BRAF analysis by fine needle aspiration biopsy of thyroid nodules improves preoperative identification of papillary thyroid carcinoma and represents a prognostic factor. A mono-institutional experience.

BACKGROUND: The current preoperative diagnosis of a thyroid mass relies on microscopic evaluation of thyroid cells obtained by fine needle aspiration biopsy (FNAB). More recently, FNAB has been combined with molecular analysis to increase the accuracy of the cytological evaluation. In this mono-institutional prospective study, we evaluated whether the routine introduction of BRAF testing in thyroid FNAB could help ameliorate the preoperative recognition of papillary thyroid carcinoma (PTC) in "suspended" or malignant cytological categories. Moreover, we investigated the prognostic role of the BRAFV600E mutation in PTC. METHODS: BRAFV600E analysis was performed in thyroid FNAB from 270 patients classified into one of five cytological categories THY1, THY2, THY3, THY4, THY5. All subsequently underwent thyroidectomy±node dissection, from October 2008 to September 2009 in our Department. For each cytological category, we considered the definitive histological diagnosis of PTC and the presence of the BRAFV600E mutation. In 141 patients with a final tissue diagnosis of PTC, we correlated the presence of BRAFV600E with gender, age, histotype, TNM, size of the lesion, extracapsular extension, node metastases and multifocality. RESULTS: The prevalence of the BRAFV600E mutation, among PTCs at final tissue diagnosis, was 69%. It improved the FNAB diagnostic accuracy from 88% to 91%. The BRAFV600E mutation was correlated with older age, classical variant of PTC, advanced stages in patients > 45 years. CONCLUSIONS: BRAFV600E testing could play a role in improving the diagnostic accuracy of FNAB for PTC, representing a useful adjuvant tool in presurgical characterization of thyroid nodes in particular cases. There is an association between the BRAFV600E mutation and some clinico-pathological characteristics of PTC.

Can we avoid inadvertent parathyroidectomy during thyroid surgery?

OBJECTIVES: To identify risk factors of inadvertent parathyroidectomy (IP) during thyroid surgery with the aim of decreasing the incidence of this unpleasant complication and to evaluate the impact on temporary and permanent hypocalcaemia following bilateral thyroidectomy. PATIENTS AND METHODS: All consecutive thyroid surgical procedures performed at the Special Surgical Pathology Department of Padova General Hospital and Padova University during one year (January-December 2005) were retrospectively reviewed. Demographic data as well as data on diagnosis, operative reports, pathology findings, and postoperative serum calcium values were collected. A total of 882 patients (F=685 M=197) were included in the study. The patients were divided into 2 groups: those with IP and those without IP, and their data were compared to find factors affecting the occurrence of IP. The impact of IP on residual early and late postoperative parathyroid function was assessed. Hypercalcaemic (calcium level below 2.10 mMol/L) patients were followed from 1 week to 3 years. RESULTS: Seventy of 882 patients (7.9%) were found to have IP. In 11 cases (16% of IP cases and 1.2 % of entire series) the parathyroid glands were completely intrathyroidal. The results of bivariate analysis showed young age (p=0.037), malignant disease (p<0.0001), total thyroidectomy with lymph node dissection (p<0.0001), low weight of thyroid specimen (p<0.0001), and non-visualisation of any parathyroid gland at operation (p<0.0001) as predictive factors for IP. Multivariate analysis revealed significant correlation between IP and malignant disease (p=0.004), and between lymph node dissection and permanent postoperative hypocalcaemia (p=0.018). The incidence rate of transient and permanent hypocalcaemia was higher in IP than in those without. The mean diameter of excised parathyroid glands was 3.2 mm, suggesting more extended or difficult surgical procedures. CONCLUSION: IP is not uncommon during thyroidectomy and is associated with a higher, though not statistically significant, incidence of transient and permanent postoperative hypocalcaemia. Malignant disease, lymph node dissection, non-visualization of any parathyroid gland at operation and younger age seem to be risk factors and should be considered by the surgeon. Further efforts must be taken to reduce the incidence beginning by avoiding parathyroid fragmentation.

99Tc Nanocolloid sentinel node procedure in thyroid carcinoma.

PURPOSE: The purposes of this study were to investigate the efficacy of radiocolloid lymphoscintigraphy and of handheld gamma probe procedure for sentinel lymph node biopsy (SLNB) in papillary thyroid carcinoma (PTC) and to evaluate its results in clinical staging. MATERIALS AND METHODS: Sixty-five PTC consecutive patients entered the study. Patients underwent radiocolloid lymphoscintigraphy before surgery. Intraoperative sentinel lymph node (SLN) localization was performed using a handheld gamma probe. They were followed up at 2, 6 months, and yearly. RESULTS: SLN metastases were diagnosed in 52%. Fifty-one patients underwent ablative 131-I therapy. The mean Tireoglobulin level in N0 vs N1 cases was 2.2 ng/ml vs 4.73 (p = 0.03) and 0.68 vs 2.1 ng/ml (p = 0.005) before and after 131-I therapy, respectively. CONCLUSIONS: In patients classified N0 by SLNB, ablative 131-I therapy could be avoided.

[The surgical treatment of the nodular goiter]. / Il trattamento chirurgico del gozzo nodulare.

BACKGROUND: The simple nodular goiter, the etiology of which is multifactorial, encompasses the spectrum from the incidental asymptomatic small solitary nodule to the large intrathoracic goiter, causing pressure symptoms as well as cosmetic complaints. The mainstay in the diagnostic evaluation is related to functional and morphological characterization with serum TSH and (some kind of) imaging. Because malignancy is just as common in patients with a multinodular goiter as patients with a solitary nodule, the increasing use of fineneedle aspiration biopsy (cytology) is supported Its management is still the cause of considerable controversy. Prevalence of nodular goiter and results of surgical treatment in a large series of patients operated on at our center are reported. METHODS: From January to December 2004, 1009 out of 1580 patients admitted to our Center underwent surgical treatment for thyroid disease. RESULTS: Nodular goiter accounted for 80% of the whole series. More in detail, toxic multinodular goiter was found in 13.5% of the patients, euthyroid multinodular goiter in 46.6%, single hyperplastic nodule in 2.3%, follicular lesion in 14%, Plummer's adenoma in 4.4%, relapsing goiter in 2.6% and thyroid cyst in 0.12%. Thyroid lobectomy was carried out in 20.8% of patients, while the remaining 79.2% underwent to total thyroidectomy. A carcinoma was incidentally found in 7.6% of the multinodular goiters. CONCLUSIONS: Surgery should be advocated for the treatment of thyroid nodules whenever a patient presents with either pressure symptoms, hyperthyroidism or follicular cytology. Serum TSH measurement, ultrasounds and fine needle aspiration cytology are the main diagnostic tools. Bilateral surgical exploration of the gland should be always carried out to assess the extension of the disease. Total or near total thyroidectomy in order to minimize the risk of recurrent nerve palsy and hypoparathyroidism represents the treatment of choice for bilateral goiter. Thyroid lobectomy with frozen section should be limited to unilateral nodular goiter.

The Hobnail Variant of Papillary Thyroid Carcinoma: Clinical/Molecular Characteristics of a Large Monocentric Series and Comparison with Conventional Histotypes.

BACKGROUND: The hobnail variant of papillary thyroid carcinoma (HPTC) has an aggressive behavior. The aims of this prospective study were to define the clinical/molecular characteristics of HPTC, and to compare them to those of conventional papillary thyroid carcinoma (PTC). METHODS: From 2010 to 2016, 25 cases of HPTC, characterized clinically and molecularly (BRAF, RAS, TERT promoter, and TP53 mutations), were compared to a series of 165 consecutive cases of PTC. All patients underwent total thyroidectomy and received radioactive iodine treatment. Follow-up was available for 19 HPTC patients. RESULTS: Among the HPTC patients, 64% had a hobnail component ≥30%, and 64% had multifocal disease. The mean tumor size was 30 mm; 96% of tumors were angio-invasive; 68% were N1, and 12% were M1; 58% harbored the BRAFV600E mutation, 12% had a mutation in the TERT promoter, 17% had a TP53 mutation, and not had a RAS mutation. At a mean follow-up of 39 months, 32% of patients had biochemical and/or structural disease. Tumor size was the only significant difference between patients with persistent disease and those with an excellent response (40 mm and 24 mm, respectively; p = 0.02). Compared to the PTC control group, the HPTC patients had larger tumors (30 mm vs. 16 mm; p < 0.001), more frequent lymph node involvement (68% vs. 38%; p = 0.01), and remote disease (16% vs. 3%; p < 0.0001), a similar prevalence of the BRAFV600E mutation (58% vs. 59%), a higher prevalence of TP53 mutations (17% vs. 1%; p < 0.05), and a worse outcome (structural/biochemical disease: 32% vs. 9%; p < 0.0001). CONCLUSIONS: HPTC is an aggressive variant, characterized by large tumor size, lymph node involvement, a tendency to metastasize, and a worse outcome.

Incidental medullary thyroid microcarcinoma revealed by mild increase of preoperative serum calcitonin levels: therapeutic implications.

To investigate whether further, diagnostic procedures should be recommended in patients with slight increase of preoperative serum basal calcitonin (bCT) levels in whom surgical treatment can be recommendable. Fourteen consecutive patients with nodular thyroid disease underwent thyroidectomy in our center for suspected medullary thyroid microcarcinoma (MTC) because their serum bCT levels were slightly higher than the upper limit of normal range. Serum bCT was measured by radioimmunoassay, normality range = 0-20 ng/L. Surgical specimens were examined by the same pathologist using histologic and immunohistochemistry techniques. An extensive search for parafollicular C-cell hyperplasia (CCH) and/or microscopic MTC foci was performed. At preoperative ultrasound, a single thyroid nodule was depicted in three patients while a multinodular goiter in 11. The bCT values ranged between 24.4 and 94.6 ng/L, median 42.2 ng/L while the pentagastrin-stimulated CT (sCT) values by pentagastrin test ranged between 61.5 and 1,262 ng/L, median 245.0 ng/L. Total thyroidectomy was performed in 13 patients, and lobectomy in the other one; central node dissection was also performed in eight cases. At histology, MTC was diagnosed in nine patients (64.3 %), showing a median maximum diameter of 6.1 mm (range, 1.5-17 mm); CCH was diagnosed in the other five patients (35.7 %). The pentagastrin stimulation test was obtained in all patients. It is worth noting that a very high increase of sCT >100 ng/mL was observed in 5/9 patients with MTC and in 2/4 patients with HCC, therefore suggesting the absence of a relationship between the entity of response to pentagastrin test with a specific pathology (MTC vs. HCC). In six patients, the MTC was the nodule on which preoperative FNAC had been performed, while in other three patients preoperative FNAC had been performed on a different nodule from the MTC. Based on our experience, in case of the pentagastrin stimulation test with sCT <100 ng/L and a single nodule, the CT assay on FNAC may be useful, subsequently lobectomy with definitive histological diagnosis is recommended. In case of the Pg test with sCT <100 ng/L and bilateral goiter, total thyroidectomy with histological diagnosis is recommended. In this way, as for the surgical procedure, total thyroidectomy is recommended in cases of bilateral goiter, while lobectomy can be offered for cases with single nodes with serum dosage of bCT in the strict follow up. In case of the pentagastrin stimulating test with sCT <100 ng/L and bilateral goiter, total thyroidectomy with histological diagnosis is recommended.

A case of anaplastic thyroid cancer with long-term survival.

Anaplastic thyroid carcinoma (ATC) (less than 10% of all thyroid cancer) is a high-grade neoplasm, characterized by an aggressive clinical course and refractoriness to currently available local and systemic modalities of treatment. It is considered the most aggressive solid tumour, there is no adequate therapy for this disease and few patients with ATC live more than 1 year following diagnosis. We report herein an unusual case of ATC in a 59-year-old woman. She presented to our Institute in December 2004. She received many kinds of chemotherapeutical and multimodal treatment; we obtained a long period of localized disease (about two years) and an excellent response to therapy. She is still alive 58 months from diagnosis.

Neck emergency due to parathyroid adenoma bleeding: a case report.

INTRODUCTION: The spontaneous rupture of a parathyroid adenoma accompanied by extracapsular hemorrhage is a rare, potentially fatal, condition and is a cervicomediastinal surgical emergency. CASE PRESENTATION: This report describes an atypical two-step spontaneous rupture of an asymptomatic parathyroid adenoma in a 56-year-old Caucasian woman who presented with a painful mass in the right side of her neck. CONCLUSION: Based on this case report and similar cases reported in the medical literature, a diagnosis of extracapsular parathyroid hemorrhage should be considered when a non-traumatic sudden neck swelling coexists with hypercalcemia and regional ecchymosis.