sign in sign up
<<
Home , Lymphadenopathy, Night sweats

Unexplained : Evaluation and HEIDI L. GADDEY, MD, and ANGELA M. RIEGEL, DO, Ehrling Bergquist Family Medicine Residency Program, Offutt Air Force Base, Nebraska

Lymphadenopathy is benign and self-limited in most patients. Etiologies include malignancy, , and autoim- mune disorders, as well as medications and iatrogenic causes. The history and alone usually identify the cause of lymphadenopathy. When the cause is unknown, lymphadenopathy should be classified as local- ized 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 . 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 , 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 depend- ing 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. (Am Fam Physician. 2016;94(11):896-903. Copyright © 2016 American Academy of Family Physicians.)

CME This clinical content ymphadenopathy refers to lymph associated symptoms, and location (localized conforms to AAFP criteria nodes that are abnormal in size vs. generalized). Table 2 lists common his- for continuing medical 2 education (CME). See (e.g., greater than 1 cm) or con- torical clues and their associated diagnoses. CME Quiz Questions on sistency. Palpable supraclavicular, Other historical questions include asking page 868. Lpopliteal, and iliac nodes, and epitrochlear about time course of enlargement, tender- Author disclosure: No rel- nodes greater than 5 mm, are considered ness to palpation, recent , recent evant financial affiliations. abnormal. Hard or matted lymph nodes may immunizations, and medications.4 suggest malignancy or infection. In primary care practice, the annual incidence of unex- AGE AND DURATION plained lymphadenopathy is 0.6%.1 Only About one-half of otherwise healthy chil- 1.1% of these cases are related to malignancy, dren have palpable lymph nodes at any one but this percentage increases with advancing time.4 Most lymphadenopathy in children is age.1 are identified in 4% of patients benign or infectious in etiology. In adults and 40 years and older who present with unex- children, lymphadenopathy lasting less than plained lymphadenopathy vs. 0.4% of those two weeks or greater than 12 months without younger than 40 years.1 Etiologies of lymph- change in size has a low likelihood of being adenopathy can be remembered with the neoplastic.2,5 Exceptions include low-grade MIAMI mnemonic: malignancies, infections, Hodgkin and indolent non- autoimmune disorders, miscellaneous and Hodgkin , although both typically unusual conditions, and iatrogenic causes have associated systemic symptoms.6 (Table 1).2,3 In most cases, the history and physical examination alone identify the cause. EXPOSURES Environmental, travel-related, animal, and History insect exposures should be ascertained. Factors that can assist in identifying the etiol- Chronic medication use, infectious expo- ogy of lymphadenopathy include patient age, sures, immunization status, and recent duration of lymphadenopathy, exposures, immunizations should be reviewed as well.

896Downloaded American from the Family American Physician Family Physician website at www.aafp.org/afp.www.aafp.org/afp Copyright © 2016 American AcademyVolume of Family 94, NumberPhysicians. 11 For ◆ theDecember private, noncom 1, 2016- mercial use of one individual user of the website. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. Unexplained Lymphadenopathy SORT: KEY RECOMMENDATIONS FOR PRACTICE

Evidence Clinical recommendation rating References

Ultrasonography should be used as the initial imaging modality for children up to 14 years C 15 presenting with a mass with or without fever. Computed tomography should be used as the initial imaging modality for children older than C 15 14 years and adults presenting with solitary or multiple neck masses. In children with acute unilateral anterior cervical lymphadenitis and systemic symptoms, empiric C 17 antibiotics that target Staphylococcus aureus and group A streptococci may be given. Corticosteroids should be avoided until a definitive diagnosis of lymphadenopathy is made because C 4 they could potentially mask or delay histologic diagnosis of or lymphoma. Fine-needle aspiration may be used to differentiate malignant from reactive lymphadenopathy. C 19-22

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.

Table 3 lists medications commonly associ- drainage patterns, as well as common etiol- ated with lymphadenopathy.2 Tobacco and ogies of lymphadenopathy in these regions.2 alcohol use and ultraviolet radiation expo- A skin examination should be performed to sure increase concerns for . An rule out other lesions that would point to occupational history that includes mining, malignancy and to evaluate for erythema- masonry, and metal work may elicit work- tous lines along nodal tracts or any trauma related etiologies of lymphadenopathy, such that could lead to an infectious source of as silicon or beryllium exposure. Asking the lymphadenopathy. Finally, abdomi- about sexual history to assess exposure to nal examination focused on , genital sores or participation in oral inter- although rarely associated with lymph- course is important, especially for ingui- adenopathy, may be useful for detecting nal and . Finally, family history may identify familial causes of lymphadenopathy, such as Li-Fraumeni 2 Table 1. MIAMI Mnemonic for Differential Diagnosis syndrome or lipid storage . of Lymphadenopathy ASSOCIATED SYMPTOMS Malignancies A thorough aids in iden- Kaposi sarcoma, , lymphomas, metastases, skin tifying any red flag symptoms. Arthralgias, Infections muscle , and rash suggest an auto- Bacterial: , cat-scratch disease (Bartonella), , cutaneous immune etiology. Constitutional symptoms infections (staphylococcal or streptococcal), , of fever, , , and indicate primary and secondary , , , typhoid fever an infectious etiology. In addition to fever, Granulomatous: , , cryptococcosis, drenching night sweats and unexplained , silicosis weight loss of greater than 10% of body Viral: adenovirus, cytomegalovirus, hepatitis, herpes zoster, human immuno­ weight may suggest or deficiency , (Epstein-Barr virus), non-Hodgkin lymphoma.2,3,6 Other: fungal, helminthic, , rickettsial, , Physical Examination Autoimmune disorders Overall state of health and height and Dermatomyositis, rheumatoid , Sjögren syndrome, Still disease, systemic erythematosus weight measurements may help identify Miscellaneous/unusual conditions signs of chronic disease, especially in chil- Angiofollicular hyperplasia (), histiocytosis, 7 dren. A complete lymphatic examination , Kikuchi lymphadenitis, Kimura disease, should be performed to rule out generalized Iatrogenic causes lymphadenopathy, followed by a focused Medications, lymphatic examination with consideration of lymphatic drainage patterns. Figures 1 Information from references 2 and 3. through 3 demonstrate typical lymphatic

December 1, 2016 ◆ Volume 94, Number 11 www.aafp.org/afp American Family Physician 897 Unexplained Lymphadenopathy

infectious mononucleosis, lymphocytic leu- qualitative characteristics are unable to reli- kemias, lymphoma, or sarcoidosis.2,5 ably predict malignancy. Painful or tender lymphadenopathy is nonspecific and may NODAL CHARACTER AND SIZE represent possible caused The quality and size of lymph nodes should by infection, but it can also be the result of be assessed. Lymph node qualities include hemorrhage into a node or .3 No spe- warmth, overlying erythema, , cific nodal size is indicative of malignancy.3 mobility, fluctuance, and consistency. Shotty lymphadenopathy is the presence of multiple Localized Lymphadenopathy small lymph nodes that feel like “buck shots” HEAD AND CERVICAL under the skin.8 This usually implies reac- Head and neck lymphadenopathy can be tive lymphadenopathy from viral infection. classified as submental, submandibular, A painless, hard, irregular mass or a firm, anterior or posterior cervical, preauricular, rubbery lesion that is immobile or fixed may and supraclavicular.9 Infection is a common represent a malignancy, although in general, cause of head and cervical lymphadenopathy.

Table 2. Clues and Initial Testing to Determine the Cause of Lymphadenopathy

Historical clues Suggested diagnoses Initial testing

Fever, night sweats, weight loss, or Leukemia, lymphoma, solid tumor CBC, nodal biopsy or bone marrow biopsy; imaging node located in supraclavicular, with ultrasonography or computed tomography popliteal, or iliac region, may be considered but should not delay referral for bruising, splenomegaly biopsy

Fever, chills, malaise, sore throat, Bacterial or viral pharyngitis, Limited illnesses may not require any additional nausea, vomiting, diarrhea; no hepatitis, influenza, testing; depending on clinical assessment, consider other red flag symptoms mononucleosis, tuberculosis CBC, monospot test, liver function tests, cultures, (if exposed), rubella and disease-specific serologies as needed

High-risk sexual behavior Chancroid, HIV infection, HIV-1/HIV-2 immunoassay, rapid plasma reagin, lymphogranuloma venereum, culture of lesions, nucleic acid amplification for syphilis , migration inhibitory factor test

Animal or food contact Cats Cat-scratch disease (Bartonella) Serology and polymerase chain reaction Toxoplasmosis Serology Rabbits, or sheep or cattle wool, Per CDC guidelines hair, or hides Brucellosis Serology and polymerase chain reaction Tularemia Blood culture and serology Undercooked meat Anthrax Per CDC guidelines Brucellosis Serology and polymerase chain reaction Toxoplasmosis Serology

Recent travel, insect bites Diagnoses based on endemic Serology and testing as indicated by suspected region exposure

Arthralgias, rash, joint stiffness, , Sjögren Antinuclear antibody, anti-doubled-stranded DNA, fever, chills, muscle weakness syndrome, dermatomyositis, erythrocyte sedimentation rate, CBC, rheumatoid systemic lupus erythematosus factor, creatine kinase, electromyography, or muscle biopsy as indicated

CBC = complete blood count; CDC = Centers for Disease Control and Prevention; HIV = human virus. Information from reference 2.

898 American Family Physician www.aafp.org/afp Volume 94, Number 11 ◆ December 1, 2016 Unexplained Lymphadenopathy

In children, acute and self-limiting viral illnesses are the most common etiologies Table 3. Medications That Can Cause Lymphadenopathy of lymphadenopathy.2 Inflamed cervical nodes that progress quickly to fluctuation Allopurinol Phenytoin (Dilantin) are typically caused by staphylococcal and Atenolol Primidone (Mysoline) streptococcal infections and require anti- Captopril Pyrimethamine (Daraprim) biotic therapy with occasional incision and Carbamazepine (Tegretol) Quinidine drainage. Persistent lymphadenopathy last- Gold Trimethoprim/sulfamethoxazole ing several months can be caused by atypical Hydralazine Sulindac mycobacteria, cat-scratch disease, Kikuchi Penicillins lymphadenitis, sarcoidosis, and Kawasaki Adapted with permission from Bazemore AW, Smucker DR. Lymphadenopathy and disease, and often can be mistaken for neo- malignancy. Am Fam Physician. 2002;66 (11):2108. plasms.2,7 Supraclavicular adenopathy in adults and children is associated with high risk of intra-abdominal malignancy and are cat-scratch disease, tularemia, and spo- must be evaluated promptly. Studies found rotrichosis due to inoculation and lymphatic that 34% to 50% of these patients had malig- drainage. Absence of an infectious source nancy, with patients older than 40 years at or traumatic lesions is highly suspicious highest risk.9,10 for a malignant etiology such as Hodgkin lymphoma or non-Hodgkin lymphoma. AXILLARY Breast, lung, thyroid, stomach, colorectal, Infections or injuries of the upper extremi- pancreatic, ovarian, kidney, and skin can- ties are a common cause of axillary lymph- cers (malignant melanoma) can metasta- adenopathy. Common infectious etiologies size to the axilla.3,5 Silicone breast implants

Preauricular nodes: Drain scalp, skin Differential diagnosis: Scalp infections, Submandibular nodes: mycobacterial infection Drain oral cavity Malignancies: Differential diagnosis: Skin neoplasm, lymphomas, Mononucleosis, upper head and neck squamous respiratory infection, cell carcinomas mycobacterial infection, toxoplasma, cytomegalovirus, dental disease, rubella Posterior cervical nodes: Malignancies: Drain scalp, neck, upper Squamous cell carcinoma thoracic skin of the head and neck, Differential diagnosis: lymphomas, leukemias Same as preauricular nodes

Anterior cervical nodes: Supraclavicular nodes: Drain larynx, tongue, Drain gastrointestinal tract, oropharynx, anterior neck genitourinary tract, pulmonary Differential diagnosis: Differential diagnosis: Same as submandibular nodes Thyroid/laryngeal disease, mycobacterial/fungal infections Malignancies: Abdominal/thoracic ILLUSTRATION DAVID BY KLEMM Figure 1. Lymph nodes of the head and neck and the regions that they drain. Reprinted with permission from Bazemore AW, Smucker DR. Lymphadenopathy and malignancy. Am Fam Physician. 2002;66(11):2106.

December 1, 2016 ◆ Volume 94, Number 11 www.aafp.org/afp American Family Physician 899 Unexplained Lymphadenopathy Infraclavicular nodes Differential diagnosis: Highly suspicious for non-Hodgkin lymphoma Axillary nodes: Drain breast, upper extremity, thoracic wall Differential diagnosis: Skin infections/trauma, cat-scratch disease, tularemia, sporotrichosis, sarcoidosis, syphilis, , brucellosis, leishmaniasis Malignancies: Breast adenocarcinomas, skin neoplasms, lymphomas, leukemias, soft tissue/Kaposi sarcoma

Epitrochlear nodes: Drain ulnar forearm, hand Differential diagnosis: Skin infections, lymphomas, and skin malignancies ILLUSTRATION CHRISTY BY KRAMES Figure 2. Axillary lymphatics and the structures that they drain. Reprinted with permission from Bazemore AW, Smucker DR. Lymphadenopathy and malignancy. Am Fam Physician. 2002;66 (11):2107.

may also cause axillary lymphadenopathy INGUINAL because of an inflammatory reaction to sili- , with nodes up to cone particles from implant leakage.11 2 cm in diameter, is present in many healthy adults. It is more common in those who EPITROCHLEAR walk outdoors barefoot, especially in tropi- Epitrochlear lymphadenopathy (nodes cal regions.3,12 Common etiologies include greater than 5 mm) is pathologic and usu- sexually transmitted infections such as ally suggestive of lymphoma or melanoma.2,3 herpes simplex, lymphogranuloma vene- Other causes include infections of the reum, chancroid, and syphilis, and lower upper extremity, sarcoidosis, and secondary extremity skin infections. Lymphomas, both syphilis. Hodgkin and non-Hodgkin, typically do not present in the inguinal region.13 Other ingui- nal lymphadenopathy–associated malignan- Differential diagnosis: cies are penile and vulvar squamous cell Benign reactive lympha­ carcinomas and melanoma. Inguinal lymph- denopathy, sexually transmitted adenopathy is present in about one-half of diseases, skin infections 14 Malignancies: penile or urethral carcinomas. Lymphomas; squamous cell Horizontal carcinoma of penis, vulva, and Generalized Lymphadenopathy node group anus; skin neoplasms; soft Generalized lymphadenopathy is the tissue/Kaposi sarcoma enlargement of more than two noncontigu- ous lymph node groups.8 Significant sys- Vertical temic disease from infections, autoimmune node group diseases, or disseminated malignancy often These groups drain lower causes generalized lymphadenopathy, and abdomen, external genitalia (skin), anal canal, lower one- specific testing is necessary to determine third of vagina, lower extremity the diagnosis. Benign causes of generalized lymphadenopathy are self-limited viral ill- nesses, such as infectious mononucleosis,

ILLUSTRATION CHRISTY BY KRAMES and medications. Other causes include acute Figure 3. Inguinal lymphatics and the structures that they drain. human immunodeficiency virus infection, Reprinted with permission from Bazemore AW, Smucker DR. Lymphadenopathy and malig- activated mycobacterial infection, crypto- nancy. Am Fam Physician. 2002;66 (11):2107. coccosis, cytomegalovirus, Kaposi sarcoma,

900 American Family Physician www.aafp.org/afp Volume 94, Number 11 ◆ December 1, 2016 Unexplained Lymphadenopathy Evaluation of Lymphadenopathy

History (includes infectious contacts, medications, travel, environmental exposures, occupational exposure, sexual history, family history)

Physical examination (includes complete lymphatic examination, regional examination as directed by lymphatic drainage [see Figures 1-3])

Diagnostic of benign Suggestive of auto­ Suggestive of A Unexplained or self-limited disease immune disease or malignancy serious infectious cause Consider miscellaneous Specific testing or or unusual causes empiric treatment Specific testing if suggestive

High risk Review risk factors for malignancy (age, duration, exposures, associated symptoms, location of lymphadenopathy) Positive Negative Specific testing if indicated Low risk Go to A Treatable? Excisional biopsy

Yes No Generalized Regional

Treat Reassure and appropriately explain expected Negative Positive CBC with manual course of disease differential, RPR, PPD, HIV, HBsAg, ANA testing Go to A Treat appropriately

Follow-up for persistent or Negative changing lymphadenopathy

Positive Biopsy most Persists Observe patient abnormal node for one month

Treat appropriately Negative Resolves

Follow-up for persistent or changing lymphaden­opathy

Figure 4. Algorithm for evaluating lymphadenopathy. (ANA = antinuclear antibody; CBC = complete blood count; HBsAg = hepatitis B surface antigen; HIV = human immunodeficienty virus; PPD = purified protein derivative; RPR = rapid plasma reagin.) Adapted with permission from Bazemore AW, Smucker DR. Lymphadenopathy and malignancy. Am Fam Physician. 2002;66(11):2109. and systemic lupus erythematosus. Gen- and follow-up arranged if lymphadenopathy eralized lymphadenopathy can occur with persists. Findings suggestive of infectious or leukemias, lymphomas, and advanced meta- autoimmune etiologies may require specific static carcinomas.3 testing and treatment as indicated. If malig- nancy is considered unlikely based on history Diagnostic Approach and physical examination, localized lymph- Figure 4 provides an algorithm for evaluating adenopathy can be observed for four weeks. lymphadenopathy.2 If history and physical Generalized lymphadenopathy should examination findings suggest a benign or self- prompt routine laboratory testing and test- limited process, reassurance can be provided ing for autoimmune and infectious causes.2

December 1, 2016 ◆ Volume 94, Number 11 www.aafp.org/afp American Family Physician 901 Unexplained Lymphadenopathy

Radiologic evaluation with computed a reactive lymph node is likely, core needle tomography, magnetic resonance imaging, biopsy can be avoided, and FNA used alone. or ultrasonography may help to characterize Combined, they allow cytologic and histo- lymphadenopathy. The American College pathologic assessment of lymph nodes. How- of Radiology recommends ultrasonography ever, the use of both techniques may not be as the initial imaging choice for cervical needed because the diagnostic accuracy of lymphadenopathy in children up to 14 years FNA in adult populations has been reported of age and computed tomography for per- to approach 90%, with a sensitivity and sons older than 14 years.15 Based on the loca- specificity of 85% to 95% and 98% to 100%, tion of the abnormal nodes, the sensitivity of respectively.19,20 False-positive diagnoses are these modalities for diagnosing metastatic rare with FNA. False-negative results occur lymph nodes varies; therefore, history and secondary to early or partial involvement of clinical examination must guide selection.16 lymph nodes, inexperience with lymph node If the diagnosis is still uncertain, biopsy is cytology, unrecognized lymphomas with recommended. heterogeneity, and sampling errors.20 There In children with acute unilateral anterior are concerns about the reliability of FNA in cervical lymphadenitis and systemic symp- the diagnosis of diseases such as lymphoma toms, antibiotics may be prescribed. Empiric because it is unable to assess lymph node antibiotics should target Staphylococcus architecture. Regardless, FNA may be a use- aureus and group A streptococci. Options ful triage tool for differentiating benign reac- include oral cephalosporins, amoxicillin/ tive lymphadenopathy from malignancy.21 clavulanate (Augmentin), orclindamycin.17 Open excisional biopsy remains a diag- Corticosteroids should be avoided until a nostic option for patients who do not wish definitive diagnosis is made because treat- to undergo additional procedures. When ment could potentially mask or delay histo- selecting nodes for any method, the largest, logic diagnosis of leukemia or lymphoma.5 most suspicious, and most accessible node should be sampled. Inguinal nodes typically Biopsy display the lowest yield, and supraclavicular Fine-needle aspiration (FNA) and core nodes have the highest.22,23 needle biopsy can aid in the diagnostic This review updates previous articles on this topic by evaluation of lymph nodes when etiology is Bazemore and Smucker 2 and Ferrer.24 unknown or malignant risk factors are pres- ent (Table 4 4,6,10). FNA cytology is a quick, Data Sources: A PubMed search was completed in Clinical Queries. Key terms: lymphadenopathy, accurate, minimally invasive, and safe tech- peripheral, generalized, evaluation, treatment, imag- nique to evaluate patients and aid in tri- ing, management. The search included meta-analyses, age of unexplained lymphadenopathy.18 If randomized controlled trials, clinical trials, and reviews. Also searched were Essential Evidence Plus, the Agency for Healthcare Research and Quality evidence reports, Clinical Evidence, Google Scholar, and the Cochrane Table 4. Risk Factors for Malignancy database. Reference lists of retrieved articles were also searched. Search dates: September 2015 and July 2016.

Age older than 40 years The opinions and assertions contained herein are the Duration of lymphadenopathy greater than four to six weeks private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Air Force Generalized lymphadenopathy (two or more regions involved) Medical Department or the U.S. Air Force at large. Male sex Node not returned to baseline after eight to 12 weeks The Authors Supraclavicular location Systemic signs: fever, night sweats, weight loss, hepatosplenomegaly HEIDI L. GADDEY, MD, is the program director at the White race Ehrling Bergquist Family Medicine Residency Program, Offutt Air Force Base, Neb. Information from references 4, 6, and 10. ANGELA M. RIEGEL, DO, is faculty at the Ehrling Bergquist Family Medicine Residency Program.

902 American Family Physician www.aafp.org/afp Volume 94, Number 11 ◆ December 1, 2016 Unexplained Lymphadenopathy

Address correspondence to Heidi L. Gaddey, MD, Ehrling 13. Mauch PM, Kalish LA, Kadin M, Coleman CN, Osteen R, Bergquist Clinic, 2501 Capehart Road, Offutt Air Force Hellman S. Patterns of presentation of Hodgkin disease. Base, NE 68113. (e-mail: [email protected]). Implications for etiology and pathogenesis. . Reprints are not available from the authors. 1993;​71(6):​2062-2071. 14. Skinner DG, Leadbetter WF, Kelley SB. The surgical management of squamous cell carcinoma of the penis. REFERENCES J Urol. 1972;​107(2):​273-277. 15. American College of Radiology. ACR Appropriateness 1. Fijten GH, Blijham GH. Unexplained lymphadenopathy Criteria:​ neck mass/adenopathy. https:​//acsearch.acr.org/ in family practice. An evaluation of the probability of docs/69504/Narrative/. Accessed December 1, 2016 malignant causes and the effectiveness of physicians’ workup. J Fam Pract. 1988;27(4):​ ​373-376. 16. Dudea SM, Lenghel M, Botar-Jid C, Vasilescu D, Duma M. Ultrasonography of superficial lymph nodes:​ benign 2. Bazemore AW, Smucker DR. Lymphadenopathy and vs. malignant. Med Ultrason. 2012;​14(4):294-306​ . malignancy. Am Fam Physician. 2002;66​ (11):2103-2110​ . 17. Meier JD, Grimmer JF. Evaluation and management of 3. Habermann TM, Steensma DP. Lymphadenopathy. Mayo neck masses in children. Am Fam Physician. 2014;​89(5):​ Clin Proc. 2000;75(7):​ 723-732​ . 353-358. 4. King D, Ramachandra J, Yeomanson D. Lymphadenopa- 18. Monaco SE, Khalbuss WE, Pantanowitz L. Benign non- thy in children:​ refer or reassure? Arch Dis Child Educ infectious causes of lymphadenopathy: ​a review of Pract Ed. 2014;99(3):​ 101-110​ . cytomorphology and differential diagnosis. Diagn Cyto- 5. Pangalis GA, Vassilakopoulos TP, Boussiotis VA, Fessas pathol. 2012;​40(10):925-938​ . P. Clinical approach to lymphadenopathy. Semin Oncol. 19. Lioe TF, Elliott H, Allen DC, Spence RA. The role of fine 1993;​20(6):​570-582. needle aspiration cytology (FNAC) in the investigation 6. Salzman BE, Lamb K, Olszewski RF, Tully A, Studdiford of superficial lymphadenopathy;​ uses and limitations of J. Diagnosing cancer in the symptomatic patient. Prim the technique. Cytopathology. 1999;10(5):​ 291-297​ . Care. 2009;​36(4):​651-670. 20. Thomas JO, Adeyi D, Amanguno H. Fine-needle aspira- 7. Rajasekaran K, Krakovitz P. Enlarged neck lymph nodes tion in the management of peripheral lymphadenopa- in children. Pediatr Clin North Am. 2013;​60(4):923-936​ . thy in a developing country. Diagn Cytopathol. 1999;​ 8. Ferrer R. Lymphadenopathy: ​differential diagnosis and 21(3):​159-162. evaluation. Am Fam Physician. 1998;​58(6):1313-1320​ . 21. Metzgeroth G, Schneider S, Walz C, et al. Fine needle 9. Rosenberg TL, Nolder AR. Pediatric cervical lymph- aspiration and core needle biopsy in the diagnosis of adenopathy. Otolaryngol Clin North Am. 2014;​47(5):​ lymphadenopathy of unknown aetiology. Ann Hematol. 721-731. 2012;​91(9):1477-1484​ . 10. Chau I, Kelleher MT, Cunningham D, et al. Rapid access 22. Steel BL, Schwartz MR, Ramzy I. Fine needle aspiration multidisciplinary lymph node diagnostic clinic:​ analysis biopsy in the diagnosis of lymphadenopathy in 1,103 of 550 patients. Br J Cancer. 2003;88(3):​ ​354-361. patients. Role, limitations and analysis of diagnostic pit- 11. Shipchandler TZ, Lorenz RR, McMahon J, Tubbs R. falls. Acta Cytol. 1995;39(1):​ ​76-81. Supraclavicular lymphadenopathy due to silicone breast 23. Karadeniz C, Oguz A, Ezer U, Oztürk G, Dursun A. The implants. Arch Otolaryngol Head Neck Surg. 2007;​ etiology of peripheral lymphadenopathy in children. 133(8):830-832​ . Pediatr Hematol Oncol. 1999;16(6):​ ​525-531. 12. Oluwole SF, Odesanmi WO, Kalidasa AM. Peripheral 24. Ferrer R. Lymphadenopathy: ​differential diagnosis and lymphadenopathy in Nigeria. Acta Trop. 1985;​42(1):​ evaluation. Am Fam Physician. 1998;​58(6):1313-1320​ . 87-96.

December 1, 2016 ◆ Volume 94, Number 11 www.aafp.org/afp American Family Physician 903