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Appendix 1. Differential Diagnosis with Comprehensive ancillary testing options for evaluation of a non-malignant adult neck massPresentationEtiology & LocationDiseaseHistory/ SymptomsPhysical findingsDiagnostic testingAcuteINFECTIOUSAll AreasViralViral URIURI symptoms, neck mass developed at similar timeBilateral lymphadenopathy, mobileRe-exam after URI resolution show improvement or absence of lymphadenopathyCytomegalovirusURI symptomsBilateral cervical lymphadenopathy, systemic lymphadenopathy, mobile, often >2cmCMV titer, WBCEpstein-Barr virusURI symptomsBilateral cervical lymphadenopathy, often >2cm, may have generalized lymphadenopathyEpstein-Barr IgM, , WBCMumpsNonspecific? viral prodomeLow grade fever, morbilliform rash, swelling or tenderness of salivary glands, orchitisClinical diagnosis,? but may isolate virus from nasopharyngeal swab or urineHIV infectionBlood exposure, sexual exposureBilateral cervical lymphadenopathy, systemic lymphadenopathy, mobileHIV enzyme-linked assay, CT neck with contrastAll AreasBacterialBartonellaExposure to cats, prior scratch or bite. Immunocompetent adultsIsolated mobile tender erythematous, 1-5cm mass near scratch. May be fluctuant.Bartonella antibody titers, WBC, CT neck with contrastActinomycesRecent dental procedure or manipulation, poor dentitionSubmandibular or mandibular border mass, non-tender, fluctuant, sinus tract may be present, may have local cervical lymphadenopathyFNA and culture (granulomas with sulfur granules), CT neck with contrast, WBCStaphylococcus or streptococcus infectionSkin infectionSore throatBilateral (if sore throat) or unilateral on side of skin infection, mobile, tender. May be erythematous, and fluctuantExamine skin and throat for sign of infection,Rapid antigen detection test for streptococcus tonsillitisWBCCT neck with contrast if fluctuantDiphtheriaHistory of exposure, URI symptomsPseudomembrane in throat, bilateral cervical lymphadenopathy >2cm and cervical edema (“bull’s neck”)Pseudomembrane culture- club shaped nonencapsulated nonmotile bacilli clusters, PCR for DNA encoding diphtheria toxin TularemiaHistory of rabbit or rodent exposure, tick bite, ingestion of infected water or food, hunting or butchering, abrupt onset of fever and chills, headache, systemic symptoms, rashMacular rash +/_ pustules, tender bilateral cervical lymphadenopathy, ulceration at entry site, may have cough or unilateral conjunctivitisWBC, microagglutination, ELIZA serology, PCR, gram stain (gram-negative coccobaccilusBrucellosisIngestion of infected food products: unpasteurized dairy products or undercooked meats, exposure to an endemic disease regionBilateral cervical and systemic lymphadenopathy, tenderness on palpation of spine or peripheral nerves, joint tendernessLiver enzymes, Brucella microagglutination test, WBCAll AreasFungalHistoplasmosisAsymptomatic, pneumonia symptoms, Exposure to area where histoplasmosis is endemic: Midwestern and Eastern United States, Central America and South America, Africa, Asia, and AustraliaShortness of breath, wheezing, arthritisUrine and serum antigen, blood culture, Chest CT with contrastAll AreasSpirochetalSyphilisSexual contact, IV drug useGeneralized unilateral or bilateral non-tender lymphadenopathy, disseminated rash, chancresRapid plasma reagin (RPR), venereal disease research laboratory (VDRL), syphilis recombinant antigen testLyme Tick exposure in Lyme endemic area, fatigue, flu-like symptoms, muscle sorenessBull’s eye-rash, bilateral cervical and generalized lymphadenopathyWBC, Lyme western blot or enzyme-linked immunoassayMycobacterialAnterior TriangleNon-tuberculosis atypical mycobacteriumSystemic symptoms, cough, more common in immunocompromisedIsolated submental or submandibular lymphadenopathy- fixed, rubbery, may have draining sinus or fluctuance. Tissue culture, CT chest with contrastPosterior TriangleMycobacterium tuberculosisTravel to endemic areas, immunocompromised, homeless, HIV positiveBilateral lymphadenopathy with multiple, matted, fixed, rubbery, may have draining sinus or fluctuance.Mantoux tuberculin skin test (PPD), Interferon gamma release assay, acid fast bacilli sputum cultureProtozoalPosterior TriangleToxoplasmosisExposure to cat fecesSingle enlarge lymph node in posterior triangle, mobileToxoplasmosis antibody titerAll Areas (localized to bite)LeishmaniasisSandfly bites weeks to months ago, painless, exposure in developing tropical and subtropical countriesCrusted ulcers, nontender nonulcerated papules, internal nasal destruction,Localized lymphadenopathyPCR, anti-K39 antigenTRAUMATICAll AreasHematomaTrauma, important to determine timeframeRecent hematoma:Soft, may have ecchymosis, neck edema, tender, may expandOrganized hematoma: may have resolving ecchymosis and edema, firm due to fibrosisUltrasoundAll AreasPseudoaneurysmTrauma, often shearing or penetratingPulsatile mass with bruit or thrill on auscultationCT angiogram neckOTHERAnterior triangle (parotid or submental)Acute sialadenitisDehydration, rapid or gradual onset, signs of infection, often in elderly, those with poor dental hygiene, recent surgery, debilitated patientsPain, local edema, erythema, tenderness. May worsen with salivation. Systemic signs of dehydration. Bimanual exam may express purulent or milky saliva. Poor dentitionWBCCulture of purulent salivaCT neck with contrast if abscess suspected Sub-acuteSYSTEMIC/AUTOIMMUNE/ SYSTEMICAll AreasAmyloidosisMay be asymptomatic, symmetric distal neuropathy, may have congestive heart failure or kidney failureMay see a localized, enlarged, firm , mass in any region, but most likely larynx, tongue, or thyroid, non-tenderWBC, Biopsy to evaluate for amyloid deposits (congo red stain)CT neck with contrastAll AreasSarcoidosisMay be asymptomatic or have variable symptoms: fatigue, cough, dry eyes, rash, joint pain, arrhythmia, more common in black patientsBilateral cervical lymphadenopathy, axilla and inguinal region lymphadenopathy, non-tender, parotid enlargementWBC, FNA/Biopsy (non-caseating granulomas) and Chest x-ray or Chest CT, Angiotensin- converting EnzymeAnterior TriangleSjogrensXerostomia, eye and/or skin dryness, often in women, may have dysphasia, epistaxisParotid gland and submandibular gland enlarged, tongue fissuresWBC, ANA, SS-A & SS-B antibodies, salivary gland biopsyAll AreasStill’s Daily spiking fevers, joint pain, sore throat, abdominal painSalmon colored non-pruritic rash, bilateral cervical lymphadenopathyMust rule out other diagnosis, WBC and LFTS (elevated)Rheumatoid factor and ANA (both negative)CRP and ESR (elevated)CT neck and abdomen with contrastAll areasSystemic Lupus ErythematosusFever, joint pain, fatigue, weight changeMalar rash, oral ulcers, discoid rash, arthritis of proximal interphalangeal and metacarpophalangeal jointsInquire about drug use (procainamide, hydralazine, isoniazid), EKG, ANA, antiphospholipid antibodies, anti-dsDNA antibodies, WBC, Plts, Urine analysisIDIOPATHICAnterior TriangleCastlemanSystemic symptoms (fever chills weight loss, etc), slow growing massSingle lymph node enlargementWBC, Rule out other causes, IL-6 level, lymph node biopsy and human herpesvirus-8 testing, CT neck with contrast – show enhancement of mass, may show mediastinum lymph node hypertrophy, FNAAll areasKikuchiFeverBilateral posterior lymphadenopathyWBCAnterior TriangleKimuraVisit to Asia ( where endemic), usually in men, pruritusPainless subcutaneous mass, poorly circumscribed, often preauricular, submandibular and may involve epicrainial and orbital regions of head.Eosinophil count, IgE count, CT neck with contrast is non-specific but may show slightly enlarged major salivary glands(rule out tuberculosis, lymphoma)All AreasRosai-DorfmanIntermittent fevers, systemic symptomsMultiple matted lymph nodes >2cm, nontender, lymphadenopathy of axilla and groinESRImmunoglobulin levelsWBCOTHERAnterior TriangleChronic sialadenitis/ sialolithiasisPrior initial episodes of acute sialadenitis and/or sialolithiasis. History of poor hydration, intake of primarily carbonated beverages.Pain, local edema, erythema, tenderness. May worsen with salivation. Systemic signs of dehydration. Bimanual exam may express purulent/milky saliva or no saliva in complete obstruction. Palpation of salivary ducts may reveal firm scar or a palpable stone. Poor dentitionCT neck with contrast- stone may or may not be radioopaqueChronicCONGENITALAnterior TriangleBranchial cleft cystsSlow growth or rapid progression after URI, may have history of drainage, may fluctuate in sizeMass anterior to mastoid or near angle of mandible, may have associated skin pit or opening, can be erythematous, tenderCan be seen on CT with contrast when enlargedMidline/ Anterior NeckDermoid/ Epidermoid cystsOften present since birth, progressive enlargement (accumulate sebaceous contents over time)Soft, non-tender, doughy, superficial, submental triangle or floor of mouthCT neck with contrastAnterior TrianglePlunging RanulaProgressively enlarging. Wax and wane in size.Neck mass presenting in association with sublingual gland or submandibular triangle, soft, compressibleCT neck with contrast (plunges through mylohyoid muscle)Midline/ Anterior NeckThyroglossal duct cystPresent in childhood or as young adult. Slow growing, may change rapidly after URIMidline mass, often near level of hyoid or suprahyoid, elevates with swallowing or tongue protrusion, thyroid gland may be absentCT neck with contrast or Ultrasound, confirm presence of normal thyroid gland on imagingPosterior TriangleLymphatic malformationsPresent in childhood or as young adult, enlarges proportionally with the patient; rapid enlargement after URIPosterior triangle, soft compressible massCT neck with contrast (cyst-like structures)All AreasHemangiomaHemangiomas: present at birth- rapidly proliferate in the first years of life and slowly involuteHemangiomas: red to blue in color, may have associated telangiectasias, scarring, atrophic skin, soft compressible, refill after compressionDiagnosis if often clinical but angiography can provide diagnosis.ENDOCRINEAnterior TriangleThyroid noduleAsymptomaticPalpable nodule in thyroid, often non-tenderTSH, ultrasound, FNA for > 1cmAnterior TriangleGraves diseaseFatigue, hyperthyroid symptomsExophthalmous, tachycardia, palpable goiter, non- pitting edemaTSH, Free T4, thyrotropin-receptor antibodies, possible nuclear scintigraphyAnterior TriangleHashimoto thyroiditisHypothyroid symptoms, more often womenFirm, enlarged thyroid, nontenderTSH, free T4, Thyroid peroxidase antibodyAnterior TriangleToxic multinodular goiterHyperthyroid symptomsIrregular nodular thyroid, tachycardia, brisk tendon reflexesTSH, Free T4, nuclear scintigraphyAnterior TriangleParathyroid cysts/adenomaHypercalcemia symptoms, Family history of multiple endocrine neoplasia, often in womenAnterior cervical mass, often near thyroid gland, may be cystic, voice changes can occur, muscular weaknessCalcium level, Parathyroid hormone level, ultrasound, sestamibi parathyroid scintigraphy, OTHERAnterior TriangleParagangliomas: vagale, jugulare, carotid bodyPalpations, flushing, history of hypertension, dyspnea, dysphasiaNon tender anterior cervical neck mass, pulsatile, compressible, thrill or bruit on auscultation, Carotid body tumors: mobile laterally onlyCT angiogram, serum plasma and urine metanepharines and catacholaminesAnterior TriangleSchwannomaSlow insidious growth, may have neurologic defecits such as eyelid drooping, hoarseness, dysphasiaOften arise from vagus nerve or superior cervical sympathetic chain, firm, well defined mass.Superior cervical sympathetic chain: Horner’s syndromeVagus: hoarseness, aspirationMRI/MRAAll AreasLipomaHistory of trauma, prior lipomasSoft, mobile, subcutaneous mass, often minimally tenderCT neck with contrastMidline/ Anterior Neck&Anterior TriangleLaryngoceleHistory of straining, coughing, nose-blowing, or playing instrument requiring blowing against pressure (trumpet), globus sensationSoft compressible mass, often may be lateral or midline above thyroid cartilageCT neck, laryngoscopyAnterior TriangleDrug Reactions (phenytoin, lithium, etc)Drug use historyThyroid enlargementTSH, Free T4CT: COMPUTED TOMOGRAPHY, URI: UPPER RESPIRATORY INFECTION, HIV: HUMAN IMMUNODEFICIENCY VIRUS, PCR: POLYMERASE CHAIN REACTION, TSH: THYROID-STIMULATING HORMONE, FREE T4: FREE THYROXINEFootnote: Tests from this list should be chosen selectively, based on clinical suspicion. Ancillary testing should not delay work up of a possible malignancy. ................
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