Differentiated Thyroid Carcinoma
	Roumiantsev et al., Obninsk, Russia, compared cytological examination and Tg level in washout samples of fine needle aspiration biopsy (FNAB) of 53 lymphnodes from 22 children with papillary thyroid carcinoma after exposure to radioactivity by the Chernobyl accident. After FNAB all lymphnodes were histologically examined. Specificity, sensitivity, and accuracy of cytology was 100%, 79%, and 86% respectively. The corresponding values for Tg detection in washouts were 100%, 97%, and 98% respectively. The authors conclude that Tg measurement in washouts of FNAB has high potential in the evaluation of lymphnode metastases. (Comment: The authors reported Tg concentrations in FNAB washouts from benign nodes varying from 0 to 22 (mean 6) ng/ml. This is apparently due to systemic circulating TG. The concentrations were much higher in washouts of metastatic lymphnodes (96– 2815 ng/ml), with no overlap values). Cailleux et al., Villejuif Cedex, France, evaluated the importance of a diagnostic 131I total body scan (TBS) 6 to 12 months after thyroid ablation for differentiated thyroid carcinoma. They investigated 200 patients with papillary carcinoma and 56 patients with follicular carcinoma. All patients initially underwent total thyroidectomy and post-operative 131I ablation with 100 mCi. A diagnostic TBS was obtained after T4 withdrawal with either 2 or 5 mCi. Thyroid uptake was undetectable in 236 patients, visible but <0.1% in 19, and 1% in only 1 patient. No uptake outside the thyroid bed was detected. Serum Tg after T4 withdrawal was <1 ng/ml in 210 patients, between 1–5 ng/ml in 27 patients, between 6–10 ng/ml in 4 patients, and was >10 ng/ml in 15 patients. A TBS with a high dose of 131I in 8 patients with Tg >10 ng/ml showed foci of uptake outside the thyroid bed in 3 patients. The authors conclude that a negative diagnostic 131I-TBS performed between 6 and 12 months after thyroid ablation in patients with serum Tg <10 ng/ml confirms completeness of thyroid ablation. (Comment: I extract from their report that the authors suggest that only in those patients who have a Tg concentration >10 ng/ml after T4 withdrawal, treatment with a high dose of 131I should be considered. However the authors have not performed high-dose TBS in patients with a TG level <10 ng/ml). Vassko et al., Kiev, Ukraine, and Marseille, France, evaluated the diagnostic importance of thyroperoxidase (TPO) immunostaining with a specific monoclonal antibody to differentiate between malignant and benign Hürthle cell neoplasms. Cytology of 62 benign tumors, 30/62 exhibited less than 80% cells positive for TPO and 32/62 had 80% or more positive for TPO. Cytology of 11 malignant tumors all had less than 80% TPO positive cells and 8 had less than 30%. The sensitivity and specificity for cytological detection of malignancy of Hürthle cell tumors was 100% and 52% respectively. From these data the authors conclude that, using this technique, routine resection of more than 50% of benign nodules can be avoided. Robuschi et al., Parma, Italy, evaluated DNA flow cytometry and S-phase of FNAB in the detection of thyroid carcinoma. DNA content was measured on FNAB’s from 194 patients with thyroid nodular disease and S-phase was evaluated in 76/194 patients. Both ploidy and S-phase were correlated with cytologic and histologic features. From their data the authors conclude that ploidy is not useful for differentiation between benign and malignant follicular or Hürthle cell neoplasms, but that aneuploidy and high S-phase seems to correlate with aggressive behaviour of carcinoma. Kapezzone et al., Pisa, Italy, studied the presence of papillary thyroid carcinoma in thyroid tissue that was subsequently removed to complete thyroidectomy in patients who initially underwent partial thyroidectomy for PTC. Of 182 patients with completion thyroidectomy after lobectomy (with a mean interval period of 16 months) in 80/182 (44%) PTC was found in the remaining thyroid lobe. No statistical difference was found between patients with low risk (age <45 years, tumour size <2 cm, and absence of local or distant metastases) and high risk patients. The authors state that on the basis of these results PTC should be treated by total thyroidectomy and patients should be submitted to total thyroidectomy if partial surgery had been performed previously. Pollina et al., Pisa, Italy, and Philadelphia, PA, USA, studied protein expression of the newly detected oncosuppressor gene Fhit in 102 thyroid neoplasms: 34 adenomas (A), 35 PTC, 3 follicular carcinomas (FTC), 19 poorly differentiated carcinomas (PDC), and 11 undifferentiated carcinomas (UC). Protein expression was always present in normal tissue adjacent to the tumour. Strong expression was present in 20/34 A, 27/35 PTC, 2/3 FTC, 8/19 PDC, and 1/11 UC. It is concluded that Fhit is altered in thyroid carcinoma and that it’s expression is inversely correlated with the aggressiveness of the tumor. Klein et al., Nancy, France, measured vascular endothelial growth factor (VEGF) by immunohistochemistry staining in thyroid samples from 25 PTC and 12 FTC. Results were correlated with biological aggressiveness of the tumour reflected by absence or presence of metastases. FEGF immunostaining score ranged between 0 and 6. The results show that a threshold value score of 4.78 has predictive power of 93.8% for the presence of metastases above this value, and a predictive power of 78.6% for the absence of metastases below this value. Bernier et al., Paris, France, studied retrospectively 107 patients (75 females, age 20–87 years) with bone metastases of differentiated thyroid carcinoma. Total thyroidectomy with subsequent 131I therapy was performed in 89/107 patients. Mean follow-up was 5 years (range 0–28 years). Survival rates at 5, 10, and 20 years were 39%, 13%, ad 2% respectively. Radioiodine therapy was most favourably associated with survival (p<0.0001). Complete surgery as compared to no surgery or palliative surgery of bone metastases was also favourably correlated with survival (p<0.01). Other favourable factors were absence of invasion of the thyroid capsule and of lymphnodes, absence of vascular tumour embolies, and a diameter of the initial thyroid tumour of <40 mm. The main conclusion from this study is that patient survival is mainly dependent on radioiodine therapy in combination with total thyroidectomy. Kobayashi et al., Kobe, Japan, studied MIB-1 labelling index of different thyroid carcinomas. This index, representing staining of nuclear antigen K-67 by a monoclonal antibody, points to activity of cellular growth in normal and neoplastic tissues. In total 245 thyroid neoplasms were studied. No differences in index were seen between well differentiated and poorly differentiated follicular carcinomas. However, poorly differentiated papillary carcinomas had significantly (p<0.01) higher index than well-differentiated papillary carcinomas. The authors conclude that this technique may be of use in the determination of prognosis of papillary carcinomas in the sense that a higher index indicates a poorer prognosis. Baldini et al., Cantalamessa, Italy, prospectively performed thyroid ultrasound scanning and FNAB’s when nodules =8 mm were present, while ultrasound was repeated yearly during follow-up and FNAB was repeated every 2 years when cytology was benign in 986 consecutive goitre patients studied from January 1983 to March 1988. The follow-up of this study was 7.6 ± 4.0 years. In 111/334 patients with Graves’ disease nodules >8 mm were detected either at the beginning of the study or during follow-up. Fifty-four nodules were present at enrolment and 57 developed during follow-up. Only in one patient malignancy was cytologically diagnosed and confirmed on histology. In 24/521 patients with non-toxic nodular goitre cytologically/histologically confirmed carcinoma was present. In 1/134 patients with toxic nodular goitre, carcinoma was diagnosed on cytology and confirmed histologically. The overall prevalence of nodules >8 mm was 33.2%. The authors conclude that the presence of carcinoma in patients with Graves’ disease is rare while the risk of malignancy appeared to be significantly higher in patients with non-toxic nodular goitre. (Comment: This is another publication on the controversy about the frequency of thyroid malignancy in Graves’ disease that, according to some authors, is increased. So far the balance between reports indicating increased- and non-increased prevalence, seems to be balanced. The rate of malignancy in patients with non-toxic nodular goitre is not different from that reported by many authors to be present in routine thyroid histological examinations from autopsies. The biological significance of these mostly occult carcinomas is generally accepted to be low or insignificant. My personal standpoint is that at present there is no firm evidence of increased biologically significant thyroid carcinoma in patients with Graves’ disease and with nodular goitre.) Franc et al., Crétiel and Paris, France, evaluated inter- and intra-observer reproducibility in histological diagnosis of follicular thyroid carcinoma (FTC) in a group of 5 thyroid pathologists from different institutions. Inter-observer agreement for diagnosis of FTC varied from 0.05 to 0.56 when considering groups of 2, 3, 4, or 5 pathologists. The intra-observer agreement was 0.68. (Comment: I wonder if such studies with other thyroid pathologists would give the same poor results. If so, we or rather the patients, are really in trouble!) Adas et al., Istanbul, Turkey, followed 78 patients (65 females) treated for papillary carcinoma with a diameter of < 1.0 cm. The mean age at surgery was 41 years. In addition 8 patients had Graves’ disease, 7 toxic multinodular goitre, and 1 toxic adenoma. Mean follow-up was 21 months. Near total thyroidectomy was performed in 34/78 patients and 44/78 underwent subtotal thyroidectomy. RAI treatment was given to 46/78 patients. All patients received TSH suppressive therapy. Mean follow-up period was 21.9 months (range 1–78 months). Distant metastases were established in 5/78 patients and 4/5 had these metastases at the time of initial diagnosis. No patient died in the follow-up period. The authors conclude that papillary carcinomas with a diameter <1.0 cm do not differ in prognosis from larger carcinomas. (Comment: The most important question is, how were these malignant nodules initially detected. Was this by clinical signs and/or symptoms or by routine ultrasound imaging of the thyroid.) Nagataki et al., Hiroshima, Japan reported form studies in atomic bomb survivors from Hiroshima and Nagasaki that there is a strong linear response for thyroid carcinoma with an estimated excess relative risk (ERR) per Sv of 1.15. Most importantly the ERR is highly dependent on age at exposure. ERR for thyroid carcinoma decreases about 37% with each 10-year increase in age at exposure. They also reported that 90% of survivors who were younger than 9 years at exposure are still alive at present. Hamilton et al., Seattle, WA, USA, studied a selected cohort of 5,199 persons who were exposed between 1944–57 to 131I as documents revealed that, during that period, approximately 740,000 Curies of 131I were released from the Hanford Nuclear Site in Washington State. The estimated thyroid doses ranged from 0.008 mGy to 2842 mGy. The cumulative incidence for thyroid cancer was 0.55% and for benign nodules 7.2%. Dose-response analyses revealed no increase in either thyroid cancer or benign nodules with increasing thyroid radiation dose. The authors conclude that, in contrast to the Chernobyl accident, and the accident in the Marshall Islands, no evidence emerged that thyroid neoplasia increased in relation to 131I irradiation from Hanford. This discrepancy may be explained by factors such as differences in type of radiation exposure, dose rate, chronic versus acute exposures, dose amplitude, and possibly dietary iodine intake.