AAO-HNSF Clinical Practice Guideline: Evaluation of the Neck Mass in Adults

1. AAO-HNSF Clinical Practice Guideline: Evaluation of the Neck Mass in Adults (Publication Date: September 10, 2017)

2. Disclaimer The clinical practice guideline is not intended as the sole source of guidance in evaluating patients with neck mass. Rather, it is designed to assist clinicians by providing an evidence-based framework for decision-making strategies. The guideline is not intended to replace clinical judgment or establish a protocol for all individuals with this condition and may not provide the only appropriate approach to diagnosing and managing this program of care. As medical knowledge expands and technology advances, clinical indicators and guidelines are promoted as conditional and provisional proposals of what is recommended under specific conditions but are not absolute. Guidelines are not mandates. These do not and should not purport to be a legal standard of care. The responsible physician, in light of all circumstances presented by the individual patient, must determine the appropriate treatment. Adherence to these guidelines will not ensure successful patient outcomes in every situation. The American Academy of Otolaryngology-Head and Neck Surgery Foundation emphasizes that these clinical guidelines should not be deemed to include all proper treatment decisions or methods of care or to exclude other treatment decisions or methods of care reasonably directed to obtaining the same results.

3. Burden of Neck Mass • About half of the 62,000 cases of head and neck cancer diagnosed in 2016 will present with a neck mass, suggesting 30,000 patients will present with a malignant neck mass (www.cancer.org) • The fact that about half of all adult neck masses are malignant suggests an additional 30,000 patients will present with a persistent neck mass of benign etiology • HNSCC has a worldwide annual incidence of 550,000 cases, representing 5% of all newly diagnosed cancers (Torre, 2015) • Patients with HPV-positive HNSCC commonly present with a neck mass as the only symptom of concern (McIlwain, 2014; Garden, 2013) • An adult patient with a neck mass who experiences delayed diagnosis of a neck mass may suffer progression of disease with increased mortality and poorer functional outcome (Seoane, 2012). • Among patients with HNSCC who present with neck mass, diagnostic delay is common. Reported delays of 3-6 months (Bruun,1976; McGurk, 2005; Smith, 2016; Brouha, 2007) are particularly disappointing knowing that delays as short as 2 months are associated with cancer recurrence and mortality (Koivunen, 2001; Teppo, 2003).

4. Clinical Practice Guideline Development Manual: Third EditionRosenfeld, Shiffman, and Robertson • Pragmatic, transparent approach to creating guidelines for performance assessment • Evidence-based, multidisciplinary process leading to publication in 12-18 months • Emphasizes a focused set of key action statements to promote quality improvement • Uses action statement profiles to summarize decisions in recommendations OtolaryngolHead Neck Surg 2013; 148(Suppl):S1-55

5. Clinical Practice Guidelines (CPG) Goals • Focus on quality improvement opportunities • Define actionable recommendations for clinicians regardless of discipline to improve care • The guideline is not intended to be comprehensive • The guideline is not intended to limit or restrict care provided by clinicians to individual patients

6. CPG Leadership Melissa A. Pynnonen, MD, MSc (Chair) M. Boyd Gillespie, MD, MSc (Assist Chair) Benjamin Roman, MD, MSHP (Assist Chair) Richard M. Rosenfeld, MD, MPH (Methods) David Tunkel, MD (Methodologist-in-Training)

7. Stakeholders as Authors

8. Purpose Purpose: To promote the efficient, effective, and accurate diagnostic work-up of neck masses to ensure that adults with potentially malignant disease receive prompt diagnosis and intervention to optimize outcomes. Target population: The target patient for this guideline is anyone 18 years or older with a neck mass. Target audience: The target clinician for this guideline is anyone who may be the first clinician whom a patient with a neck mass encounters. This includes clinicians in primary care, dentistry, and emergency medicine, as well as subsequent specialists in pathology and radiology who have a role in HNSCC diagnosis.

9. Literature Search • Information specialist • Clinical Practice Guidelines – 3 in final CPG • Systematic Reviews – 10 in final CPG • Randomized Controlled Trials – 51 in final CPG

10. Strength of Action Terms/Implied Levels of Obligation

11. External Review & Public Comment External Peer Review (December 2016) 16 organizations, 27 reviewers, 352 comments 197 subsequent changes Public Comment (February 2017) 106 individuals, 9 provided feedback, 33 comments 10 changes

12. KAS 1. Avoidance of Antibiotic Therapy Clinicians should not routinely prescribe antibiotics for patients with a neck mass unless there are signs and symptoms of bacterial infection. Recommendation Benefits: Promote early diagnosis of malignancy, promote judicious antibiotic therapy, reduce cost Risks, harms, costs: Missed bacterial infection Evidence: GradeC, observational studies

13. KAS 2A. Stand-Alone Suspicious History Clinicians should identify patients with a neck mass who are at increased risk for malignancy when the patient lacks a history of infectious etiology and the mass has been present for 2 weeks or longer, or the mass is of uncertain duration. Recommendation Benefits: Earlier diagnosis, prioritize testing for high-risk patients, psychological benefit of timely evaluation Risks, harms, costs: False-positive diagnosis Value judgments: The risk of missing or delaying diagnosis of a malignancy is more important than false-positive clinical diagnosis in a patient with benign disease.

14. KAS 2B. Stand-Alone Suspicious Physical Examination Clinicians should identify patients with a neck mass who are at increased risk for malignancy based on one or more of the following: fixation to adjacent tissues, firm consistency, size greater than 1.5 cm, and/or ulceration of overlying skin. Recommendation Benefits, Risks, harms, costs: Same as 2a Evidence: Grade C Differences of opinion: Firm consistency predicts malignancy (14 of 18 agreed); Absolute size, regardless of location predicts malignancy.

16. KAS 2C. Additional Suspicious Signs and Symptoms Clinicians should conduct an initial history and physical for all adults with a neck mass to identify those patients with an increased risk for malignancy. Recommendation Evidence: Grade C case series Value judgments:Assumption that early identification of at-risk status can improve outcomes, despite any direct clinical evidence. Assumption that the listed signs and symptoms can predict risk of cancer above and beyond lack of infectious etiology, 2-weeks or greater duration of mass, reduced mobility, firm texture, size >1.5cm, ulceration.

17. KAS 3. Follow-Up of Patient Not at Increased Risk for Malignancy For patients with a neck mass who are not at increased risk for malignancy, clinicians or their designees should advise patients of criteria that would trigger the need for additional evaluation. Clinicians or their designees should also document a plan for follow up to assess resolution or final diagnosis. Recommendation Benefits: Avoid false-negative diagnosis based on initial assessment Risks, harms, costs: Admin burden, cost of follow up Intentional vagueness: The timing and method of follow up is not specified

18. KAS 4. Patient Education For patients with a neck mass who are deemed at increased risk for malignancy, clinicians or their designees should explain to the patient the significance of being at increased risk, and explain any recommended diagnostic tests. Recommendation Benefits: Improve understanding of risk, need for follow up exam and tests, establish expectations Aggregate evidence quality: Grade C

19. Follow-Up Education Sheet What does it mean I have a neck mass at increased risk for malignancy? What do I do next? How urgently should I be evaluated? How will the doctor examine my mouth and throat? What is a computerized tomography (CT) scan? What is a magnetic resonance imaging (MRI) scan? What is an FNA?

21. KAS 5. Targeted Physical Examination Clinicians should perform, or refer the patient to a clinician who can perform, a targeted exam (including the larynx, base of tongue, and pharynx), for patients with a neck mass deemed at increased risk for malignancy. Recommendation Benefits: Identify primary malignancy Value judgments: Consensus that imaging is not a substitute for a complete examination of mucosal surfaces Intentional vagueness: The method (mirror or endoscope) of exam is at discretion of clinician, as is the decision to refer the patient to another clinician if they are unable to visualize the pharynx, base of tongue, and larynx.

22. Targeted Physical Examination

26. KAS 6. Imaging Clinicians should order a contrast-enhanced CT (or MRI) of the neck for patients with a neck mass deemed at increased risk for malignancy. Strong recommendation based on randomized controlled trials. Benefits: Ensure right test is selected and contrast is given Risks, harms, costs: Radiation (CT), contrast adverse reactions, anxiety, claustrophobia, cost, incidental findings, false positives, false negatives Intentional vagueness:The clinician may choose whether to order a CT or MRI based on the specific clinical situation.

27. KAS 6. Imaging Clinicians should order a contrast-enhanced CT (or MRI) of the neck for patients with a neck mass deemed at increased risk for malignancy. Role of patient preferences:Small role. Claustrophobic patients may prefer CT over MRI. MRI may be preferable if radiation exposure is a concern. Exceptions: Imaging recommendations may be altered in pregnancy. The protocol for contrast administration may be altered in the setting of contrast allergy, or renal insufficiency as well as in the setting of a previously established diagnosis (such as thyroid cancer) that does not require contrast-enhanced CT or MRI of the neck.

28. KAS 7. Fine Needle Aspiration Clinicians should perform FNA instead of open biopsy, or refer the patient to someone who can perform FNA, for patients with a neck mass deemed at increased risk for malignancy when the diagnosis of the neck mass remains uncertain. Strong recommendation based on systematic reviews with a consistent reference standard. Benefits: Rapid, cost-effective, accurate test, minimal discomfort, low risk of seeding tumor, does not impact imaging results, can prioritize further imaging or work up Risks, harms, costs: Discomfort, direct cost, risk of non-diagnostic or indeterminate test

29. KAS 7. Fine Needle Aspiration Clinicians should perform FNA instead of open biopsy, or refer the patient to someone who can perform FNA, for patients with a neck mass deemed at increased risk for malignancy when the diagnosis of the neck mass remains uncertain. Quality improvement opportunity: Avoid unnecessary open biopsy; promote timely FNA as the initial pathologic test for a patient with a neck mass at increased risk of malignancy Evidence: GradeA, systematic reviews Value judgments: Perception that some patients undergo inappropriate open biopsy prior to FNA. Some patients experience unwarranted delay prior to tissue biopsy Intentional vagueness: There are a variety of techniques, operators and settings in which neck mass FNA may be performed; these choices are left to the discretion of the clinician and patient.

30. Neck Mass Biopsy: What Should the Patient Expect? What is a biopsy? What are the different types of biopsies? Fine needle aspiration (FNA) Core needle biopsy Open biopsy What should I do to prepare? When should I get my results?

31. KAS 8. Cystic Masses For patients with a neck mass deemed at increased risk for malignancy, clinicians should continue evaluation of patients with a cystic neck mass, as determined by FNA or imaging studies, until a diagnosis is obtained and should not assume the mass is benign. Recommendation based on observational studies with more benefit than harm. Benefits: Avoid misdiagnosis of malignant lesions, avoid inappropriate care (e.g., excision, open biopsy), avoid delays in diagnosis, reduce false sense of security

32. KAS 8. Cystic Masses Risks, harms, costs: Cost of additional diagnostic tests Evidence: Grade C Value judgments: Concern by the GDG that some patients receive false reassurance that a cystic mass is not of concern despite studies showing a high-rate of malignancy and false-negative biopsies in such masses

33. KAS 9. Ancillary Tests Clinicians should obtain additional ancillary tests based on the patient's history and physical examination when a patient with a neck mass is at increased risk for malignancy and/or does not have a diagnosis after FNA and imaging. Recommendation Benefits: Obtain a diagnosis Risks, harms, costs: Costs of tests, false positive tests, incidental findings, overlook a concurrent malignancy Evidence: Grade C, case-control and observational studies, case series Intentional vagueness: Tests/timing at clinician’s discretion

34. KAS 10. Exam Under Anesthesia Before Open Biopsy Clinicians should recommend examination of the upper aerodigestive tract under anesthesia, before open biopsy, for patients with a neck mass who are at increased risk for malignancy and without a diagnosis or primary site identified, with FNA, imaging, and/or ancillary tests Recommendation Benefits: May identify primary malignancy or rule out malignancy, obtain tissue for diagnosis Risks, harms, costs: Costs, adverse effects of anesthesia, dental or cranial nerve injury, complications of endoscopy Evidence quality: Grade C

35. KAS 10. Exam Under Anesthesia Before Open Biopsy Value judgments: Perception that some clinicians may perform open biopsy before, or without, endoscopy during the same trip to the operating room. Endoscopy should preferably be performed prior to open biopsy Intentional vagueness: After indeterminate FNA, the decision for open biopsy is at the discretion of the clinician. Usually performed after endoscopy fails to reveal a primary site and clinician remains suspicious of malignancy Exceptions: Patients at increased risk of anesthesia Differences of opinion: Should surgeon be prepared for neck dissection at time of open biopsy and frozen section?

36. Exam Under Anesthesia: What Should the Patient Expect? What is exam (endoscopy) under anesthesia? Why do I need exam under anesthesia? How is it performed? How will I feel afterward? What are the risks? When will I receive my results? When should I call my doctor?

37. In Summary

38. Research Needs During the process of guideline development, several important gaps in knowledge were identified regarding the epidemiology and appropriate management of adult neck masses. The guideline recommendations would be strengthened with research seeking to clarify this information. Several questions arose regarding the etiology and epidemiology of neck masses: • What is the overall incidence of neck masses as a presenting symptom, for all diagnoses (including inflammatory masses)? • What is the incidence of persistent neck masses (noninflammatory)? • How is the incidence of persistent neck masses expected to change as a result of increased incidence of HPV-positive HNSCC? • What is the overall cost burden of evaluation and diagnosis of neck masses? • What is the current length of delay in diagnosis of HNSCC presenting as a neck mass, and what is the impact of delay on outcomes?

39. Research Needs (cont’d) Other questions arose regarding management issues: • How long is too long in terms of the duration of a neck mass before workup is indicated? (The GDG, citing other literature, states that the period should be 2 weeks.) • Does an FNA performed before CT scan interfere with appropriate radiology read of the neck mass? • For cystic masses, are there any radiologic findings that can be identified that would lead to a higher suspicion for malignancy? • What is the incidence of open biopsy, and what is the long-term impact on outcomes?

40. Thank you for your attention QUESTIONS?