Chronic Lymphocytic Thyroiditis Research Articles

A Nomogram Based on Clinical and Ultrasound Characteristics to Predict Central Lymph Node Metastasis of Papillary Thyroid Carcinoma.

BackgroundThe status of lymph nodes in the central compartment is crucial to determining the surgical strategies for papillary thyroid carcinoma (PTC). We aimed to develop a nomogram for predicting central lymph node metastasis (CLNM).MethodsA total of 886 PTC patients who underwent total thyroidectomy or lobectomy with central neck dissection (CND) from July 2019 to June 2020 were retrospectively retrieved. Clinical and ultrasound features were collected. Univariate and multivariate analysis were performed to determine risk factors of CLNM. A nomogram for predicting CLNM was developed, internal and external calibration was performed for the established model.ResultsVariables (sex, chronic lymphocytic thyroiditis, tumor size, the number of foci, tumor location, margin) significantly associated with CLNM were included in the nomogram. The nomogram showed excellent calibration in the training group and validation group, with area under curves of 0.806 (95% CI, 0.771 to 0.825), and 0.799 (95% CI, 0.778–0.813) respectively.ConclusionThrough this accurate and easy-to-use nomogram, the possibility of CLNM can be objectively quantified preoperatively. Clinicians can use this nomogram to evaluate the status of lymph nodes in PTC patients and consider prophylactic CND for those with high scores.

NTRK Fusion Genes in Thyroid Carcinomas: Clinicopathological Characteristics and Their Impacts on Prognosis.

Simple SummaryNTRK fusion genes are important but not well studied molecular markers in thyroid cancer. Their identification could help improve diagnosis and prognosis, and determine appropriate treatment. The aims of this study were to identify NTRK fusion-positive thyroid tumors in a large cohort of different thyroid tumors, to characterize these tumors by molecular, clinical and pathological features and to evaluate the impact of NTRK-rearranged tumors on prognosis of the disease. A suitable approach for selective NTRK fusion gene testing in thyroid cancer samples was created and utilized. In a cohort of 59 NTRK-rearranged carcinomas, characteristic features were described and recommendations for surgery and prognostic factors were determined thanks to the long-term follow-up of patients.Chromosomal rearrangements of NTRK genes are oncogenic driver mutations in thyroid cancer (TC). This study aimed to identify NTRK fusion-positive thyroid tumors and to correlate them with clinical and pathological data and determine their prognostic significance. The cohort consisted of 989 different TC samples. Based on the detected mutation, samples were triaged, and those that were positive for a BRAF, HRAS, KRAS, NRAS, RET, RET/PTC or PAX8/PPARγ mutation were excluded from further analyses. NTRK fusion gene testing was performed in 259 cases, including 126 cases using next-generation sequencing. NTRK fusion genes were detected in 57 of 846 (6.7%) papillary thyroid carcinomas and in 2 of 10 (20.0%) poorly differentiated thyroid carcinomas. A total of eight types of NTRK fusions were found, including ETV6/NTRK3, EML4/NTRK3, RBPMS/NTRK3, SQSTM1/NTRK3, TPM3/NTRK1, IRF2BP2/NTRK1, SQSTM1/NTRK1 and TPR/NTRK1. NTRK fusion-positive carcinomas were associated with the follicular growth pattern, chronic lymphocytic thyroiditis and lymph node metastases. NTRK1-rearranged carcinomas showed a higher frequency of multifocality and aggressivity than NTRK3-rearranged carcinomas. Tumor size, presence of metastases, positivity for the NTRK3 or NTRK1 fusion gene and a late mutation event (TERT or TP53 mutation) were determined as factors affecting patient prognosis. NTRK fusion genes are valuable diagnostic and prognostic markers.

Thyroiditis and SARS-CoV-2 pandemic: a review.

The world is dealing with the Covid-19 pandemic due to the coronavirus SARS-CoV-2. Amongst the extra-pulmonary manifestations presented by Covid-19 patients, thyroiditis form part of the spectrum of visceral involvement linked to SARS-CoV-2. In this review, we will describe the various documented clinical forms of thyroiditis (inflammatory thyroiditis, subacute or de Quervain’s thyroiditis, chronic lymphocytic thyroiditis or Hashimoto’s disease, painless (silent) postpartum thyroiditis) to facilitate their diagnosis in more or less symptomatic Covid-19 patients and to provide guidance for patient treatment.

Bilateral multifocality, a marker for aggressive disease, is not an independent prognostic factor for papillary thyroid microcarcinoma: A propensity score matching analysis.

Multifocality and bilaterality are common in patients with papillary thyroid microcarcinoma (PTMC). However, their clinical behaviours and prognostic implications remain controversial. To investigate the relationship between multifocality and classically aggressive characteristics and outcomes in patients with PTMC. Clinical data of 3005 patients with PTMC were retrospectively reviewed at a tertiary medical centre. The role of unilateral and bilateral multifocality in aggressive characteristics and clinical outcomes of PTMC was evaluated using propensity score matching (PSM). A total of 573 patients had bilateral multifocal disease (B-MFD), 272 had unilateral multifocal disease (U-MFD), and 2160 had unifocal disease (UFD). Univariate analysis showed that patients in the multifocal disease (MFD) groups showed significantly different characteristics compared to patients in the UFD group in terms of age, chronic lymphocytic thyroiditis (CLT), follicular variant PTMC, tumour diameter, aggressive growth, including extrathyroidal extension (ETE), central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM), and TNM stage, and underwent radioactive iodine (RAI) therapy. Further stratified analysis revealed that patients in the B-MFD group reflected the differences between the MFD and UFD groups. However, those in the U-MFD group showed slight differences only in sex, CLT and cell subtypes, compared to the UFD group. In addition, PSM indicated differences in ETE, CLNM and LLNM between the B-MFD and UFD groups (p<.001), while only ETE differed between the U-MFD and UFD groups (p<.001). After a median follow-up period of 60months, no difference was observed in recurrence-free survival between the UFD and B-MFD (p=.294) or U-MFD (p=.603) groups using PSM. This propensity score matching analysis provides strong evidence that bilateral multifocality, rather than unilateral multifocality, should be considered as an aggressive marker at presentation, and neither is an independent prognostic factor for clinical outcome in PTMC.

An unusual case of struma ovarii.

IntroductionStruma ovarii is a teratoma of the ovaries predominantly composed of thyroid tissue. Hyperthyroidism associated with struma ovarii is rare, occurring in approximately 8% of cases. Due to the rarity of struma ovarii, available data are limited to case reports and small case series.Methods and resultsWe report on a 61-year-old female patient with known Hashimoto’s thyroiditis on levothyroxine replacement therapy for years with transition to clinical and biochemical hyperthyroidism despite antithyroid medication with carbimazole (10 mg/day), new diagnosis of urothelial carcinoma and an adnexal mass suspicious of ovarian cancer. The patient underwent resection of the adnexal mass and histopathology revealed a mature teratoma predominantly composed of thyroid tissue showing high levels of sodium iodide symporter protein expression. Following struma ovarii resection and disappearance of autonomous production of thyroid hormones, the patient developed hypothyroidism with severely decreased thyroid hormone levels fT4 and fT3 (fT4 0.4 ng/dL, reference interval 0.9–1.7 and fT3 < 1.0 pg/mL, reference interval 2.0–4.4). This has previously been masked by continued thyroid-stimulating hormone suppression due to long-term hyperthyroidism pre-surgery indicating secondary hypothyroidism, in addition to primary hypothyroidism based on the known co-existing chronic lymphocytic thyroiditis of the orthotopic thyroid gland. Levothyroxine administration was started immediately restoring euthyroidism.ConclusionThis case illustrates possible diagnostic pitfalls in a patient with two concurrent causes of abnormal thyroid function.Learning pointsStruma ovarii is an ovarian tumor containing either entirely or predominantly thyroid tissue and accounts for approximately 5% of all ovarian teratomas.In rare cases, both benign and malignant struma ovarii can secrete thyroid hormones, causing clinical and biochemical features of hyperthyroidism.Biochemical features of patients with struma ovarii and hyperthyroidism are similar to those of patients with primary hyperthyroidism. In such cases, thyroid scintigraphy should reveal low or absent radioiodine uptake in the thyroid gland, but the presence of radioiodine uptake in the pelvis in a whole body radioiodine scintigraphy.We give advice on possible diagnostic pitfalls in a case with two simultaneous causes of abnormal thyroid function due to the co-existence of struma ovarii.

The effect of the area proportion of the metastatic lesion within the central metastatic lymph node on response to therapy in papillary thyroid carcinoma.

Lymph node (LN) metastasis has been strongly associated with locoregional recurrence and decreased survival time of patients with papillary thyroid carcinoma (PTC). Although the characteristics of the metastatic LNs (mLN) have been determined, including size, number, micro-metastasis and extra-nodal extension (ENE), further analysis is warranted. The present study introduced a new parameter known as the area proportion of the metastatic lesion within the central mLNs (APmCLN). The objective was to evaluate the impact of the APmCLN on response to therapy in patients with PTC. In total, 355 patients with PTC treated with total thyroidectomy and neck dissection, post-operative radioactive iodine and thyroid-stimulating hormone suppression were retrospectively studied. The patients were classified into two groups: Group A (APmCLN ≤75%) and group B (APmCLN >75%). The association of various clinicopathological characteristics between these two groups was investigated. Univariate and multivariate analyses were used to evaluate risk factors associated with a non-Excellent response to therapy and recurrence-free survival (RFS). The analysis showed that APmCLN >75% was significantly associated with extra-thyroidal extension, clinically apparent nodes (cN1), pathological N1b (pN1b), ENE, greater number and larger size of central mLN and larger size of the central LN metastatic lesion. Furthermore, it was reported that chronic lymphocytic thyroiditis, larger central mLN size and APmCLN >75% were independent risk factors for a non-excellent response to therapy. Finally, it was determined that the rate of excellent response to therapy was significantly higher in pathological N1 (pN1) patients with APmCLN ≤75% (108/144, 75.0%) compared with patients with APmCLN >75% (27/47, 57.4%) (P=0.022). However, there was no significant difference (P=0.247) between patients with APmCLN ≤75% and pN0 (132/164, 80.5%). RFS was 89.4% in patients with pN1-APmCLN >75%, whereas those with pN1-APmCLN ≤75% and pN0 did not experience a relapse. Patients with PTC with APmCLN >75% should be regarded as high-risk and may require more aggressive treatment and careful follow-up.

Thyroid disorders in childhood and adolescence. Part 2: Hypothyroidism

Hypothyroidism is the most frequent thyroid dysfunction. It is the consequence of a decrease in the biological activity of thyroid hormones in target tissues. The aim of this paper is to review and update acquired hypothyroidism in childhood and adolescence with emphasis on primary hypothyroidism due to its greater frequency. Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis, is the most common cause of primary acquired hypothyroidism. The distinctive feature is the profound impact on skeletal growth, maturation, and pubertal development, with potential implications on adult height. Signs and symptoms of acquired hypothyroidism are similar to those reported in adults and are generally not associated with neurodevelopmental impairment. Biochemical confirmation of primary hypothyroidism requires the finding of elevated thyrophine and decreased free thyroxine levels. Treatment goals are to achieve normal growth and maturation as well as cognitive development. In most of the patients, replacement treatment reverses symptoms and signs of hypothyroidism and may decrease goiter size.

Is Vitamin D Deficiency Associated with Chronic Lymphocytic Thyroiditis?

Objectives:Vitamin D deficiency is a very common global health problem. Evidence from recent studies focuses on the extraskeletal effects of vitamin D (Vit D) deficiency. Chronic lymphocytic thyroiditis (or Hashimoto’s thyroiditis) is an autoimmune disease of the thyroid. Although there are many studies reporting that autoimmune thyroid diseases may be associated with Vitamin D deficiency, this is still a controversial issue that has not yet been proven. In this study, we aimed to appraise whether there is a relationship between lymphocytic thyroiditis diagnosed by histopathological evaluation and Vitamin D deficiency.Methods:Data of 256 patients whom were operated by a single surgeon in a single center between 2012 and 2017 and whose preoperative vitamin D tests and thyroid pathologies have been collected, were retrospectively evaluated. Due to the pathological examination, two groups were formed considering the presence of lymphocytic thyroiditis (Group 1), and the absence of lymphocytic thyroiditis (Group 2). Vitamin D deficiency was defined as the level <20 ng/mL (50 nmol/L) and Vitamin D insufficiency was defined as the level 21–29 ng/mL (525–725 nmol/L).Results:There were 108 (92F/16M) patients in Group 1, and 148 (116F/32M) patients in Group 2, and the mean age was lower in Group 1 (p=0.053). The mean vitamin D levels (16.6±15.2 vs. 14±10, p=0.409) and vitamin D deficiency rates (67.6% vs. 72.3%, p=0.416) were found similar between the Groups 1 and 2. No positive significant correlation was found between lymphocytic thyroiditis and vitamin D level or vitamin D deficiency rates. There was a positive correlation between lymphocytic thyroiditis and age, preoperative thyroid-stimulating hormone level, preoperative anti-thyroglobulin ,and anti-thyroid peroxidase levels, but no significant relationship was found with Vitamin D level.Conclusion:According to our results, lymphocytic thyroiditis was not associated with either Vitamin D deficiency or Vitamin D level.

Diagnostic Utility of Cell Block Technique As an Adjunct to Cytological Smears in Evaluation of Thyroid Aspirates on Fine Needle Aspiration Cytology

Background: Direct smears and cell blocks prepared from residual tissue fluids complement each other for establishing a conclusive cytopathologic diagnosis in thyroid lesions. Aim of the Study: Evaluation of the diagnostic utility of fine-needle aspiration cytology (FNAC) alone and in combination with cell blocks in the diagnosis of thyroid lesions. Materials and Methods: A hospital-based prospective longitudinal study was conducted in which 100 thyroid smears were categorized as neoplastic, nonneoplastic and inadequate using FNAC and cell block technique. All specimens were classified using point scoring system modified by Mair et al. Direct smears were compared with cell-block specimens on variables of cellularity, background blood and clot, cellular degeneration and retention of appropriate architecture using Fisher's exact and unpaired t-test. Results: Sixty-two percent of cell block specimens showed a moderate amount of background material (P = 0.01), display of excellent architecture was also significantly more in cell block (20%) technique than direct smears (9%), and degree of cellular degeneration was minimal in significantly more cell blocks (26%) than direct smears (12%), thereby making diagnosis easy as opposed to FNAC which yielded more cellular material than cell blocks (P = 0.02). Four cases showing hemorrhagic material on direct smears were diagnosed on cell block as one case each of colloid goiter and chronic lymphocytic thyroiditis and two cases of adenomatous goiter and two cases showing hemorrhagic material on cell block were diagnosed with chronic lymphocytic thyroiditis on direct smears. Conclusion: FNAC and cell block complement each other and combining both techniques improves the diagnostic yield and facilitates accurate diagnosis. It is advisable to perform cell-block for each case of FNAC of thyroid lesions.

Hashimoto’s Thyroiditis Autoimmune Disease: Background and Current Status, Update Overview of Biotechnological and Biomedical Fields and Future Trends for 3D Models

Hashimoto thyroiditis, also known as chronic autoimmune thyroiditis or chronic lymphocytic thyroiditis, is an autoimmune illness in which thyroid cells are damaged by immunological mechanisms involving cells and antibodies. Thyroid peroxidase and/or thyroglobulin autoantibodies in the serum are biochemical indicators of the condition, with females having a higher incidence than males and increasing with age. It’s the leading cause of hypothyroidism in affluent countries. Inadequate dietary iodine intake, on the other hand, is the most common cause of hypothyroidism worldwide. The development of antithyroid antibodies that target the thyroid tissue, causing gradual fibrosis, is the pathogenesis of Hashimoto thyroiditis. The diagnosis can be difficult, and as a result, the problem is frequently not detected until late in the disease process. The most prevalent laboratory findings are raised TSH and low thyroxine (T4) levels, as well as enhanced antithyroid peroxidase (anti-TPO) antibodies. The pathogenesis, diagnosis, and management of Hashimoto thyroiditis are discussed in this article.

Reversible thyrotropin elevation in case of primary Addison's disease

The association of Addison's disease and chronic lymphocytic thyroiditis is a well-known disease complex, historically known as Schmidt disease. Here, we present the case of a patient who presented with primary Addison's disease and on further evaluation was also found to have a subclinical hypothyroidism without a positive marker of autoimmunity. The coexistence of these endocrine disorders simultaneously without thyroid peroxidase antibody positivity and steroid replacement alone in such a case resulting in complete recovery of thyroid function had not described in the literature.

Incidence and types of thyroid tumour in chronic lymphocytic thyroiditis

Incidence and types of thyroid tumour in chronic lymphocytic thyroiditis

Study of Correlation of Cytomorphological Features of Lymphocytic Thyroiditis with Biochemical Parameters and Vitamin D Deficiency

Introduction: Fine Needle Aspiration Cytology (FNAC) of the thyroid is a reliable and common method used for diagnosis of chronic Lymphocytic Thyroiditis (LT) which is an autoimmune disease. Vitamin D (Vit D) deficiency, a prevalent health problem, is known to have correlation with various autoimmune diseases especially chronic LT. Aim: To evaluate the relationship between Vit D levels, biochemical parameters with cytomorphological features of LT. Materials and Methods: The present cohort study was conducted on 88 patients with cytological evidence of LT at a thyroid research centre in northern India between June 2017 to September 2018. Thyroid Stimulating Hormone (TSH), Antithyroid Peroxidase (ATPO) Antibody and Vit D levels along with patient’s clinical presentation, and thyroid ultrasound were evaluated for all subjects. The cytological grades and other cytomorphological features were correlated with these parameters. Results: Most of the patients were females (82, 93.2%) who presented with diffuse thyromegaly (69, 78.4%) and had hypothyroidism (58, 65.9%). By cytology grade I thyroiditis (40, 45.5%) was commonest followed by grade II (38, 43.2%). The Vit D deficiency and elevated ATPO were seen in 72 (81.8%) and 78 (88.6%) patients, respectively. Lowest level of Vit D (7.8±4.9 ng/mL) was seen in grade III patients. Significant correlation was observed between ATPO and Vit D levels with cytomorphological grades and some cytomorphological features like Hurthle cell change and plasma cells presence. While TSH levels correlated significantly with cytological grades only in hypothyroid group. Conclusion: This study found that Vit D deficiency and ATPO levels significantly correlates with cytological grades of thyroiditis and affect certain cytomorphological features like plasma cells presence, suggesting lower levels of Vit D and higher ATPO may be related to more active disease.

Cytological Grading of Chronic Lymphocytic Thyroiditis and Correlation with Thyroid Profile

Background: Chronic lymphocytic thyroiditis is a thyroid specific autoimmune disease often seen in middle aged women, although rarely do occur in men, children1. This disease is characterized by antibody directed against thyroid peroxidase, called antimicrosomal antibody. The present study was undertaken to evaluate the various cytological features occurring in HT and to correlate with clinical and serological findings.&#x0D; Methods: The study was conducted in department of Pathology from May 2017 to August 2017. The cases diagnosed as HT by FNAC were taken up for the study. Cytomorphologic features were reviewed microscopically and graded as per Bhatia et al.&#x0D; Result: Fifty cases were diagnosed as lymphocytic thyroiditis. Age of the patient ranged from 7-56 years. Clinically 41 of 50 cases (82%) presented with diffuse thyroid enlargement. In our study we had 31 cases (62 %) of grade 2 thyroiditis, 15 and 4 cases each of grade 1 and grade 3 respectively. We observed increased TSH values in 100% of G3 thyroiditis and 64.5% of G2 thyroiditis. None of the Grade 1 thyroiditis had increased TSH levels. The statistical correlation between grades of thyroiditis with T3, T4 and TSH levels was found to be significant with p values &lt; 0.05.&#x0D; Conclusion: FNAC is simple cost effective and quick method for diagnosing HT. Also combined evaluation of HT with clinical findings and thyroid profile promotes more accurate diagnosis and early institution of therapy and follow up. FNAC is also necessary to rule out malignant lesions like lymphoma and papillary carcinoma at preliminary cytological level.

The Association of Histologically Proven Chronic Lymphocytic Thyroiditis with Clinicopathological Features, Lymph Node Metastasis, and Recurrence Rates of Differentiated Thyroid Cancer.

The influence of chronic lymphocytic thyroiditis (CLT) on clinicopathological features and behavior of differentiated thyroid carcinoma (DTC) is still debated. In the present study, we aimed to evaluate the prognosis of DTC on the presence of CLT. A total of 649 total thyroidectomized patients (379 female, 270 male) with DTC, who had follow-up data for at least 36months were included. Clinical, histopathological data, preoperative thyroid peroxidase antibody (TPO-ab), thyroglobulin antibody (Tg-ab), thyroid-stimulating hormone (TSH) levels, and presence of recurrent/persistent disease (R/PD) were evaluated retrospectively. Presence of CLT was defined by histopathology. Frequency of CLT was 32% (n=208) among DTC patients. Mean tumor size (maximal diameter) was smaller in CLT group when compared to non-CLTs (p=0.006). Capsular invasion, vascular invasion, tumor stage, risk groups, and R/PD were negatively associated with CLT (p<0.01, p=0.04, p=0.03, p=0.02, p<0.01, respectively). Extrathyroidal extension was more frequent in non-CLT group when compared CLT (p=0.052). Preoperative TSH level was positively associated with lymph node metastasis (LNM) and higher in patients with lateral LNM when compared to central LNM (p<0.01). Central LNM, lateral LNM, stage 4 tumor, and intermediate- and high-risk tumor groups increased the risk of R/PH, 2.5-, 2.9-, 12.7-, 2.3-, and 4.2-fold, respectively. Presence of CLT was independently related with favorable outcomes, as the risk of R/PD was decreased by 0.49-fold. In conclusion, coexistence of CLT was negatively associated with tumor size, capsular invasion, vascular invasion, and tumor stage in DTC. Risk of R/PD was decreased by approximately half in patients with CLT.

Risk Factors and Outcomes of Postoperative Neck Hematomas: An Analysis of 5,900 Thyroidectomies Performed at a Cancer Center.

Introduction Postoperative neck hematoma (PNH) is an uncommon but potentially-lethal complication of thyroid surgery. Objective To identify the risk factors for postthyroidectomy hematoma requiring reoperation, the timing, the source of the bleeding, the related respiratory distress requiring tracheotomy, and the late outcomes. Methods We retrospectively analyzed the records of 5,900 consecutive patients submitted to surgery for thyroid diseases at a single institution. Results In total, PNH occurred in 62 (1.1%) patients. Most cases of bleeding occurred within the first 6 hours after thyroidectomy, but 12.5% of the hematomas were observed after 24 hours. Obvious bleeding points were detected in 58.1% of the patients during the reoperation, with inferior thyroid artery branches and superior thyroid vessels being the most frequent bleeding sources. Only two patients required urgent tracheostomy. There were no hematoma-related deaths. Permanent hypoparathyroidism and recurrent laryngeal nerve injury are more frequent following reoperation for PNH. The factors significantly associated with PNH were: older age, concurrent lymph node dissection, and chronic lymphocytic thyroiditis. Gender, previous neck irradiation, presentation at diagnosis (symptomatic or incidental), substernal goiter, thyroidectomy for hyperthyroidism, prior thyroid surgery, malignant histology, the extent of the surgery (total versus non-total thyroidectomy), the use of energy-based vessel sealing devices, the use of the hemostatic agent Surgicel, and the placement of a surgical drain were not significantly associated with PNH. Conclusion Hematoma after thyroid surgery is an uncommon complication, but it is related to significant postoperative morbidity. A better understanding of the risk factors and of the time until hematoma formation can help target high-risk patients for preventive measures and closer postoperative observation.

PD-L1, PDK-1 and p-Akt are correlated in patients with papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma. To investigate the clinical significance of programmed death ligand 1 (PD-L1) and phosphoinositide-dependent protein kinase 1 (PDK1) in PTC. A total of 194 PTC patients were recruited. Contralateral normal thyroid tissues were obtained and used as controls (n = 80). The expression levels of PD-L1, PDK1 and p-Akt were determined using immunohistochemistry. The PD-L1, PDK1 and p-Akt were upregulated in cancer tissues compared to the normal tissues. The mean optical density (MOD) values of PD-L1, PDK1 and p-Akt were significantly higher in the PTC tissues. The expression of PD-L1 positively correlated with the levels of PDK1 and p-Akt. In addition, the expression of PD-L1, PDK1 and p-Akt in PTC patients without chronic lymphocytic thyroiditis (CLT) was significantly higher than the expression of those proteins in the CLT patients. The patients with higher expression levels of PD-L1, PDK1 or p-Akt had remarkably larger tumors and higher rates of TNM III-IV, capsular infiltration, lymph node metastasis, and of recurrence. The Kaplan-Meier curve showed that patients with lower expression of PD-L1, PDK1 or p-Akt had significantly longer recurrence-free time. The logistic regression analysis revealed that only CLT, PD-L and capsular infiltration were risk factors for patients' five-year recurrence. The PD-L1, PDK1 and p-Akt were found to be positively correlated with a poor prognosis in PTC.

Hypothyroidism.

Hypothyroidism is a common condition in which the thyroid gland provides insufficient amounts of thyroid hormone for the needs of peripheral tissues. The most common cause in adults is chronic lymphocytic thyroiditis (Hashimoto thyroiditis), but there are many other causes. Because most of the clinical features of hypothyroidism are nonspecific, the diagnosis requires laboratory testing. Serum thyroid-stimulating hormone (TSH) measurement is the best diagnostic test; an elevated TSH level almost always signals primary hypothyroidism. Serum free thyroxine levels may be below the reference range (overt hypothyroidism) or within the reference range (subclinical hypothyroidism). All patients with overt hypothyroidism should be treated, but those with subclinical hypothyroidism do not always benefit from treatment, especially elderly patients and those with baseline TSH levels below 10 mU/L. Oral L-thyroxine is the treatment of choice because of its well-demonstrated efficacy, safety, and ease of use. Therapy goals are symptom relief and maintenance of serum TSH levels within the reference range. Myxedema coma is a life-threatening form of decompensated hypothyroidism that must be treated with aggressive L-thyroxine replacement and other supportive measures in the inpatient setting.

RET, NTRK, ALK, BRAF, and MET Fusions in a Large Cohort of Pediatric Papillary Thyroid Carcinomas.

Background: Pediatric papillary thyroid carcinoma (PTC) is a rare malignancy, but with increasing incidence. Pediatric PTCs have distinct clinical and pathological features and even the molecular profile differs from adult PTCs. Somatic point mutations in pediatric PTCs have been previously described and studied, but complex information about fusion genes is lacking. The aim of this study was to identify different fusion genes in a large cohort of pediatric PTCs and to correlate them with clinical and pathological data of patients. Methods: The cohort consisted of 93 pediatric PTC patients (6-20 years old). DNA and RNA were extracted from fresh frozen tissue samples, followed by DNA and RNA-targeted next-generation sequencing analyses. Fusion gene-positive samples were verified by real-time polymerase chain reaction. Results: A genetic alteration was found in 72/93 (77.4%) pediatric PTC cases. In 52/93 (55.9%) pediatric PTC patients, a fusion gene was detected. Twenty different types of RET, NTRK3, ALK, NTRK1, BRAF, and MET fusions were found, of which five novel, TPR/RET, IKBKG/RET, BBIP1/RET, OPTN/BRAF, and EML4/MET, rearrangements were identified and a CUL1/BRAF rearrangement that has not been previously described in thyroid cancer. Fusion gene-positive PTCs were significantly associated with the mixture of classical and follicular variants of PTC, extrathyroidal extension, higher T classification, lymph node and distant metastases, chronic lymphocytic thyroiditis, and frequent occurrence of psammoma bodies compared with fusion gene-negative PTCs. Fusion-positive patients also received more doses of radioiodine therapy. The most common fusion genes were the RET fusions, followed by NTRK3 fusions. RET fusions were associated with more frequent lymph node and distant metastases and psammoma bodies, and NTRK3 fusions were associated with the follicular variant of PTC. Conclusions: Fusion genes were the most common genetic alterations in pediatric PTCs. Fusion gene-positive PTCs were associated with more aggressive disease than fusion gene-negative PTCs.

Programmed Death-Ligand 1 (PD-L1) Is a Potential Biomarker of Disease-Free Survival in Papillary Thyroid Carcinoma: a Systematic Review and Meta-Analysis of PD-L1 Immunoexpression in Follicular Epithelial Derived Thyroid Carcinoma.

The expression of programmed death-ligand 1 (PD-L1) is an established prerequisite for the administration of checkpoint inhibitor therapy and is of prognostic value in several cancer types. Data concerning the potential effect of PD-L1 on the prognosis of thyroid carcinoma are limited. Therefore, this study aimed to provide a systematic review of the published data on this topic. The literature was reviewed to gather and quantify evidence on the prognostic role of PD-L1 in follicular epithelial derived thyroid carcinomas and determine its association with clinicopathological parameters. A meta-analysis was performed using the DerSimonian-Laird random-effects model. The quality of studies was evaluated with the Newcastle-Ottawa Scale and a modified GRADE approach used to rate the quality of evidence. Out of 445 papers, 18 were included and 15 provided adequate data for meta-analysis. The quality of evidence ranged from low to high. PD-L1 expression was significantly associated with a reduced disease-free survival (DFS) (RR 1.63, CI 1.04-2.56, p= 0.03, I2 68%, τ2 0.19 and HR 1.90, CI 1.33-2.70, p< 0.001, I2 0%, τ2 0.00); however, no association was found with the overall survival (OS). Furthermore, a significant association was found with respect to underlying chronic lymphocytic thyroiditis and BRAFV600E mutation status in papillary thyroid carcinomas. In the subgroup analysis, the association of PD-L1 and DFS remained strong in papillary thyroid carcinoma when compared with dedifferentiated thyroid carcinomas (anaplastic and poorly differentiated thyroid carcinomas) that failed to demonstrate a significant association with respect to PD-L1. These findings underscore the role of PD-L1 immunohistochemistry as a potential prognostic biomarker of disease recurrence in patients with papillary thyroid carcinoma.