Radioactive iodine administration is not associated with improved disease-specific survival in classic papillary thyroid carcinoma greater than 4 cm confined to the thyroid.

BACKGROUND: We aimed to evaluate the impact of radioactive iodine on disease-specific survival in intrathyroidal (N0M0) papillary thyroid carcinoma >4 cm, given conflicting data in the American Thyroid Association guidelines regarding their management. METHODS: The Surveillance, Epidemiology, and End Results database was queried for N0M0 classic papillary thyroid carcinoma >4 cm. Kaplan-Meier estimates were performed to compare disease-specific survival between radioactive iodine-treated and untreated groups. A multivariable Cox regression was performed to identify predictors of disease-specific survival. RESULTS: There were more patients aged ≥55 (41.7% vs 32.3%, P = .001) and fewer multifocal tumors (25.3% vs 30.6%, P = .006) in the no radioactive iodine group. Ten-year disease-specific survival was similar between the radioactive iodine treated and untreated groups (97.2% vs 95.6%, P = .34). Radioactive iodine was not associated with a significant disease-specific survival benefit (adjusted hazard ratio = 0.78, confidence interval [0.39-1.58], P = .49). Age ≥55 (adjusted hazard ratio = 3.50, confidence interval [1.69-7.26], P = .001) and larger tumor size (adjusted hazard ratio = 1.04, confidence interval [1.02-1.06], P < .001) were associated with an increased risk of disease-specific death. Subgroup analyses did not demonstrate improved disease-specific survival with radioactive iodine in patients ≥55 and in tumors >5 cm. CONCLUSION: Adjuvant radioactive iodine administration in classic papillary thyroid carcinoma >4 cm confined to the thyroid did not significantly impact disease-specific survival. Thus, these patients may not require routine treatment with adjuvant radioactive iodine.

Transoral incisionless fundoplication for recurrent symptoms after laparoscopic fundoplication.

BACKGROUND: Revision of a failed laparoscopic fundoplication carries higher risk of complication and lower chance of success compared to the original surgery. Transoral incisionless fundoplication (TIF) may be an endoscopic alternative for select GERD patients without need of a moderate/large hiatal hernia repair. The aim of this study was to assess feasibility, efficacy, and safety of TIF 2.0 after failed laparoscopic Nissen or Toupet fundoplication (TIFFF). METHODS: This is a multicenter retrospective cohort study of patients who underwent TIFFF between September 2017 and December 2020 using TIF 2.0 technique (EsophyX Z/Z+) performed by gastroenterologists and surgeons. Patients were included if they had (1) recurrent GERD symptoms, (2) pathologic reflux based upon pH testing or Grade C/D esophagitis or Barrett's esophagus, and (3) hiatal hernia ≤ 2 cm. The primary outcome was improvement in GERD Health-Related Quality of Life (GERD-HRQL) post-TIFFF. The TIFFF cohort was also compared to a similar surgical re-operative cohort using propensity score matching. RESULTS: Twenty patients underwent TIFFF (median 4.1 years after prior fundoplication) and mean GERD-HRQL score improved from 24.3 ± 22.9 to 14.75 ± 21.6 (p = 0.014); mean Reflux Severity Index (RSI) score improved from 14.1 ± 14.6 to 9.1 ± 8.0 (p = 0.046) with 8/10 (80%) of patients with normal RSI (< 13) post-TIF. Esophagitis healed in 78% of patients. PPI use decreased from 85 to 55% with 8/20 (45%) patients off of PPI. Importantly, mean acid exposure time decreased from 12% ± 17.8 to 0.8% ± 1.1 (p = 0.028) with 9/9 (100%) of patients with normalized pH post-TIF. There were no statistically significant differences in clinical efficacy outcomes between TIFFF and surgical revision, but TIFFF had significantly fewer late adverse events. CONCLUSION: Endoscopic rescue with TIF is a safe and efficacious alternative to redo laparoscopic surgery in symptomatic patients with appropriate anatomy and objective evidence of persistent or recurrent reflux.

Coexisting Papillary and Anaplastic Thyroid Cancer: Elucidating the Spectrum of Aggressive Behavior.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a rare and lethal form of thyroid cancer. Overall prognosis is unclear when it arises focally in a background of papillary thyroid cancer (PTC). Clinicopathologic features and outcomes of tumors with coexisting PTC and ATC histologies (co-PTC/ATC) were categorized. METHODS: The National Cancer Database was queried for histologic codes denoting PTC, ATC, and co-PTC/ATC, defined as Grade 4 PTC, diagnosed from 2004 to 2017. Clinicopathologic features, OS, and treatment outcomes were analyzed by histologic type. RESULTS: A total of 386,862 PTC, 763 co-PTC/ATC, and 3,880 ATC patients were identified. Patients with co-PTC/ATC had clinicopathologic features in-between those of PTC and ATC, including rates of tumor size >4 cm, extrathyroidal extension, and distant metastases. On multivariable Cox proportional hazards modeling, age >55 years, Charlson-Deyo score ≥2, positive lymph nodes, lymphovascular invasion, distant metastases, and positive surgical margins were associated with worse OS, whereas radioactive iodine (RAI) and external beam radiation therapy (EBRT) were associated with improved OS, irrespective of margin status. OS was worse for co-PTC/ATC than for PTC but better than for ATC and differed based on the presence or absence of "aggressive" tumor features, including lymph node positivity, lymphovascular invasion, distant metastases, and positive surgical margins. CONCLUSIONS: Survival of patients with co-PTC/ATC is dependent on the presence of aggressive clinicopathologic features and lies within a spectrum between that of PTC and ATC. Adjuvant RAI and EBRT treatment may be beneficial, even after R0 resection.

Proposed Risk Stratification and Patterns of Radioactive Iodine Therapy in Malignant Struma Ovarii.

Introduction: Malignant struma ovarii (MSO) is a rare thyroid cancer arising within an ovarian teratoma. While surgical excision of the primary tumor is widely accepted as standard of care, recommendations for adjuvant treatment of MSO-whether or not to administer radioactive iodine (RAI)-are based largely on case reports and remain debated. In this study, we aimed to propose a risk stratification and analyze RAI utilization patterns in MSO cases. Methods: The National Cancer Database (NCDB) was queried for patients with MSO between 2004 and 2016. Demographic, oncological, and clinicopathologic data were compared between groups using Fisher's exact test. Kaplan-Meier curves were used to estimate overall survival (OS), and variables associated with OS were assessed via univariate Cox regression. We adapted the 2015 American Thyroid Association risk guidelines for MSO patients. We stratified patients into low-, intermediate-, and high-risk groups using metastasis, extraovarian extension, lymphovascular invasion, lymph node status, surgical margins, tumor size, and grade. Risk stratification, demographic, oncological, and clinicopathologic data were compared between the groups receiving and not receiving RAI therapy. We then queried the Surveillance, Epidemiology, and End Results (SEER) 18 registry for patients with MSO between 2000 and 2018 to confirm our risk stratification analysis. Results: In the NCDB analysis, a total of 158 patients were identified, and 19 received RAI. RAI therapy was associated with distant metastasis (p = 0.005) and lymph node status (p = 0.012). Twenty-one NCDB patients were stratified as high risk, and 30% of high-risk patients received RAI. High-risk stratification was associated with decreased OS via univariate Cox regression (hazard ratio = 4.0 [95% confidence interval 1.11-14.26], p = 0.034). In our subsequent analysis using the SEER registry, there were 95 MSO patients, and 18 received RAI. Again, the majority of high-risk patients did not receive RAI, with only 41% of high-risk patients receiving RAI. Conclusions: MSO is a rare malignancy with apparently variable and inconsistent patterns of postoperative RAI administration. The risk stratification described here provides a framework to identify patients potentially at risk for mortality, and utilization of RAI in this group should be studied further.

Insurance type is associated with appropriate use of surgical and adjuvant care for differentiated thyroid carcinoma.

BACKGROUND: We aimed to characterize the association between differentiated thyroid cancer (DTC) patient insurance status and appropriateness of therapy (AOT) regarding extent of thyroidectomy and radioactive iodine (RAI) treatment. METHODS: The National Cancer Database was queried for DTC patients diagnosed between 2010 and 2016. Adjusted odds ratios (AOR) for AOT, as defined by the American Thyroid Association guidelines, and hazard ratios (HR) for overall survival (OS) were calculated. A difference-in-differences (DD) analysis examined the association of Medicaid expansion with outcomes for low-income patients aged <65. RESULTS: A total of 224,500 patients were included. Medicaid and uninsured patients were at increased risk of undergoing inappropriate therapy, including inappropriate lobectomy (Medicaid 1.36, 95% confidence interval [CI]: 1.21-1.54; uninsured 1.30, 95% CI: 1.05-1.60), and under-treatment with RAI (Medicaid 1.20, 95% CI: 1.14-1.26; uninsured 1.44, 95% CI: 1.33-1.55). Inappropriate lobectomy (HR 2.0, 95% CI: 1.7-2.3, P < .001) and under-treatment with RAI (HR 2.3, 95% CI: 2.2-2.5, P < .001) were independently associated with decreased survival, while appropriate surgical resection (HR 0.3, 95% CI: 0.3-0.3, P < .001) was associated with improved odds of survival; the model controlled for all relevant clinico-pathologic variables. No difference in AOT was observed in Medicaid expansion versus non-expansion states with respect to surgery or adjuvant RAI therapy. CONCLUSION: Medicaid and uninsured patients are at significantly increased odds of receiving inappropriate treatment for DTC; both groups are at a survival disadvantage compared with Medicare and those privately insured.

Response of Laryngopharyngeal Symptoms to Transoral Incisionless Fundoplication in Patients with Refractory Proven Gastroesophageal Reflux.

OBJECTIVE: Patients with laryngopharyngeal reflux (LPR) symptoms may not respond to proton pump inhibitors (PPI) if they have an alternative laryngeal diagnosis or high-volume reflux. Transoral incisionless fundoplication (TIF) or TIF with concomitant hiatal hernia repair (cTIF) are effective in decreasing symptoms of gastroesophageal reflux disease (GERD) but are not well studied in patients with LPR symptoms. This prospective multicenter study assessed the patient-reported and clinical outcomes after TIF/cTIF in patients with LPR symptoms and proven GERD. METHODS: Patients with refractory LPR symptoms (reflux symptom index [RSI] > 13) and with erosive esophagitis, Barrett's esophagus, and/or pathologic acid reflux by distal esophageal pH testing were evaluated before and after a minimum of 6 months after TIF/cTIF. The primary outcome was normalization of RSI. Secondary outcomes were >50% improvement in GERD-Health-Related Quality of Life (GERD-HRQL), normalization of esophageal acid exposure time, discontinuation of PPI, and patient satisfaction. RESULTS: Forty-nine patients had TIF (n = 26) or cTIF (n = 23) with at least 6 months follow-up. Mean pre- and post TIF/cTIF RSI were 23.6 and 5.9 (mean difference: 17.7, P < .001). Post TIF/cTIF, 90% of patients had improved GERD-HQRL score, 85% normalized RSI, 75% normalized esophageal acid exposure time, and 80% discontinued PPI. No serious procedure-related adverse events occurred. Patient satisfaction was 4% prior to TIF/cTIF and 73% after TIF/cTIF (P < .001). CONCLUSION: In patients with objective evidence of GERD, TIF, or cTIF are safe and effective in controlling LPR symptoms as measured by normalization of RSI and improvement in patient satisfaction after TIF/cTIF. LEVEL OF EVIDENCE: Level 4.

Association of medicaid expansion of the Affordable Care Act with the stage at diagnosis and treatment of papillary thyroid cancer: A difference-in-differences analysis.

BACKGROUND: The Affordable Care Act's (ACA) Medicaid expansion has increased insurance coverage and improved various cancer outcomes. Its impact in papillary thyroid cancer (PTC) remains unclear. METHODS: Non-elderly patients (40-64 years-old) with PTC living in low-income areas either in a 2014 expansion, or a non-expansion state were identified from the National Cancer Database between 2010 and 2016. Insurance coverage, stage at diagnosis, and RAI administration were analyzed using a difference-in-differences analysis. RESULTS: 10,644 patients were included. Compared with non-expansion states, the percentage of uninsured patients (adjusted-DD -2.6% [95%-CI -4.3to-0.8%],p = 0.004) and patients with private insurance decreased, and those with Medicaid coverage increased (adjusted-DD 9.7% [95%-CI 6.9-12.5%],p < 0.001) in expansion states after ACA implementation. The percentage of patients with pT1 did not differ between expansion and non-expansion states; neither did the use of RAI. CONCLUSIONS: Medicaid expansion has resulted in a smaller uninsured population in PTC patients, but without earlier disease presentation nor change in RAI treatment.

Ablation therapy using a low dose of radioiodine may be sufficient in low- to intermediate-risk patients with follicular variant papillary thyroid carcinoma.

OBJECTIVES: Follicular variant papillary thyroid carcinoma (FVPTC) is treated similarly to classical variant papillary thyroid carcinoma (cPTC). However, FVPTC has unique tumour features and behaviours. We investigated whether a low dose of radioiodine was as effective as a high dose for remnant ablation in patients with FVPTC and evaluated the recurrence of low-intermediate risk FVPTC. METHODS: Data from cPTC and FVPTC patients treated with I-131 from 2004 to 2014 were reviewed. Demographics, tumour behaviour, lymph node metastasis, and local recurrence data were compared between FVPTC and cPTC patients. Then, low-intermediate risk FVPTC patients were divided into low, intermediate, and high I-131 dose groups, and postoperative I-131 activities were analysed to evaluate the effectiveness of I-131 therapy for thyroid remnant ablation. RESULTS: In total, 799 cases of FVPTC (n = 168) and cPTC (n = 631) treated with I-131 were identified. Patients with FVPTC had a larger primary nodule size than cPTC, but lymph node metastases and local recurrence were more prevalent in cPTC than in FVPTC. For the low-, intermediate-, and high-dose groups, success rates of ablation did not differ (82.0%, 80%, and 81.3%, respectively). CONCLUSION: FVPTC differs from cPTC in behaviour. Low-dose ablation may be sufficient in FVPTC patients with low-intermediate disease risk.

Insurance Status Is Associated with Extent of Treatment for Patients with Papillary Thyroid Carcinoma.

Background: Health insurance has been shown to be a key determinant in cancer care, but it is unknown as to what extent insurance status affects treatments provided to papillary thyroid cancer (PTC) patients. We hypothesized that insured patients with PTC would have lower-risk tumors at diagnosis and be more likely to receive adjuvant therapies at follow-up. Methods: The American College of Surgeons' National Cancer Database was queried to identify all patients diagnosed with PTCs >2 mm in size from 2004 to 2015. Patients were grouped according to insurance status, and frequency of high-risk features and microcarcinoma at diagnosis were assessed. Multivariable analyses were used to identify independent predictors of more extensive treatment: total thyroidectomy (vs. lobectomy), lymphadenectomy, and radioactive iodine (RAI). Results: There were 190,298 patients who met inclusion criteria; the majority of patients had private insurance (139,675 [73.4%]) and were female (144,824 [76.1%]). Uninsured patients, as compared with privately insured patients, had higher rates of extrathyroidal extension of their cancers (25.2% vs. 18.9%, p < 0.001), lymphovascular invasion (16.2% vs. 12.0%, p < 0.001), and positive margins on final pathology (16.0% vs. 12.2%, p < 0.001). Conversely, patients with private insurance were 51% more likely to have microcarcinomas at diagnosis (odds ratio [OR] = 1.51 [confidence interval {CI} 1.35-1.68], p < 0.001) than uninsured patients, controlling for demographic, socioeconomic, and hospital factors. Private insurance was an independent predictor for treatment with total thyroidectomy (OR = 1.18 [CI 1.01-1.37], p < 0.05), formal lymphadenectomy (OR = 1.22 [CI 1.09-1.36], p < 0.001), and adjuvant RAI therapy (OR = 1.35 [CI 1.18-1.54], p < 0.001) as compared with no insurance, adjusted for socioeconomic, demographic, hospital, and oncologic differences. Patients with Medicare or Medicaid were no more likely to receive these treatments than uninsured patients. Conclusions: Privately insured patients have less aggressive PTCs at diagnosis, and they are more likely to be treated with total thyroidectomy, lymphadenectomy, and RAI compared with uninsured patients. Clinicians should take caution to ensure proper referral and follow-up for under- and uninsured patients to reduce disparities in treatment.

High-dose radioactive iodine therapy is associated with decreased risk of recurrence in high-risk papillary thyroid cancer.

OBJECTIVES: We aimed to determine the effect of adjuvant radioactive iodine dose on recurrence rate in high-risk papillary thyroid cancer. METHODS: More than 1,500 patients treated for papillary thyroid cancer at high-volume centers in France and the United States from 2004-2014 were reviewed. Patients considered at high risk for recurrence per the 2015 American Thyroid Association guidelines were analyzed and grouped by initial radioactive iodine dose: intermediate (median 100 mCi) or high dose (median 150 mCi). Propensity score matching was performed to control for baseline characteristics. RESULTS: In a propensity-matched cohort of 66 patient pairs, there were equivalent rates of gross extrathyroidal extension (71% vs 71%, P = 1.00), positive margins (55% vs 55%, P = 1.00), lymph node metastases ≥ 3 cm (9% vs 9%, P = 1.00), extranodal extension (32% vs 33%, P = .85), and distant metastases (2% vs 5%, P = .31). Over a median follow-up of 4.5 years (interquartile ratio 2.0-7.5 years), the intermediate-dose radioactive iodine group had a significantly higher rate of recurrence than patients in the high-dose radioactive iodine group: 24 out of 66 (36%) vs 13 out of 66 (20%), P = .03. CONCLUSION: High-dose radioactive iodine is associated with lower recurrence rate compared with intermediate-dose radioactive iodine for patients with American Thyroid Association high-risk papillary thyroid cancer.

Current controversies and future directions in the diagnosis and management of differentiated thyroid cancers.

Despite the development of novel diagnostic, surgical, and chemotherapeutic approaches to differentiated thyroid cancers (DTCs), the diagnosis and management of these tumors remains controversial. The most recent American Thyroid Association (ATA) guidelines, released in 2015, reflect a recent shift towards less aggressive management for patients with DTCs. However, many clinicians have expressed concern that more conservative management will put patients at risk for disease recurrence and metastasis. In particular, the management of indeterminate nodules on fine needle aspiration (with special attention to genetic and epigenetic markers of malignancy), the extent of surgery for known differentiated cancers, the role of adjuvant radioactive iodine (RAI) therapy, and novel targeted treatments with tyrosine kinase inhibitors (TKIs) represent current areas of uncertainty and opportunities for future research. In this review, we examine the current state of the art in these areas, and address some of the questions that remain.

Less is More: The Impact of Multidisciplinary Thyroid Conference on the Treatment of Well-Differentiated Thyroid Carcinoma.

BACKGROUND: In 2006, a multidisciplinary thyroid conference (MDTC) was implemented to better plan management of thyroid cancer patients at our institution. This study assessed the clinical impact of a MDTC on radioactive iodine (RAI) treatment patterns. METHODS: A prospective database (2003-2014) collected patient and tumor characteristics, RAI doses, and tumor recurrences. Patients treated with total thyroidectomy for differentiated thyroid carcinoma ≥1 cm were stratified based on American Thyroid Association (ATA) risk classification. RAI regimens were compared before initiation of MDTC (2003-2005, n = 88), after establishment of MDTC (2007-2009, n = 95), and after the release of 2009 ATA guidelines (2011-2014, n = 181). RAI doses were defined as low (≤75 mCi), intermediate (76-150 mCi), and high (>150 mCi). RESULTS: There was a significant decrease in the number of patients who received high-dose RAI after implementation of MDTC compared to before initiation of MDTC in the intermediate and high-risk patient groups (p = 0.04 and p < 0.01) without an associated increase in tumor recurrence (11 vs. 7%, p = 0.74). On multivariable analysis, presentation of a patient at MDTC was a negative predictor for receiving high-dose RAI (p = 0.002). As might be expected, there was also a significant decrease in use of RAI after the 2009 ATA guidelines were issued compared to after implementation of MDTC (p < 0.01). CONCLUSION: In conjunction with implementation of a thyroid malignancy multidisciplinary conference, we observed significantly decreased postoperative dosing of RAI without increased tumor recurrence. The 2009 ATA guidelines were associated with a further decrease in RAI administration. Treatment for patients with thyroid carcinoma is optimized by a multidisciplinary approach.

Thyroid stimulating hormone increases iodine uptake by thyroid cancer cells during BRAF silencing.

BACKGROUND: The BRAF(V600E) mutation is present in 62% of radioactive iodine-resistant thyroid tumors and is associated with downregulation of the sodium-iodide symporter (NIS) and thyroid stimulating hormone receptor (TSHr). We sought to evaluate the combined effect of BRAF inhibition and TSH supplementation on (131)I uptake of BRAF(V600E)-mutant human thyroid cancer cells. MATERIALS AND METHODS: WRO cells (a BRAF(V600E)-mutant follicular-derived papillary thyroid carcinoma cell line) were transfected with small interfering RNA targeting BRAF for 72 h in a physiological TSH environment. NIS and TSHr expression were then evaluated at three levels: gene expression, protein levels, and (131)I uptake. These three main outcomes were then reassessed in TSH-depleted media and media supplemented with supratherapeutic concentrations of TSH. RESULTS: NIS gene expression increased 5.5-fold 36 h after transfection (P = 0.01), and TSHr gene expression increased 2.8-fold at 24 h (P = 0.02). NIS and TSHr protein levels were similarly increased 48 and 24 h after transfection, respectively. Seventy-two hours after BRAF inhibition, (131)I uptake was unchanged in TSH-depleted media, increased by 7.5-fold (P < 0.01) in physiological TSH media, and increased by 9.1-fold (P < 0.01) in supratherapeutic TSH media. CONCLUSIONS: The combined strategy of BRAF inhibition and TSH supplementation results in greater (131)I uptake than when either technique is used alone. This represents a simple and feasible approach that may improve outcomes in patients with radioactive iodine-resistant thyroid carcinomas for which current treatment algorithms are ineffective.

Selenium decreases thyroid cancer cell growth by increasing expression of GADD153 and GADD34.

Selenium (Se) supplementation is reported to decrease the incidence and total mortality of cancer. Whereas in vitro and in vivo studies have shown a decrease in prostate, lung, and liver cancers, this has not been shown in thyroid cancer. ARO (anaplastic), NPA (BRAF positive papillary), WRO (BRAF negative papillary), and FRO (follicular) cells treated with 150 microM seleno-l-methionine (SM) were assessed for viability at 24, 48, and 72 h. Treated FRO cells were examined for cell cycle using flow cytometry, for apoptosis using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, and for gene expression using microarray. Genes identified as upregulated were confirmed by real-time PCR (RT-PCR) and proteins by Western blot analysis. SM treatment significantly decreased the proliferation of all cell lines. TUNEL assay showed no evidence of apoptosis, and flow cytometry showed a significant cell-cycle arrest in S (271% increase, P = 0.006) and G2/M (61% increase, P = 0.002) compared to control. Microarray revealed 21 differentially expressed genes with greater than twofold change. A relative overexpression of growth arrest and DNA damage inducible (GADD)34 and GADD153 in treated cells was confirmed with RT-PCR and Western blot. SM inhibits thyroid cancer cell proliferation through a time dependent upregulation of the GADD family of genes and arrest in S and G2/M phases of the cell cycle. This is the first report of selenium induced inhibition of thyroid cancer cell growth.

Papillary thyroid carcinoma and microcarcinoma: is there a need to distinguish the two?

BACKGROUND: The clinical significance of papillary thyroid microcarcinoma (PTMC) tumors < or =1 cm is widely debated. The objective of this study was to compare conventional papillary thyroid carcinoma (PTC) (tumors >1 cm) to PTMC and assess for differences in tumor characteristics and patient outcome. METHODS: A retrospective chart review of patients with PTC or PTMC who were followed for a minimum of 3 years postoperatively and managed at a single academic institute was performed. RESULTS: Of 202 patients in the study, 66 (32.7%) had PTMC and 136 (67.3%) had conventional PTC. Patient and tumor characteristics including tumor multifocality, extrathyroidal extension, angiolymphatic invasion, and lymph node metastasis were similar between both groups. Twenty-one percent of the PTMC tumors were discovered incidentally. Patients with conventional PTC were significantly more likely to undergo treatment with radioactive iodine therapy compared to PTMC patients (86.4% vs. 66.7%, respectively, p < 0.003). Disease recurrence was observed in 40 patients and was not statistically different between the two groups; 11 (16.7%) in PTMC and 29 (21.3%) in conventional PTC, p = 0.57. Within the PTMC group, tumors of patients that recurred were significantly larger than those who remained disease free (8.1 mm vs. 6.4 mm, p < 0.05). None of the patients with incidental PTMC had disease recurrence. Angiolymphatic invasion was the only significant prognostic indicator of recurrence on multivariate analysis (p < 0.02). CONCLUSIONS: Nonincidental PTMC can have aggressive tumor features and disease recurrence similar to conventional PTC. These tumors should be managed like any other papillary thyroid malignancy.