Evaluation of Neck Masses in Adults JAMES HAYNES, MD; KELLY R

Evaluation of Neck Masses in Adults JAMES HAYNES, MD; KELLY R. ARNOLD, MD; CHRISTINA AGUIRRE-OSKINS, MD; and SATHISH CHANDRA, MD, University of Tennessee Health Science Center College of Medicine, Chattanooga, Tennessee

Neck masses are often seen in clinical practice, and the family physician should be able to determine the etiology of a mass using organized, efficient diagnostic methods. The first goal is to determine if the mass is malignant or benign; malignancies are more common in adult smokers older than 40 years. Etiologies can be grouped according to whether the onset/duration is acute (e.g., infectious), subacute (e.g., squamous cell carcinoma), or chronic (e.g., thyroid), and further narrowed by patient demographics. If the history and physical examination do not find an obvious cause, imaging and surgical tools are helpful. Contrast-enhanced computed tomography is the initial diagnostic test of choice in adults. Computed tomography angiography is recommended over magnetic resonance angiography for the evaluation of pulsatile neck masses. If imaging rules out involvement of underlying vital structures, a fine-needle aspiration biopsy can be performed, providing diagnostic information via cytology, Gram stain, and bacterial and acid-fast bacilli cultures. The sensitivity and specificity of fine-needle aspiration biopsy in detecting a malignancy range from 77% to 97% and 93% to 100%, respectively. (Am Fam Physician. 2015;91(10):698-706. Copyright © 2015 American Academy of Family Physicians.)

CME This clinical content he primary concern in adults with creating a hematoma. Small hematomas conforms to AAFP criteria a persistent neck mass is malig- are typically self-limited, but large, rapidly for continuing medical education (CME). See nancy. Fortunately, a history and expanding hematomas require immediate CME Quiz Questions on physical examination coupled intervention and possible surgical explora- page 680. Twith an organized diagnostic evaluation tion. Similar mechanisms of trauma, plus Author disclosure: No rel- typically reveal a definitive diagnosis. When the addition of shearing forces, potentiate evant financial affiliations. the etiology is elusive, a head and neck sur- the formation of pseudoaneurysms or arte- geon should be consulted. riovenous fistulas characterized by soft, pulsatile masses with a thrill or bruit. Computed Anatomic Considerations tomography (CT) angiography delineates Neck anatomy is divided into triangles with the extent of any possible vascular injury, the sternocleidomastoid being the central and treatment is usually surgical ligation.1 component of each division. The anterior By far, the most common cause of cervical and posterior cervical triangles share a com- lymphadenopathy is infection or inflamma- mon border with the sternocleidomastoid. tion created by an array of odontogenic, sal- The common pattern of lymphatic drain- ivary, viral, and bacterial etiologies. These age is helpful in diagnosing metastases from lymph nodes are often swollen, tender, and various organs (Figure 1). mobile, and can be erythematous and warm. Upper respiratory symptoms caused by Differential Diagnosis common viruses usually last for one to two A clinically relevant approach to differenti- weeks, whereas lymphadenopathy gener- ating neck masses depends on whether the ally subsides within three to six weeks after mass is acute, subacute, or chronic (Tables 1 symptom resolution.2 Although unknown and 2). viruses cause 20% to 30% of upper respiratory infections, which occur an average of ACUTE NECK MASSES two to four times per year in adults, more Neck masses that appear over a short period common viral pathogens include rhino- are generally symptomatic. Blunt or sharp viruses, coronaviruses, and influenza.3,4 trauma may damage tissue and vasculature, Biopsy is appropriate if an abnormal node

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Upper jugular chain area or jugulodigastric area (posterior auricular nodes): nasopharynx

Sternocleidomastoid muscle

Submandibular triangle (submandibular group): anterior two-thirds of the tongue, floor of the mouth, Posterior triangle lymph nodes: gums, mucosa of the cheek nasopharynx, posterior scalp, ear, temporal bone, or skull base Submental triangle (submental nodes): rarely involved early except from cancer of the lip

Midjugular chain area (deep lateral cervical Posterior cervical triangle nodes): any portion of the oral cavity, pharynx, or larynx, especially growths in the Waldeyer ring (nasopharynx, tonsil, base of the tongue)

Lower jugular chain area (supraclavicular nodes): thyroid, piriform sinuses, upper esophagus; rarely from primary below the clavicle Anterior cervical triangle ILLUSTRATION DAVE BY KLEMM Figure 1. Cervical triangle anatomy with common lymph node locations and drainage areas. has not resolved after four to six weeks, and should be performed promptly in patients Table 1. Relative Prevalence of Neck Mass Etiologies with other findings suggestive of malignancy, such as night sweats, fever, weight Type Common Uncommon Rare 5 loss, or a rapidly growing mass. Certain Acute Cytomegalovirus Acute sialadenitis — infectious etiologies (human immunode- infection Arteriovenous fistula ficiency virus [HIV], Epstein-Barr virus, Epstein-Barr virus Bartonella henselae cytomegalovirus, toxoplasmosis) tend to infection infection cause generalized lymphadenopathy, which Staphylococcal or Hematoma streptococcal emphasizes the need for a comprehensive Human immunodeficiency infection lymph node evaluation.1 virus infection Toxoplasmosis Bacterial infections of the head and neck Mycobacterium Viral upper tuberculosis infection predominantly cause cervical lymphade- respiratory Parotid lymphadenopathy nopathy. Lymphadenopathy caused by infection Pseudoaneurysm Staphylococcus aureus or group A beta Strep- Subacute Squamous cell Amyloidosis Castleman tococcus has no predictable sites of lymph carcinoma Lymphoma disease of the upper node inflammation. DisseminatedEpstein- Metastatic cancer Kikuchi disease aerodigestive Barr virus or HIV infection often involves Parotid tumor Kimura disease 2 tract the cervical chain. Common antibiotics Sarcoidosis Rosai-Dorfman disease used for lymphadenopathy include first- Sjögren syndrome generation cephalosporins, amoxicillin/ Chronic Thyroid Branchial cleft cyst Liposarcoma clavulanate (Augmentin), or clindamycin. pathology Carotid body tumor Parathyroid Bartonella henselae infection causes Glomus jugulare tumor carcinoma mobile, fluctuant, erythematous, and tender, Glomus vagale tumor but characteristically isolated, lymph nodes Laryngocele similar to lymphadenopathy caused by Lipoma staphylococcal and streptococcal infections. Thyroglossal duct cyst Cat-scratch disease develops when a kitten

May 15, 2015 ◆ Volume 91, Number 10 www.aafp.org/afp American Family Physician 699 Neck Masses Table 2. Differential Diagnosis of Neck Masses in Adults

Condition History/risk factors Physical findings Diagnosis Management

Acute Acute sialadenitis Older, debilitated persons with dehydration Rapid or gradual onset of pain and swelling; local Contrast-enhanced CT Sialagogues, gentle massage; or recent dental procedures edema, erythema, tenderness, or fluctuance abscess, express by compressing consistent with an abscess the gland Hematoma Trauma Soft, possible overlying ecchymosis Ultrasonography or contrast-enhanced CT Monitor if small; surgical drainage if large or expanding Pseudoaneurysm or arteriovenous Trauma with shearing forces Lateral; soft, pulsatile mass with a thrill or bruit CT with or without CT angiography Surgical evaluation for ligation fistula Reactive lymphadenopathy Bartonella henselae infection Kitten or flea exposure Isolated, mobile, fluctuant, tender, warm, Bartonella antibody titers Azithromycin (Zithromax) erythematous, > 2 cm near site of inoculation Cytomegalovirus URI symptoms Rubbery, mobile, cervical, and generalized; > 2 cm Cytomegalovirus titer Biopsy if no resolution after 8 weeks Epstein-Barr virus infection URI symptoms Rubbery, mobile, cervical, and generalized; > 2 cm Monospot, Epstein-Barr virus titer Biopsy if no resolution after 8 weeks HIV infection Blood/sexual contact Rubbery, mobile, cervical, and generalized HIV enzyme-linked immunoassay Highly active antiretroviral therapy Mycobacterium tuberculosis Travel to or immigration from an endemic Diffuse, bilateral lymph nodes (multiple, fixed, firm, Purified protein derivative test to rule out Antibiotics: rifampin and isoniazid; (extrapulmonary) area, homelessness, immunocompromise nontender) atypical mycobacteria infection; acid- add pyrazinamide and ethambutol fast bacilli culture or streptomycin in endemic areas; refer to a head and neck surgeon if persistent after initial diagnosis and treatment Staphylococcal or streptococcal Skin infections Mobile, fluctuant, tender, warm, erythematous Clinical Antibiotics infection Toxoplasmosis Cat feces exposure Rubbery, mobile, cervical, and generalized Toxoplasmosis antibody titer Supportive care or treat with pyrimethamine and sulfadiazine Viral URI URI symptoms Mobile, rubbery, bilateral; subsides in 3 to 6 weeks Clinical Biopsy if no resolution 3 to 6 weeks after symptom resolution Subacute (weeks to months) Cancer Hodgkin lymphoma 15 to 34 years of age and > 55 years, con- Painless, rapidly growing lymph node; rubbery, soft, Contrast-enhanced CT of the neck, Refer to oncology stitutional symptoms, later splenomegaly mobile chest, abdomen, pelvis; biopsy Human papillomavirus–related 35- to 55-year-old white men with a Rapidly enlarging, lateral, cystic lymph nodes; Nasal endoscopy, laryngoscopy, 2-week trial of antibiotics; refer for squamous cell carcinoma history of smoking, heavy alcohol use, persistent cervical nodal hypertrophy; palatine bronchoscopy with biopsies biopsy if no resolution and multiple sex partners (especially or lingual tonsillar asymmetry; dysphagia; voice involving orogenital contact) changes; pharyngeal bleeding Metastatic cancer History of melanoma or lung, breast, Matted, firm, fixed lymph nodes Contrast-enhanced CT of the neck, Refer to oncology colon, genitourinary cancer thorax, abdomen, pelvis Non-Hodgkin lymphoma Older persons Painless, rapidly growing lymph node; rubbery, soft, Contrast-enhanced CT of the neck, Refer to oncology mobile; may involve the tonsillar ring in the pharynx chest, abdomen, pelvis; biopsy Parotid tumors Asymptomatic Slow-growing, unilateral, mobile, asymptomatic; Contrast-enhanced CT and/or FNAB Refer to ENT for excisional biopsy cranial nerve (often VII [facial]) involved if malignant Upper aerodigestive tract Male sex; use of tobacco, alcohol, betel nut Nonhealing ulcers, dysarthria, dysphagia, Nasal endoscopy, laryngoscopy, 2-week trial of antibiotics; refer for squamous cell carcinoma odynophagia, loose or misaligned teeth, globus, bronchoscopy with biopsies biopsy if no resolution hoarseness, hemoptysis, oropharyngeal paresthesias Chronic sialadenitis Mild to severe pain, often after meals Firm gland CT Sialagogues, gentle massage, refer to ENT Idiopathic diseases Castleman disease (angiofollicular Constitutional symptoms Solitary lymph node Contrast-enhanced CT (shows no Refer to hematology lymphoproliferative disease) enhancement, unlike lymphoma); FNAB Kikuchi disease (histiocytic Lymphadenopathy, fever, leukopenia Posterior lymphadenopathy resolves in 3 months FNAB Refer to hematology necrotizing lymphadenitis) Kimura disease Endemic in Asia; painless subcutaneous Submandibular triangle, orbital, epicranial, Eosinophilia, elevated immunoglobulin E Refer to hematology mass, eosinophilia periauricular; nontender, ill-defined level, biopsy Rosai-Dorfman disease Occasional fever in healthy young adults Matted lymphadenopathy Elevated erythrocyte sedimentation rate, Refer to hematology polyclonal hypergammaglobulinemia continues

CHF = congestive heart failure; CT = computed tomography; ENT = ear, nose, throat; FNAB = fine-needle aspiration biopsy; FT4 = free thyroxine; HIV = human immunodeficiency virus; TSH = thyroid-stimulating hormone; URI = upper respiratory infection.

700 American Family Physician www.aafp.org/afp Volume 91, Number 10 ◆ May 15, 2015 Neck Masses Table 2. Differential Diagnosis of Neck Masses in Adults

Condition History/risk factors Physical findings Diagnosis Management

Acute or flea transmitsB. henselae, producing a Acute sialadenitis Older, debilitated persons with dehydration Rapid or gradual onset of pain and swelling; local Contrast-enhanced CT Sialagogues, gentle massage; regional lymphadenopathy, usually near the or recent dental procedures edema, erythema, tenderness, or fluctuance abscess, express by compressing 1,2 consistent with an abscess the gland site of inoculation. Hematoma Trauma Soft, possible overlying ecchymosis Ultrasonography or contrast-enhanced CT Monitor if small; surgical drainage if The extrapulmonary form of Mycobacte- large or expanding rium tuberculosis infection causes a cervi- Pseudoaneurysm or arteriovenous Trauma with shearing forces Lateral; soft, pulsatile mass with a thrill or bruit CT with or without CT angiography Surgical evaluation for ligation cal lymphadenopathy. The diffuse, bilateral fistula lymph nodes are characteristically multiple, Reactive lymphadenopathy fixed, firm, nontender masses located in the Bartonella henselae infection Kitten or flea exposure Isolated, mobile, fluctuant, tender, warm, Bartonella antibody titers Azithromycin (Zithromax) posterior triangle/cervical chain.1 Suspicion erythematous, > 2 cm near site of inoculation Cytomegalovirus URI symptoms Rubbery, mobile, cervical, and generalized; > 2 cm Cytomegalovirus titer Biopsy if no resolution after 8 weeks should be high in those who have recently Epstein-Barr virus infection URI symptoms Rubbery, mobile, cervical, and generalized; > 2 cm Monospot, Epstein-Barr virus titer Biopsy if no resolution after 8 weeks immigrated from or traveled to tuberculosis- HIV infection Blood/sexual contact Rubbery, mobile, cervical, and generalized HIV enzyme-linked immunoassay Highly active antiretroviral therapy endemic areas such as India, Southeast Asia, Mycobacterium tuberculosis Travel to or immigration from an endemic Diffuse, bilateral lymph nodes (multiple, fixed, firm, Purified protein derivative test to rule out Antibiotics: rifampin and isoniazid; or sub-Saharan Africa, and purified protein (extrapulmonary) area, homelessness, immunocompromise nontender) atypical mycobacteria infection; acid- add pyrazinamide and ethambutol derivative testing should be performed in fast bacilli culture or streptomycin in endemic areas; these patients. A negative result on purified refer to a head and neck surgeon protein derivative testing does not rule out if persistent after initial diagnosis and treatment atypical mycobacterial infections, which also Staphylococcal or streptococcal Skin infections Mobile, fluctuant, tender, warm, erythematous Clinical Antibiotics should be considered. A fine-needle aspira- infection tion biopsy (FNAB) of the lymph nodes or Toxoplasmosis Cat feces exposure Rubbery, mobile, cervical, and generalized Toxoplasmosis antibody titer Supportive care or treat with referral to a head and neck surgeon may be pyrimethamine and sulfadiazine warranted if the lymphadenopathy persists Viral URI URI symptoms Mobile, rubbery, bilateral; subsides in 3 to 6 weeks Clinical Biopsy if no resolution 3 to 6 weeks after initial diagnosis and treatment. after symptom resolution Inflammation of salivary glands (acute Subacute (weeks to months) sialadenitis) commonly occurs in older, Cancer Hodgkin lymphoma 15 to 34 years of age and > 55 years, con- Painless, rapidly growing lymph node; rubbery, soft, Contrast-enhanced CT of the neck, Refer to oncology debilitated persons in the setting of dehydra- 1 stitutional symptoms, later splenomegaly mobile chest, abdomen, pelvis; biopsy tion or recent dental procedures. Affected Human papillomavirus–related 35- to 55-year-old white men with a Rapidly enlarging, lateral, cystic lymph nodes; Nasal endoscopy, laryngoscopy, 2-week trial of antibiotics; refer for salivary glands cause rapid or gradual onset squamous cell carcinoma history of smoking, heavy alcohol use, persistent cervical nodal hypertrophy; palatine bronchoscopy with biopsies biopsy if no resolution of pain and swelling, possibly with local and multiple sex partners (especially or lingual tonsillar asymmetry; dysphagia; voice edema, erythema, and tenderness or fluctu- involving orogenital contact) changes; pharyngeal bleeding ance consistent with an abscess. Bimanual Metastatic cancer History of melanoma or lung, breast, Matted, firm, fixed lymph nodes Contrast-enhanced CT of the neck, Refer to oncology colon, genitourinary cancer thorax, abdomen, pelvis compression toward the duct opening may Non-Hodgkin lymphoma Older persons Painless, rapidly growing lymph node; rubbery, soft, Contrast-enhanced CT of the neck, Refer to oncology expel purulent discharge into the oral cavity. mobile; may involve the tonsillar ring in the pharynx chest, abdomen, pelvis; biopsy Neck CT with intravenous contrast media Parotid tumors Asymptomatic Slow-growing, unilateral, mobile, asymptomatic; Contrast-enhanced CT and/or FNAB Refer to ENT for excisional biopsy may be warranted to confirm this diagno- cranial nerve (often VII [facial]) involved if malignant sis and rule out other contributing etiolo- Upper aerodigestive tract Male sex; use of tobacco, alcohol, betel nut Nonhealing ulcers, dysarthria, dysphagia, Nasal endoscopy, laryngoscopy, 2-week trial of antibiotics; refer for gies such as a dental abscess or local tumor squamous cell carcinoma odynophagia, loose or misaligned teeth, globus, bronchoscopy with biopsies biopsy if no resolution 1 hoarseness, hemoptysis, oropharyngeal paresthesias compression. Chronic sialadenitis Mild to severe pain, often after meals Firm gland CT Sialagogues, gentle massage, refer SUBACUTE NECK MASSES to ENT Idiopathic diseases Subacute masses are noticed within weeks Castleman disease (angiofollicular Constitutional symptoms Solitary lymph node Contrast-enhanced CT (shows no Refer to hematology to months. Although these masses might lymphoproliferative disease) enhancement, unlike lymphoma); FNAB grow somewhat quickly, they often go Kikuchi disease (histiocytic Lymphadenopathy, fever, leukopenia Posterior lymphadenopathy resolves in 3 months FNAB Refer to hematology unnoticed at onset because of their asymp- necrotizing lymphadenitis) tomatic nature. A persistent asymptomatic Kimura disease Endemic in Asia; painless subcutaneous Submandibular triangle, orbital, epicranial, Eosinophilia, elevated immunoglobulin E Refer to hematology mass, eosinophilia periauricular; nontender, ill-defined level, biopsy neck mass in an adult should be considered 6 Rosai-Dorfman disease Occasional fever in healthy young adults Matted lymphadenopathy Elevated erythrocyte sedimentation rate, Refer to hematology malignant until proven otherwise. Because polyclonal hypergammaglobulinemia delayed diagnosis contributes to decreased continues survival in conditions such as laryngeal can-

CHF = congestive heart failure; CT = computed tomography; ENT = ear, nose, throat; FNAB = fine-needle aspiration biopsy; FT4 = free thyroxine; cer, it is paramount for family physicians to HIV = human immunodeficiency virus; TSH =thyroid-stimulating hormone; URI = upper respiratory infection. recognize common presentations of head and neck cancers.7,8

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Condition History/risk factors Physical findings Diagnosis Management

Subacute (weeks to months) continued Systemic diseases Amyloidosis Asymptomatic or associated CHF, Painless systemic lymphadenopathy FNAB or excisional biopsy Refer to hematology nephrotic syndrome, neuropathy Sarcoidosis 20- to 40-year-old black persons, variable Painless cervical, axillary, inguinal lymphadenopathy FNAB or excisional biopsy; chest Refer to pulmonary/rheumatology if presentation: persistent cough, skin radiography or CT necessary rash/patch, joint pain, arrhythmias Sjögren syndrome Xerophthalmia, xerostomia Parotid gland enlargement Antinuclear antibodies, SS-A and SS-B Symptomatic treatment with antibodies, FNAB sialagogues, frequent water intake Chronic (usually evident as long-standing) Carotid body tumors Flushing, palpitations, hypertension if Painless oropharyngeal or upper anterior triangle of CT, CT angiography (lyre sign); Refer to ENT hormonally active, dysphagia, dyspnea, the neck; pulsatile, compressible with a bruit or thrill, plasma and urine metanephrines, eustachian tube dysfunction mobile from medial to lateral direction catecholamines Congenital cysts Branchial cleft cyst Often diagnosed as a child; slow or rapidly Mandibular angle, anterior to sternocleidomastoid Ultrasonography Antibiotics; refer to ENT for excision growing after URI; acute or subacute after repeated infections Dermoid cyst Children and young adults Submental triangle; soft, doughy, painless CT Surgical excision Thyroglossal duct cyst Often diagnosed in childhood; slow Midline, adjacent to the hyoid bone; rises with CT (assures no thyroid cancer Antibiotics; refer to ENT for excision growing or may arise quickly after URI; deglutition calcifications) after repeated infections may present as acute or subacute Glomus vagale, glomus jugulare Flushing, palpitations, hypertension if Similar to carotid body tumors; ipsilateral tonsil may CT, plasma and urine metanephrines, Refer to ENT tumors hormonally active, dysphagia, dyspnea, pulsate and be deviated to midline catecholamines eustachian tube dysfunction Goiters (enlarged thyroid) Graves disease Hyperthyroid symptoms Associated exophthalmos, pretibial myxedema TSH-receptor antibody; diffuse uptake Radioactive iodine ablation, on scintigraphy thyroidectomy, methimazole (Tapazole) or propylthiouracil Hashimoto thyroiditis Hypothyroid symptoms Enlarged thyroid Thyroid peroxidase antibody Levothyroxine Iodine deficiency Reduced dietary iodine; exposure to Diffusely enlarged thyroid Dietary history Increase iodine/decrease thiocyanate thiocyanate (cassava, various vegetables) containing compounds Lithium use Bipolar disease Diffusely enlarged thyroid/rare nodular thyroid History of exposure Monitor thyroid function at 6 to 12 months, treat dysfunction, discontinuation not required Toxic multinodular Hyperthyroid symptoms Diffusely nodular Multiple foci on scintigraphy Radioactive iodine ablation, thyroidectomy, methimazole or propylthiouracil Laryngocele Repetitive nose blowing, coughing, or Midline, superior to thyroid cartilage; resonant, CT or laryngoscopy Refer to ENT blowing into a musical instrument intermittent, globus sensation Lipomas Age > 35 years, possible history of trauma Soft, mobile, discrete subcutaneous tumors CT Monitor or excise Liposarcoma Middle-aged Slowly enlarging, painless, nonulcerated or rapidly CT; excisional biopsy Excision growing and ulcerated Parathyroid cysts or cancer Hypercalcemia symptoms, family history of Anterior cervical triangle Serum calcium, parathyroid hormone Refer to endocrinology, ENT multiple endocrine neoplasia immunoassay Thyroid nodules

Cold thyroid nodule Usually asymptomatic Solitary nodules TSH, FT4, thyroid ultrasonography, FNAB Refer to endocrinology, repeat if > 1 cm ultrasonography in 6 to 18 months

Thyroid cancer Radiation, childhood lymphoma, family Solitary nodules TSH, FT4, thyroid ultrasonography, FNAB Refer for excision history, age < 45 years, hoarseness if > 1 cm

Toxic thyroid adenoma Hyperthyroid symptoms Solitary nodules TSH, FT4, thyroid ultrasonography, FNAB Radioactive iodine or thyroidectomy if > 1 cm

Squamous cell carcinomas of the upper aerodigestive of cervical lymphadenopathy of unknown origin.8 Com- tract are the most common primary neoplasms of the mon presenting symptoms include nonhealing ulcers, head and neck, and their metastases are often the source dysarthria, dysphagia, odynophagia, loose or misaligned

702 American Family Physician www.aafp.org/afp Volume 91, Number 10 ◆ May 15, 2015 Neck Masses Table 2. Differential Diagnosis of Neck Masses in Adults (continued)

Condition History/risk factors Physical findings Diagnosis Management

Subacute (weeks to months) continued any persistent cervical lymphadenopathy Systemic diseases or symptoms in the setting of risk factors, Amyloidosis Asymptomatic or associated CHF, Painless systemic lymphadenopathy FNAB or excisional biopsy Refer to hematology nephrotic syndrome, neuropathy nonresponse to antibiotics, or unclear eti- 7 Sarcoidosis 20- to 40-year-old black persons, variable Painless cervical, axillary, inguinal lymphadenopathy FNAB or excisional biopsy; chest Refer to pulmonary/rheumatology if ology warrants further investigation. Risk presentation: persistent cough, skin radiography or CT necessary factors for upper aerodigestive tract cancers rash/patch, joint pain, arrhythmias include male sex and use of alcohol, tobacco, Sjögren syndrome Xerophthalmia, xerostomia Parotid gland enlargement Antinuclear antibodies, SS-A and SS-B Symptomatic treatment with or betel nut (commonly chewed by South- antibodies, FNAB sialagogues, frequent water intake eastern Asians).8 Additional risk factors for Chronic (usually evident as long-standing) oropharyngeal cancer include a family his- Carotid body tumors Flushing, palpitations, hypertension if Painless oropharyngeal or upper anterior triangle of CT, CT angiography (lyre sign); Refer to ENT tory of squamous cell carcinoma of the head hormonally active, dysphagia, dyspnea, the neck; pulsatile, compressible with a bruit or thrill, plasma and urine metanephrines, 9 eustachian tube dysfunction mobile from medial to lateral direction catecholamines and neck and poor oral hygiene. Congenital cysts A subset of squamous cell carcinomas Branchial cleft cyst Often diagnosed as a child; slow or rapidly Mandibular angle, anterior to sternocleidomastoid Ultrasonography Antibiotics; refer to ENT for excision with increasing prevalence includes those growing after URI; acute or subacute after repeated infections related to human papillomavirus infection Dermoid cyst Children and young adults Submental triangle; soft, doughy, painless CT Surgical excision (especially high-risk human papillomavi- Thyroglossal duct cyst Often diagnosed in childhood; slow Midline, adjacent to the hyoid bone; rises with CT (assures no thyroid cancer Antibiotics; refer to ENT for excision rus 16).9,10 These lesions present with rapidly growing or may arise quickly after URI; deglutition calcifications) after repeated infections enlarging, lateral, cystic lymph nodes; per- may present as acute or subacute sistent cervical nodal hypertrophy; palatine Glomus vagale, glomus jugulare Flushing, palpitations, hypertension if Similar to carotid body tumors; ipsilateral tonsil may CT, plasma and urine metanephrines, Refer to ENT tumors hormonally active, dysphagia, dyspnea, pulsate and be deviated to midline catecholamines or lingual tonsillar asymmetry; dysphagia; eustachian tube dysfunction voice changes; or pharyngeal bleeding.10 The Goiters (enlarged thyroid) population most at risk is 35- to 55-year-old Graves disease Hyperthyroid symptoms Associated exophthalmos, pretibial myxedema TSH-receptor antibody; diffuse uptake Radioactive iodine ablation, white men with a history of smoking, heavy on scintigraphy thyroidectomy, methimazole alcohol use, and multiple sex partners (espe- (Tapazole) or propylthiouracil cially involving orogenital contact).9 Hashimoto thyroiditis Hypothyroid symptoms Enlarged thyroid Thyroid peroxidase antibody Levothyroxine Nearly 80% of salivary gland tumors Iodine deficiency Reduced dietary iodine; exposure to Diffusely enlarged thyroid Dietary history Increase iodine/decrease thiocyanate 1 thiocyanate (cassava, various vegetables) containing compounds are benign and arise in the parotid gland. Lithium use Bipolar disease Diffusely enlarged thyroid/rare nodular thyroid History of exposure Monitor thyroid function at 6 to These tumors are unilateral, asymptomatic, 12 months, treat dysfunction, slow-growing, mobile masses, in contrast to discontinuation not required malignant tumors, which may have rapid Toxic multinodular Hyperthyroid symptoms Diffusely nodular Multiple foci on scintigraphy Radioactive iodine ablation, growth, skin fixation, pain, or cranial nerve thyroidectomy, methimazole or propylthiouracil involvement (especially cranial nerve VII 1,11 Laryngocele Repetitive nose blowing, coughing, or Midline, superior to thyroid cartilage; resonant, CT or laryngoscopy Refer to ENT [facial]). An intraparotid or isolated pre- blowing into a musical instrument intermittent, globus sensation auricular lymph node is another diagnostic Lipomas Age > 35 years, possible history of trauma Soft, mobile, discrete subcutaneous tumors CT Monitor or excise possibility. Excisional biopsy is the preferred Liposarcoma Middle-aged Slowly enlarging, painless, nonulcerated or rapidly CT; excisional biopsy Excision diagnostic approach for these tumors fol- growing and ulcerated lowing review of contrast-enhanced CT or Parathyroid cysts or cancer Hypercalcemia symptoms, family history of Anterior cervical triangle Serum calcium, parathyroid hormone Refer to endocrinology, ENT FNAB results.11 Persistent glandular enlarge- multiple endocrine neoplasia immunoassay ment with symptoms of xerophthalmia and Thyroid nodules xerostomia may point to Sjögren syndrome, Cold thyroid nodule Usually asymptomatic Solitary nodules TSH, FT4, thyroid ultrasonography, FNAB Refer to endocrinology, repeat if > 1 cm ultrasonography in 6 to 18 months whereas a hypertrophied, fibrotic gland may suggest chronic sialadenitis caused by a duct Thyroid cancer Radiation, childhood lymphoma, family Solitary nodules TSH, FT4, thyroid ultrasonography, FNAB Refer for excision 12 history, age < 45 years, hoarseness if > 1 cm stone (sialolith) or stenosis.

Toxic thyroid adenoma Hyperthyroid symptoms Solitary nodules TSH, FT4, thyroid ultrasonography, FNAB Radioactive iodine or thyroidectomy Skin cancers, especially melanoma, also if > 1 cm metastasize to local lymph nodes. When a primary head and neck cancer is not evident CHF = congestive heart failure; CT = computed tomography; ENT = ear, nose, throat; FNAB = fine-needle aspiration biopsy; FT4 = free thyroxine; HIV = human immunodeficiency virus; TSH = thyroid-stimulating hormone; URI = upper respiratory infection. to explain regional lymphadenopathy, physicians should search mucosal areas (nose, paranasal sinuses, oral cavity, and nasophar- teeth, globus, hoarseness, hemoptysis, and oropharyn- ynx) for melanoma.7 Rarely, metastases from basal cell geal paresthesias.8 Lymph nodes associated with malig- and squamous cell carcinoma lead to lymphadenopathy.7 nancy are usually firm, fixed, and matted. However, Constitutional symptoms of fever, chills, night sweats,

May 15, 2015 ◆ Volume 91, Number 10 www.aafp.org/afp American Family Physician 703 Neck Masses

and weight loss may point to distant metastases. When pathogens using first-generation cephalosporins, amoxi- metastases manifest as supraclavicular lymphadenopa- cillin/clavulanate, or clindamycin is appropriate in the thy, FNAB reveals a malignancy in more than one-half initial management of a presumed congenital cyst infec- of cases, with age older than 40 years being the major tion.2 Excision is the definitive treatment for these cysts predictor of malignancy.13 The most common primary and tracts and may be considered after repeat infections. malignancy sites that produce cervical lymphadenopa- Thyroid pathology accounts for most chronic ante- thy include the lungs, breasts, lymphomas, uterine cer- rior neck masses, and these masses are often insidious. vix, gastroesophageal area, ovaries, and pancreas.13 A diffusely enlarged thyroid gland may be due to Graves The neck is a common area for lymphoma to present as disease, Hashimoto thyroiditis, or iodine deficiency, but a painless lymph node that may grow rapidly, and subse- can be caused by goitrogenic exposures such as lithium.6 quently become painful. Early constitutional symptoms Thyroid nodules are common, with an estimated preva- often precede development of diffuse lymphadenopa- lence of 4% to 7% in adults; only 5% of these are malig- thy and splenomegaly. In comparison to lymph nodes nant.1 Physical examination is unreliable in detecting associated with metastatic disease characterized above, nodules smaller than 1 cm.6 A review of thyroid nodules those associated with lymphoma are usually rubbery, was recently published in American Family Physician.17 soft, and mobile.11 Hodgkin lymphoma has a bimodal A laryngocele may also develop in the anterior trian- age distribution (15 to 34 years and older than 55 years)14 gle as a traumatic neck mass created by chronic cough- and rarely presents extranodally, whereas non-Hodgkin ing or repetitive blowing (e.g., from nose blowing or lymphoma is more common in older adults and is likely blowing into a musical instrument), which causes her- to present extranodally in the tonsillar ring located in niation of the laryngeal diverticulum through the lat- the pharynx.1 Contrast-enhanced CT of the neck, chest, eral thyrohyoid membrane. Increased airway pressure abdomen, and pelvis helps stage the lymphoma and pro- causes an intermittent air-filled swelling of the neck vides possible biopsy sites.1 that is resonant to percussion. The swelling can poten- Rheumatologic diseases account for 3% of disorders tially become a laryngopyocele, which can obstruct the presenting with enlarged salivary glands and 4% of those airway.18 Contrast-enhanced CT or laryngoscopy can presenting with cervical lymphadenopathy.15 The rheu- confirm a laryngocele or laryngopyocele, which requires matic entities that most commonly cause salivary gland surgical excision.19 or cervical node enlargement include Sjögren syndrome Paragangliomas are neuroendocrine tumors involv- and sarcoidosis.15 ing the chemoreceptors of the carotid body, jugular vein, or vagus nerve in the lateral neck. Carotid body CHRONIC NECK MASSES and glomus jugulare tumors commonly present in the Congenital masses are more common in childhood but upper anterior triangle near the carotid bifurcation as can grow slowly, persisting into adulthood. Thyroglossal a pulsatile, compressible mass with a bruit or thrill.11 duct cysts, the most common congenital cyst, are mid- Although mobile from medial to lateral direction, these line, adjacent to the hyoid bone, and rise with degluti- tumors are fixed in the cranial to caudal plane. They are tion. These cysts are normally recognized by five years of usually asymptomatic, but when functional they cause age, with 60% diagnosed by 20 years of age. However, in flushing, palpitations, and hypertension as a result one autopsy series, thyroglossal duct cysts were present of catecholamine release. Diagnostic testing includes in 7% of adults, although most were not clinically appar- plasma or 24-hour urine collection for catecholamines ent. Branchial cleft cysts usually present anterior to the and metanephrines.1 sternocleidomastoid muscle, and represent 22% of con- Lipomas are common soft, mobile, discrete, subcu- genital neck masses.16 Patients may describe a discrete, taneous adipose tumors. They usually appear on the tender, erythematous mass, which often coincides with trunk and extremities but may be found anywhere on recurrent upper respiratory symptoms. Dermoid cysts, the neck.1 They commonly occur in patients older than typically located in the submental triangle, are soft, 35 years or posttraumatically.11 doughy, painless masses that enlarge with entrapment of epithelium in deeper tissue and are less prevalent than Diagnostic Approach thyroglossal or branchial cleft cysts.16 The initial diagnostic test of choice in an adult with a Similar to treatment for bacterial lymphadenopathy persistent neck mass is contrast-enhanced CT, 20 which discussed earlier, empiric antibiotic coverage for staph- provides valuable initial information regarding the ylococcal, streptococcal, and gram-negative anaerobe size, extent, location, and content or consistency of the

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mass. Additionally, contrast media may help identify malignant lymph nodes that are Table 3. Preferred Imaging Modalities for Neck Masses not enlarged and distinguish vessels from or Adenopathy in Adults lymph nodes.20 Table 3 shows the preferred imaging Scenario Recommended test Comments modalities for neck masses and lymphade- Nonpulsatile solitary mass Contrast-enhanced CT — nopathy according to American College of or multiple neck masses 20 Radiology Appropriateness Criteria. Of Pulsatile neck mass Contrast-enhanced CT May be performed note, contrast can obscure visualization of and contrast-enhanced at the same time sialoliths, and non–contrast-enhanced CT CT angiography is recommended for suspected swollen sali- Patient with a neck mass Contrast-enhanced CT Positron emission 20 and history of cancer or CT with positron tomography is vary glands due to sialolith obstruction. treatment emission tomography superior in this Iodine-based contrast media should be subset of patients avoided in patients with a history of thyroid disease or when metastatic thyroid cancer CT = computed tomography. is a concern.20 Although positron emission Information from reference 20. tomography (PET) with CT can be used to distinguish between malignant and unaf- fected tissues, its use in the preliminary diagnosis is not as effective and should be limited SORT: KEY RECOMMENDATIONS FOR PRACTICE 20 to definitive management of a malignancy. Evidence When ultrasonography is indicated Clinical recommendation rating References instead of or in addition to CT, it is useful to A persistent neck mass in an adult older than C 1, 6, 8, 10 distinguish cystic from solid lesions, detect 40 years should prompt a search for a malignant nodal size, and differentiate high-flow from source. low-flow vascular malformations.20 Ultra- Contrast-enhanced computed tomography is the C 20 sonography may also be helpful in guiding initial diagnostic test of choice in an adult with a persistent neck mass. FNAB of nonpalpable or small superficial 20 Fine-needle aspiration biopsy is an effective tool C 7, 13, 14, 21 lesions. Although CT and ultrasonography to determine the etiology of a neck mass. share similar capabilities, ultrasonography is often preferred initially in younger patient A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited- populations to reduce radiation exposure. quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence It may also be preferred to avoid contrast rating system, go to http://www.aafp.org/afpsort. media–induced nephropathy in patients with underlying renal disease. CT angiography is recommended for evaluating a should never be performed on a pulsatile mass or a mass pulsatile neck mass and is preferred over magnetic that appears to be vascular in origin. resonance angiography (MRA).20 CT, MRA, and PET Patients with suspected infectious and inflammatory with CT are all useful in the evaluation of patients after masses should be tested for HIV, Epstein-Barr virus, cancer treatment. PET with CT appears to be superior cytomegalovirus, toxoplasmosis, tuberculosis, and to MRA or CT for detecting recurrent tumors, but it B. henselae, when clinically appropriate. Endocrine should be considered only on request from the surgical masses can be assessed further with blood work, includ- oncology team.20 ing thyroid and parathyroid hormone panels. Visualiza- The clinician may proceed with FNAB, if indicated, tion with laryngoscopy, bronchoscopy, or esophagoscopy once appropriate imaging has ruled out involvement of may have an important role in further evaluation of neck underlying vital structures. FNAB can provide further masses that are not adequately characterized by ultraso- information through cytology, Gram stain, and bacte- nography, contrast-enhanced CT, or FNAB. rial and acid-fast bacilli cultures while avoiding com- plications of open biopsy. The sensitivity of FNAB for Data Sources: A PubMed search was completed in Clinical Queries using the key terms neck mass, diagnosis, and adult. The search detecting a malignancy ranges from 77% to 97%, and included meta-analyses, randomized controlled trials, clinical trials, the specificity ranges from 93% to 100%.7,13,14,21 FNAB and reviews. We also searched the Agency for Healthcare Research and

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Quality evidence reports, Clinical Evidence, the Cochrane database, 6. Miller MC. The patient with a thyroid nodule. Med Clin North Am. Essential Evidence Plus, the Institute for Clinical Systems Improvement, 2010;94(5):1003-1015. the National Guideline Clearinghouse database, Family Physicians Inqui- 7. Lee J, Fernandes R. Neck masses: evaluation and diagnostic approach. ries Network, and the TRIP database. Search dates: August 30, 2014, Oral Maxillofac Surg Clin North Am. 2008;20(3): 321-337. and January 19, 2015. 8. Crozier E, Sumer BD. Head and neck cancer. Med Clin North Am. 2010; 94(5):1031-1046 . 9. D’Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human The Authors papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356(19): JAMES HAYNES, MD, is an assistant professor in and program director of 1944-1956. the Department of Family Medicine at the University of Tennessee Health 10. Koch WM. Clinical features of HPV-related head and neck squamous Science Center College of Medicine in Chattanooga. cell carcinoma: presentation and work-up. Otolaryngol Clin North Am. 2012;45(4):779-793. KELLY R. ARNOLD, MD, is an assistant professor in the Department of 11. McGuirt WF. The neck mass. Med Clin North Am. 1999;83(1):219-234. Family Medicine at the University of Tennessee Health Science Center Col- 12. Brown JR, Skarin AT. Clinical mimics of lymphoma. Oncologist. 2004; lege of Medicine. 9(4):406-416. CHRISTINA AGUIRRE-OSKINS, MD, is a resident in the Department of Fam- 13. Ellison E, LaPuerta P, Martin SE. Supraclavicular masses: results of a ily Medicine at the University of Tennessee Health Science Center College series of 309 cases biopsied by fine needle aspiration. Head Neck. of Medicine. 1999;21(3): 239-246 . 14. Glass C. Role of the primary care physician in Hodgkin lymphoma. Am SATHISH CHANDRA, MD, is a resident in the Department of Family Fam Physician. 2008;78(5):615-622. Medicine at the University of Tennessee Health Science Center College 15. Knopf A, Bas M, Chaker A, et al. Rheumatic disorders affecting the of Medicine. head and neck: underestimated diseases. Rheumatology (Oxford). Address correspondence to James Haynes, MD, University of Tennes- 2011;50 (11):2029-2034. see Health Science Center, 1100 E. Third St., Chattanooga, TN 37403 16. Al-Khateeb TH, Al Zoubi F. Congenital neck masses: a descriptive ret- (e-mail: [email protected]). Reprints are not available from rospective study of 252 cases. J Oral Maxillofac Surg. 2007;65(11): the authors. 2242-2247. 17. Knox MA. Thyroid nodules. Am Fam Physician. 2013;88(3):193-196. 18. Vasileiadis I, Kapetanakis S, Petousis A, Stavrianaki A, Fiska A, Karakos- REFERENCES tas E. Internal laryngopyocele as a cause of acute airway obstruction: an extremely rare case and review of the literature. Acta Otorhinolaryngol 1. Rosenberg TL, Brown JJ, Jefferson GD. Evaluating the adult patient with Ital. 2012;32(1):58-62. a neck mass. Med Clin North Am. 2010;94(5):1017-1029. 19. Goffart Y, Hamoir M, Deron P, Claes J, Remacle M. Management of 2. Al-Dajani N, Wootton SH. Cervical lymphadenitis, suppurative parotitis, neck masses in adults. B-ENT. 2005;(suppl 1):133-140. thyroiditis, and infected cysts. Infect Dis Clin North Am. 2007;21(2):523- 541, viii. 20. Wippold FJ II, Cornelius RS, Berger KL, et al.; Expert Panel on Neurologic Imaging. American College of Radiology ACR Appropriateness Crite- 3. Mäkelä MJ, Puhakka T, Ruuskanen O, et al. Viruses and bacteria in the ria. 2012. http://www.acr.org/~/media/ACR/Documents/AppCriteria/ etiology of the common cold. J Clin Microbiol. 1998;36(2):539-542. Diagnostic/NeckMassAdenopathy.pdf. Accessed February 10, 2014. 4. Heikkinen T, Järvinen A. The common cold. Lancet. 2003;361(9351): 21. Smallman LA, Young JA, Oates J, Proops DW, Johnson AP. Fine needle 51-59. aspiration cytology in the management ENT of patients. J Laryngol Otol. 5. National Institute for Health and Care Excellence. Referral guidelines for 1988;102(10):909-913. suspected cancer. NICE clinical guideline 27. April 2011. http://www. nice.org.uk/guidance/cg27/resources/guidance-referral-guidelines-for- suspected-cancer-pdf. Accessed September 13, 2014.

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