Indeterminate thyroid nodules: a challenge for the surgical strategy.

BACKGROUND: Because no clinical parameter can establish the final status of a cytologically indeterminate thyroid nodule (ITN) or nodal-metastases in case of malignancy, the initial surgical strategy should define an oncologically adequate procedure with low morbidity. METHODS: The prognostic relevance of sex, age, tumor sizes, multifocality, thyroid function, and recurrence was analyzed in 156 consecutive patients according to the presence of malignancy and nodal metastases. The accuracy of frozen sections to reveal malignancy was determined. Clinical parameters were compared with regard to their ability to identify malignancy and nodal metastases in an ITN to determine an appropriate initial operative strategy. RESULTS: One hundred and eighteen (75.6%) patients underwent (total) thyroidectomy, 37 (23.7%) patients underwent hemithyroidectomy, and 1 patient underwent isthmus resection. Fifty-five (35.3%) patients showed malignancy. First step lymphadenectomy (lymph node dissection along the recurrent laryngeal nerve before removing the thyroid lobe) was performed in 142 patients documenting 10 nodal metastases. Comparing benign and malignant ITN, no association was found for sex (P = .17), age (P = 1.0), tumor sizes (P = .33, P = .12, P = .19 for < or =30 mm, < or =40 mm, and < or =50 mm, respectively), or thyroid function (P = .26). The determination of malignancy by frozen section showed a sensitivity of 30.9% and a specificity of 100%. No permanent hypoparathyroidism or recurrent laryngeal nerve palsy was observed postoperatively. CONCLUSION: Because of the failure of available clinical parameters to predict malignancy in cytologically ITN, hemithyroidectomy in unilateral goiter and thyroidectomy in bilateral goiter is recommended. Ipsilateral "first step central neck dissection" on the side of ITN offers the advantages of oncologically adequate resection and staging with a low morbidity, as well as avoids reoperation.

Timing and extent of surgery in patients with familial medullary thyroid carcinoma/multiple endocrine neoplasia 2A-related RET mutations not affecting codon 634.

In hereditary medullary thyroid carcinoma (MTC), recommendations regarding timing and extent of surgery are mainly based on the data of patients with the codon 634 RET mutation, which is the most often affected codon. Little is known about whether these recommendations may also be applied to patients with less common RET mutations. We ascertained the data from 140 patients with FMTC/MEN2A-related RET mutation not affecting codon 634 who have been treated at three specialized centers. The several RET mutations found affected codons 611 (n = 17), 618 (n = 22), 620 (n = 17), 768 (n = 9), 790 (n = 24), 791 (n = 21), 804 (n = 23), and 891 (n = 7). For each codon, the age of the youngest patient with MTC only (41, 7, 18, 29, 13, 47, 20, and 15 years, respectively), MTC with lymph node metastases (46, 24, 21, 34, 46, 47, 50, and 76 years, respectively), and MTC with distant metastases (52, 69, 43, 68, 57, - , - , and 75 years, respectively) was determined. All patients with lymph node metastases had elevated basal calcitonin levels. Based on these data, a more individual recommendation regarding timing and extent of surgery can be given. Because neither gender nor the type of nucleotide substitution for a specific codon appeared to have a significant influence on the age of onset, this recommendation should be based on the affected codon, the age of the patient, and the calcitonin level. Recurrent laryngeal nerve palsy (n = 6) and hypoparathyroidism (n = 3) were rather rare and were found only in patients older than 30 and 43 years, respectively, giving evidence that surgery in young patients can be performed safely.

Follicular variant of papillary thyroid carcinoma: a long-term follow-up.

HYPOTHESIS: The clinical behavior of the follicular variant of papillary thyroid carcinoma (FVPTC) is similar to pure papillary thyroid carcinoma (PPTC) and completely different from follicular thyroid carcinoma (FTC). DESIGN: Retrospective analysis of prospectively documented data. SETTING: Referral center of a university hospital. PATIENTS: Two hundred thirty-seven consecutive patients with follicular cell-derived thyroid carcinomas were operated on in our institution during a 15-year period, from January 1, 1980, to December 31, 1994. Of the 154 PTC patients, 37 (24%) had FVPTC. The mean follow-up was 128.2 months (10.7 years). MAIN OUTCOME MEASURES: Demographic features, tumor characteristics, local and distant spread, persistence or recurrence of disease, and carcinoma-related mortality were compared between the groups with FVPTC, PPTC, and non-Hürthle cell FTC (NHFTC). RESULTS: The frequency of multicentricity was significantly higher in the FVPTC group than in the PPTC group (P =.03) or in the NHFTC group (P =.01) (12 [32%] of 37 patients vs 17 [15%] of 117 patients vs 6 [10%] of 58 patients, respectively). The incidence of cervical lymph node metastases was lower in the FVPTC group than in the PPTC group (P =.30) and higher than in NHFTC group (P =.004) (12 [32%] of 37 patients vs 53 [45%] of 117 patients vs 6 [10%] of 58 patients, respectively). At diagnosis, no patient with FVPTC showed distant metastases, compared with 5 patients (4%) with PPTC (P =.34) and 19 (33%) with NHFTC (P<.001). There was no carcinoma-related death in the FVPTC group. The strikingly poorer prognosis for the NHFTC group was statistically significant (P<.001), whereas the difference in carcinoma-specific survival between the PPTC and the FVPTC groups did show a trend toward better survival in the FVPTC group. CONCLUSION: The clinical behavior of the FVPTC group did not differ significantly from that of the PPTC group, whereas compared with the NHFTC group, the FVPTC group showed statistically significant differences for most of the analyzed variables.

RET proto-oncogene mutations affecting codon 790/791: A mild form of multiple endocrine neoplasia type 2A syndrome?

BACKGROUND: In patients with multiple endocrine neoplasia type 2A syndrome, prophylactic thyroidectomy is generally recommended at the age of 5 to 6 years. Whether this recommendation is justified for exon 13 mutations is unknown. METHODS: We analyzed the clinical data from 40 patients harboring RET codon 790/791 mutations (exon 13) who had been treated in 4 specialized centers. RESULTS: Mean age was 35.2 +/- 21.6 years (range, 5.1-69.0 years). Thirteen patients were index patients (mean age, 57.7 +/- 11.3 years), 27 patients were screening patients (mean age, 24.4 +/- 16.5 years). In the index group, pT-category was: T0, n = 2; T1, n = 6; T2, n = 2; T3, n = 1; and T4, n = 2. Lymph node metastases were found in 5 patients and distant metastases in 1 patient. Postoperatively, 69% of index patients were biochemically cured. In the screening group, pT-category was: T0, n = 19; T1, n = 7; and T2, n = 1. Lymph node metastases were found in 2 patients. Postoperatively, 93% of screening patients were biochemically cured. The youngest patient with medullary thyroid carcinoma was 13.8 years, the youngest patient with lymph node metastases was 46.4 years. CONCLUSIONS: Patients with RET codon 790/791 mutations seemed to have a less aggressive clinical course compared with patients with classic multiple endocrine neoplasia type 2A syndrome. Still, index patients had a lower biochemic cure rate in comparison with screening patients. Timely total thyroidectomy including lymph node dissection is warranted.