Embolization of iliac metastasis during lenvatinib treatment in patient with advanced Hürthle cell thyroid carcinoma.

Lenvatinib is a tyrosine kinase inhibitor (TKI) with antiproliferative and antiangiogenic effects indicated for the treatment of progressive, locally advanced or metastatic progressive thyroid carcinoma, refractory to radioactive iodine therapy. Antiangiogenic therapies induce ischemic necrosis of tumor tissue, with increased risk of hemorrhagic complications. The management of hemorrhagic risk is based on precautionary measures and for any surgical procedure, it is advised to interrupt the treatment in order to avoid complications. 'Flare-up' of tumor activity may follow TKI interruption. However, it is not known if continuing TKIs during minimally invasive interventions is safe. We report here the first case in which an embolization of metastasis is performed without interrupting lenvatinib treatment. The procedure was successful and free of complications.

Diffuse C-Cells Hyperplasia Is the Source of False Positive Calcitonin Measurement in FNA Washout Fluids of Thyroid Nodules: A Rational Clinical Approach to Avoiding Unnecessary Surgery.

PURPOSE: The FNA-CT is useful for the diagnosis of MTC. The aim of this study was to evaluate the performance of FNA-CT in TNs coexisting with CCH. METHODS: This study retrospectively reviewed the records of 11 patients with TNs submitted to thyroidectomy on the basis of elevated basal and/or stimulated serum CT values, which at histology were not confirmed to be MTC. The results obtained in this group were compared with those of a previously reported group of histologically proven MTC patients submitted to an identical presurgical evaluation. All patients, negative for known mutations in the RET proto-oncogene, were preoperatively submitted to neck ultrasound, FNA-cytology, and FNA-CT. RESULTS: Approximately 6 of 11 patients showed increased (>36 ng/mL, as established in previous studies not involving patients with CCH) FNA-CT. All these patients showed diffuse CCH at histology in the thyroid lobe submitted to FNA; 5 of them were benign at histology, while only one was malignant (papillary thyroid carcinoma, PTC). The remaining 5 of 11 patients had low FNA-CT (<36 ng/mL), and all of them showed only focal CCH in the lobe submitted to FNA; three of them were malignant (2 PTC, 1 follicular carcinoma), while two were benign. CONCLUSIONS: Employing the currently proposed cut-off values, false-positive FNA-CT results may be observed in benign/malignant TNs with coexisting diffuse CCH. FNA-CT must therefore be cautiously used in the diagnostic approach for patients with TNs and a slightly increased basal or stimulated serum CT concentration in order to avoid unnecessary surgery.

Risk factors for postoperative cervical haematoma in patients undergoing thyroidectomy: a retrospective, multicenter, international analysis (REDHOT study).

Background: Postoperative cervical haematoma represents an infrequent but potentially life-threatening complication of thyroidectomy. Since this complication is uncommon, the assessment of risk factors associated with its development is challenging. The main aim of this study was to identify the risk factors for its occurrence. Methods: Patients undergoing thyroidectomy in seven high-volume thyroid surgery centers in Europe, between January 2020 and December 2022, were retrospectively analysed. Based on the onset of cervical haematoma, two groups were identified: Cervical Haematoma (CH) Group and No Cervical Haematoma (NoCH) Group. Univariate analysis was performed to compare these two groups. Moreover, employing multivariate analysis, all potential independent risk factors for the development of this complication were assessed. Results: Eight thousand eight hundred and thirty-nine patients were enrolled: 8,561 were included in NoCH Group and 278 in CH Group. Surgical revision of haemostasis was performed in 70 (25.18%) patients. The overall incidence of postoperative cervical haematoma was 3.15% (0.79% for cervical haematomas requiring surgical revision of haemostasis, and 2.35% for those managed conservatively). The timing of onset of cervical haematomas requiring surgical revision of haemostasis was within six hours after the end of the operation in 52 (74.28%) patients. Readmission was necessary in 3 (1.08%) cases. At multivariate analysis, male sex (P < 0.001), older age (P < 0.001), higher BMI (P = 0.021), unilateral lateral neck dissection (P < 0.001), drain placement (P = 0.007), and shorter operative times (P < 0.001) were found to be independent risk factors for cervical haematoma. Conclusions: Based on our findings, we believe that patients with the identified risk factors should be closely monitored in the postoperative period, particularly during the first six hours after the operation, and excluded from outpatient surgery.

Association between hashimoto thyroiditis and differentiated thyroid cancer: A single-center experience.

Hashimoto's thyroiditis is the most common cause of hypothyroidism in the iodine-sufficient areas of the world. Differentiated thyroid cancer is the most common thyroid cancer subtype, accounting for more than 95% of cases, and it is considered a tumor with a good prognosis, although a certain number of patients experience a poor clinical outcome. Hashimoto's thyroiditis has been found to coexist with differentiated thyroid cancer in surgical specimens, but the relationship between these two entities has not yet been clarified. Our study aims to analyze the relationship between these two diseases, highlighting the incidence of histological diagnosis of Hashimoto thyroiditis in differentiated thyroid cancer patients, and assess how this autoimmune disorder influences the risk of structural disease recurrence and recurrence rate.

Association between High Normal TSH Levels and Obesity in Women with Anti-Thyroid Autoantibodies (ATAs).

A positive correlation between Thyroid-Stimulating Hormone (TSH) and Body Mass Index (BMI) has been reported in many studies, but data on this topic remain controversial, especially when TSH values are in the normal range. Moreover, few studies have evaluated the co-existence of thyroid autoimmunity. This study investigated the role of thyroid autoimmunity in the interconnection between TSH, BMI, and waist circumference (WC) in euthyroid patients with overweight or obesity. We enrolled 902 patients (213 males; mean age ± SD: 45 ± 14 years; mean BMI ± SD: 35.8 ± 6.5 kg/m2), with normal serum TSH concentration; anti-thyroid autoantibodies (ATAs) were evaluated in 752 patients (186 males). Patients were divided into four BMI classes, based on WHO criteria, and the relationship between BMI, WC, and TSH was evaluated in the whole sample and compared to ATAs positivity, observed in 235 patients (44 males). No significant difference was found between TSH levels in the BMI classes. A statistically significant correlation between TSH and BMI was found only in ATAs-positive females (N = 191, Spearman rho: 0.149; p-value: 0.040). However, this finding was not confirmed when considering the WC. Our study shows a positive correlation only between TSH and BMI in obese women with positive ATAs, suggesting that in these patients, the high normal levels of TSH could be attributed to a mild thyroid failure with a possible worsening obesity-related effect, and both need a careful evaluation.

Gene expression profile in metastatic and non-metastatic parathyroid carcinoma.

Parathyroid carcinoma (PC) is one of the rarest and aggressive malignancies of the endocrine system. In some instances, the histological diagnosis remains uncertain unless there is evidence of gross local invasion or secondary spread. The identification of molecular markers could improve the diagnostic accuracy of these lesions. The expression of 740 genes involved in the tumor progression processes was assessed in 8 parathyroid adenomas (PAs), 17 non-metastatic and 10 metastatic PCs using NanoString technology. Clustering analysis and Ingenuity Pathway Analysis (IPA) were interrogated to compare the gene expression profiles among the three analyzed groups and to evaluate the potential role of differentially expressed genes, respectively. The 103 differentially expressed genes between metastatic PCs and PAs are able to discriminate perfectly the two groups from a molecular point of view. The molecular signatures identified in non-metastatic PCs vs PAs and in metastatic PCs vs non-metastatic PCs comparisons, although with some exceptions, seem to be histotype-specific IPA reveals that hepatic fibrosis/hepatic stellate cell activation and GP6 signaling pathway are involved in malignant behavior of parathyroid tumors, whereas the activation of the HOTAIR regulatory pathway are involved in the metastatization process. Our investigation identified differentially expressed genes in non-metastatic PCs mainly encoding ECM proteins and in metastatic PCs driving endothelial-to-mesenchymal transition or encoding mediators of angiogenesis. The identified genes might be promising molecular markers potentially useful in the clinical practice for the early diagnosis and prognosis of PC.

Predictive Factors of Lymph Node Metastasis in Patients With Papillary Microcarcinoma of the Thyroid: Retrospective Analysis on 293 Cases.

Introduction: Papillary thyroid microcarcinoma (PTMC) is defined as a tumor with a larger diameter ≤ 1 cm and is considered having an indolent course and an excellent prognosis. Nevertheless, the incidence of lymph node metastasis in PTMC is not negligible, reaching up to 65% in some series. The aim of this study was to assess the incidence of lymph node metastasis in patients with PTMC and to evaluate predictive factors for lymph node metastasis. Methods: We included in this retrospective observational study patients who underwent thyroidectomy with pathological diagnosis of PTMC at our department from January 2003 to June 2019. Results: Two hundred ninety-three patients were included in the study. The incidence of lymph node metastasis was 13.7%. Multivariate analysis revealed as independent risk factors for lymph node metastasis age <45 years, nodule size ≥6 mm, tall cell variant of PTC, extrathyroidal extension, and angioinvasion. Conversely, autoimmune thyroiditis was found as a protective factor for lymph node metastasis. A subgroup of patients, with nodule size ≤ 5 mm, presented non-aggressive features. Conclusion: The incidence of lymph node metastasis in PTMC is considerable; the size of the tumor appears to be the most significant predictive factor for lymph node metastasis. The traditional cut-off value used for definition of microcarcinoma could be reconsidered to identify patients with an indolent course of the tumor, where active surveillance could be the appropriate treatment, and on the other hand, patients with potentially aggressive tumors requiring an adequate surgical intervention. Clinical Trial Registration: The trial was registered at ClinicalTrials.gov (ID: NCT04274829).

Is prophylactic central neck dissection justified in patients with cN0 differentiated thyroid carcinoma? An overview of the most recent literature and latest guidelines.

To date, in patients with differentiated thyroid cancer, central neck dissection is recommended in the presence of central compartment lymph node metastases. Differently, the efficacy of prophylactic central neck dissection in case of clinically node-negative differentiated thyroid carcinoma remains still uncertain. There are many arguments in favor and many against the execution of this surgical procedure. The most recent literature and latest guidelines have been reviewed and illustrated, paying particular attention to currently hottest and most discussed points. Prophylactic central neck dissection is associated with higher rates of postoperative complications, such as recurrent laryngeal nerve injury and hypoparathyroidism, with unclear oncological benefits. Thus, in the absence of lymph node involvement, this procedure should be avoided, reserving it for high-risk patients with advanced primary tumors. Moreover, to avoid serious complications, prophylactic central neck dissection should be performed by high-volume surgeons. KEY WORDS: Clinically node-negative differentiated thyroid cancer, Differentiated thyroid carcinoma, Prophylactic central neck dissection.

Impact of a Moderately Hypocaloric Mediterranean Diet on the Gut Microbiota Composition of Italian Obese Patients.

Although it is known that the gut microbiota (GM) can be modulated by diet, the efficacy of specific dietary interventions in determining its composition and diversity in obese patients remains to be ascertained. The present work aims to evaluate the impact of a moderately hypocaloric Mediterranean diet on the GM of obese and overweight patients (OB). The GM of 23 OB patients (F/M = 20/3) was compared before (T0) and after 3 months (T3) of nutritional intervention (NI). Fecal samples were analyzed by Illumina MiSeq sequencing of the 16S rRNA gene. At baseline, GM characterization confirmed typical obesity-associated dysbiosis. After 3 months of NI, patients presented a statistically significant reduction in body weight and fat mass, along with changes in the relative abundance of many microbial patterns. In fact, an increase in the abundance of several Bacteroidetes taxa (i.e., Sphingobacteriaceae, Sphingobacterium, Bacteroides spp., Prevotella stercorea) and a depletion of many Firmicutes taxa (i.e., Lachnospiraceae members, Ruminococcaceae and Ruminococcus, Veillonellaceae, Catenibacterium, Megamonas) were observed. In addition, the phylum Proteobacteria showed an increased abundance, while the genus Sutterella, within the same phylum, decreased after the intervention. Metabolic pathways, predicted by bioinformatic analyses, showed a decrease in membrane transport and cell motility after NI. The present study extends our knowledge of the GM profiles in OB, highlighting the potential benefit of moderate caloric restriction in counteracting the gut dysbiosis.

Predictive Factors of Recurrence in Patients with Differentiated Thyroid Carcinoma: A Retrospective Analysis on 579 Patients.

Differentiated thyroid carcinoma (DTC) is usually associated with a favorable prognosis. Nevertheless, up to 30% of patients present a local or distant recurrence. The aim of this study was to assess the incidence of recurrence after surgery for DTC and to identify predictive factors of recurrence. We included in this retrospective study 579 consecutive patients who underwent thyroidectomy for DTC from 2011 to 2016 at our institution. We observed biochemical or structural recurrent disease in 36 (6.2%) patients; five-year disease-free survival was 94.1%. On univariate analysis, male sex, histotype, lymph node yield, lymph node metastasis, extrathyroidal invasion and multicentricity were associated with significantly higher risk of recurrence, while microcarcinoma was correlated with significantly lower risk of recurrence. On multivariate analysis, only lymph node metastases (OR 4.724, p = 0.012) and microcarcinoma (OR 0.328, p = 0.034) were detected as independent predictive factors of recurrence. Postoperative management should be individualized and commensurate with the risk of recurrence: Patients with high-risk carcinoma should undergo strict follow-up and aggressive treatment. Furthermore, assessment of the risk should be repeated over time, considering individual response to therapy.

Correlation between iPTH Levels on the First Postoperative Day After Total Thyroidectomy and Permanent Hypoparathyroidism: Our Experience.

Permanent hypoparathyroidism is the most common long-term complication after thyroidectomy. We evaluated whether iPTH concentrations on the first postoperative day may be a good predictor of this complication. Patients undergoing thyroidectomy in our Unit between January 2017 and February 2018 who developed postsurgical hypoparathyroidism were analysed. According to iPTH values on the first postoperative day and on the basis of the detection threshold of the iPTH test used, patients were divided into 2 groups: Group A (iPTH < 6.3 pg/mL, undetectable), Group B (iPTH ≥ 6.3 pg/mL). Seventy-five patients were included in this study: 64 in Group A and 11 in Group B. Permanent hypoparathyroidism occurred in 14 (21.88%) patients in Group A, while none developed this complication in Group B. When iPTH was < 6.3 pg/mL, the sensitivity for the prediction of permanent hypoparathyroidism was 100%, the specificity was 18.03%, the positive predictive value was 21.88% and the negative predictive value was 100%. No patient with iPTH ≥ 6.3 pg/mL on the first postoperative day developed permanent hypoparathyroidism. On the other hand, iPTH concentrations < 6.3 pg/mL have not proved to be a strong predictor of this condition. However, this cut-off value can be useful to identify patients at risk of developing this complication.

Sense of coherence and physical health-related quality of life in Italian chronic patients: the mediating role of the mental component.

OBJECTIVE: To examine the relationship between sense of coherence (SOC) and physical health-related quality of life in patients with chronic illnesses by focusing on the mediating role of the mental component of quality of life. DESIGN: Cross-sectional survey design. SETTING: Secondary care; three departments of an Italian university hospital. METHODS: The participants (n=209) in the study were adult (≥18 years) outpatients with a chronic pathology (eg, diabetes, thyroid disorders or cancer) at any phase in the care trajectory (eg, pre-treatment, undergoing treatment, follow-up care). They agreed to participate in the study after providing their informed consent. Data were collected using a structured self-reporting questionnaire. Data analysis was carried out using SPSS, and mediation analysis was performed via PROCESS macro. RESULTS: The SOC score of the study sample was equivalent to that of the general population (mean difference=-2.50, 95% CI -4.57 to 0.00). Correlation analysis showed that SOC was mainly correlated to the mental component (MCS) (r=0.51, p<0.01) of quality of life and then to the physical component (PCS) (r=0.35, p<0.01). Mediation analysis showed that SOC was directly related to MCS (p<0.001, 95% CI 0.62 to 0.99) but not to PCS (p=0.42, 95% CI -0.27 to 0.12). In turn, MCS was directly related to PCS (p<0.001, 95% CI 0.76 to 1.01). The indirect effect of SOC on PCS through MCS was significant (0.71, p<0.001, bootstrap 95% CI 0.54 to 0.91), thus supporting the mediating role of the mental component of quality of life. CONCLUSION: The indirect effect suggests that SOC is a marker of quality of life, especially of the mental component. The findings show that SOC is a psychological process that impacts patients' mental health status, which in turn affects physical health. Better knowledge of a person's SOC and how it affects his/her quality of life may help to plan tailoring interventions to strengthen SOC and improve health-related quality of life.

Calcitonin measurement in wash-out fluid from fine needle aspiration of neck masses in patients with primary and metastatic medullary thyroid carcinoma.

OBJECTIVE: The aim of the study was to evaluate the usefulness of calcitonin (CT) assay in fine-needle aspiration biopsy (FNAB) wash-out fluid alone or combined with cytology in the presurgical study of medullary thyroid carcinoma (MTC) patients with thyroid nodules (TNs) and of suspicious neck MTC recurrences/metastases. SUBJECTS AND METHODS: A total of 36 ultrasound-guided FNABs were performed in neck masses from 23 patients with borderline or high basal and pentagastrin-stimulated serum CT. Cytology and CT-FNAB were performed on a total of 18 TNs and three neck lymph nodes (LNs) from 12 patients examined before thyroidectomy, and on six suspicious local recurrences (LRs) and nine LNs from nine totally thyroidectomized MTC patients. On the basis of CT-FNAB values found in 15 non-MTC lesions, CT-FNAB more than 36 pg/ml was considered as indicative of MTC. RESULTS: All 21 positive CT-FNAB lesions (10 TNs, six LNs, and five LRs), 13 with positive cytology, were confirmed as MTC at histology. Of the 15 negative CT-FNAB suspicious masses (eight TNs, six LNs, and one LR), five displayed a benign lesion at histology. The remaining 10 cases, all with benign cytology, were not operated on, and no evidence of MTC was detected at follow-up. CT-FNAB reached 100% sensitivity and specificity for MTC, while cytology displayed 61.9% sensitivity and 80% specificity. CONCLUSIONS: Ultrasound-guided CT-FNAB was the best tool to identify primary MTC and LRs/node metastases in MTC operated subjects. This may have important implications in the management of MTC.

Thyroid Autoimmunity and Thyroid Cancer: Review Focused on Cytological Studies.

The association between Hashimoto thyroiditis (HT) and papillary thyroid carcinoma (PTC) has been originally suggested by retrospective pathological studies and has recently been re-evaluated and proposed on the basis of several fine-needle aspiration cytology (FNAC) studies. In FNAC studies, the association between HT and PTC is based on the comparison of anti-thyroid autoantibodies (ATA) (anti-thyroperoxidase [TPOAb] and anti-thyroglobulin [TgAb]), thyroid function (TSH), and cytology with histology of thyroid nodules and lymphocytic thyroid infiltration (LTI) of operated thyroid glands. Most of the pathological studies found a high prevalence rate of PTC in HT. In most FNAC studies, the risk ratio of PTC in HT patients was evaluated using multivariate statistical analysis: increased TSH levels represented the main and common independent risk factor of malignancy, although it resulted not consistently related to HT. On the other hand, several studies provided a positive relationship between ATA and PTC, particularly with TgAb. Two recent FNAC studies from the same referral center clearly demonstrated an independent risk for thyroid malignancy conferred by both TPOAb and TgAb, confirming the role of increased TSH levels, and found a significant association between PTC and ATA and diffuse LTI at histology. These studies are consistent with the hypothesis that autoimmune thyroid inflammation and increased serum TSH concentration may be involved in thyroid tumor growth. The complex relationship between HT and PTC, which involves immunological/hormonal pathogenic links, needs to be further investigated with prospective studies.

Aggressive differentiated thyroid cancer with multiple metastases and NRAS and TERT promoter mutations: A case report.

Sorafenib, a tyrosine kinase inhibitor, is approved for the treatment of advanced differentiated thyroid carcinoma (DTC). Resistance to sorafenib may appear under treatment and may be associated with increased aggressiveness of the neoplasia. The present study reports the case of a 65-year-old male who underwent total thyroidectomy for a follicular thyroid carcinoma, Hürthle cell variant, in February 2005. Until January 2010, the patient received four consecutive 131I doses (total dose, 612 mCi) for increased serum thyroglobulin (Tg) and initial faint lung uptake (which eventually became undetectable). Subsequently, the patient developed several sequential bone (humerus, rib and skull), adrenal and lung metastases, the majority of which were surgically removed. Histological examination in all cases revealed evidence of DTC metastases that were strongly positive for Tg, as revealed by immunohistochemistry. In March 2014, sorafenib therapy was initiated, but it was discontinued 10 months later to allow an undelayable prostatectomy. Immediately upon surgery, the patient developed a large metastatic lesion in the right gluteal muscle, whose biopsy revealed undifferentiated neoplasia of epithelial origin, and the patient succumbed shortly afterwards. An extensive comparative search for biochemical and molecular markers was performed on all available tissues (primary tumor, and differentiated and undifferentiated metastases). The primary tumor and all the available metastases exhibited the same molecular oncogenic markers (namely, the RAS mutation p.Q61R and the telomerase promoter mutation C228T). In addition, the undifferentiated metastasis exhibited a p53 mutation. The present study reports a case of a sudden acceleration of DTC metastatic progression following sorafenib discontinuation, which could have been due to the emergence of sorafenib-resistant undifferentiated p53-positive tumor cell clones.

Median eminence dopaminergic nerve terminals: a novel target in autoimmune polyendocrine syndrome?

CONTEXT: Autoantibodies to adenohypophyseal endocrine cells or to vasopressin neurohypophyseal neurons have long been known. Conversely, autoimmune targeting of further hypothalamic-hypophyseal structures, such as the blood-brain barrier-deprived median eminence, has been little studied. OBJECTIVE AND METHODS: We studied a case of autoimmune polyendocrine syndrome type I with GH secretory deficiency, a distinctly rare event in autoimmune polyendocrine syndrome type I. We used rat and bovine tissue substrates to study autoantibodies against hypothalamic-hypophyseal nerve structures and endocrine cells. RESULTS: In the study case, circulating autoantibodies selectively decorated median eminence dopaminergic nerve terminals, as well as pituitary gonadotropes, but not GHRH nerve terminals or pituitary somatotropes. Such autoantibodies appeared de novo in parallel with the onset of GH secretory deficiency, whereas no median eminence labeling was found in patients suffering of idiopathic GH deficiency (n = 7) or in healthy controls (n = 23). CONCLUSIONS: The pathophysiological significance of our patient's autoantibodies remains to be confirmed. Nonetheless, the heterogeneous neuroendocrine structures of the median eminence are pointed out as potential immune targets, relevant to autoimmune polyendocrinopathy, as well as to a wide range of other conditions.

Thyroid Dysfunction in Patients with Metastatic Carcinoma Treated with Sunitinib: Is Thyroid Autoimmunity Involved?

BACKGROUND: Sunitinib is a tyrosine kinase inhibitor (TKI) inducing thyroid dysfunction, but the precise mechanism(s) involved remains to be explained, including the role of thyroid autoimmunity. The objective of this study was to evaluate thyroid function, parameters of autoimmunity, and thyroid ultrasound findings in patients with metastatic cancer and normal thyroid function/autoimmunity before the initiation of sunitinib therapy. This was a prospective, observational cohort study. METHODS: Twenty-seven patients with metastatic carcinomas at comparable tumor stages were evaluated over 12-18 months after initiating therapy with sunitinib given at a daily oral dose of 50 mg for four weeks (ON), followed by one to two weeks off therapy (OFF). Serum thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and antithyroglobulin (TgAb), and antithyroid peroxidase (TPOAb) autoantibodies were measured in all cases. Thyroid morphology and volume were evaluated by echo-color Doppler ultrasound. RESULTS: A total of 16/27 patients (60%) became hypothyroid (TSH range 7-114 mIU/L) within 30-120 days of therapy. The thyroid volume decreased in 24/27 (89%) patients (from M = 14.6 mL, SD = 6.4 mL to M = 3.8 mL, SD = 2.6 mL after 12 months; p < 0.001), together with the appearance of mild to severe hypoechogenicity. TPOAb (40-3000 IU/mL) became detectable in 7/27 (25%) patients, and TPOAb-positive patients displayed a higher degree of hypothyroidism and volume reduction. The progression-free survival (PFS) was significantly longer in patients developing TPOAb (10.8 months) than in the other group of patients (5.8 months). CONCLUSIONS: These data confirm the thyroid inhibitory effect of sunitinib, in keeping with the key role of kinases in controlling thyroid function and growth. However, the novel appearance of TPOAb in a subgroup of patients with more severe hypothyroidism and longer survival indicates that sunitinib may also trigger/exacerbate thyroid autoimmunity contributing to thyroid failure. The development of TPOAb was associated with a longer PFS.

Optimizing detection of RET and PPARg rearrangements in thyroid neoplastic cells using a home-brew tetracolor probe.

BACKGROUND: Fluorescence in situ hybridization (FISH) to identify specific DNA target sequences in the nuclei of nondividing cells of numerous solid neoplasms has contributed to the introduction of molecular cytogenetics as a useful adjunct to cytology, leading recently to the "marriage" of the 2 disciplines. Numerous cancer molecular markers can now be investigated using different technical approaches, at both the gene and expression levels, in biopsies of various suspected cancers, including differentiated thyroid carcinoma. The limited amount of bioptic material is often insufficient to carry out multiple tests, and optimizing handling of the biopsy is desirable. METHODS: We have developed a home-brew tetracolor break-apart probe able to simultaneously identify the 2 most common genetic alterations in differentiated thyroid carcinoma: RET/PTC variants in papillary thyroid carcinoma and PAX8/PPARg fusion and variants in follicular thyroid carcinoma. RESULTS: The probe had 100% specificity, 99.5% sensitivity, and ≥ 3% cutoff. The probe was tested on RET/PTC and PAX8/PPARg RT-PCR positive controls, and feasibility was assessed in 368 thyroid nodule fine-needle aspirations (FNA). In the latter analysis, 24 FNAs had split RET signal, and 9 had split PPARg signal. FISH analysis of available surgically removed nodules confirmed the sensitivity of FISH in detecting abnormal clones and oligoclones. CONCLUSIONS: The home-brew tetracolor probe showed high feasibility, optimizing the use of the biological material in relation to the available molecular tests and maximizing the FISH experimental and slide-scoring times. This probe may be considered an alternative to RT-PCR when recovery and quality of RNA amplification from FNA are insufficient.

Differentiated thyroid cancer: indications and extent of central neck dissection--our experience.

The aim of this retrospective study was to determine the rate of metastases in the central neck compartment and examine the morbidity and rate of recurrence in patients with differentiated thyroid cancer treated with or without a central neck dissection. Two hundred and fifteen patients undergoing total thyroidectomy with preoperative diagnosis of differentiated thyroid cancer, in the absence of suspicious nodes, were divided in two groups: those who underwent a thyroidectomy only (group A; n = 169) and those who also received a central neck dissection (group B; n = 46). Five cases (2.32%) of nodal recurrence were observed: 3 in group A and 2 in group B. Tumor histology was associated with a risk of recurrence: Hürthle cell-variant and tall cell-variant carcinomas were associated with a high risk of recurrence. Multifocality and extrathyroidal invasion also presented a higher risk, while smaller tumors were at lower risk. The results of this study suggest that prophylactic central neck dissection should be reserved for high-risk patients only. A wider use of immunocytochemical and genetic markers to improve preoperative diagnosis and the development of methods for the intraoperative identification of metastatic lymph nodes will be useful in the future for the improved selection of patients for central neck dissections.

Thyroid diseases cause mismatch between MIBI scan and neck ultrasound in the diagnosis of hyperfunctioning parathyroids: usefulness of FNA-PTH assay.

DESIGN: To evaluate the efficacy of the main tools in the diagnostic localization of hyperfunctioning parathyroids (HP) in primary hyperparathyroidism (pHPT) with concomitant thyroid diseases. METHODS: Forty-three patients with pHPT associated with nodular goiter (NG, n=32) and/or autoimmune thyroid diseases (AITDs, n=11) for a total of 63 neck lesions were considered. Sixteen patients displaying HP (16 lesions), unequivocally localized by sestaMIBI scintigraphy (MIBI) and neck ultrasound (US) (group I), were compared with 27 patients (47 neck lesions) displaying equivocal parathyroid localization (group II). In all cases, neck US, MIBI scan, cytology, and parathyroid hormone assay in fine-needle aspiration washout fluid (FNA-PTH) were performed. All patients finally underwent surgery. RESULTS: According to histological examination, high FNA-PTH values (>103 pg/ml) correctly identified all HP in both groups of patients (100% of sensitivity and specificity). Both MIBI and US correctly identified all HP only in group I patients; in contrast, four patterns of mismatch between these techniques were observed in group II patients, leading to low diagnostic performances of neck US (71.4% sensitivity and 78.9% specificity) and of MIBI scan (35.7% sensitivity and 42.1% specificity). The latter was due to both false-negative (mainly in AITD) and false-positive (mainly in NG) scan images. CONCLUSIONS: Coexistent thyroid diseases are responsible for mismatch between MIBI and US images resulting in equivocal HP localization. In these cases, FNA-PTH resulted in the most accurate tool to identify HP. However, although safe, it should be advised only to patients with uncertain HP localization.