Serum microRNA-146a-5p and microRNA-221-3p as potential clinical biomarkers for papillary thyroid carcinoma.

PURPOSE: Papillary thyroid carcinoma (PTC) is the most common malignant thyroid neoplasm, accounting for approximately 85% of all follicular cell-derived thyroid nodules. This study aimed to assess the diagnostic potential of circulating microRNA-146a-5p and microRNA-221-3p as biomarkers for PTC and their usefulness in monitoring disease progression during patient follow-up. METHODS: An observational study was conducted on two cohorts of PTC patients and healthy controls (HCs) using digital PCR. We collected patients' clinical, biochemical, and imaging data during the post-surgery surveillance. We analyzed the levels of circulating miRNAs in serum samples of patients before surgery and during the follow-up, including those with indeterminate/biochemical incomplete response (IndR/BIR) and residual thyroid tissues (Thy Residue). RESULTS: Both miR-146a-5p and miR-221-3p were confirmed as effective biomarkers for PTC diagnosis. They enabled differentiation between pre-surgery PTC patients and HCs with an area under the curve (AUC) of 92% and 87.3%, respectively, using a threshold level of 768,545 copies/uL for miR-146a-5p and 389,331 copies/uL for miR-221-3p. It was found that miRNA fold change levels, rather than absolute levels, can be useful during patient follow-up. In particular, we found that a fold change of 2 for miR-146a-5p and 2.2 for miR-221-3p can identify a progressive disease, regardless of the presence of TgAbs or remnant thyroid. CONCLUSION: MiRNA-146a-5p and miRNA-221-3p, particularly the former, could be valuable diagnostic biomarkers for PTCs. They also seem to be effective in monitoring disease progression during patient follow-up by evaluating their fold change, even when thyroglobulin is uninformative.

Diagnostic Performance of Neck Ultrasonography in the Preoperative Evaluation for Extrathyroidal Extension of Suspicious Thyroid Nodules.

BACKGROUND: A preoperative neck ultrasound (US) is recommended for all patients with suspected thyroid cancer, to identify features potentially changing surgical extent. The extrathyroidal extension (ETE) is considered an indication for total thyroidectomy, but there is limited consensus on its US definition, and the interobserver reliability is low. This study aimed to evaluate the predictive value of neck US for ETE before surgery and to estimate the diagnostic performance of different US findings, evaluated during real-time examinations. METHODS: Patients referred to surgery between November 1, 2015, and May 31, 2019, for a suspicious thyroid cancer underwent a preoperative neck US, with systematic assessment for ETE. Three definitions were tested: very restrictive (capsular disruption with suspicious images of surrounding tissues invasion), restrictive (including also capsular abutment with evidence of capsular disruption), and nonrestrictive (capsular abutment is sufficient). Histopathology report of ETE involving at least soft tissues was considered positive. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: The study cohort included 128 patients, with 102 (79.7%) confirmed malignancies, and 44 (43.1%) histological ETE. The nonrestrictive definition had good sensitivity (86.4%) but low specificity (29.8%), with an NPV of 80.6%; the restrictive definition had higher specificity (81%), while the very restrictive had specificity and PPV of 100%. CONCLUSIONS: A more extensive surgical approach should not be based on US suspicion of ETE alone, with the possible exception of gross invasion appearance. The absence of any sign of ETE, on the other hand, has a substantial negative predictive value.

Nipple-Sparing Mastectomy Long-Term Outcomes: Early and Late Complications.

Background and Objectives: The surgical choice treatment of the breast cancer mostly depends on the stage of the disease. In the last years, breast cancer surgery has moved from being destructive to being more respectful of the anatomical and physiological integrity of the gland. The aim of the breast surgery should be finalized to obtain the best aesthetic and functional results, respecting the principles of oncologic radicality. The present study is a retrospective analysis aimed to evaluate the long-term outcomes of a conservative technique like the nipple-sparing mastectomy. Materials and Methods: We observed 894 patients with a median age of 47.5 years old, underwent nipple-sparing mastectomy between 2002-2017. The data acquired include population and tumor characteristics, patient reconstructive outcomes, including locoregional, regional, and distant metastases; other variables, among nipple-areola complex necrosis and infection were collected. Results: The complications detected were considered as "early" within 1 month later the nipple-sparing mastectomy or "late" after this time. The overall complications rate (early and late) and the overall survival and the relapses detected by this study were comparable with those reported in the literature. In order to identify factors that correlate with complications, either early or later, it has been processed an evaluation of the univariate analysis showing adjuvant chemotherapy as the only predictive factor for late complications, while we encountered no predictors for early complications. Conclusions: The present study adds to the data already present in literature, demonstrating that the nipple-sparing mastectomy is a safe procedure, providing good oncological and aesthetic results in patients carefully selected.

IS IT WORTH SUPPRESSING TSH IN LOW- AND INTERMEDIATE-RISK PAPILLARY THYROID CANCER PATIENTS BEFORE THE FIRST DISEASE ASSESSMENT?

OBJECTIVE: Guidelines recommend thyroid-stimulating hormone (TSH) suppression before the first response to treatment assessment in papillary thyroid cancer (PTC) patients. The aim of this study was to assess the rate of structural disease (SD) in low- and intermediate-risk PTC patients according to TSH levels measured 1 year after primary treatment. METHODS: A consecutive, prospective series of low- and intermediate-risk PTC patients with 3-years follow-up was collected. TSH, thyroglobulin (Tg), antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) 1 and 3 years after primary treatment were analyzed. Recurrence risk and disease status at 1 year were defined according to the American Thyroid Association (ATA) guidelines and as the presence or absence of SD after 3 years. Patients were grouped according to TSH level at 1 year: group 1, TSH <0.1 µUI/mL; group 2, TSH 0.1 to 0.5 µUI/mL; group 3, 0.5 to 2 µUI/mL; and group 4 >2 µUI/mL. RESULTS: This study included 263 patients (70.9% female, median age 47.2 years) of whom the risk of recurrence was low in 170 (65%), intermediate-low in 63 (24%), and intermediate-high in 30 (11%). The response to initial treatment at 1 year was excellent in 149 (57%), biochemical incomplete in 18 (7%), indeterminate in 84 (32%), and structural incomplete in 12 (4%). Group 1 consisted of 53 (20%) patients, group 2 of 85 (32%), group 3 of 61 (23%), and group 4 of 64 (24%). The rate of SD at 1 and 3 years from primary treatment was not significantly different between TSH groups. CONCLUSION: TSH suppression before the first response to treatment assessment does not appear to influence the rate of SD evaluated 1 and 3 years after primary treatment. ABBREVIATIONS: ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; LT4 = levothyroxine; PTC = papillary thyroid cancer; SD = structural disease; Tg = thyroglobulin; TgAb = antithyroglobulin antibodies; TSH = thyroid-stimulating hormone; US = ultrasonography.

Prospective Evaluation of Semiquantitative Strain Ratio and Quantitative 2D Ultrasound Shear Wave Elastography (SWE) in Association with TIRADS Classification for Thyroid Nodule Characterization.

PURPOSE: To evaluate the diagnostic performance of strain ratio elastography (SRE) and shear wave elastography (SWE) alone and in combination with Thyroid Imaging Reporting and Data System (TIRADS) classification parameters to improve differentiation between benign and malignant thyroid nodules. MATERIALS AND METHODS: In this prospective study benign (n = 191) and malignant (n = 52) thyroid nodules were examined with high-resolution ultrasound (US) features using the TIRADS lexicon and SRE semiquantitative and SWE quantitative findings using histology or cytology as the gold standard with a 12-month follow-up. Sensitivity (Se), specificity (Sp) and the area under the ROC curve (AUROC) were used to evaluate the diagnostic performance of each feature and combinations of the methods. RESULTS: TIRADS score showed a sensitivity of 59.6 %, a specificity of 83.8 % with an AUROC of 0.717, a PPV of 50.0 % and an NPV of 88.4 %. SRE yielded the highest performance with a sensitivity of 82.7 %, a specificity of 92.7 % with AUROC of 0.877, a PPV 75.4 % and an NPV of 95.2 %. SWE (kPa) had a sensitivity and specificity of 67.3 % and 82.7 %, respectively, with an AUROC of 0.750, a PPV of 51.5 % and an NPV of 90.3 %. Differences were significant for SRE only but not for SWE. CONCLUSION: Ultrasound elastography may improve thyroid nodule discrimination. In particular, SRE has a better performance than TIRADS classification, while their combination improves sensitivity.

PD-1 Ligand Expression in Epithelial Thyroid Cancers: Potential Clinical Implications.

The new immunotherapy targeting the programmed cell death 1 (PD-1) receptor and its cognate ligand PD-L1 has renewed hopes of eradicating the most difficult human cancers to treat. Among these, there are the poorly differentiated and anaplastic thyroid cancers, unresponsive to all the therapies currently in use. In the present review we will summarize information regarding the expression of PD-L1 in the different thyroid cancer histotypes, its correlation with clinicopathological features, and its potential prognostic value. Then, we will evaluate the available data indicating the PD-1/PD-L1 axis as a promising target for thyroid cancer therapy.

A possible role for selenoprotein glutathione peroxidase (GPx1) and thioredoxin reductases (TrxR1) in thyroid cancer: our experience in thyroid surgery.

BACKGROUND: Oxidative stress is responsible for some alterations in the chemical structure and, consequently, in the function of proteins, lipids, and DNA. Recent studies have linked oxidative stress to cancers, particularly thyroid cancer, but the mechanisms remain unclear. Here, we further characterize the role of oxidative stress in thyroid cancer by analyzing the expression of two selenium antioxidant molecules, glutathione peroxidase (GPx1) and thioredoxin reductase (TrxR1) in thyroid cancer cells. METHODS: Samples of both healthy thyroid tissue and thyroid tumor were taken for analysis after total thyroidectomy. The expression of GPx1 and TrxR1 was revealed by Western blot analysis and quantified by densitometric analyses, while the evaluation of free radicals was performed by Electron Paramagnetic Resonance (EPR)-spin trapping technique. RESULTS: Our results show a decrease in the expression of GPx1 and TrxR1 (- 45.7 and - 43.2% respectively, p < 0.01) in the thyroid cancer cells compared to the healthy cells. In addition, the EPR technique shows an increase of free radicals in tumor tissue, significantly higher than that found in healthy thyroid tissue (+ 116.3%, p < 0.01). CONCLUSIONS: Our findings underscore the relationship between thyroid cancer and oxidative stress, showing the imbalance of the oxidant/antioxidant system in thyroid cancer tissue. These results suggest that either the inability to produce adequate antioxidant defense or an increased consumption of antioxidants, due to the hyper-production of free radicals, may play a crucial role in thyroid cancer.

Thyroid diseases and skin autoimmunity.

The skin is the largest organ of the body, at the boundary with the outside environment. Primarily, it provides a physical and chemical barrier against external insults, but it can act also as immune organ because it contains a whole host of immune-competent cells of both the innate and the adaptive immune systems, which cooperate in eliminating invading pathogens following tissue injury. On the other hand, improper skin immune responses lead to autoimmune skin diseases (AISD), such as pemphigus, bullous pemphigoid, vitiligo, and alopecia. Although the interplay among genetic, epigenetic, and environmental factors has been shown to play a major role in AISD etiology and progression, the molecular mechanisms underlying disease development are far from being fully elucidated. In this context, epidemiological studies aimed at defining the association of different AISD with other autoimmune pathologies revealed possible shared molecular mechanism(s) responsible for disease progression. In particular, over the last decades, a number of reports have highlighted a significant association between thyroid diseases (TD), mainly autoimmune ones (AITD), and AISD. Here, we will recapitulate the epidemiology, clinical manifestations, and pathogenesis of the main AISD, and we will summarize the epidemiological evidence showing the associations with TD as well as possible molecular mechanism(s) underlying TD and AISD pathological manifestations.

Diagnosis and management of a mediastinal ectopic thyroid laying on the right bronchus: case report and review of literature.

BACKGROUND: The mediastinal ectopic thyroid is very rare, accounting for less than 1% of all cases of ectopic thyroid tissue. The differential diagnoses with other diseases such as lymphomas, thymic tumors and dermoid cysts is mandatory, in fact each one, needs different management and treatment. CASE PRESENTATION: Here, we discuss a rare case of mediastinal ectopic thyroid presenting with a paratracheal mass laying on the right bronchus without symptoms. A 63-year-old male presented with an abnormal well-defined mass along the right paratracheal side, detected by chest x-ray. The CT scan confirmed the presence of a 6 × 8 cm heterogeneously enhanced mass, located behind the superior vena cava and left brachiocephalic artery, reaching azygos vein and right bronchus, without a mass effect. Taking into account the clinical importance of a mediastinal mass, we removed it surgically, through a double surgical approach consisting in a classical transverse cervicotomy for the left thyroid lobe, followed then by a longitudinal sternal splitting to remove the mediastinal mass and complete the thyroidectomy. CONCLUSIONS: In case of mediastinal masses, the surgical excision is recommended, presenting the double advantage to clarify the diagnosis and to treat the pathology. As demonstrated in this case, a mediastinal ectopic thyroid should be taken into account in the differential diagnosis, considering its clinical importance.

Strain ratio ultrasound elastography increases the accuracy of colour-Doppler ultrasound in the evaluation of Thy-3 nodules. A bi-centre university experience.

OBJECTIVES: To assess whether ultrasound elastography (USE) with strain ratio increases diagnostic accuracy of Doppler ultrasound in further characterisation of cytologically Thy3 thyroid nodules. METHODS: In two different university diagnostic centres, 315 patients with indeterminate cytology (Thy3) in thyroid nodules aspirates were prospectively evaluated with Doppler ultrasound and strain ratio USE before surgery. Ultrasonographic features were analysed separately and together as ultrasound score, to assess sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Receiver operating characteristic (ROC) curves to identify optimal cut-off value of the strain ratio were also provided. Diagnosis on a surgical specimen was considered the standard of reference. RESULTS: Higher strain ratio values were found in malignant nodules, with an optimum strain ratio cut-off of 2.09 at ROC analysis. USE with strain ratio showed 90.6% sensitivity, 93% specificity, 82.8% PPV, 96.4% NPV, while US score yielded a sensitivity of 52.9%, specificity of 84.3%, PPV 55.6% and NPV 82.9%. The diagnostic gain with strain ratio was statistically significant as proved by ROC areas, which was 0.9182 for strain ratio and 0.6864 for US score. CONCLUSIONS: USE with strain ratio should be considered a useful additional tool to colour-Doppler US, since it improves characterisation of thyroid nodules with indeterminate cytology. KEY POINTS: • Strain ratio measurements improve differentiation of thyroid nodules with indeterminate cytology • Elastography with strain ratio is more reliable than ultrasound features and ultrasound score • Strain ratio may help to better select patients with Thy 3 nodules candidate for surgery.

Q-elastosonography of solid thyroid nodules: assessment of diagnostic efficacy and interobserver variability in a large patient cohort.

OBJECTIVE: Evaluation of the diagnostic efficacy and interobserver agreement of Q-elastography in the differentiation of benign from malignant thyroid nodules. METHODS: A total of 344 thyroid nodules in 288 patients were examined with grey-scale and colour Doppler ultrasound (CDUS) and Q-elastography by two independent operators. Nodules with hypoechogenicity, poorly defined margins, microcalcifications, and intralesional vascularity were classified as suspicious. Diagnostic performances of CDUS features and Q-elastography for predicting thyroid malignancy were estimated using ROC analysis. Cytology or histopathology was the reference standard. Interobserver agreement in the evaluation of CDUS and Q-elastography was assessed using Cohen's k-statistic. RESULTS: Q-elastography showed excellent diagnostic performance for the prediction of thyroid malignancy, with sensitivity of 93 % and specificity of 92 % for operator 1 (best cutoff at 2.02), and sensitivity of 84 % and specificity of 79 % for operator 2 (best cutoff at 1.86). Performance of Q-elastography was superior to that of CDUS. Reproducibility of the findings was excellent for both Q-elastography and CDUS features as assessed with Cohen's k, which was highest for strain ratio measurements (0.95) and lowest for the echogenicity score (0.83). CONCLUSIONS: Q-elastography showed excellent performance. It is a valid and reproducible diagnostic method as well as a promising tool for identifying suspicious solid thyroid nodules needing cytological assessment and surgery. KEY POINTS: • Elastography is an additional tool for optimal characterisation of malignant thyroid nodules. • The use of semiquantitative elastographic evaluation increases the diagnostic performance, • The interobserver agreement of quantitative elastography can be considered to be good.

Peer assisted learning: a meta-ethnographic synthesis of qualitative studies and recommendations for cardiovascular training, practice, and research.

INTRODUCTION: Peer assisted learning (PAL) is a common method to complement more traditional teaching. Several systematic reviews and meta-analyses described the most used ways of implementation and showed that it is effective in fostering learning. A synthesis of qualitative data is missing, to highlight the perceived value by the students and to drive a successful implementation. EVIDENCE ACQUISITION: The search was performed in Pubmed, Scopus and ERIC databases, with a combination of the search strings. The quality of the retrieved articles was assessed through the Critical Appraisal Skills Checklist. The analysis was performed according to the meta-ethnographic method. Fifteen articles were considered for the analysis, saturation was reached after 12 articles. EVIDENCE SYNTHESIS: Three main themes emerged from the analysis: PAL is effective when implemented in a safe environment, PAL is a driver of development of students' abilities and identity, and the "dark side" of PAL. Nine sub-themes emerged as components of the themes. The final line of argument highlighted the ambivalence of PAL, as an expression of the ambivalence of the still developing professional identity of students. CONCLUSIONS: This meta-ethnographic synthesis summarizes the elements of success and the threats of PAL, a method that is particularly suitable for the cardiovascular domain. It must be implemented according to some precautions, such as organization and protected time, tutor selection, training and support, a clear integration and endorsement in the framework of the medical curriculum.

What Is a Disease for Doctors? A Realist Thematic Qualitative Analysis of the Interpretation of Clinical Vignettes.

Given the long-standing debate about the nature of the concept of disease, the objective of this study was to understand how doctors categorize a condition as a disease or not, and what the kind of information they use is. A survey with a set of eighteen clinical vignettes was designed, and nineteen physicians and senior students purposefully selected were asked to interpret those situations as diseases or not and to produce an anonymous short written piece of text providing the motivation of their choice. Realist thematic analysis was used to analyse the answers, and four themes emerged: the temporal dimension of a disease, reification of disease, disease as an existential condition, and disease as a motivation to action. The respondents' interpretations were very heterogeneous, supporting the idea that physicians do not share a common prototypical concept of disease. The results suggested that the interpretation of a condition as a disease or not is the final outcome of a process, in which information from objective, subjective, and socially mediated elements is taken into consideration. According to a critical realist and systemic approach, we hypothesize that the context of doctor-patient relationship could influence the interpretation of the same condition as being a disease or not.

How to Manage Advanced Differentiated Thyroid Cancer: Step-by-Step Analysis from Two Italian Tertiary Referral Centers.

BACKGROUND: Differentiated thyroid carcinoma (DTC) has an excellent prognosis; however, advanced disease is associated with a worse prognosis and is relatively common. Surgery followed by RAI treatment remains the mainstream treatment for a large majority of patients with high- and intermediate-risk DTC, but its benefits should be carefully weighed against the potential for harm. The aim of this paper is to critically review the experience in treating advanced DTC at two tertiary referral centers in Italy. METHODS: Retrospective analysis of 300 patients who underwent surgery for ADTC over 30 years. RESULTS: The complication rate was 50.33%. A total of 135 patients (45%) remained at regular follow-up, 118 (87.4%) were alive, while 17 (12.6%) were deceased. The mean overall survival at 12 years was 84.8% with a mean of 238 months. Eleven patients (8.1%) experienced a relapse after a median of 13 months. CONCLUSIONS: ADTC patients adequately treated can achieve prolonged survival even in the case of metastasis or disease relapse. Patients with ADTC should be referred to high-volume centers with the availability of an extended multidisciplinary team to receive tailored treatment.

Drawing as a Way of Knowing: How a Mapping Model Assists Preoperative Evaluation of Patients with Thyroid Carcinoma.

Background: Effective pre-surgical planning is crucial for achieving successful outcomes in endocrine surgery: it is essential to provide patients with a personalized plan to minimize operative and postoperative risks. Methods: Preoperative lymph node (LN) mapping is a structured high-resolution ultrasonography examination performed in the presence of two endocrinologists and the operating surgeon before intervention to produce a reliable "anatomical guide". Our aim was to propose a preoperative complete model that is non-invasive, avoids overdiagnosis of thyroid microcarcinomas, and reduces medical expenses. Results: The use of 'preoperative echography mapping' has been shown to be successful, particularly in patients with suspected or confirmed neoplastic malignancy. Regarding prognosis, positive outcomes have been observed both post-surgery and in terms of recurrence rates. We collected data on parameters such as biological sex, age, BMI, and results from cytologic tests performed with needle aspiration, and examined whether these parameters predict tumor malignancy or aggressiveness, calculated using a multivariate analysis (MVA). Conclusions: A standard multidisciplinary approach for evaluating neck lymph nodes pre-operation has proven to be an improved diagnostic and preoperative tool.

The Size of a Thyroid Nodule with ACR TI-RADS Does Not Provide a Better Prediction of the Nature of the Nodule: A Single-Center Retrospective Real-Life Observational Study.

We investigated if thyroid nodule size has a predictive value of malignancy on a par with composition, echogenicity, shape, margin, and echogenic foci, and what would be the consequence of observing the rule of the American College of Radiology (ACR) to perform a fine-needle aspiration biopsy (FNAB). We conducted a retrospective real-life observational study on 86 patients who underwent surgery after a standardized diagnostic protocol. We divided the TR3, TR4, and TR5 classes into sub-classes according to the size threshold indicating FNAB (a: up to the threshold for no FNAB; b: over the threshold for FNAB suggested). We computed sensitivity, specificity, and positive (PPV) and negative predictive value (NPV) for the different sub-classes and Youden's index (Y) for the different possible cutoffs. Each sub-class showed the following PPV (0.67, 0.68, 0.70, 0.78, 0.72), NPV (0.56, 0.54, 0.51, 0.52, 0.59), and Y (0.20, 0.20, 0.22, 0.31, 0.30). In this real-life series, we did not find a significant difference in prediction of malignancy between the sub-categories according to the size threshold. All nodules have a pre-evaluation likelihood of being malignant, and the impact and utility of size thresholds may be less clear than suggested by the ACR TIRADS guidelines in patients undergoing standardized thyroid work up.

Laterocervical lymph node metastases from suspected thyroidal primary site that turned out to be metastases of lung cancer: A case report.

Incidental sonographic discovery of thyroid nodules is an increasingly common event in clinical practice. Less frequently, patients with cytological benign thyroid nodules have suspicious cervical lymph nodes detected by ultrasound examination or by cytological exam. Here, we discuss an intriguing case of cervical lymph node metastasis with a probable thyroid origin in a 65-year-old asymptomatic male smoker. He underwent thyroidectomy and unilateral cervical lymphadenectomy. Despite a negative chest X-ray, the postoperative histological examination revealed that the lymph node metastasis was actually from a lung carcinoma. Metastatic lesions in cervical lymph nodes from non-thyroidal origins must be excluded when evaluating lesions in the region, especially when thyroid nodules subjected to fine needle aspiration biopsy yield negative results, or lymph node cytological evaluations are inconsistent with thyroid cytological findings and sonographic features. Thyroid and lung adenocarcinomas share some epithelial and mesenchymal markers. Thyroglobulin helps differentiate primary thyroid tumors from lung ones, but in cases of poor differentiation, distinguishing metastatic lesions in the thyroid gland can be challenging. Lung cancer (LC) is the leading cause of cancer mortality worldwide, and survival rates have only marginally improved over the last several decades. The ongoing clinical challenge is detecting LC at earlier stages of the disease.

Tumor Inflammatory Microenvironment of the Thyroid Cancer: Relationship between Regulatory T-Cell Imbalance, and p-NFΚB (p65) Expression-A Preliminary Study.

BACKGROUND: Inflammatory microenvironment is an essential component of all tumors, including thyroid cancer. Autoimmune thyroid diseases are often associated with thyroid cancer. CD25, expressed in Treg cells and B cells, has been found to be associated with autoimmune thyroid diseases and the NFkB pathway is critical to tumor formation, regulating immune-related genes, and pro-inflammatory cytokine. METHODS: Protein expression of CD25 and NFkB and its phosphorylated form was analyzed by immunohistochemistry in 80 patients with thyroid cancer (10 cases of cancers with Hashimoto's thyroiditis and 70 cases without). RESULTS: CD25 was mainly detected in the nucleus of the inflammatory cells such as in the thyrocytes and neoplastic cells. Protein staining was detected in the T-lymphocytes of the outermost zone of the lymphoid follicles. Moreover, in all cancer alterations, there were a higher level of p-NFkB than in the surrounding tissues. Again, p-NFkB staining was evident in neoplastic cells but not evident in inflammatory cells. CONCLUSIONS: Strong inflammatory infiltrate in the tumor microenvironment is correlated with an invasive phenotype. CD25 and p-NFkB levels were statistically significantly overexpressed in cancer cells.

C-Cell Hyperplasia and Cystic Papillary Thyroid Carcinoma in a Patient with Type 1B Pseudohypoparathyroidism and Hypercalcitoninaemia: Case Report and Review of the Literature.

Hypercalcitoninaemia has been described in patients with pseudohypoparathyroidism (PHP) type 1A and 1B. Elevated calcitonin levels are thought to result from impaired Gsα receptor signaling, leading to multiple hormone resistance. Evidence on the risk of medullary thyroid carcinoma (MTC) or C-cell hyperplasia in PHP patients with hypercalcitoninaemia is lacking. A 43-year-old Caucasian man was referred to our endocrinology clinic for chronic hypocalcemia associated with elevated serum parathormone levels and a single cystic thyroid nodule. The patient did not show skeletal deformities, and screening for concomitant hormone resistances was negative, except for the presence of elevated serum calcitonin levels. The workup led to a molecular diagnosis of sporadic PHP1B. Fine needle aspiration of the thyroid nodule was not diagnostic. The calcium stimulation test yielded an abnormal calcitonin response. Given the scarcity of data on the risk of thyroid malignancy in PHP and calcium stimulation test results, total thyroidectomy was performed. Histological examination revealed cystic papillary thyroid cancer in a background of diffuse C-cell hyperplasia. To our knowledge, we are the first to describe a rare form of thyroid cancer combined with C-cell hyperplasia in a patient with PHP and hypercalcitoninaemia. In the present case, a mere receptor resistance might not fully explain the elevated calcitonin levels, suggesting that hypercalcitoninaemia should be carefully evaluated in PHP patients, especially in the case of concomitant thyroid nodules. Further studies on larger cohorts are needed to elucidate this topic.

Parathyroid Retrospective Analysis of Neoplasms Incidence (pTRANI Study): An Italian Multicenter Study on Parathyroid Carcinoma and Atypical Parathyroid Tumour.

BACKGROUND: Parathyroid cancer (PC) is a rare sporadic or hereditary malignancy whose histologic features were redefined with the 2022 WHO classification. A total of 24 Italian institutions designed this multicenter study to specify PC incidence, describe its clinical, functional, and imaging characteristics and improve its differentiation from the atypical parathyroid tumour (APT). METHODS: All relevant information was collected about PC and APT patients treated between 2009 and 2021. RESULTS: Among 8361 parathyroidectomies, 351 patients (mean age 59.0 ± 14.5; F = 210, 59.8%) were divided into the APT (n = 226, 2.8%) and PC group (n = 125, 1.5%). PC showed significantly higher rates (p < 0.05) of bone involvement, abdominal, and neurological symptoms than APT (48.8% vs. 35.0%, 17.6% vs. 7.1%, 13.6% vs. 5.3%, respectively). Ultrasound (US) diameter >3 cm (30.9% vs. 19.3%, p = 0.049) was significantly more common in the PC. A significantly higher frequency of local recurrences was observed in the PC (8.0% vs. 2.7%, p = 0.022). Mortality due to consequences of cancer or uncontrolled hyperparathyroidism was 3.3%. CONCLUSIONS: Symptomatic hyperparathyroidism, high PTH and albumin-corrected serum calcium values, and a US diameter >3 cm may be considered features differentiating PC from APT. 2022 WHO criteria did not impact the diagnosis.