Stefano Christian Londero

Papillary Thyroid Microcarcinoma in Denmark 1996–2008: A National Study of Epidemiology and Clinical Significance

BACKGROUND With an observed general rise in papillary thyroid carcinoma incidence, papillary microcarcinoma (PMC) is accordingly found more frequently and often incidentally by histological examination of surgical specimens from presumed benign thyroid disease. Only a few studies have specifically addressed the prognosis of incidentally found PMC, and they have been limited to retrospective single-center studies. METHODS This was a national, unselected, prospective cohort study of 406 papillary thyroid microcarcinoma patients diagnosed in Denmark from 1996 to 2008. OBJECTIVE The aim of this study was to evaluate incidence, outcome, and extent of necessary treatment, with special attention given to incidentally detected PMC. RESULTS Age-standardized ratios were found to increase from 0.35 per 100,000 per year in 1996 to 0.74 per 100,000 per year in 2008. A total of 240 out of 406 cases were found incidentally, and a significant rise in incidence was only found for the incidental cases. Median follow-up was 7.6 years for the incidental cases, and in this time span, five cases of recurrence and no deaths from thyroid cancer occurred. The five-year recurrence-free survival was 98.1%, and only occurrence of lymph-node metastasis was found to affect the recurrence rate. A total of 160 incidental cases were initially treated with lobectomy, and the incidence of recurrence was not significantly different in the cases receiving completion thyroidectomy. CONCLUSION The rising incidence of PMC in Denmark is explained by incidental cases. When the carcinoma is not the index tumor for surgery, this study implies that completion thyroidectomy does not improve prognosis.

Papillary thyroid carcinoma in Denmark 1996-2008: An investigation of changes in incidence

BACKGROUND A rise in the incidence of thyroid cancer has been reported in several countries, and the increase is only seen in the papillary type. Increased detection due to higher resolution ultrasound and fine needle aspiration has been proposed as the explanation, recent registry studies however question this assumption. METHODS National, unselected, prospective cohort study of 1350 papillary thyroid cancer patients in Denmark from 1996 to 2008. OBJECTIVE To analyze changes in incidence by time and to identify factors which might influence detection rate. RESULTS A rise in incidence is seen with age standardized ratios increasing from 1.43 per 100.000 per year in 1996 to 2.16 per 100.000 per year in 2008. The median age at presentation was 46 years and median tumor size was 18 mm. Male/female ratio was 1/2.9. By dichotomizing the material in a time period before and after the 30th of June 2001, no significant change in the proportion of diagnosed tumors smaller than 1 or 2 cm was found, and 42.8% of the rise in incidence was explained by tumors larger than 2 cm. No significant change in diagnostic use of ultrasound or fine needle aspiration was found, and a significant change toward more extensive thyroid surgery could not be confirmed. CONCLUSION This study shows a significant rise in incidence of papillary thyroid carcinoma in Denmark from 1996 to 2008, which is not explained by increased use of preoperative diagnostic modalities. Other reasons need to be considered.

Papillary microcarcinoma of the thyroid gland: Is the immunohistochemical expression of cyclin D1 or galectin-3 in primary tumour an indicator of metastatic disease?

Introduction. Papillary microcarcinomas (PMC) of the thyroid gland are defined according to The WHO Committee as papillary carcinomas measuring 10 mm or less in diameter. A large proportion of these tumours are found coincidentally in the treatment of symptomatic goitre and most cases follow an indolent course with an excellent prognosis. However, a more aggressive behaviour with regional and distant metastases does occur. The aim of this study was to evaluate if the immunohistochemical markers cyclin D1 or galectin-3 might indicate the presence of metastatic disease in patients with PMC at the time of diagnosis. Material and methods. From the 1st of January 1996 to 31st of December 2002 a total of 169 PMC patients were diagnosed and registered in the national Danish thyroid cancer database DATHYRCA and 131 of these were eligible for the study. Forty-three (33%) had histologically verified regional or distant metastases. Slides were cut from the primary tumour and immunostaining and quantification was subsequently performed. Results. The percentage of positive cells was examined for patients with and without metastases. For cyclin D1 the median values were 31% (range: 0–59) and 21% (range: 0–75), respectively, showing a statistically significant difference (p=0.02). For galectin-3 the medians were 87% (range: 6–96) and 85% (range: 0–99) and no significant difference was found. Conclusion. Cyclin D1 showed significantly higher median expression in patients with metastases compared to those without, indicating a correlation to tumour aggressiveness. However, both groups showed large variation in expression, which disqualify the marker as a discriminator for the detection of metastases. Galectin-3 was without any significant correlation to the presence of metastases from PMC.

Papillary thyroid carcinoma in Denmark, 1996-2008

BACKGROUND Regional as well as national series show an increasing incidence of thyroid cancer largely small size papillary thyroid carcinoma (PTC). Prognostic scoring systems have been developed, but these do not take into account the rapidly changing case mix, and adjustments may be required. The purposes of this study were to evaluate treatment outcomes and to analyze the value of older prognostic scoring systems tested on a relatively new, unselected national cohort of PTC patients. METHODS This was a national prospective cohort study conducted in Denmark, which has a population of 5.5 million. RESULTS A total of 1350 patients were diagnosed with PTC during 1996-2008, and the median follow-up time was 7.9 years. The 10-year recurrence-free survival rate was 90.2%, and the 10-year crude and cause-specific survival (CSS) rates were 83.7% and 93.8% respectively. By multivariate Cox regression, it was possible to confirm age, metastases (distant and nodal), extrathyroidal extension, and tumor size as predictors of mortality, whereas only nodal metastases, extrathyroidal extension, and tumor size were predictors of recurrence. In analyses of older prognostic scoring systems, a significant correlation between the risk group ranks was found for survival as well as recurrence. The c-index for CSS was highest for MACIS (0.92) and lowest for AMES (0.80). In the TNM, MACIS, and EORTC systems, most patients were classified as stage 1, and for these patients, the 10-year CSS rate was approximately 99.5%, confirming the generally excellent survival. CONCLUSION This national study provides further evidence that a favorable prognosis is to be expected for patients diagnosed with PTC. Also, it was possible to confirm age, metastases, extrathyroidal extension, and tumor size as predictors of mortality, whereas only nodal metastases, extrathyroidal extension, and tumor size were predictors of recurrence. All the scoring systems evaluated were able to produce a highly significant risk group stratification, showing that in spite of the changes in the case mix of PTC, these systems are still applicable, and in fact contain valuable prognostic information useable for treatment planning.

Completeness and validity in a national clinical thyroid cancer database: DATHYRCA

BACKGROUND Although a prospective national clinical thyroid cancer database (DATHYRCA) has been active in Denmark since January 1, 1996, no assessment of data quality has been performed. The purpose of the study was to evaluate completeness and data validity in the Danish national clinical thyroid cancer database: DATHYRCA. STUDY DESIGN AND SETTING National prospective cohort. Denmark; population 5.5 million. Completeness of case ascertainment was estimated by the independent case ascertainment method using three governmental registries as a reference. The reabstracted record method was used to appraise the validity. For validity assessment 100 cases were randomly selected from the DATHYRCA database; medical records were used as a reference. RESULT The database held 1934 cases of thyroid carcinoma and completeness of case ascertainment was estimated to 90.9%. Completeness of registration was around or above 90% in most instances. Perfect agreement on the diagnosis of thyroid carcinoma was found, both inter- and intra-observer, and κ values of selected variables showed overall good to excellent agreement. CONCLUSION In a setup with public health insurance, personal identity numbers and extended governmental databases, it is possible to establish national clinical cancer databases with a satisfactory completeness and validity. The DATHYRCA database is considered reliable in terms of describing thyroid carcinoma at a national level.

Nonanaplastic follicular cell-derived thyroid carcinoma: mitosis and necrosis in long-term follow-up

Nonanaplastic follicular cell-derived thyroid carcinoma (NAFCTC) includes differentiated- (DTC) and poorly differentiated thyroid carcinoma (PDTC). DTC has an excellent prognosis, while PDTC is situated between DTC and anaplastic carcinomas. Short-term studies suggest that PDTC patients diagnosed only on tumor necrosis and/or mitosis have a prognosis similar to those diagnosed according to the TURIN proposal. The purpose of this study was to evaluate prognosis for NAFCTC based on long-term follow-up illuminating the significance of tumor necrosis and mitosis. A cohort of 225 patients with NAFCTC was followed more than 20 years. Age, sex, distant metastasis, histology, tumor size, extrathyroidal invasion, lymph node metastasis, tumor necrosis and mitosis were examined as possible prognostic factors. Median follow-up time for patients alive was 28 years (range 20–43 years). Age, distant metastasis, extrathyroidal invasion, tumor size, tumor necrosis and mitosis were independent prognostic factors in multivariate analysis for overall survival (OS). In disease specific survival (DSS) age was not significant. Using only necrosis and/or mitosis as criteria for PDTC the 5-, 10- and 20-year OS for DTC was 87, 79 and 69%, respectively. In DSS it was 95, 92 and 90%. For PDTC the 5-, 10- and 20-year OS was 57, 40 and 25%, respectively. In DSS it was 71, 55 and 48%. Tumor necrosis and mitosis are highly significant prognostic indicators in analysis of long time survival of nonanaplastic follicular cell-derived thyroid carcinoma indicating that a simplification of the actually used criteria for poorly differentiated carcinomas may be justified.