Differentiated thyroid carcinoma
	Fogelfeld et al., Chicago, IL, USA, studied the prevalence of mutated p53 gene in 22 patients with radiation-induced thyroid carcinoma. They found in 5/22 patients missense point mutations and in 1 patient a neutral mutation. Two patients had intronic mutations. 3/5 patients with missense mutations had invasion beyond the thyroid capsule compared to 2/17 patients without missense mutations. The results suggest a role of mutations in the p53 gene, in the generation of radiation-induced thyroid carcinoma and also in their local spread. Lin et al., Beijing, China, studied expression of p53 mutations and of epidermal growth factor receptor (EGFR) in 32 papillary carcinomas, 10 follicular carcinomas, 6 medullary carcinomas and 4 anaplastic carcinomas. 4/6 Medullary carcinomas were positive for mutant p53 and 3/4 of anaplastic carcinomas. Only 3/32 of papillary carcinomas and 2/10 of follicular carcinomas were also positive for mutant p53. 5/6 Of medullary carcinomas, 4/4 of anaplastic carcinomas, 8/24 of papillary carcinoma and 3/10 of follicular carcinoma were positive for EGFR. It is concluded that p53 mutations and EGFR expression are correlated with thyroid carcinomas with the poorest prognosis. Chen and co-workers, Sendai, Japan, and Changchun, China, compared overexpression and mutation of p53 in Chinese and Japanese patients with poorly differentiated carcinoma. They found p53 expression in 14/15 Chinese patients and 16/19 Japanese patients. They conclude that overexpression of p53 tumor suppressor gene is frequent in patients with poorly differentiated thyroid carcinoma. They also found mutations in the p53 gene which were different between Chinese and Japanese patients. Bogdanova et al., Kiev, Ukraine and Cambridge, UK, compared the type of thyroid carcinoma of 115 children from Ukraine exposed to fall-out from Chernobyl detected between 1990-1994 and compared the results with 154 cases from England and Wales, detected between 1963 and 1992. The main difference was that 76% of carcinomas from Chernobyl children was of the solid follicular papillary type and this was only 23 % in the UK children. The following types were distinguished: solid follicular papillary carcinoma, classic papillary carcinoma, other papillary carcinoma, follicular carcinoma, medullary carcinoma and other carcinoma. It is suggested that the solid follicular papillary carcinoma type is related to exposure to irradiation. Simonet et al., Paris, France, and Baschieri et al., Pisa, Italy, report about children transferred to their institutions from areas exposed to fall-out from the Chernobyl accident in 1986. Both groups report a high incidence of agressive papillary tumors with extension to lymphnodes and lungs. Many of those children were treated with radioactive iodine to irradicate metastases. Duh, San Francisco, CA, USA, studied the expression of vascular endothelial growth factor m-RNA and protein in human thyroid neoplasia. This factor controls angiogenesis and may play a role in the degree of malignancy of thyroid tumors. They found increased expression in the messenger RNA and the factor itself in malignant tissue as compared to benign tissue, suggesting indeed that this growth factor may play a role in vasoinvasiveness in malignant thyroid tumors. Jaffiol et al., Montpellier, France, studied the influence of TSH suppression on relapsefree survival in patients after total thyroidectomy combined with RAI treatment during subsequent T4 suppression therapy. Two groups were distinguished, group I with annual TSH values < 0.1 mU/L (n = 30) and group II with TSH values > 1 mU/L (n = 15). The relapsefree survival in group I was 235.5 months and in group II 112.4 months. (p < 01). (Comment: Although this result is not surprising, this study is important because there are only few studies showing that TSH suppression in patients treated for thyroid carcinoma is indeed of prime importance in mangagement of these patients.) Postema et al., Berne, Switzerland and Rotterdam, The Netherlands, compared lllIn-labeled octreotide scanning and 123I scanning in 21 consecutive patients with thyroid carcinoma, including 2 with anaplastic and 19 with follicular or papillary carcinoma. All primary differentiated carcinomas were octreoscan and 123I scan positive. Anaplastic carcinomas were also octreoscan positive. Octreoscan visualized metastases in 6/7 follicular carcinomas and 3/8 papillary carcinomas and was especially sensitive in bone metastases of patients with follicular carcinoma. It revealed new and more metastases than 123I scan in some patients. In patients undergoing octreoscan, T4 was not withdrawn. However it is not known whether endogenous TSH stimulation would improve sensitivity. The authors conclude that lllIn-labeled octreotide may provide a future radiotherapeutic option in cancers which do not store radioiodine. Alam, Kyoto, Japan, studied the value of technetium diphosphonate and thallium scintigraphy on the sensitivity of detection of bone metastases of differentiated thyroid carcinoma. They studied 75 bone lesions in 24 postthyroidectomized patients. 41/57 (72 %) of lesions were positive on diphosphonate scanning. 11/16 of negative lesions were still positive on technetium scanning, leading to a sensitivity of the combination of the tests to 91 °X0. (Comment: Although these two techniques on detection of bone metastases have value, it is obvious that RAI scanning is the first line of approach.) Wemeau et al., Lille, France, report a patient who had a recurrence of a Hurthle cell carcinoma that did not concentrate l3lI, but was positive on 99mTc-MIBI scanning. (Comment: As Hurthle cell tumors usually do not concentrate l3lI, 99mTc-MIBI scanning may be a useful tool to detect tumor tissue and has theoretical potential even for treatment-management.) Mutations in the TSH receptor or coupled Gsaprotein (this membrane protein plays a role in intracellular signalling when TSH binds to the membrane receptor) have been shown to cause thyroid hyperfunctioning adenomas and are probably the main cause of this type of thyroid lesion. Russo et al., Catanzaro, Italy and Villejuif, France, did find a mutation in the gene of the TSH receptor in 3 patients with differentiated carcinoma showing for the first time that this (somatic) mutation may also be the cause not only of adenoma, but apparently also of carcinoma. Fugazzola et al., Milano and Pisa, Italy, performed a complete molecular analysis of fresh tissue samples of 12 cases of papillary carcinoma from children exposed to the Chernobyl nuclear accident. They found overexpression of RET oncongene in 66.6% of cases. This suggests a relationship between activation of this oncogene and development of papillary carcinoma after exposure to radioactive fallout. Belfiore, Catania, Italy, studied the prognostic value of c-Met (a transmembrane tyrosine kinase receptor) expression in papillary carcinoma. They found that c-Met expression is undetectable in normal thyroid tissue, but is expressed strongly in papillary carcinoma without distant metastases (n = 24) but when not or moderately expressed in 34 patients, distant metastases were found in 8 patients (23.5 %). Apparently expression of c-Met carries a relatively good prognosis. Koshiishi et al., Tokyo, Japan, studied survival rate in 202 patients (150 females) with distant and local metastases of differentiated thyroid carcinoma after RAI treatment. 131 were papillary type and 71 follicular type. It appeared that 10 year survival rate was 70.7% of patients under 40, but 12.5% for those over 40 years. Furthermore 10 year survival rate was lower when bone metastases were present than when only lung and lymphnode metastases were detected. Matsubayashi et al., Kobe, Japan, studied the effect of present (36 patients) or absent (59 patients) thyroidal lymphocytic infiltration, when patients were operated for papillary carcinoma, on local tumor invasion and on tumor recurrence. In the group with lymphocytic infiltration no local tumor invasion was found at operation and after a mean follow-up period of 9 years, only 1 patient showed tumor recurrence. For the group without lymphocytic infiltration these figures were 7 and 11 patients respectively. The authors conclude that local lymphocytic infiltration, surrounding the primary tumor, is correlated with a better prognosis than if lymphocytic infiltration is absent. Figge et al., Albany, NY, USA, and Moscow, Russia, studied the expression of the adhesion molecule CD44, which is a membrane associated glycoprotein that plays a role in tumor metastases. They found intense expression in 65/67 papillary carcinomas, 9/16 follicular adenomas, 4/8 Hurthle cell tumors, 6/15 medullary carcinomas, and 3/8 follicular carcinomas. CD44 is also known to direct lymphocyte trafficking and the results suggest that this adhesion molecule is responsible for the ability of papillary carcinoma to reach the lymphnodes and then to remain dormant for many years. Funahashi et al., Nagoya, Japan, report results of parathyroid autotransplantation in 18 children after total thyroidectomy for thyroid carcinoma. Their technique consists of selectively taking out 4 parathyroid glands and after mashing the glands, they are replaced into the sternocleidomastoid pocket which is closed afterwards with nylon suture. Only 1/18 patients developed permanent hypoparathyroidism. Postoperative supplementation with calcium was only necessary for 10 days. McDougall, Stanford, CA, USA, studied the effect of 30 mCi of 13lI on irradication of residual thyroid tissue after subtotal or total thyroidectomy for carcinoma. They found total irradication in 47/57 patients 6-12 months later. Their analysis revealed that in 94% of patients irradication was successful if 13lI uptake in residual tissue was equal or less then 10%. Sisson, Ann Arbor, MI, USA, studied the effects of 13lI treatment on micronodular pulmonary metastases of papillary carcinoma in 10 patients. The evaluation of effects was based on 3 indices: X-ray/CT,13lI scintigraphy, and serum thyroglobulin. The initial dose ranged between 60-260 mCi resulting in insufficient effect in all patients. A second treatment (123-350 mCi) was given to 9 patients. Results: 1/7 normalization of all indices, 4/7 only X-ray/CT normalized, and 3/7 abnormalities were unchanged or worse. It is concluded that I13l therapy will reduce micronodular pulmonary metastases in half of the patients but that high doses have to be delivered. The results were evaluated 9/12 months after therapy, and in this period no toxicity was seen. DeGroot et al., Chicago, IL, USA, evaluated the course of disease of 49 patients with follicular carcinoma and compared the results with 249 patients with papillary carcinoma. Overall death was 60%, being double of that in papillary carcinoma. Recurrences were almost invariably followed by death and occurred no later than 13 years after original diagnosis. No death occurred in patients who were under 45 years of age at diagnosis with tumors less than 2.5 cm and with intrathyroidal disease or only positive necknodes. Mortality was increased with increasing size of tumor, distant spread of disease and age over 45 years. Hurthle cell pathology did not influence prognosis. In contrast to papillary carcinoma more extensive surgery and postoperative l3lI ablation did not clearly influence prognosis. The authors philosophize if patients with follicular carcinoma who are above 45 years and have tumors > 2.5 cm should have more agressive therapy with 3lI, X-ray therapy to the neck or chemotherapy. (Comment: The results of this study have been published in J Clin Endocrinol Metab 80:29462953,1995. These results are remarkable in that l3lI ablation had no positive effect on prognosis in follicular carcinoma. In their article it is also reported that prognosis is not different in patients who were treated with less or more than 75 mCi l3lI.) Daumerie et al., Brussels, Belgium, followed a total of treatments with l3lI in 3 patients after thyroidectomy for papillary carcinoma, who were under dialysis for chronic renal disease. Analysis of the variations of radioactivity in arterial blood in control and clialysis patients showed that whole body irradiation was 1.9 times higher if dialysis was carried out 48 hours after Il3l administration. Radioactive hazard to medical personel was minimal. Uptake in residual thyroid tissue occurs within 1 hour after l3lI administration. It is advised to give patients half of the current dose and to perform the first dialysis 2-3 hours after l3lI administration in order to minimize whole body irradiation.