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A family with germline tandem V804M/Y806C mutations in the RET proto-oncogene was reported. The in vitro study results showing that these mutations were on the same allele and that RET with these mutations had a moderate transforming activity were confirmed by the clinical features of the offspring as a natural experiment. Thus, the tandem double RET mutations are pathogenetic for MEN 2B.
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Background: We previously reported that the Ki-67 labeling index (LI) in primary tumors and the thyroglobulin (Tg)-doubling time (DT) were potent prognostic indicators in patients with papillary thyroid carcinoma (PTC). Objectives: To elucidate the relationship between these two factors. Methods: A total of 390 patients with PTC who underwent total thyroidectomy between 1998 and 2004 and in whom the Tg-DT was calculated were enrolled. We determined the Ki-67 LI in primary tumors and compared these values with the patients' clinicopathological factors, postoperative Tg status, Tg-DT, and prognosis. Tg status was categorized by postoperative serum Tg values: biochemically persistent disease (BPD), equivocal state, and biochemical remission. Results: The Ki-67 LI was ≤5% in 312 patients (80%), 5%-10% in 48 patients (12%), and >10% in 30 patients (8%). Ki-67 LI was significantly associated with BPD (p < 0.0001). The proportion of BPD patients increased with the higher Ki-67 LI category: 24, 67, and 87%, respectively. The Ki-67 LI had a significant inverse correlation with the Tg-DT (Spearman's ρ = −0.5267, p < 0.0001). Of the 378 patients without distant metastasis at surgery, 68 patients had recurrence, and 6 of the 390 patients died of PTC during the follow-up (mean 88 months). On multivariate analyses, the Ki-67 LI remained an independent predictor of disease-free survival and disease-specific survival when Tg-DT and Tg status were excluded from the analyses. Conclusions: Evaluation of the Ki-67 LI in primary tumors may allow the prediction of the postoperative Tg status, Tg-DT and prognosis of patients with PTC.
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Background: It is generally considered impossible to differentiate follicular carcinomas from follicular adenomas by means of ultrasonography or cytology before surgery. Therefore, follicular carcinoma is histopathologically diagnosed by verifying capsular and/or vascular invasion after surgery. However, ultrasonography may play an important role in diagnosing follicular carcinoma preoperatively in a small number of cases. Case Description: Four cases of follicular carcinoma or follicular neoplasm that transformed from a benign thyroid tumor and demonstrated a “nodule in nodule” appearance on ultrasonography are presented in this report. Characteristic ultrasound features of such patients are: (1) a “nodule in nodule” appearance, (2) a well-defined boundary line between the nodules, and (3) separate distribution of blood signals within each nodule. Conclusion: A small number of patients with follicular carcinomas or follicular neoplasms may present with a “nodule in nodule” appearance on ultrasonography. It was suggested a long time ago that follicular carcinomas may develop from benign thyroid tumors. The fact that follicular carcinomas appear within benign tumors may be evidence of thyroid tumorigenesis.