p16 positive oropharyngeal small cell cancer: A case report.

Extra-pulmonary small cell carcinomas (EPSCC) are rare malignancies. Like small cell lung cancer (SCLC), they are aggressive malignancies with dismal prognosis. We here report a case of a middle-aged man who presented with odynophagia and cervical lymphadenopathy. Diagnostic workup confirmed the diagnosis of locally-advanced p16-positive oropharyngeal cancer (OPC) with a surprising histology of small cell cancer, suggesting a human papilloma virus (HPV)-related oropharyngeal cancer with small cell differentiation. HPV oropharynx infection is a well-known risk factor for squamous cell carcinoma of the oropharynx, but it is unknown if it may increase the risk of other OPC histology.

Development and Assessment of a Novel Composite Pathologic Risk Stratification for Surgically Resected Human Papillomavirus-Associated Oropharyngeal Cancer.

Importance: Human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is a distinct form of head and neck squamous cell carcinoma (HNSCC) with its own American Joint Committee on Cancer staging system. However, pathologic risk stratification for HPV+ OPSCC largely remains based on the experience with HPV-unassociated HNSCC. Objective: To compare the survival discrimination of traditional pathologic risk stratification for both HPV+ OPSCC and HPV-unassociated HNSCC and derive a novel pathologic risk stratification system for HPV+ OPSCC with improved survival discrimination. Design, Setting, and Participants: In this retrospective cohort study, we used the National Cancer Database to identify 15 324 patients diagnosed with nonmetastatic HNSCC between January 1, 2010, and December 31, 2013, who were treated with upfront surgery and neck dissection. We compared traditional pathologic risk stratification for HPV+ OPSCC and HPV-unassociated HNSCC and then derived a novel pathologic risk stratification system. Analyses were performed from July 1, 2018, to January 31, 2019. Exposures: Definitive primary surgical resection and neck dissection. Main Outcomes and Measures: Survival discrimination of pathologic risk stratification systems measured with concordance indices. Results: This retrospective cohort study included 15 324 patients (10 779 men and 4545 women; mean [SD] age, 59.9 [11.8] years) with surgically treated nonmetastatic HNSCC. Separation of survival curves for HPV-unassociated HNSCC using traditional pathologic risk stratification (5-year overall survival for the low-, intermediate-, and high-risk groups) were 76.2%, 54.5%, and 40.9%, respectively. Separation curves for HPV+ OPSCC were 93.2%, 88.9%, and 83.7%, respectively. Human papillomavirus-unassociated HNSCC had a concordance index of 0.68, whereas HPV+ OPSCC had a concordance index of 0.58. A novel risk stratification system for HPV+ OPSCC that more closely fits actual survival rates for HPV+ OPSCC was derived. The system incorporated the composite number of pathologic adverse features. This composite risk stratification system was associated with an improved concordance index of 0.67 for HPV+ OPSCC. Adjuvant treatment with radiation was not associated with improved survival for patients categorized as low risk according to the new risk stratification system, but this treatment was associated with improved survival for patients in the intermediate- and high-risk groups. Conclusions and Relevance: Traditional pathologic risk stratification shows poor survival discrimination for HPV+ OPSCC and classifies many patients with an excellent prognosis as high risk. We derived a novel composite pathologic risk stratification system for HPV+ OPSCC that may be associated with improved survival discrimination.

Negative Pressure Wound Therapy in the Head and Neck: An Evidence-Based Approach.

OBJECTIVE: To perform an evidence-based review with recommendations that evaluates the indications and utility of negative pressure wound therapy (NPWT) in the head and neck. METHODS: The authors searched the PubMed, Medline, Embase, Web of Science, and Cochrane Library databases for relevant literature. The primary outcome was successful intended use of NPWT, be it for granulation tissue formation, infection control, or complete wound closure. Patient demographics, etiology, and other clinical characteristics were explored. Meta-analysis of observational studies was used to examine response rates and wound sizes. RESULTS: Fifty-seven articles encompassing 522 patients were included. The most common etiologies reported included: neoplasm (343 patients [65.7%]), oro-/pharyngocutaneous fistula (9.8%), infection (10.5%), and trauma (9.6%). The majority of wounds treated were in the neck (61.6%). Potential risk factors that may compromise wound healing were noted in 217 of 522 patients (41.6%). Of these 217 patients, 135 had properly documented risk factors, with the most common being prior irradiation (63%). The overall mean response across studies was 85.7% (95% confidence interval: 0.806-0.896, P < 0.001, I2 = 0 %). CONCLUSION: Negative pressure wound therapy is useful for the management of head and neck wounds and should be considered for patients in whom wound healing is progressing insufficiently, including those with a history of head and neck cancer, oro-/pharyngocutaenous fistula, and trauma. Randomized controlled trials further comparing NPWT versus other modalities may be invaluable in further delineating its appropriate role. Laryngoscope, 129:671-683, 2019.

Laryngeal cancer: Global socioeconomic trends in disease burden and smoking habits.

OBJECTIVES/HYPOTHESIS: To characterize health burden and determine the associated level of equality of laryngeal carcinoma (LC) burden at a global level. METHODS: One hundred eighty-four countries were organized by socioeconomic status using Human Development Index (HDI) categorizations provided by the United Nations Development Program. Disability-adjusted life years (DALYs), obtained from The Global Health Data Exchange, were calculated and compared between each HDI category for the period from 1990 to 2015. Equality of LC burden was then evaluated with concentration indices. RESULTS: Global LC burden, as measured by age-standardized DALYs, has improved significantly over the 25-year period studied. This burden has declined for very high, high, and medium HDI countries, whereas it has remained unchanged for low HDI countries. The majority of LC global burden was found in high socioeconomic countries before 2010 and has shifted toward low socioeconomic countries, as indicated by concentration indices. Over the last 25 years, Central and Eastern Europe continue to have the largest disease burden in the world. CONCLUSION: This is the first analysis that we are aware of investigating health disparities of LC at a global level. The global burden of the disease has declined, which is a trend corresponding with significantly reduced smoking behaviors in developed countries. Although the global inequality gap decreased between 2010 and 2015, there remain reasons for concern. Smoking continues to trend upward in low socioeconomic countries, which could increase LC burden in low socioeconomic countries in the near future. A new global initiative directed toward low socioeconomic countries may yield dividends in preventing subsequent disparities in the LC burden. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:2039-2053, 2018.

Oropharyngeal lymphoma: A US population based analysis.

OBJECTIVES: To describe the epidemiology and analyze factors determinant of survival in patients with oropharyngeal lymphoma, using the Surveillance Epidemiology and End Results (SEER) database. METHODS: 2504 patients with oropharyngeal lymphoma were identified using the most recent SEER database entry from 1976 to 2016. Demographic information, Ann Arbor stage, tumor histopathology and location were collected. Multivariate analysis was used to analyze patient and tumor characteristics associated with survival. RESULTS: The mean age of the patients studied was 60.5years, 58.4% of the subjects were male and 81% were white. Diffuse large B cell lymphoma (DLBCL) was the most common histologic subtype involving 56.9% of cases. The most common subsite of origin was the tonsil, with 71% of lymphomas originating from there. The association of survival with stage, age, tumor location, presence of B symptoms, tumor pathology, gender and race was analyzed using multivariate regression. Decreased survival was significantly associated with patient age p<0.0001, Ann Arbor staging p=0.005, the presence of B symptoms p=0.003 and tumor histopathology (T cell tumors) p=0.01. Patients with tumors originating from the soft palate were significantly more likely to die asa result of their disease p=0.03. CONCLUSION: Oropharyngeal lymphoma most commonly originates from the tonsil. DLBCL is the most common subtype and has a good prognosis. The presence of B symptoms, tumors originating from the soft palate and patients with T cell tumors have the worst prognosis. This information can potentially be of great utility to the head and neck surgeon discussing prognosis with patients suffering from oropharyngeal lymphoma.

Systemic therapy for head and neck squamous cell carcinoma: Historical perspectives and recent breakthroughs.

OBJECTIVES: Despite dramatic developments in drugs established for other malignancies, historically there have been few novel systemic agents available for the management of head and neck squamous cell carcinoma (HNSCC). However, the last decade has observed increased interest in targeted therapies for HNSCC. In 2006, cetuximab became the first major drug for HNSCC to gain Food and Drug Administration (FDA) approval in 3 decades. Recently, both pembrolizumab and nivolumab gained FDA approval for treatment of recurrent or metastatic HNSCC, and trials for other indications in HNSCC are actively underway. As older agents including cisplatin and 5-fluorouracil continue to play a significant role in the management of advanced HNSCC, an understanding of their legacy is paramount. This historical review is not meant to exhaustively catalog every finding relating to HNSCC systemic therapy, but rather is meant to highlight important advances. DATA SOURCES: Case series and clinical trials available in the literature. REVIEW METHODS: Historically significant series and trials evaluating HNSCC systemic therapy were evaluated. RESULTS: Standard regimens employed today are largely comprised of drugs discovered over 4 decades ago, although a number of recent phase III clinical trials have shown great promise, leading to the adoption of several new chemotherapeutic agents and treatment strategies. CONCLUSIONS: These findings reinforce the importance of supporting further HNSCC drug discovery as modern treatment strategies using systemic therapy have resulted in measurable improvements in oncologic outcomes. Laryngoscope, 127:2565-2569, 2017.

Recent trends in oropharyngeal cancer funding and public interest.

OBJECTIVES/HYPOTHESIS: The incidence of oropharyngeal cancer (OPC) has increased in the United States. This has been driven by an increase in human papillomavirus (HPV)-positive OPC. Our objective is to determine trends in National Institutes (NIH)-supported research funding and public interest in OPC. METHODS: The NIH Research Portfolio Online Reporting Tools database was evaluated for projects related to OPC between 2004 and 2015. Projects were evaluated for total funding, relation to HPV, principal investigator departmental affiliation and degree, and NIH agency or center responsible for grant. The Google Trends database was evaluated for relative Internet search popularity of oropharyngeal cancer and related search terms between 2004 and 2015. RESULTS: In terms of NIH funding, 100 OPC-related projects representing 242 grant years and $108.5 million were funded between 2004 and 2015. Total NIH funding for OPC projects increased from $167,406 in 2004 to $16.2 million in 2015. Funding for HPV-related OPC increased from less than $2 million yearly between 2004 and 2010 up to $12.7 million in 2015. Principal investigators related to radiation oncology ($41.8 million) and with doctor of medicine degrees ($52.8 million) received the largest share of total funding. Relative Internet search popularity for oropharyngeal cancer has increased from 2004 to 2015 compared to control cancer search terms. CONCLUSION: Increased public interest and NIH funding has paralleled the rising incidence of OPC. NIH funding has been driven by projects related to the role of HPV in OPC. LEVEL OF EVIDENCE: 2c. Laryngoscope, 127:1345-1350, 2017.

Tumor Differentiation as a Prognostic Factor for Major Salivary Gland Malignancies.

Objective The effect of tumor differentiation on prognosis of major salivary gland malignancies is controversial. The aim of this study was to determine the effect of tumor differentiation on prognosis by stage in patients with major salivary gland malignancies and to analyze which patient factors are associated with tumor differentiation. Study Design and Setting Cross-sectional analysis of Surveillance, Epidemiology, and End Results (SEER) database. Subjects and Methods In total, 9810 patients who had a major salivary gland malignancy from 2004 to 2012 were identified using the SEER database. Patients with no staging information or no information on histologic differentiation were excluded. A total of 5366 patients were included in the study. For analysis, patients were categorized by American Joint Committee on Cancer (AJCC) stage and subdivided by tumor differentiation. Multivariate analysis was used to analyze the impact of tumor differentiation on survival, tumor location (parotid, submandibular, sublingual), and sex within each AJCC stage of disease. Results Data analysis demonstrated a significant difference in histologic differentiation by stage, with P < .0001. Within stages II, III, and IV, tumor differentiation was significantly associated with a decrease in survival. There was no significant difference in tumor differentiation between the parotid and submandibular gland. Conclusion For patients with stage II, III, and IV disease, tumor differentiation was an independent predictor of survival. This information can be useful when discussing prognosis and can potentially influence management of disease.

Topical agents for oral cancer chemoprevention: A systematic review of the literature.

OBJECTIVES/HYPOTHESIS: We review the use of topical chemoprevention agents in patients with oral potentially malignant disorders (PMD). METHODS: A systematic review of studies on topical chemoprevention agents for oral PMD from 1946 to November 2016 was conducted using the MEDLINE database, Embase, and Cochrane Library. Data were extracted and analyzed from selected studies including study type, sample size, demographics, treatment length, response rate, follow-up time, adverse effects, and recurrence. RESULTS: Of 108 studies, twenty-four, representing 679 cases met the inclusion criteria. The clinical lesions evaluated included oral leukoplakia, erythroplakia (OEL), verrucous hyperplasia (OVH), oral lichen planus, larynx squamous cell carcinoma, and oral squamous cell carcinoma (OSCC). The mean complete response rate for topical retinoid therapy was 32%. The mean complete response rate for 1% bleomycin therapy and 0.5% bleomycin was 40.2% and 25%, respectively. The complete response rate of OVH, OEL, and OSCC to photodynamic therapy ranged from 66.7% to 100%. CONCLUSION: There are a paucity of data examining topical treatment of oral PMDs. However, the use of topical agents among patients with oral lesions may be a viable complement or even alternative to traditional surgery, radiation, or systemic chemotherapy, with the advantage of reducing systemic side effects and sparing important anatomic structures. This study of 679 cases represents the largest pooled sample size to date, and the preliminary studies in this systematic review provide support for further inquiry.

Thyroglossal Duct Cyst Carcinoma: A Systematic Review of Clinical Features and Outcomes.

Objective Although thyroglossal duct cysts (TGDCs) are relatively common, malignancies within these lesions are infrequent. As a result, there are no large-scale series describing clinical characteristics. Our objectives were to perform a systematic review of the literature evaluating patient demographics, pathology, management, and prognosis of these patients. Data Sources PubMed, Embase, Cochrane reviews, and Google Scholar were searched for relevant articles. Articles meeting inclusion criteria were reviewed for data detailing epidemiology, treatment, and outcomes. Review Methods Inclusion criteria included English-language articles with original reports on human subjects. Two investigators independently reviewed all articles for the data collected, including epidemiology, treatment, and outcomes. Results Ninety-eight articles comprising 164 patients were included in the final analysis. The mean age at presentation was 39.5 years (9-83 years); 68.3% of patients were female. In total, 73.3% of cases were found on final pathologic analysis. The most common pathology was papillary cancer (92.1%). Of the patients, 98.9% underwent a Sistrunk procedure and 61.0% underwent total thyroidectomy. There was a 4.3% recurrence rate with a mean time to recurrence of 42.1 months from initial treatment. One patient died of TGDC carcinoma, while all other patients were disease free at the time of last follow-up (mean follow-up was 46.1 months). Conclusion TGDC carcinoma is typically diagnosed on final pathology. While management encompasses a Sistrunk procedure, further consideration should be given to thyroidectomy among patients ≥45 years of age and individuals with aggressive disease. TGDC carcinoma harbors an exceedingly low rate of mortality.

Pediatric Thyroidectomy.

Objectives/Hypothesis To evaluate hospital course and associated complications among pediatric patients undergoing thyroidectomy. Study Design and Setting Retrospective database review of the Kids' Inpatient Database (2009, 2012). Methods The Kids' Inpatient Database was evaluated for thyroidectomy patients for the years 2009 and 2012. Surgical procedure, patient demographics, length of stay, hospital charges (in US dollars), and surgical complications were evaluated. Results Of an estimated 1099 nationwide partial thyroidectomies and 1654 total thyroidectomies, females accounted for 73.5% and 79.1% of patients, respectively. Children <1 year of age had significantly longer hospital courses ( P < .0001), and patients 1 to 5 years of age had a significantly greater length of stay than individuals 6 to 20 years of age (7.8 vs 2.1 days, P < .001). The most common complications overall included hypocalcemia, respiratory complications, vocal cord paresis/paralysis, postoperative infection, and bleeding. Vocal cord paralysis was noted in 1.7% of pediatric thyroidectomy patients. The presence of these complications among total thyroidectomy patients significantly increased one's length of stay and hospital charges. A neck dissection was reported in 22.9% of malignant thyroidectomy patients. Conclusion Nearly 20% of children who underwent total thyroidectomy experienced postoperative hypocalcemia, positing a need for the development of postoperative calcium replacement algorithms to minimize the sequelae of hypocalcemia. A greater incidence of respiratory and infectious complications among younger patients (<6 years) suggests a need for closer monitoring, possibly encompassing routine postoperative intensive care unit utilization, in an attempt to minimize these sequelae.

Head and Neck Cancer.

Despite a considerable expansion in our therapeutic repertoire for management of other malignancies, mortality from head and neck cancer (HNC) has not significantly improved in recent decades. Upon normalizing National Institutes of Health-awarded R01 and R01-equivalent grants by incidence, thyroid cancer ($214) and HNC ($1329) received the fewest funding dollars. Upon adjusting funding totals by mortality, HNC was 7th out of 9 cancers evaluated ($6138). These findings highlight HNC as an underfunded disease versus other cancers. As data detailing grant applications (including unsuccessful grants) are not publicly available, it is not clear if these disparities stem from fewer applications or fewer opportunities. Our hope is that this commentary will spur further investigation into strategies to increase HNC inquiry and funding for trainees as well as early-stage and established investigators.

Mobile applications and patient education: Are currently available GERD mobile apps sufficient?

OBJECTIVES/HYPOTHESIS: Despite the increasing role of mobile applications (apps) in patient education, there has been little inquiry evaluating the quality of these resources. Because poor health literacy has been associated with inferior health outcomes, evaluating the quality of patient education materials takes on great importance. Our objective was to employ validated readability tools for the evaluation of gastroesophageal reflux (GERD) mobile apps. METHODS: GERD-specific apps found in the Apple App Store (Apple Inc., Cupertino CA) were evaluated using the Readability Studio Professional Version 2015 for Windows (Oleander Software, Ltd, Vandalia, OH). All text was evaluated using nine validated algorithms measuring readability including Flesch-Kincaid Grade Level, Simple Measure of Gobbledygook grading, Gunning Fog index, Coleman-Liau, New Fog Count formula, Raygor Readability Estimate, FORCAST, Fry graph, and Flesch Reading Ease score. RESULTS: Average reading grade levels for individual GERD apps ranged from 9.6 to 12.9 (interquartile range 10.3-12). The average reading grade level for all apps analyzed was 11.1 ± 0.2 standard error of the mean (SEM), with an average Flesch Reading Ease score for all mobile apps analyzed of 51 ± 2.05 (SEM), falling into the "fairly difficult" category given by this measure. Raygor Readability estimates that most mobile apps have a reading grade level between 10 and 12, with the majority of this outcome due to long words. CONCLUSION: This analysis demonstrates the feasibility of assessing readability of mobile health apps. Our findings suggest significant gaps in potential comprehension between the apps analyzed and the average reader, diminishing the utility of these resources. We hope our findings influence future mobile health-related app development and thereby improve patient outcomes in GERD and other chronic diseases. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:1775-1779, 2017.

A critical analysis of melanoma malpractice litigation: Should we biopsy everything?

OBJECTIVES/HYPOTHESIS: The aim of this study was to evaluate factors raised in malpractice litigation related to the diagnosis and management of melanoma and to further assess issues impacting outcome. STUDY DESIGN: Retrospective chart review. METHODS: The Westlaw legal database was searched for malpractice litigation resolved over the last 20 years relating to melanoma. Cases were evaluated for allegations, defendant specialty, outcome, and other issues raised. RESULTS: Of the 80 cases evaluated, 49% were resolved in the defendants' favor. In greater than 80% of cases, there was alleged misdiagnosis. In 35% of cases, the patient had expired secondary to melanoma at the time of litigation. There was no statistical difference in payments upon comparison of cases with and without mortality. A greater proportion of cases with dermatologists and pathologists as defendants involved alleged misdiagnosis. The most common locations for melanoma were the extremities and the head-and-neck region, at 32.5% and 22.5%, respectively. Location did not significantly impact the outcome of cases. CONCLUSION: Malpractice litigation relating to melanoma involves numerous physicians, including dermatologists, pathologists, and otolaryngologists. Alleged misdiagnosis of a pigmented lesion was the most common cause of litigation and involved physicians from numerous specialties. Patients who were misdiagnosed had a significantly higher likelihood of having active disease at the time of litigation. Ultimately improved methods of detecting concerning pigmented lesions need to be developed. Factors such as death and poor cosmetic outcome did not significantly impact litigation outcome. LEVEL OF EVIDENCE: NA Laryngoscope, 127:134-139, 2017.

PD1/PD-L1 inhibition as a potential radiosensitizer in head and neck squamous cell carcinoma: a case report.

BACKGROUND: Immunotherapy targeting the checkpoint PD1 (programmed cell death protein 1) or PDL1 (programmed death ligand 1) has led to advances in the treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such therapies has also been introduced into the treatment of other malignancies, including head and neck cancer. The combined effects of checkpoint inhibitors and anti-PD1(L1) antibodies and radiation therapy have not yet been sufficiently investigated. CASE PRESENTATION: We report a case of locally relapsed non-resectable oral cavity squamous cell carcinoma, with excellent local control after pembrolizumab (MK3475) followed by radiotherapy. CONCLUSION: T cell activation induced by checkpoint inhibition may dramatically improve tumor response to radiation. More data are needed to identify the toxicity and efficacy of sequential or concurrent checkpoint inhibitors and radiotherapy.

Perioperative considerations and complications in pediatric parathyroidectomy.

OBJECTIVES/HYPOTHESIS: To evaluate perioperative considerations and post-operative complications associated with parathyroidectomy in the pediatric population. METHODS: The Kids' Inpatient Database 21 (KID) was searched for patients who underwent parathyroidectomy in 2009 and 2012. Patient demographics, hospital stay, associated charges, and post-operative adverse sequelae were evaluated in all patients and included patient comorbidity and additional procedure requirement analysis. RESULTS: There were 182 patients extrapolating to 262 parathyroidectomies over the two years analyzed. Although a minority of patients were male (45.4%), these patients had greater rates of complications, length of stay, and hospital charges. Importantly, minorities and younger patients (≤15y) also had more complicated post-operative courses. The lengths of stay for patients experiencing post-operative altered mental status (18.7d), post-operative infection (15.5d), respiratory complications (19d), and cardiac complications (13d) were significantly increased compared to individuals without major complications (3.4d) (p < 0.001). Patients with pre-existing chronic kidney disease, dialysis-dependence, and bone sequelae (most commonly from hungry bone syndrome) also had significantly lengthier stays and greater associated costs. CONCLUSION: Findings from this analysis can be included in a comprehensive pre-operative informed consent process between physicians and patients discussing perioperative considerations and potential complications of parathyroidectomy. Males, younger children, and patients with preexisting renal conditions experienced lengthier and more complicated hospital stays, suggesting the need for closer monitoring of these cohorts.

Diagnosing allergic rhinitis: effectiveness of the physical examination in comparison to conventional skin testing.

OBJECTIVE: To evaluate the effectiveness of physical examination alone in diagnosing nasal allergic patients. DESIGN: A cross-sectional study of 15 consecutive evaluable patients. SETTING: A tertiary care otolaryngology clinic at the Jewish General Hospital, McGill University, Montreal. METHODS: All patients were assessed by three physicians in random order. Each conducted a specific examination, made a clinical impression, and then took a directed history to make a second impression. Both impressions were compared to skin testing. Multivariate regression analyses assessed the linear relationships of both examination and history variables to impressions and skin testing results. Fleiss kappa tests assessed interrater reliabilities. MAIN OUTCOME MEASURES: Accuracy in diagnosing allergic rhinitis by examination alone and inter-rater reliability in this diagnosis. RESULTS: When comparing physical examination variables to history variables relative to the second impression, history variables had a stronger relationship (R²  =  .90 vs .52). This was also true when comparing both sets of variables to skin testing (R²  =  .81 vs .60). The interrater reliability of physical examination variables was poorer than that of the history variables (.377 and .494, respectively). Taking all physicians, the average sensitivity, specificity, positive predictive value, and negative predictive value of the history impression were all higher than those of the examination impression. CONCLUSION: Physical examination alone yields unreliable and inconsistent results in diagnosing allergic rhinitis. This is likely secondary to the relative subjectivity involved in evaluating the nasal cavity. Adding a history to the examination is essential to increase diagnostic accuracy.

Risk factors for well-differentiated thyroid carcinoma in patients with thyroid nodular disease.

OBJECTIVES: Evaluate current accepted risk factors for well-differentiated thyroid carcinoma, and develop a predictive model to determine one's risk of malignancy given a thyroid nodule. STUDY DESIGN: Retrospective analysis of 600 patients. SUBJECTS AND METHODS: Patients with benign thyroid nodular disease and with well-differentiated thyroid cancer were randomly selected. Patient, clinical, and investigational data were compared by means of univariate and multivariate regression analyses. RESULTS: Age, regional lymphadenopathy, ipsilateral vocal cord palsy, solid and/or calcified nodules, and an aspiration biopsy being malignant or suspicious predicted for cancer (P < 0.05). Regional lymphadenopathy and vocal cord palsy are perfect predictors of malignancy. Multivariate analysis indicated age, solid and/or calcified nodules, and all fine-needle aspiration biopsy results to be significant in assessing risk (P < 0.05). CONCLUSION: Taking individual risk factors in isolation is not always reliable. Using a predictive model, one can anticipate a patient's risk of malignancy when the diagnosis is unclear.