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Sumana Devata

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date: 20 May 2022

  1. A. Introduction

    1. a. Definition. Lymphadenopathy occurs when the lymph nodes are of an abnormal consistency or increased size (>1 cm). Lymphadenopathy can be regional (i.e., involvement of one or a few contiguous groups of nodes) or generalized (i.e., involving more than two separate sites).

    2. b. Lymphadenopathy usually signals the presence of disease and therefore warrants medical evaluation.

  2. B. Approach to the Patient

    1. a. Assess for truly pathologic lymph nodes. Certain lymph nodes (e.g., the submandibular and inguinal nodes) are commonly palpable.

    2. b. Generate a differential diagnosis based on the location, duration, and physical attributes of the lymphadenopathy, including HIV status, and the clinical scenario. This information guides further laboratory tests and studies (e.g., complete blood count [CBC] and peripheral smear evaluation, Monospot test, hepatitis serologies, serum lactate dehydrogenase [LDH], erythrocyte sedimentation rate [ESR], Venereal Disease Research Laboratories [VDRL] test, and radiographic imaging).

      1. i. Location of the lymphadenopathy. The location of the lymphadenopathy allows you to form an initial differential diagnosis.

        1. 1. If the lymphadenopathy is generalized, the most likely etiologies can be remembered with the mnemonic, “SHE HAS CUTE LAN”:

          • MNEMONIC: Causes of Generalized Lymphadenopathy (“SHE HAS CUTE LAN”)

          • Syphilis

          • Hepatitis

          • Epstein-Barr virus infection

          • Histoplasmosis

          • AIDS/HIV infection

          • Serum sickness

          • Cytomegalovirus (CMV) infection/Castleman’s disease

          • Unusual drugs (e.g., hydantoin derivatives, antithyroid medications, antileprosy medications, isoniazid)

          • Toxoplasmosis

          • Erythrophagocytic lymphohistiocytosis

          • Leishmaniasis

          • Arthritis (rheumatoid)

          • Neoplasm: lymphoma, leukemia, metastatic cancer

        2. 2. If the lymphadenopathy is localized, refer to Table 68.1.

          Table 68.1 Major Causes of Localized Lymphadenopathy

          Affected Lymph Nodes

          Causes of Lymphadenopathy


          Head and neck malignancy, bacterial infection, Epstein-Barr virus, cytomegalovirus, tuberculosis, lymphoma


          Lung, breast, gastrointestinal, or genitourinary malignancy, lymphoma


          Hand or arm infections, trauma for bites, cat-scratch disease, lymphoma, brucellosis, breast cancer, reactive changes secondary to breast implants


          Hand infections, lymphoma, tularemia, syphilis


          Leg or foot infections, pelvic malignancy, lymphoma, sexually transmitted disease


          Sarcoidosis, tuberculosis, lymphoma, fungal infections, lung cancer


          Lymphoma, tuberculosis, Mycobacterium avium complex infection, metastatic malignancy

      2. ii. HIV must always be considered when regional or generalized lymphadenopathy is present. In HIV-infected patients, generalized lymphadenopathy typically occurs early in the course of disease (often during seroconversion) and may be associated with low-grade, nonspecific fevers. Lymphadenopathy can be caused either by the virus itself or other systemic diseases that are common in HIV-infected patients.

      3. iii. Clinical scenario. Considering the patient’s age and associated findings can help narrow the differential diagnosis.

        1. 1. Patient age. Lymphadenopathy in patients younger than 30 years is most often benign (and often caused by an infection). In patients older than 30 years, the possibility of malignancy becomes much more worrisome.

        2. 2. Signs and symptoms. Symptoms of fever, chills, night sweats, and weight loss should always be sought and, if present, usually imply a serious systemic infection or malignancy. Symptoms or signs of a local infection (e.g., pharyngitis, conjunctivitis, otitis, skin infection, or trauma) imply an infectious etiology.

        3. 3. Historical data. Pertinent historical data should be ascertained, including a history of smoking, tick bites, travel, high-risk behavior (e.g., multiple sexual partners, intravenous drug use), tuberculosis exposure, and animal contact.

      4. iv. Characteristics of lymphadenopathy on palpation. The physical attributes of lymphadenopathy can help but may be misleading; therefore, these findings alone should not deter from further evaluation. In general, abnormal nodes are greater than 1 cm in diameter, and the likelihood of a malignancy increases proportionally with the size of the node. The following general rules tend to be true:

        1. 1. Infections tend to cause tender lymphadenopathy because of rapid growth of the node and subsequent capsular stretching. The nodes tend to be asymmetric with erythematous skin overlying the node in the acute stages of infection.

        2. 2. Lymphoma classically leads to large, firm, rubbery, nontender lymphadenopathy.

          Hot Key

          Alcohol-induced pain in a lymph node is Hodgkin’s disease until proven otherwise.

        3. 3. Metastatic cancer usually results in very firm (sometimes “rock hard”), nontender nodes that are immobile (i.e., fixed to the underlying tissue).

          Hot Key

          Infamous lymph nodes include Virchow’s node (a left supraclavicular lymph node) and Sister Mary Joseph’s node (a periumbilical lymph node), both of which can be seen with gastrointestinal malignancies.

    3. c. Evaluation

      1. i. In cases of generalized lymphadenopathy, an evaluation should begin with a CBC and differential, comprehensive metabolic panel, and an LDH level. Additional specific testing for HIV, tuberculosis, and syphilis may be considered in appropriate patients.

      2. ii. If lymphoma or metastatic malignancy is high on the differential diagnosis, then proceed to biopsy of the node. Fine-needle aspiration biopsy is sensitive for metastatic solid tumor malignancies and infections but is not sensitive for lymphoma. If lymphoma is suspected, then core needle biopsy or excisional biopsy is required.

      3. iii. If bacterial infection is the likely diagnosis, a period of observation (2–3 weeks, with or without antibiotics) is reasonable. If the lymphadenopathy fails to resolve, then fine-needle aspiration, core needle, or excisional biopsy would aid in the diagnosis.

      4. iv. If the etiology of the lymphadenopathy is unclear, close follow-up is essential because a small but significant percentage of these patients develop lymphoma within 1 year.

  3. C. Treatment

    Treatment varies considerably and depends on the underlying cause.

Suggested Further Readings

Ebell MH, Call M, Shinholser J, Gardner J. Does this patient have infectious mononucleosis? The rational clinical examination systematic review. JAMA 2016;315:1502–9.Find this resource:

Gaddey HL, Riegel AM. Unexplained lymphadenopathy: evaluation and differential diagnosis. Am Fam Physician 2016;94:896–903.Find this resource:

Habermann TM, Steensma DP. Lymphadenopathy. Mayo Clinic proceedings 2000;75:723–32. (Classic Article.)Find this resource:

Ioachim HL, Lerner CW, Tapper ML. Lymphadenopathies in homosexual men: relationships with the acquired immune deficiency syndrome. JAMA 1983;250:1306–9. (Classic Article.)Find this resource: