Staging systems for follicular thyroid carcinoma: application to 171 consecutive patients treated in a tertiary referral centre.

A number of risk-group stratification or staging systems have been found useful at stratifying patients with differentiated thyroid carcinoma into risk groups. Those identified as high risk could be subjected to more aggressive treatment, while those at low risk could be spared of such treatment. However, the best stratification system in patients with follicular thyroid carcinoma (FTC) remains unclear. Through a comprehensive MEDLINE search from 1965 to 2005, a total of 18 different staging systems were identified in the literature and 14 of them were applicable to 171 patients, with FTC managed at our institution from 1961 to 2001. Cancer-specific survivals (CSS) were calculated by Kaplan-Meier method and were compared by log-rank test. Using Cox proportional hazards analysis, the relative importance of each staging system in determining CSS was calculated by the proportion of variation in survival time explained (PVE). CSS were predicted by 13 out of the 14 staging systems significantly (P < 0.001). The three highest ranked staging systems by PVE were the new American Joint Committee on Cancer/Union Internationale Centre le Cancer 6th edition, tumour, node, metastases (TNM; 22.4), followed by the Clinical Class (21.2) and the metastases, age, completeness of resection, invasion, size (MACIS; 20.4). In conclusion, 13 out of the 14 presently available staging systems predicted CSS significantly in FTC. When predictability was measured by PVE, the TNM system was found to have the best predictability and thus, should be the stratification system of choice for FTC in the future.

Aberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma.

3p21 is an important locus harbouring critical tumour suppressor genes (TSG), which are implicated in the pathogenesis of multiple tumours, including oesophageal carcinoma. RASSF1A is a 3p21.3 candidate TSG frequently inactivated by promoter methylation in multiple tumours. We investigated RASSF1A promoter methylation and gene expression in Chinese oesophageal squamous cell carcinoma (ESCC) to compare it to data from Japanese patients. Methylation-specific PCR (MSP) showed that RASSF1A was partially methylated in 3/7 (43%) cell lines; 22/64 (34%) primary tumours and 3/64 (5%) corresponding non-tumour samples; and was not methylated in 2 immortalized normal oesophageal epithelial cell lines and 6 normal oesophageal epithelium samples. Bisulfite genome sequencing confirmed the MSP results. Promoter hypermethylation correlated well with RASSF1A mRNA down-regulation. Treatment of cell lines with 5-aza-2'-deoxycytidine activated RASSF1A mRNA expression along with promoter demethylation. RASSF1A hypermethylation in the Chinese cohort was much lower than in a published report of Japanese ESCC patients (52%) and cell lines (74%). Our own analysis of Japanese ESCC cell lines for direct comparison also detected a high frequency of RASSF1A hypermethylation (8/10; 80%) and high levels of hypermethylation at each CpG site. No significant association between RASSF1A hypermethylation and histological differentiation (p=0.953), tumour staging (p=0.117), or survival (p=0.7571) was found in Chinese ESCC, unlike the results of Japanese patients. The incidence of oesophageal cancer shows marked variation by geographic area and ethnic group; it is almost three times higher in China than in Japan, indicating possible different pathogenetic mechanisms. Our results show that RASSF1A hypermethylation in ESCC has epidemiological/ethnic differences, and suggest that Chinese ESCC may result from different pathogenetic mechanisms.

Increased expression of vascular endothelial growth factor C in papillary thyroid carcinoma correlates with cervical lymph node metastases.

PURPOSE: Despite recent studies showing that vascular endothelial growth factor C (VEGF-C) mRNA is up-regulated in papillary thyroid carcinoma (PTC), the role of VEGF-C in lymph node metastasis is still unclear. The aim of this study is to investigate the expression pattern of VEGF-C immunoreactive protein in PTC and its relationship with cervical lymph node metastasis. EXPERIMENTAL DESIGN: Tissue samples were obtained from 39 specimens of PTC (20 with and 19 without lymph node metastasis) as well as 20 benign thyroid nodules. Overexpression of the VEGF-C protein was evaluated by immunoblotting with specific anti-VEGF-C antibody in paired tumor and nontumor tissues from PTC. The data were compared with patients' clinicopathologic features and lymph node metastasis. Immunohistochemical staining was done on selected paraffin sections to determine cellular localization of VEGF-C and to assess flt-4 (or VEGFR-3)-positive vessel density in PTC lesions. RESULTS: Overexpression of VEGF-C was detected in 69% of the PTC and in 5% of the benign thyroid specimens. When comparing between the metastatic and nonmetastatic groups of PTC, a higher expression level of VEGF-C was detected in both the tumor (P = 0.004) and adjacent nontumor tissues (P = 0.011). Positive immunostaining for VEGF-C was confirmed in PTC tumor tissues and metastatic lymph nodes, which correlated with flt-4-positive vessel density in tumor and peritumor tissues. The increased expression of VEGF-C protein in PTC is associated with lymph node metastasis (P = 0.004) and lymphovascular permeation (P = 0.001) but is independent of other clinicopatholgic variables. CONCLUSIONS: The VEGF-C immunoreactive protein is overexpressed in PTC lesions, which correlates with lymph node metastases. VEGF-C expression may play a role in lymphangiogenesis of PTC and further study is necessary to evaluate the clinical application of VEGF-C as a molecular marker for tumor metastases to cervical lymph nodes.

Warthin tumor-like variant of papillary thyroid carcinoma: a case with dedifferentiation (anaplastic changes) and aggressive biological behavior.

Warthin tumor-like variant of papillary thyroid carcinoma is uncommon and approx 80 cases have been reported in the literature. This tumor is often associated with a favorable prognosis. In this report, a Warthin tumor-like variant of the papillary thyroid carcinoma, 5-cm in maximum dimension, underwent anaplastic changes in a 74-yr-old woman. The tumor was positive for CD15 and EMA, and a high proliferative index was noted in the anaplastic area. The patient developed distant metastases after operation and died of the disease 18 mo after the operation. The present case is the first reported case of Warthin tumor-like variant of papillary thyroid carcinoma with anaplastic changes.

Regulation and expression of a renin-angiotensin system in human pancreas and pancreatic endocrine tumours.

OBJECTIVE: Evidence exists for the presence of a renin-angiotensin system (RAS) in the pancreas. The aims of this study were to prove the presence of an intrinsic RAS in the human pancreas and to analyse the role of such an RAS in pancreatic endocrine tumours (PETs). METHODS: Gene expression of key RAS components (angiotensinogen and angiotensin II receptors, namely AT1 and AT2) was investigated in human pancreas and in PETs by semi-quantitative RT-PCR and immunohistochemistry. RESULTS: Expression of mRNAs of RAS components was found in human pancreas and in PETs. Data from semi-quantitative RT-PCR analysis demonstrated an increase in the mRNA expression of angiotensinogen and AT2 receptor in PETs when compared with that in normal pancreas. By immunohistochemistry, angiotensinogen protein was predominantly localized in the pancreatic islets while AT1 receptor protein was in the pancreatic ducts. CONCLUSIONS: The data support the notion of the existence of an intrinsic RAS in the human pancreas. It also indicates, for the first time, that such a local pancreatic RAS is subject to regulation by PETs and its significant change may have pathophysiological relevance in patients with PETs.

High prevalence of RET proto-oncogene activation (RET/PTC) in papillary thyroid carcinomas.

OBJECTIVE: The activation of RET proto-oncogene, through different types of chromosomal translocation and inversion, is unique to papillary thyroid carcinomas (PTC) and its frequency is variable in different populations. The aim of this study was to investigate the frequency and types of PTC genetic rearrangements in papillary carcinoma in a population of Hong Kong Chinese. METHODS: The presence of RET/PTC1, RET/PTC2 and RET/PTC3 activation was analyzed by RT-PCR in twenty PTC from adult patients (age range 24-63 years), one PTC from a 12-year-old boy and anaplastic carcinomas in two adult patients. RESULTS: RET/PTC3 was the only activation of RET proto-oncogene identified in the samples. Seventeen PTC from adult patients (85%t) were positive for RET/PTC3. RET/PTC3 was also identified in PTC from the child and one of the two patients with anaplastic thyroid carcinoma. CONCLUSIONS: The prevalence of RET/PTC activation in PTC is high and RET/PTC3 is the only type of activation identified in Hong Kong Chinese and is an important genetic event underlying the development of PTC in the population.

Surgical treatment for primary hyperparathyroidism in Hong Kong: changes in clinical pattern over 3 decades.

HYPOTHESIS: With the introduction of the blood chemistry multichannel autoanalyzer, primary hyperparathyroidism (HPT) is increasingly diagnosed. The clinical pattern of primary HPT has undergone a significant evolution in Western countries. A similar change can be documented in a geographic region where this condition is considered to be relatively uncommon. DESIGN: Unselected case series. SETTING: A tertiary referral endocrine surgical unit. PATIENTS: All patients with primary HPT surgically treated over the past 30 years. MAIN OUTCOME MEASURES: The prevalence of patients per 100,000 hospital admissions, clinical presentation, biochemistry study results, pathologic status, and main outcome were compared over three 10-year spans according to the introduction of the multichannel autoanalyzer in 1982: 1973-1982 (n = 20), 1983-1992 (n = 31), and 1993-2002 (n = 190). RESULTS: A 7-fold increase in the prevalence of patients with primary HPT who were surgically treated per 100,000 hospital admissions was observed over the past 10 years. The clinical presentation of patients with primary HPT had evolved progressively with a higher proportion of older patients (P<.001) being asymptomatic. On presentation, the condition had decreased in severity with lower serum calcium (P =.04), parathyroid hormone (P<.001), and alkaline phosphatase levels (P<.001) as well as a smaller adenoma size (P<.001). There was no significant change in the underlying pathologic condition and surgical success. CONCLUSION: Similar to the West but in contrast to that observed in other Asian countries, an increase in the prevalence of patients surgically treated for primary HPT is documented and a change in disease presentation as well as its severity is observed in our population group.

Autopsy findings in diabetic patients: a 27-yr clinicopathologic study with emphasi on opportunistic infections and cancers.

Diabetes mellitus has become a growing epidemic in the Asia-Pacific region. The aims of this study were to determine at autopsy the prevalence and characteristics of pathologic lesions in patients with diabetes mellitus. The 13,215 autopsy reports in our institution were examined for the diagnosis of diabetes mellitus. In patients with diabetes mellitus, the demographic data and the different pathologic lesions noted were analyzed. Diabetes mellitus was found in 820 patients (426 men and 394 women), comprising 6.2% of all autopsies. The two most common types of disease were cardiovascular diseases and infections, found in 69 and 53% of diabetic patients, respectively. Bacterial infection, in particular tuberculosis, was the most common type of infection noted. Localized and disseminated fungal infections were also common. In addition, urinary tract diseases were noted in 48%, hepatobiliary tract lesions in 42%, central nervous system disorders in 25%, and tumors in 29% of the diabetic patients. Malignant tumors were more often seen than benign tumors (18 vs 11% of patients, respectively). Many of the tumors were adenocarcinomas, and the most common neoplastic lesions were carcinomas of the lung, pancreas, liver, large intestine, stomach, and esophagus. Diabetic complications and associated diseases are common problems in this population. Adequate health care resources are needed for their prevention and treatment.

Neurothekeoma of the paranasal sinuses in a 3-year-old boy.

Neurothekeoma is a benign soft tissue tumor commonly located on the skin. In this report, a 3-year-old boy presented with restricted right eye movement and decrease in visual acuity. The patient was found to have a 6-cm neurothekeoma involving the maxillary and ethmoid sinuses. To our knowledge, this is the first reported case of neurothekeoma with involvement of the maxillary and ethmoid sinuses. This uncommon lesion should be considered as the differential diagnosis of pediatric soft tissue tumors in the head and neck region.

Staging systems for papillary thyroid carcinoma: a study of 2 tertiary referral centers.

OBJECTIVE: To find out the most applicable and consistent staging system for papillary thyroid carcinoma (PTC) available in the literature. BACKGROUND: The commonly used staging systems for PTC have predicted cancer-specific survival (CSS) well. However, their applicability and generalizability have not yet been evaluated in different clinical settings. METHODS: A MEDLINE search from 1965 to 2005 was carried out to identify different staging systems available in the literature and 9 systems were applicable to 1634 PTC patients within 2 tertiary-referral centers. The CSS of each staging system within individual centers were calculated using Kaplan-Meier method and the CSS of each tumor stage in one individual center was compared with that of the other by log-rank test. In addition, within each center, the predictability of each staging system relative to the others was ranked based on the proportion of variation explained (PVE) value. RESULTS: Clinicopathologic features, treatment received, and tumor stages were significantly different between the 2 centers. There were also significant differences in CSS within at least one tumor stage between the 2 centers in 8 of the 9 staging systems. The TNM was a highly predictive and consistent staging system within the 2 centers. Although the absolute PVE values differed between the 2 centers, the relative ranking of the 9 staging systems within each center correlated significantly to each other (P < 0.05). CONCLUSIONS: Despite referral, treatment, and data collection biases inherent within each center, the TNM system remained to be the most applicable and consistent staging system for PTC in 2 centers managing the same population group.

Staging systems for papillary thyroid carcinoma: a review and comparison.

OBJECTIVE: To find out the most predictive staging system for papillary thyroid carcinoma (PTC) currently available in the literature. BACKGROUND: Various staging systems or risk group stratifications have been used extensively in the clinical management of patients with PTC, but the most predictive system for cancer-specific survival (CSS) based on distinct histologic types remains unclear. METHODS: Through a comprehensive MEDLINE search from 1965 to 2005, a total of 17 staging systems were found in the literature and 14 systems were applied to the 589 PTC patients managed at our institution from 1961 to 2001. CSS were calculated by Kaplan-Meier method and were compared by log-rank test. Using Cox proportional hazards analysis, the relative importance of each staging system in determining CSS was calculated by the proportion of variation (PVE). RESULTS: All 14 staging systems significantly predicted CSS (P < 0.001). The 3 highest ranked staging systems by PVE were the Metastases, Age, Completeness of Resection, Invasion, Size (MACIS) (18.7) followed by the new AJCC/UICC 6th edition tumor, node, metastases (TNM) (17.9), and the European Organization for Research and Treatment of Cancer (EORTC) (16.6). CONCLUSIONS: All of the currently available staging systems predicted CSS well in patients with PTC regardless of which histologic type from which they were derived. When predictability was measured by PVE, the MACIS system was the most predictive staging system and so should be the staging system of choice for PTC in the future.

Prognostic factors in papillary and follicular thyroid carcinoma: their implications for cancer staging.

BACKGROUND: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are two distinct histological types of thyroid carcinoma but have often been studied and staged as a collective group, known as differentiated thyroid carcinoma (DTC). However, this may not be an optimal approach to cancer staging. METHODS: A total of 760 patients with DTC, comprising 589 (77.5%) with PTC and 171 with (22.5%) FTC, being managed at our institution from 1961 to 2001 were retrospectively reviewed. Their clinicopathological features, treatment modalities received, and postoperative outcome were analyzed. Both univariate and multivariate analyses were performed to identify prognostic factors related to cancer-specific survival (CSS) for PTC and FTC. RESULTS: There were statistically significant differences between PTC and FTC in terms of age >/=50 years at diagnosis (P = .040), tumor size (P < .001), lymph node metastases (P < .001), distant metastases (P < .001), extrathyroidal extension (P < .001), multifocality (P = .002), capsular invasion (P < .001), extent of thyroid resection (P < .001), radioiodine ablation (P < .001), and external-beam irradiation (P = .003). Although PTC and FTC had similar 10-year and 15-year CSS (P = .846), each possessed its own set of independent prognostic factors for CSS. Age at diagnosis and completeness of resection were independent prognostic factors in both PTC and FTC. CONCLUSIONS: There were marked differences in clinicopathologic features, treatment, and prognostic factors between the two histologic types of DTC. Different staging systems should be evaluated and validated for PTC and FTC individually in the future.

Restaging of differentiated thyroid carcinoma by the sixth edition AJCC/UICC TNM staging system: stage migration and predictability.

BACKGROUND: The AJCC/UICC TNM staging system (TNM) is a widely accepted system for differentiated thyroid carcinoma (DTC). The objective of the present study was to evaluate the potential changes in cancer-specific survival (CSS) after reclassification from fifth to sixth edition TNM. METHODS: A total of 760 DTC patients managed at our institution from 1961 to 2001 were retrospectively restaged from the fifth to sixth edition TNM. CSS were calculated using Kaplan-Meier method and were compared by the log-rank test. The relative ability of each edition in predicting CSS was calculated by the proportion of variance explained (PVE). RESULTS: Upon reclassification, the proportion of T1 and T3 tumors increased from 14.2 to 33.4% and 10.0 to 33.7%; T2 and T4 decreased from 44.2 to 25.0% and 31.6 to 7.9%, respectively; N0 remained unchanged at 66.0%; N1a decreased from 25.7 to 4.7%; N1b increased from 8.4 to 29.3%; stages I and IV tumors increased from 55.7 to 60.3% and 3.4 to 17.6%, respectively; stages II and III tumors decreased from 20.5 to 13.9% and 20.4 to 8.2%, respectively. The sixth edition had a higher PVE value than the fifth edition. Significant differences in CSS were observed between stage III (fifth edition) and stage III (sixth edition) and between stage IV (fifth edition) and stage IVA (sixth edition). CONCLUSIONS: The sixth edition TNM caused marked changes in the pT, pN and allocation of patients into different tumor stages. It appeared to have superior predictability over the fifth edition.

Papillary microcarcinoma: is there any difference between clinically overt and occult tumors?

INTRODUCTION: Papillary microcarcinoma (PMC) is a subtype of papillary thyroid carcinoma (PTC) associated with excellent prognosis. However, clinical and biologic behaviors of PMC may vary considerably between tumors that are clinically overt and those that are occult. MATERIALS AND METHODS: From 1964 to 2003, 185 of 628 patients with PTC were identified as having PMC, based on tumor size < or = 1 cm. There were 110 overt and 75 occult PMCs detected based on clinical presentation. The clinicopathologic features, treatment, and long-term outcome of PMCs were evaluated and compared between the two groups. RESULTS: There were 37 men and 148 women with a median age of 45 years (range: 11-84 years). The median tumor size was 6.2 mm. Thirty-eight (21%) patients presented with cervical nodal metastases. Three (1.6%) had distant metastases and 5 (2.7%) underwent incomplete resection. Bilateral procedures were performed for 129 patients (70%) and 53 (29%) received postoperative I131 treatment. During a mean follow-up of 8.2 years, 4 patients died of the disease and 13 developed recurrence. Clinically overt PMCs were significantly larger, were more likely to be multifocal, and more likely to lead to bilateral thyroidectomy. Extrathyroidal or lymphovascular invasion, nodal metastases, I131 ablation, high-risk tumors, and postoperative recurrence occurred in overt PMC only. Patients with nodal metastases had a decreased survival and an increase in locoregional recurrence. CONCLUSIONS: Despite a relatively good prognosis in PMC, a distinction should be made between clinically overt and occult PMCs in which clinically overt PMC should be managed according to tumor risk profile and clinical presentation.

Follicular thyroid carcinoma: the role of histology and staging systems in predicting survival.

OBJECTIVE: To evaluate the risk factors including tumor histomorphology for survival specific to follicular thyroid carcinoma (FTC) and to apply commonly employed staging systems in predicting survival for patients with FTC. SUMMARY BACKGROUND DATA: FTC is usually analyzed collectively with papillary thyroid carcinoma (PTC) in risk group analysis. Risk factors and risk group analysis are important in the management of patients with FTC, although current published therapeutic guidelines call for total thyroidectomy followed by radioactive iodine (I) ablation for all FTC patients. METHODS: Over a 40-year period, 156 patients surgically treated for FTC with an average follow-up of 14.4 years were retrospectively studied after histologic reclassification according to the type and degree of invasiveness of the tumor. Potential risk factors for survival were calculated using multivariate analysis, and the prognostic accuracy of AMES risk group stratification, UICC/AJCC pTNM staging, Degroot classification, and MACIS scoring schemes in predicting survival was compared. RESULTS: Seventeen (11%) patients had distant metastases at presentation, and bilateral thyroid resection was performed for 131 (84%) patients. Seventeen (11%) patients died of recurrent or metastatic disease. The overall and cancer-specific survival (CSS) rates at 10 years were 79% and 88%, respectively. None of the patients with minimally invasive (n = 49) or angioinvasive (n = 23) carcinomas died compared with 17 of 84 patients with widely invasive carcinomas (P = 0.0007). Using the Cox proportional hazards model, old age, the presence of distant metastases, and incomplete tumor excision were independent prognostic factors for survival. For patients who underwent curative treatment, old age and widely invasive carcinoma were risk factors for poor survival. All staging systems studied accurately predicted CSS, and the pTNM UICC/AJCC staging system yielded the best prognostic information. CONCLUSIONS: Commonly adopted staging systems can be applied specifically to patients with FTC. The distinction of FTC in minimally invasive and widely invasive carcinoma based on the extent of invasiveness rather than vascular invasion is important in identifying low-risk FTC patients for a more conservative management.

The Clinicopathologic Significance of Unilateral Adrenal Cortical Hyperplasia: Report of an Unusual Case and a Review of the Literature.

We report a case of unilateral primary adrenal cortical hyperplasia associated with hyperaldosteromsm in a 39-yr-old Chinese man. The patient presented with hypertension hy pokalemia, primary hyperaldosteronism(1) suppressed renin activity, and was complicated with aortic dissection. The aortic dissection required emergency realignment while unilateral laparoscopic adrenalectomy was performed subsequently Pathologic examination of the adrenal lesion revealed multiple cortical nodules (up to 1 4 cm in diameter). No telomerase activity was detected in the adrenal lesion. A review of the literature showed that unilateral adrenal cortical hyperplasia has a predilection for the left side occurring more often in males. We conclude that unilateral adrenal cortical hyperplasia is a rare but unique entity and that unilateral adrenalectomy is the treatment of choice.

Composite Pheochromocytoma-Ganglioneuroma of the Adrenal Gland: An Uncommon Entity with Distinctive Clinicopathologic Features.

Background: Adrenal composite pheochromocytoma-ganglioneuroma is uncommon. The aim of this study is to investigate the characteristics of patients with this tumor. Methods: Histologic features of 46 pheochromocytomas diagnosed over a 28-year period (1971-1998) were reviewed. The clinical records, pathologic features, and ploidy patterns of patients with composite pheochromocytoma-ganglioneuroma were studied. Cases reported in the literature were also reviewed and compared with typical pheochromocytomas. Results: Four patients (two men; two women) with composite pheochromocytoma-ganglioneuromas were found. The tumors comprised 8.7% of pheochromocytomas. The two male patients with composite tumors were younger than the two female patients (age = 32, 52 vs 73, 75, respectively). The radiologic, gross, and microscopic appearances of the tumors were heterogeneous. One patient had malignant tumor with distant metastases. Flow cytometric analysis showed that the pheochromocytoma component was aneuploid and the ganglioneuroma portion was diploid. A review of the literature showed 31 adrenal composite pheochromocytoma-ganglioneuromas. Composite tumors were seen in older patients and were bigger than typical pheochromocytomas. Conclusion: Composite pheochromocytoma-ganglioneuromas had distinctive clinicopathologic features. Life-long clinical and biochemical follow-up of these patients is essential in view of the non-diploid DNA pattern.

Optimizing the treatment of AMES high-risk papillary thyroid carcinoma.

A minority of patients with papillary thyroid carcinoma (PTC) is at high-risk of developing recurrent disease and death. Risk group stratification as defined by age, metastases to distant site, extrathyroidal invasion, and tumor size (AMES) criteria is frequently employed to identify high-risk patients for aggressive surgical and adjuvant treatments. The present study aimed at evaluating risk factors and the impact of treatment on cause-specific mortality (CSM) in this group of high-risk patients. From 1961 to 2000,150 of 499 patients surgically treated for PTC were considered as high-risk by AMES criteria. At 10-years CSM was significantly higher in high-risk patients (28%) than in low-risk patients (2%) (p < 0.0001). The clinicopathologic features, treatment, and outcome of AMES high-risk patients were retrospectively studied and risk factors for CSM were analyzed. There were 58 men and 92 women with a median age of 62 years (range: 18-87 years). Bilateral thyroidectomy was performed for 143 (95%) patients and concomitant neck dissection was performed for 82 patients (55%). Thirty-six patients (24%) underwent incomplete tumor excision with residual disease. Radioactive iodine (I131) ablation and external-beam irradiation were administered to 102 (68%) and 46 patients (31%), respectively. Over a median follow-up of 7.6 years, the overall mortality was 23% and 44%, whereas the CSM was 14% and 28% at 5 and 10 years, respectively. Using the Cox proportional hazard model, distant metastasis at presentation, incomplete tumor excision, and no postoperative I131 treatment were independent prognostic factors of poor survival. Patients who underwent an incomplete excision showed improved survival after I131 ablation (p = 0.0008), external-beam irradiation (p = 0.02), or both forms of treatment (p = 0.04). Within this high-risk AMES group, International Union Against Cancer (UICC) pTNM staging and MACIS (Metastasis, Age, Completeness, Invasion, Size) scoring correlated significantly with CSM. AMES high-risk PTC patients should undergo total thyroidectomy aiming at complete tumor resection followed by I131 ablation. External-beam irradiation should be added for patients with residual disease after an incomplete excision.