Differentiated thyroid carcinoma: initial evaluation and follow-up

Thyroid carcinoma accounts for roughly 1% of all new malignant diseases. Of these, at least 94% are differentiated thyroid carcinoma (DTC), either papillary thyroid carcinoma or follicular thyroid carcinoma. Patients with DTC are usually considered as having a good prognosis, 80% of patients are cured, 20% will develop loco-regional recurrence and 5-10% distant metastasis. However, the disease may have an aggressive course in some patients. The identification of these patients has a major impact in the clinical management of DTC. Several prognostic factors and classification will be addressed, as well the most useful tests for patients follow-up.     

Classification of thyroid follicular cell tumors: with special reference to borderline lesions

We propose a new classification of thyroid follicular cell tumors which is correlated with patient's prognosis. It is unique as to two new categories: borderline malignancy between benign and malignant, and moderately differentiated adenocarcinoma (MDA) as a differentiation classification to stratify tumor aggressiveness. As to diagnostic criteria, we recommend invasiveness (capsular and vascular invasion) to separate benign and malignant and it should not be based on presence or absence of papillary thyroid carcinoma (PTC) type nuclear features (PTC-N). Thus borderline malignancy in our new classification includes some of the formerly malignant tumors and they are 1) papillary microcarcinoma, 2) encapsulated conventional PTC (EncPTC), 3) encapsulated follicular variant PTC (EnFVPTC), 4) well differentiated tumor of uncertain malignant potential (WDT-UMP), 5) follicular tumors of uncertain malignant potential (FT-UMP), and 6) capsular invasion only follicular thyroid carcinoma (FTC). Review of the literature revealed that those thyroid tumors have consistently excellent outcome. Well differentiated follicular cell adenocarcinoma (WDA) in our classification includes common type PTC and low-risk follicular carcinoma (FTC). They are invasive (diffuse infiltrative) common type PTC and minimally invasive type FTC with less than 4 foci of angioinvasion. Moderately differentiated follicular cell adenocarcinoma (MDA) includes FTC with angioinvasion (more than 4), aggressive variants of PTC, such as tall cell, columnar cell, solid, loss of cellular polarity/cohesiveness (hobnail) variants and encapsulated carcinoma with high grade histology. Poorly differentiated carcinoma (PDC) includes PDC of WHO definition, insular carcinoma, tumors with minor anaplastic transformation and tumors with distant metastasis at presentation.     

Iodine and cancer.

Thyroid carcinomas are the most frequent endocrine malignancies. Among thyroid carcinomas the most frequent types are the differentiated forms (follicular, papillary or mixed papillary-follicular), whereas anaplastic thyroid carcinoma and medullary thyroid carcinomas are rare. Animal experiments have demonstrated a clear increase in incidence of thyroid epithelial cell carcinomas after prolonged iodine deficiency leading to a situation of the thyroid gland by thyrotropin and possibly other growth factors. However, the overall incidence of differentiated thyroid carcinoma is generally not considered to be influenced by the iodine intake of a population, whereas the distribution of the types of thyroid carcinoma seems to be related to the intake of iodine, with fewer of the more aggressive follicular and anaplastic carcinomas and more papillary carcinomas in iodine rich areas. Populations starting iodine prophylaxis demonstrate an increase in the ratio of papillary to follicular carcinoma. Because a population with higher iodine intake usually has fewer benign nodules in the thyroid gland and the incidence of thyroid carcinomas is similar to an iodine-deficient region, the diagnostic work-up of nodules in the thyroid gland may become affected. The incidence of other cancers, such as breast cancer, may be influenced by the iodine intake, but too few studies are available at present. The present article summarizes available data from both epidemiological studies, animal experiments, and basic gene transfection studies. The overall incidence for a relationship between iodine and cancer is poor and future studies are warranted.     

Prognostic variables of papillary and follicular thyroid carcinoma patients with lymph node metastases and without distant metastases

From 1977 through 1995, 1,013 thyroid carcinoma patients received treatment and were followed up at Chang Gung Medical Center in Taiwan. To evaluate the prognostic variables of papillary and follicular thyroid carcinomas with limited lymph node metastases, a retrospective review of these patients was performed. Of these patients, 910 had papillary or follicular thyroid carcinoma, and 119 patients were categorized as clinical stage 2 with limited neck lymph node metastases only at the time of diagnosis. The patients were categorized into two groups as no recurrence and local recurrence or distant metastasis at the end of 1997. After the operations, radioactive iodide (131I) treatments were performed in 114 patients and external radiotherapy for neck region or distant metastases in 18 patients. The median follow-up period of these patients was 5.4 years. Clinical variables were coded in our computer for statistical analysis. After the treatments, 93 patients remained disease-free; 10 were in stage 2; 5 in stage 3; and 11 aggravated to stage 4. Of the clinical variables, age, post-operative first 1311 uptake scans, and 1-month post-operative thyroglobulin levels revealed statistically significant differences between the group which improved and the group which did not. During the follow-up period, five patients died; three patients died of thyroid cancer and two died of intercurrent diseases. Patients with papillary thyroid carcinoma revealed a higher percentage of lymph node metastases. Although limited lymph node metastases did not influence survival rate, patients with poor prognostic factors need more aggressive treatment to avoid progression of the cancer.     

Follicular thyroid carcinomas with lung metastases: a 23-year retrospective study

Limited clinical information is specified in the presentations, results of treatment and prognostic factors of follicular thyroid carcinoma with lung metastases. In order to better characterize the information, we retrospectively analyzed the data of 2,003 thyroid cancer patients who received treatment and follow-up at the Chang Gung Memorial Hospital during the period from January 1979 to December 2002. There were 1,516 cases of papillary and 272 cases of follicular thyroid carcinomas. In the study, lung metastases of the follicular thyroid carcinomas were defined as post-operative or follow-up chest X-ray, diagnostic or therapeutic (131)I scan with positive finding of lung metastases. Serum thyroglobulin (Tg) levels under thyroxine treatment of patients with lung metastases had to be over 1.5 ng/mL. Of the follicular thyroid carcinomas, there were 70 (25.7%) with lung metastases including 50 females (mean age 54.1 +/- 12.6 years old) and 20 males (mean age 59.4 +/- 12.0 years old). Of the 70 patients, there were 53 patients (75.7%) who presented with lung metastases at the time of diagnosis. Of the 70 patients of follicular thyroid carcinoma with lung metastases, 30 patients (42.9%) died at the end of the follow-up, and only 4 patients improved to disease free status. The 5, 10, 15, and 20 year survival rates in these patients were 68.5%, 54.0%, 41.6%, 27.7%, respectively. Age, post-operative Tg level and tumor size are important prognostic factors which are demonstrated to be significantly different statistically between lung metastases group and the group of the patients without distant metastasis. Otherwise, only the tumor size and accumulative dose of (131)I therapy demonstrate a significant difference between survival and mortality groups. Seventeen of the 70 patients developed lung metastases during the follow-up period. Mean period between diagnosis and recurrence of these patients was 3.6 +/- 0.9 years. Over 75% of follicular thyroid carcinoma with lung metastases was diagnosed at the time of presentation. Forty percent (28/70 cases) of the follicular thyroid carcinoma with lung metastases had history of thyroid surgery in this study. If lung metastases are diagnosed in follicular thyroid carcinoma, it will be followed by a poor prognosis. Older patients, higher postoperative Tg, and larger tumor size in follicular thyroid carcinoma need aggressive postoperative treatment.     

Prognostic factors and therapeutic strategies for differentiated carcinomas of the thyroid

Differentiated thyroid carcinoma originates from thyroid follicular cells and is the most prominent malignancy of the endocrine organs. There are two histological types of differentiated carcinoma, namely, papillary and follicular carcinoma. According to reports from Western countries, papillary carcinoma comprises 85.3% of thyroid malignancies in whites, and 72.3% in blacks. In Japan, a previous study showed that the prevalence of papillary carcinoma was 78.4% based on material registered between 1977 and 1986, but according to recent findings reported in 2004 by Japanese Society of Thyroid Surgeons (JSTS), papillary carcinoma accounted for as much as 93% of all thyroid carcinomas. Papillary carcinoma frequently metastasizes to the regional lymph node and shows multicentricity in the thyroid gland. It usually shows a typical ultrasonographic appearance and can be rather easily diagnosed by fine needle aspiration biopsy (FNAB). Follicular carcinoma accounts for 10.9-20.5% of the patients in the United States. In Japan, the prevalence of follicular carcinoma was reported to be 17.2%, but it decreased to 5% in a report by JSTS in 2004. This carcinoma is only occasionally diagnosed preoperatively, because it is hard to discriminate follicular carcinoma from benign adenoma on imaging studies and cytologic findings. In contrast to papillary carcinoma, follicular carcinoma more often metastasizes to distant organs than regional lymph nodes. In Japan, the prevalence of papillary carcinoma increased and that of follicular carcinoma decreased between reports from 1977 to 1986 and that in 2004, which may be because follicular variant of papillary carcinoma was classified into follicular carcinoma in the previous results. Generally, these carcinomas show an indolent character, but when the lesion dedifferentiates and becomes undifferentiated carcinoma, it displays very rapid growth with an adverse prognosis and is regarded even as the most aggressive malignancy among human solid carcinomas. Furthermore, cases showing certain characteristics are likely to be constantly progressive and even become life-threatening. Such cases should be regarded as "high-risk" requiring careful and extensive surgical treatment and postoperative follow-up. Indeed, it is most important for physicians to correctly distinguish high-risk cases from those with an indolent character, although how to evaluate the biological characteristics of thyroid carcinoma and how to identify high-risk cases remains highly controversial. In this review, the methods of distinguishing high-risk cases and the appropriate therapeutic strategies for papillary and follicular carcinomas predominantly based on our experience are emphasized and our proposals for therapies including surgical treatment are demonstrated.     

nm23-H1 immunoreactivity as a prognostic factor in differentiated thyroid carcinoma

Several prognostic factors have been proposed to identify the patients at risk to develop metastases in differentiated thyroid carcinoma. Reduced nm23-H1 expression (a metastatic suppressor gene) has been correlated with high tumor metastatic potential in various human carcinomas, but the results obtained in differentiated thyroid carcinoma remain controversial. To elucidate the usefulness of nm23-H1 as a differentiated thyroid carcinoma prognosis factor, we evaluate the relationship between nm23-H1 immunoreactivity as well as both clinical status and patient outcome. For this purpose, thyroid resected specimens obtained from 94 differentiated thyroid carcinoma consecutive patients (64 papillary and 30 follicular) with at least 5 yr of follow-up were stained using monoclonal antibody to nm23-H1. We did not observe any relationship between nm23-H1 immunoreactivity and age, gender, initial differentiated thyroid carcinoma stage, local recurrence, or distant metastases in patients with papillary carcinoma. However, in patients with follicular carcinoma, a significant inverse association between metastatic disease and the expression of nm23-H1 product was obtained (P < 0.05). In addition, significant differences were found in the survival curves according to nm23-H1 immunoreactivity (log-rank P < 0.01). Finally, nm-23-H1 immunoreactivity was more specific but less sensitive than AMES score to predict metastases. In conclusion, our results suggest that nm23-H1 immunostaining could be added to the classic prognostic factors currently used to predict the outcome of patients with follicular thyroid carcinoma.     

Familial adenomatous polyposis (Gardner's syndrome) and thyroid carcinoma

Summary The case history of a 24-year-old woman with Gardner's syndrome [familial adenomatous polyposis (FAP)] and papillary thyroid carcinoma is presented, representing the 37th report of this association. Although FAP is transmitted as an autosomal dominant trait with similar penetrance in both sexes, thyroid carcinoma has been found almost exclusively in women (94.3%). The majority have been papillary carcinomas (88.5%), which have become apparent during the third decade (average 23.6, range 16–40 years). Most (55.5%) thyroid carcinomas have been discovered 1–17 years after FAP was identified, although some have been found before (29.6%), or at the same time (14.8%) FAP was diagnosed. Multicentric papillary carcinomas have been reported in 64% (14 of 22) of FAP patients, a frequency at least twofold greater than usual. Although papillary carcinoma found before age 30 (as it was in most patients with FAP) typically has an excellent prognosis, one patient with FAP developed distant metastases from thyroid carcinoma and a 28-year-old woman's death was attributed to papillary carcinoma. The high frequency of multicentric papillary thyroid carcinoma in young patients with FAP and the potential for metastases and death due to thyroid carcinoma warrant aggressive diagnostic screening at regular intervals with neck palpation, ultrasonography, and if necessary, fineneedle aspiration biopsy. When thyroid carcinoma is found, total or near-total thyroidectomy should be considered because of the tumor's high likelihood of being multifocal. Since almost 30% of the thyroid carcinomas associated with FAP have been diagnosed 4–12 years before polyposis was identified, young patients presenting with thyroid carcinoma should be questioned regarding bowel function and a family history of gastrointestinal disease, and consideration should be given to periodic testing for fecal occult blood.The views expressed herein are those of the authors and do not necessarily reflect those of the Army or the Department of Defense.     

Papillary thyroid carcinomas with lung metastases.

BACKGROUND: Limited information is available on the presentation, treatment outcomes, and prognostic factors of papillary thyroid carcinoma with lung metastases. METHODS: This study retrospectively analyzed the data of 2003 patients with thyroid cancer who were treated and followed up at Chang Gung Memorial Hospital from January 1979 to December 2002. In total, 1516 papillary thyroid carcinomas were enrolled. One hundred two (6.7%) papillary thyroid carcinomas with lung metastases were followed including 57 women with mean age of 41.7 +/- 17.3 years and 45 men with mean age of 49.6 +/- 17.2 years. These patients included 52 patients with papillary thyroid carcinoma who presented with lung metastases at the time of diagnosis. The 102 cases of papillary thyroid carcinomas with lung metastases included 72 cases with lung metastases only, and 30 cases with other organ involvement. RESULTS: After mean follow-up periods of 8.8 +/- 0.6 years, 28 (27.5%) of the patients with lung metastasis died, while 6 improved to clinical stage I. The 5-, 10-, 15-, and 20-year survival rates in patients with papillary thyroid carcinoma without distant metastasis and in the lung metastases groups were 99.0%, 98.5%, 98.0%, 98.0%, and 91.3%, 75.0%, 64.0%, 51.2%, respectively. Comparing the Kaplan-Meier survival curves between the patients with papillary thyroid carcinomas with lung metastases only and those with multiorgan metastases demonstrates no statistically significant difference in mortality rates. However, age, gender, postoperative thyroglobulin (Tg) level and tumor size displayed statistically significant differences between the lung metastases and no distant metastasis groups. Fifty of the 102 patients with papillary thyroid carcinomas with lung metastases developed lung metastases during follow-up. Larger amounts of remnant thyroid tissues with higher Tg levels were noted in these patients compared to those without distant metastasis. CONCLUSIONS: The prognosis of patients with papillary thyroid carcinoma with lung metastases at time of diagnosis is the same as for those whose lung metastases are discovered later. Survival analysis demonstrates no difference between lung metastases and multiorgan metastases.     

Thyroid cancer: new knowledge and therapeutic strategy in an endemic area

The epidemiological data of thyroid carcinoma are difficult to evaluate. Several variables influence the biologic behaviour and the great number of occult papillary carcinomas obscure the picture. Among our 1116 patients we found as first symptoms solitary nodules in 41,4% being localized in differentiated carcinomas significantly more frequently in the right than is the left lobe. Multinodular goiter was seen in 24,2%, cervical lymph nodes in 10,9% and distant metastases in 3,2%. In medullary carcinoma cervical lymph nodes were seen in 27% and thus the second most frequent leading symptom. Together with sonography, thyroid scan and fine needle biopsy it is possible today to assure preoperatively at a high degree the diagnosis. A differentiated therapy is generally applied taking into account the particular prognosis of the patient, especially in papillary carcinoma. A more radical initial treatment is necessary in follicular carcinoma. In medullary carcinoma only the thyroidectomy without radiation has been proven as effective means.     

Clinical implication of hot spot BRAF mutation,V599E,in papillary thyroid cancers

Activating mutations in the BRAF kinase gene have recently been reported in human cancers. The aim of the present study was to determine the frequency of BRAF mutations in thyroid cancer and their correlation with clinicopathological parameters. We analyzed exons 11 and 15 of BRAF gene in six human thyroid cancer cell lines and 207 paraffin-embedded thyroid tumor tissues. A missense mutation was found at T1796A (V599E) in exon 15 in four of the six cell lines and 51 of 207 thyroid tumors (24.6%; 0 of 20 follicular adenoma, 0 of 11 follicular carcinoma, 49 of 170 papillary carcinomas, and 2 of 6 undifferentiated carcinomas). Activation of MAPK kinase-MAPK pathway was observed in cell lines harboring BRAF mutation. BRAF mutation-associated enhanced cell growth was suppressed by MAPK kinase inhibitor, U0126. Examination of 126 patients with papillary thyroid cancer showed that BRAF mutation correlated significantly with distant metastasis (P = 0.033) and clinical stage (P = 0.049). Our results indicate that activating mutation of BRAF gene could be a potentially useful marker of prognosis of patients with advanced thyroid cancers.     

Clinical features and prognostic factors for survival in patients with poorly differentiated thyroid carcinoma and comparison to the patients with the aggressive variants of papillary thyroid carcinoma

We performed this study to compare the clinicopathologic features and outcomes between the patients with poorly differentiated thyroid carcinoma (PDTC) and the patients with the aggressive variants of papillary thyroid carcinoma (PTC). To evaluate the prognostic factors for survival of the patients with PDTC, we selected 49 patients with PDTC and 23 patients with the aggressive variants of PTC from three hospitals during the recent 15 years. The five-year survival rate and clinicopathologic features of the patients with PDTC were not different from those of the patients with the aggressive variants of PTC. Univariate analysis revealed the significant poor prognostic factors for survival of the patients with PDTC and the aggressive variants of PTC as follows: 1) an age more than 45 years, 2) a tumor size larger than 4 cm, 3) the presence of tumor invasion to extrathyroidal tissue or the trachea, 4) the presence of cervical lymph node invasion, 5) the presence of distant metastasis, 6) the absence of high-dose radioactive iodine (RAI) therapy, and 7) TNM stage II, III and IV. Distant metastasis and high-dose RAI therapy were independent significant predictors for survival of the patients with PDTC and the aggressive variants of PTC on multivariate analysis. However, distant metastasis was the only independent significant predictors for survival of the patients with PDTC excluding patients with the aggressive variants of PTC.     

BRAF mutation in papillary thyroid carcinoma in a Japanese population: its lack of correlation with high-risk clinicopathological features and disease-free survival of patients

Recent studies have demonstrated that BRAF(V600E) mutation is a common event in papillary thyroid carcinoma and a majority of these lesions have shown a direct relationship between BRAF(V600E) mutation and aggressive characteristics, including a worse patient prognosis. However, there are no studies from Japan regarding this issue in a large series with adequate postoperative follow-up periods. We investigated BRAF(V600E) mutation in 631 patients with papillary carcinoma having median follow-up periods of 83 months. The prevalence of BRAF(V600E) mutation was 38.4%, and the rate was higher in carcinoma larger than 1.0 cm but did not successively increase with tumor size. Furthermore, the prevalence did not significantly increase in cases demonstrating high-risk biological features such as clinically apparent lymph node metastasis, massive extrathyroid extension, advanced age, distant metastasis at surgery, and advanced Stage. The disease-free survival of patients with BRAF(V600E) mutation did not differ from that of those without BRAF(V600E) mutation. These findings indicate that, although BRAF(V600E) mutation may play some roles in local carcinoma development, there is no evidence that BRAF(V600E) mutation significantly reflects the aggressive characteristics and poor prognosis of patients with papillary carcinoma in Japan.     

Familial non-medullary thyroid carcinoma: pathology review in 27 affected cases from 13 French families

BACKGROUND AND OBJECTIVES: When familial non-medullary thyroid cancer (FNMTC) develops with no obvious associated pathogenetic factor, an inherited predisposition may underlie the process. The present study was conducted because detailed pathological findings are lacking in most series of FNMTC. PATIENTS AND METHODS: Thirteen families comprising 27 cases of FNMTC were included (1.8% of differentiated thyroid carcinoma). The family relationship (20 F, 7 M; age 46 +/- 16 years; mean +/- SD) was 'siblings' in eight families, 'parent and child' in four and 'aunt and niece' in one. Careful pathological review of the thyroid tumours (papillary/follicular: 25/2, size: 16 +/- 11 mm) was performed. RESULTS: Initial staging according to extension was as follows: grade I (n = 16), II (n = 2), III (n = 6), IV (n = 3). Fourteen tumours were papillary microcarcinomas (size: 8 +/- 2 mm). No tumour phenotype that may be considered specific for FNMTC was found when considering either age, pathological findings or tumour aggressiveness. Although rare events were found in both relatives of some families suggesting a putative 'familial' phenotype of FNMTC, this may be fortuitous. CONCLUSION: Micro familial non-medullary thyroid cancers are more common than previously reported and further studies are required to be able to distinguish this subgroup from sporadic papillary microcarcinomas. The careful pathological review of the familial non-medullary thyroid cancer in this study does not seem to point to a distinct subgroup of familial differentiated thyroid carcinoma although the data are intriguing. Genetic studies are now required to investigate this issue.     

Increased expression of the vascular endothelial growth factor is a pejorative prognosis marker in papillary thyroid carcinoma

Vascular endothelial growth factor (VEGF) is a potent stimulator of endothelial cell proliferation. It has been implicated in tumor growth of human thyroid carcinomas. Using the VEGF immunohistochemistry staining score, we correlated the level of VEGF expression with the metastatic spread of 19 cases of thyroid papillary carcinoma. The VEGF immunostaining score, ranging from 0-9, was determined as the multiplication of a percentage of labeled thyrocytes score (0, no labeling; 1, <30%; 2, 31--60%; 3, >61% of labeled thyrocytes) and an intensity score (0, no staining; 1, weak; 2, mild; 3, strong staining). The mean score +/- SD was 5.74 +/- 2.59 for all carcinomas. The mean score for metastatic papillary carcinoma was 8.25 +/- 1.13 vs. 3.91 +/- 1.5 for nonmetastatic papillary cancers (P < 0.001). By discriminant analysis, we found a threshold value of 6.0, with a sensitivity of 100% and a specificity of 87.5%. There were no statistical differences between metastatic and nonmetastatic carcinomas when age, tumor size, or thyroglobulin levels were considered. The VEGF immunostaining score seems to be a helpful marker for metastasis spread in differentiated thyroid cancers. An increased production of VEGF could assess an aggressive disease and be the hallmark of a trend to produce metastasis. We propose the VEGF immunostaining score as a marker for the prognosis in differentiated thyroid cancers. A value of 6 or more, should be considered as at high risk for metastasis threat, prompting the physician to institute a tight follow up of the patient.     

BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas

Activating point mutations of the BRAF gene have been recently reported in papillary thyroid carcinomas. In this study, we analyzed 320 thyroid tumors and six anaplastic carcinoma cell lines and detected BRAF mutations in 45 (38%) papillary carcinomas, two (13%) poorly-differentiated carcinomas, three (10%) anaplastic carcinomas, and five (83%) thyroid anaplastic carcinoma cell lines but not in follicular, Hürthle cell, and medullary carcinomas, follicular and Hürthle cell adenomas, or benign hyperplastic nodules. All mutations involved a T-->A transversion at nucleotide 1796. In papillary carcinomas, BRAF mutations were associated with older age, classic papillary carcinoma or tall cell variant histology, extrathyroidal extension, and more frequent presentation at stages III and IV. All BRAF-positive poorly differentiated and anaplastic carcinomas contained areas of preexisting papillary carcinoma, and mutation was present in both the well-differentiated and dedifferentiated components. These data indicate that BRAF mutations are restricted to papillary carcinomas and poorly differentiated and anaplastic carcinomas arising from papillary carcinomas. They are associated with distinct phenotypical and biological properties of papillary carcinomas and may participate in progression to poorly differentiated and anaplastic carcinomas.     

Intraocular and orbital metastasis as a rare form of clinical presentation of insular thyroid cancer

Insular carcinoma of thyroid is a rare tumor, which accounts for 4 to 6% of thyroid malignancies. Clinically and morphologically it is considered to be in an intermediate position between well-differentiated carcinoma of the thyroid (papillary or follicular) and undifferentiated or anaplastic carcinoma of the thyroid. Capsular and blood vessel invasion is seen frequently, and metastases to regional lymph nodes, lungs and bones are common. The initial presentation of distant metastasis in patients with thyroid cancer is rare. Thus metastatic thyroid carcinoma rarely involves the orbit. We report a rare case of choroidal metastasis from insular thyroid carcinoma.     

Metastasis as the first sign of thyroid cancer

The aim of this paper is to review our experience with patients who presented with a metastatic tumor in the lymph nodes or other organs as the first sign of thyroid cancer. In 1974-1998, 18 602 patients were operated on due to goitre. There were 975 (5.2%) patients with thyroid malignant neoplasms. The group comprised 449 (46.1%) patients with papillary carcinoma, 309 (31.7%) with follicular carcinoma, 54 (5.5%) with medullary carcinoma, 106 (10.9%) with anaplastic carcinoma, and 57 (5.8%) with other types of thyroid malignant neoplasms. Out of these 975 patients, thyroid cancer was diagnosed on the basis of the detection of a metastatic tumor in 26 (2.7%) patients. In 16 (61.5%) of these patients the metastatic tumor was located in the regional lymph nodes. In 10 (38.5%) patients distant metastasis beyond the regional lymph nodes was the first sign of thyroid cancer. In (50%) patients metastasis was located in the bones, in 2 (20%) in the lung, in 1 (10%) in the heart, in 1 (10%) in the buttock, and in 1 (10%) in a central neck cyst. Metastasis was the initial manifestation of thyroid cancer in 18 (4%) of 449 papillary carcinoma patients, in 6 of 309 (1.9%) follicular carcinoma patients, and in 2 (3.7%) of 54 medullary carcinoma patients. Lymph node metastasis was the first sign of thyroid cancer in 13 (2.9%) patients with papillary carcinoma, 1 (0.3%) patients with follicular carcinoma and in 2 (3.7%) medullary carcinoma patients, and distant metastasis in 5 (1.1%) patients with papillary carcinoma and in 5 (1.6%) patients with follicular carcinoma. After the detection of the primary focus of thyroid cancer total thyroidectomy and modified neck dissection were performed in all patients. Differentiated thyroid carcinoma patients were treated complementarily with 131I and TSH suppressive doses of L-thyroxine, and medullary cancer patients with teleradiotherapy and substitutive doses of L-thyroxine.     

Prognostic factors of differentiated thyroid cancers. 536 cases

Five hundred thirty-six patients with papillary (n = 327) or follicular (n = 209) carcinoma of the thyroid treated between 1957 and 1985 in the same endocrine department are presented. Treatment was either an unilateral extracapsular lobectomy with isthmectomy, for isolated nodules only (n = 253), or a total thyroidectomy - with or without radio-iodine administration - or, exceptionally, a partial thyroidectomy. The impact of histologic type, age and sex of the patients, type of presentation and limited surgery (i.e. unilateral lobectomy in nodular carcinoma) were tested for prognostic value (total or relapse-free survival). The main factors are: initial tumour extension (almost no survival after 10 years in case of metastasis; 87.98 +/- 0.04% 20 years estimate of percent surviving in exclusive thyroid localization); histologic type (relative death rate: predominant papillary: 0.28, follicular well differentiated: 0.88, moderately differentiated: 2.54 (p less than 0.01); age (prognosis as better as the patient is younger); sex (worse prognosis for men above 40 years). Unilateral lobectomy is an unhazardous treatment with a survival rate 92.41 +/- 0.03% at 20 years for follicular and papillary nodular carcinoma.