Unexplained Lymphadenopathy: Evaluation and Differential Diagnosis

 

Am Fam Physician. 2016 Dec 1;94(11):896-903.

Author disclosure: No relevant financial affiliations.

Lymphadenopathy is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as medications and iatrogenic causes. The history and physical examination alone usually identify the cause of lymphadenopathy. When the cause is unknown, lymphadenopathy should be classified as localized or generalized. Patients with localized lymphadenopathy should be evaluated for etiologies typically associated with the region involved according to lymphatic drainage patterns. Generalized lymphadenopathy, defined as two or more involved regions, often indicates underlying systemic disease. Risk factors for malignancy include age older than 40 years, male sex, white race, supraclavicular location of the nodes, and presence of systemic symptoms such as fever, night sweats, and unexplained weight loss. Palpable supraclavicular, popliteal, and iliac nodes are abnormal, as are epitrochlear nodes greater than 5 mm in diameter. The workup may include blood tests, imaging, and biopsy depending on clinical presentation, location of the lymphadenopathy, and underlying risk factors. Biopsy options include fine-needle aspiration, core needle biopsy, or open excisional biopsy. Antibiotics may be used to treat acute unilateral cervical lymphadenitis, especially in children with systemic symptoms. Corticosteroids have limited usefulness in the management of unexplained lymphadenopathy and should not be used without an appropriate diagnosis.

Lymphadenopathy refers to lymph nodes that are abnormal in size (e.g., greater than 1 cm) or consistency. Palpable supraclavicular, popliteal, and iliac nodes, and epitrochlear nodes greater than 5 mm, are considered abnormal. Hard or matted lymph nodes may suggest malignancy or infection. In primary care practice, the annual incidence of unexplained lymphadenopathy is 0.6%.1 Only 1.1% of these cases are related to malignancy, but this percentage increases with advancing age.1 Cancers are identified in 4% of patients 40 years and older who present with unexplained lymphadenopathy vs. 0.4% of those younger than 40 years.1  Etiologies of lymphadenopathy can be remembered with the MIAMI mnemonic: malignancies, infections, autoimmune disorders, miscellaneous and unusual conditions, and iatrogenic causes (Table 1).2,3 In most cases, the history and physical examination alone identify the cause.

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

Ultrasonography should be used as the initial imaging modality for children up to 14 years presenting with a neck mass with or without fever.

C

15

Computed tomography should be used as the initial imaging modality for children older than 14 years and adults presenting with solitary or multiple neck masses.

C

15

In children with acute unilateral anterior cervical lymphadenitis and systemic symptoms, empiric antibiotics that target Staphylococcus aureus and group A streptococci may be given.

C

17

Corticosteroids should be avoided until a definitive diagnosis of lymphadenopathy is made because they could potentially mask or delay histologic diagnosis of leukemia or lymphoma.

C

4

Fine-needle aspiration may be used to differentiate malignant from reactive lymphadenopathy.

C

1922


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

Ultrasonography should be used as the initial imaging modality for children up to 14 years presenting with a neck mass with or without fever.

C

15

Computed tomography should be used as the initial imaging modality for children older than 14 years and adults presenting with solitary or multiple neck masses.

C

15

In children with acute unilateral anterior cervical lymphadenitis and systemic symptoms, empiric antibiotics that target Staphylococcus aureus and group A streptococci may be given.

C

17

Corticosteroids should be avoided until a definitive diagnosis of lymphadenopathy is made because they could potentially mask or delay histologic diagnosis of leukemia or lymphoma.

C

4

Fine-needle aspiration may be used to differentiate malignant from reactive lymphadenopathy.

C

1922


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

View/Print Table

Table 1.

MIAMI Mnemonic for Differential Diagnosis of Lymphadenopathy

Malignancies

Kaposi sarcoma, leukemias, lymphomas, metastases, skin neoplasms

Infections

Bacterial: brucellosis, cat-scratch disease (Bartonella), chancroid, cutaneous infections (staphylococcal or strep

The Authors

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HEIDI L. GADDEY, MD, is the program director at the Ehrling Bergquist Family Medicine Residency Program, Offutt Air Force Base, Neb....

ANGELA M. RIEGEL, DO, is faculty at the Ehrling Bergquist Family Medicine Residency Program.

Address correspondence to Heidi L. Gaddey, MD, Ehrling Bergquist Clinic, 2501 Capehart Road, Offutt Air Force Base, NE 68113. (e-mail: heidi.gaddey@us.af.mil). Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

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