RAS/BRAF mutational status in familial non-medullary thyroid carcinomas: A retrospective study.

There are contrasting views on whether familial non-medullary thyroid carcinomas (FNMTCs) are characterized by aggressive behavior, and limited evidence exists on the prognostic value of BRAF and RAS mutations in these tumors. Thus, in the present study, clinicopathological features were analyzed in 386 non-medullary thyroid carcinomas (NMTCs), subdivided in 82 familial and 304 sporadic cases. Furthermore, the RAS and BRAF mutational statuses were investigated in a subgroup of 34 FNMTCs to address their clinical and biological significance. The results demonstrated that, compared with sporadic NMTCs, FNMTCs are characterized by significantly higher rates of multicentricity and bilaterality and are more frequently associated with chronic autoimmune thyroiditis. Notably, a statistically significant difference in the rates of multicentricity was observed by subgrouping familial tumors according to the number of relatives involved; those with ≥3 affected relatives were more likely to be multicentric. Furthermore, the FNMTC cohort exhibited higher rates of tumors >4 cm in size with extrathyroidal or lymph node involvement. However, no significant difference was observed. Similarly, no differences were observed with respect to the age of onset or the patient outcome. The mutational profiling exhibited a rate of 58.8% for BRAF V600E mutations in familial tumors, which is at the upper limit of the mutational frequency observed in historical series of sporadic thyroid cancer. A high rate of NRAS mutations (17.6%) was also observed, mostly in the follicular variant histotype. Notably, compared with BRAF/RAS-wild type FNMTCs, the familial carcinomas bearing BRAF or NRAS mutations exhibited slightly higher rates of bilaterality and multicentricity, in addition to increased frequency of locally advanced stage or lymph node involvement. The present data support the theory that FNMTCs are characterized by clinicopathological features that resemble a more aggressive phenotype and suggest that RAS/BRAF mutational analysis deserves to be further evaluated as a tool for the identification of FNMTCs with a potentially unfavorable prognosis.

Cold benign thyroid nodule volume reduction predictability after percutaneous ethanol injection.

OBJECTIVE: To determine the effect of percutaneous ethanol injection (PEI), a suppressive therapy for cold benign thyroid nodules (CBNs), on cytology. STUDY DESIGN: The study group consisted of 31 CBNs, treated with PEI for 1 year, aspirated before and while the patients were on suppressive therapy. A control group consisting of 22 patients, whose nodule characteristic, PEI treatment and follow-up were similar to those of the study patients group, was monitored to confirm the results. By analogy with a similar study, the following factors were considered: an initial volume of the CBNs > 25 mL, abundant colloid, degree of cellular hyperplasia and presence ofdegenerative changes. To verify these hypotheses, we tested the differences using the t test for the initial volume and the Mann-Whitney U test for the remaining features. RESULTS: The study has proved the unpredictability of the volume reduction in a single nodule on the basis of cytologic evaluation. CONCLUSION: The lack of cytologic features that can be considered statistically predictive of large nodule reduction as a result of PEI treatment confirms that fine needle aspiration cytology may help establish the correct diagnosis.

Radioiodine treatment of Plummer and multinodular toxic and nontoxic goiter disease by the first approximation dosimetry method.

The aim of this study was to assess the efficacy of mean radioiodine activities of 12.6 MBq/mL in order to achieve a successful treatment of hyperthyroidism with a single radioiodine dose and a low incidence of hypothyroidism. We evaluated 51 patients with Plummer disease, 41 patients with multinodular toxic goiter, and 9 patients with compressive toxic and nontoxic goiter, after a short suspension of antithyroid drugs, with the exclusion of patients with critical cardiovascular conditions, an expanded iodine pool, and a nodular volume larger than 120 mL. Target volume was measured by ultrasonography and calculated by the ellipsoid method. All the patients underwent a thyroid uptake test with 1.85 MBq of (131)I and measurements on the neck and thigh at 2, 6, and 24 hours. Target volume was 21.5 +/- 21.4 mL for group 1, 15.4 +/- 10.7 mL for group 2, and 56.4 +/- 12.8 mL for group 3. The 24 hours uptake (mean % +/- standard deviation) was 43.1 +/- 19.9, 48.5 +/- 15.4, 56.4 +/- 12.8, respectively, for groups 1, 2 and 3. Mean follow-up was group 1: 23 +/- 17 months; group 2: 23 +/- 14 months; and group 3: 28 +/- 20 months. First approximation dosimetry took into account thyroid volume and the 24-hour uptake percentage. A euthyroidism condition was reached in 40 of 51 patients (78.4%) of group 1, 35 of 41 patients (85.4%) of group 2, and 6 of 9 patients (66.7%) of group 3. Hypothyroidism was observed in 13 of 101 patients (12.9%). Only 9 of 101 (8.9%) patients were subclinically hyperthyroid at the end of follow-up. The over-all efficacy of treatment was 91.1%. Reduction (%) of nodule volume was 66 +/- 23, 57 +/- 18, and 79 +/- 13, respectively, in groups 1, 2, and 3, with scintigraphic disappearance of hot nodules or persistence of cold nodules with the recovery of extranodular thyroid tissue in 76 patients.

Percutaneous ethanol injection plus radioiodine versus radioiodine alone in the treatment of large toxic thyroid nodules.

UNLABELLED: Therapeutic options for toxic thyroid nodules (TTNs) are surgery, radioiodine (RAI), and percutaneous ethanol injection (PEI). Surgery is generally considered for TTNs larger than 4 cm. However, some patients may be at high surgical risk. The purpose of the study was to evaluate the efficacy of 2 nonsurgical modalities for these TTNs. METHODS: Twenty-two patients with TTNs larger than 4 cm were randomly assigned to 2 different treatments: to 11 (subgroup A), RAI was administered at a dose of 12,580 kBq/mL of nodular volume (NV) and was corrected for 100% 24-h (131)I uptake (RAIU); to 11 (subgroup B), 2-4 PEI sessions (ethanol injected = 30% NV) preceded 2 mo of 24-h RAIU and RAI dosing. Inclusion criteria were clinical and biochemical hyperthyroidism; a single palpable, hot nodule at (99m)Tc scintigraphy; and high surgical risk or refusal to have surgery. Patients gave informed consent. Local symptoms were evaluated by a previously validated score (symptom score, or SYS). RESULTS: Both treatments were well tolerated. Subgroup B showed a significant reduction of NV 2 mo after PEI: 33.6 +/- 18.5 versus 60.8 +/- 29.5 mL. Their 24-h RAIU was similar to that of subgroup A: 53.9 +/- 13.9 versus 61.8% +/- 11.0%. Consequently, the administered RAI dose was significantly lower for subgroup B (730 +/- 245 MBq) than for subgroup A (1,048 +/- 392 MBq). Twelve months after RAI, subgroup B had a higher NV reduction and a lower SYS than did subgroup A. In subgroup A, 1 patient was subclinically hyperthyroid, 2 showed a slight increase of thyroid-stimulating hormone, and 1 was clinically hypothyroid. In subgroup B, 1 patient had a slight increase of thyroid-stimulating hormone. CONCLUSION: We demonstrated that RAI, alone or with PEI, can be considered a valid alternative for TTNs larger than 4 cm when surgery is either refused or contraindicated. PEI plus RAI can be considered when marked shrinkage of a nodule is required or when reduction of the RAI dose can prevent hospitalization.