” due to adenoviral conjunctivitis, sarcoidosis, tularemia, catscratch disease, and other processes. Posterior auricular or posterior cervical adenopathy frequently reflects infections of the scalp but may also be prominent in systemic processes, such as rubella or toxoplasmosis.
Supraclavicular.
Isolated supraclavicular node enlargement is indicative of lymphoma or metastatic cancer. The right supraclavicular nodes drain the mediastinum, esophagus, and thorax, whereas the left supraclavicular system (Virchow node) serves the thoracic duct, which conducts flow from the abdomen.
Axillary.
Breast cancer is the chief concern, but nodes in the axilla also become enlarged in response to infection of the upper extremities.
Hilar.
Bilateral hilar adenopathy in an asymptomatic patient raises the possibilities of sarcoidosis and fungal exposure. Unilateral hilar disease suggests lymphoma, cancer, and granulomatous disease, as does bilateral disease in a symptomatic patient or one with abnormal physical findings.
Abdominal.
Most isolated mesenteric lymph node enlargement is due to adenocarcinoma of the gut. Isolated retroperitoneal adenopathy is a manifestation of Hodgkin disease, other lymphomas, metastatic adenocarcinoma, tuberculosis, bladder cancer, and leukemias. A palpable periumbilical abdominal node (the Sister Joseph nodule) is a noted sign of metastatic gastric adenocarcinoma.
Inguinal.
Nodes in this area are often palpable in healthy persons, especially if they walk barefoot, but these nodes can enlarge substantially in infections of the genitalia or perineum and in infections of the lower extremities. Cancers are also important causes of inguinal adenopathy, particularly lymphoma, melanoma, and squamous cell carcinomas of the genitalia.
Epitrochlear.
Enlargement of these nodes traditionally suggested the generalized adenopathy of secondary syphilis— the proverbial sailor’s handshake supposedly included a check for epitrochlear nodes—but topping the list of modern etiologies are lymphoma, chronic lymphocytic leukemia, infectious mononucleosis, and HIV infection, usually in the setting of more-generalized nodal involvement. Local hand infections may also trigger epitrochlear enlargement.
Other Lymphatic Abnormalities
In addition to lymphadenopathy, abnormalities of the lymphatic system may present in other ways. Lymphangitis, appearing as red, warm streaks along the course of superficial lymphatic networks, suggests an acute inflammatory response to pyogenic infection in the drainage area; staphylococci and streptococci are frequently responsible. Lymphadenitis, presenting as a tender, warm, soft, rapidly enlarging node, has a similar significance and often reflects acute pyogenic infection of the node itself. An idiopathic variant, necrotizing lymphadenitis (Kikuchi disease), causes self-limited tender cervical adenopathy. Lymphedema results from the interruption of lymphatic drainage; surgical node dissection, radiotherapy, and fibrosis caused by chronic infections such as filariasis or lymphogranuloma venereum are causes of lymphedema.
The causes of lymphadenopathy can be conveniently considered in terms of location of the enlarged nodes (Table 12-1). In children and young adults, most adenopathy is a result of reactive hyperplasia and is less likely to represent serious pathology than it is in adults. In persons less than the age of 30 years, the cause proves to be benign in 80% of cases; in persons greater than age 50 years, the rate of benign disease falls to 40%.
