Differences in Clinicopathological Characteristics of Papillary Thyroid Carcinoma between Symptomatic and Asymptomatic Patients with Primary Hyperparathyroidism

Background. Popularization of cervical ultrasound led to higher detection of papillary thyroid carcinoma (PTC) and primary hyperparathyroidism (PHPT), as well as increasing percentage of asymptomatic PHPT in China. Although the coexistence of PTC and PHPT has been reported, it is unknown whether the clinicopathological features of PTC differ between asymptomatic and symptomatic PHPT patients. Methods. We retrospectively reviewed the medical records of 304 PHPT patients treated in our hospital between January 2009 and July 2020, including 217 females and 87 males with the average age of 53.27 ± 13.54 years. Of the 304 patients, 181 were symptomatic PHPT patients and 123 were asymptomatic PHPT patients. We analyzed the laboratory results, postoperative pathology, and the TNM stage of PTC between asymptomatic and symptomatic PHPT patients. Results. Concurrent thyroid nodules were found in 61.51% of PHPT patients, and the prevalence of PTC in thyroidectomized PHPT patients was 29.89% in our cohort. Lower serum parathyroid hormone (PTH) ( p < 0.05 ) and calcium ( p < 0.05 ) were found in PHPT patients with PTC compared to patients with benign thyroid lesion. Compared with the symptomatic PHPT patients, the asymptomatic PHPT patients showed lower serum calcium ( p < 0.05 ), serum chlorine ( p < 0.05 ), alkaline phosphatase ( p < 0.05 ), PTH ( p < 0.05 ), and bone turnover markers ( p < 0.05 ) but higher prevalence of thyroid nodules (70.73% versus 55.24%, p < 0.05 ) and PTC (15.44% versus 3.87%, p < 0.05 ). All the PTC in symptomatic PHPT patients were papillary microcarcinoma limited to the thyroid, while 68.42% and 15.78% of the PTC in asymptomatic PHPT patients showed microscopic extrathyroidal extension and lymph node metastases, respectively. Moreover, 36.84% (7/19) of the PTC patients in asymptomatic group showed multifocality, which was much higher than 14.29% (1/7) in the symptomatic group; however, no statistical significance was found ( p = 0.24 ). Conclusions. The concomitant PTC in asymptomatic PHPT patients showed a higher rate of microscopic extrathyroidal invasion when compared to symptomatic PHPT patients. So the FNA is essential to the asymptomatic PHPT patients with suspicious thyroid nodules and once the PTC is confirmed, concurrent parathyroidectomy should be performed with thyroidectomy in asymptomatic PHPT patients.

Circulating Tumour Cells and MicroRNA in Thyroid Cancer - a Systematic Review

Background: Thyroid cancer (TC) is the most common endocrine malignancy worldwide. Currently available circulating biomarkers such as thyroglobulin and calcitonin present severe limitations to the diagnosis and management of often difficult-to-diagnose lesions. There is increasing interest in the utility of circulating tumour cells (CTCs) and microRNAs to diagnose and optimise the management of patients with TC. Methods: In this study, we undertake a systematic review to gain a better understanding of the utility of CTCs and microRNAs in the diagnosis and management of patients with TC. A systematic review of the literature was performed by searching electronic bibliographic databases MEDLINE, EMBASE, SCOPUS and Web of Science. Studies which measured CTCs or microRNA levels in peripheral blood from TC patients were included. Review articles, conference abstracts, and foreign language papers were excluded. Results: There were 238 records screened for inclusion. Full texts of 47 articles were reviewed and included for qualitative analysis. CTCs demonstrated value in disease monitoring by distinguishing between disease recurrence and remission in patients with papillary thyroid cancer (PTC) and differentiated thyroid cancer (DTC). Higher CTC counts were associated with poorer progression free survival. This is consistent with CTC studies in other cancers such as breast and colorectal. A total of 31 microRNA biomarker candidates were investigated in studies reviewed. Circulating miR-222, miR-221 and miR-146b were most commonly increased in patients with PTC compared to benign nodules and healthy controls, and were associated with poorer prognostic factors including extrathyroidal invasion and metastatic lymph nodes. Circulating miR-222-3p and miR-17-5p demonstrated discriminatory power between medullary thyroid cancer (MTC) and benign nodules and healthy controls. Conclusion: CTCs demonstrate a promising avenue for disease monitoring and detection of local and distant recurrence in patients with DTC. Several microRNA candidates demonstrate value in diagnosis of PTC and MTC. There is a large degree of heterogeneity in studies assessing the utility of microRNA biomarker candidates. Further studies are warranted to ascertain the value of circulating microRNA in disease monitoring and prognosis.

Selective use of radioactive iodine therapy for papillary thyroid cancers with low or lower-intermediate recurrence risk

Context Current guidelines recommend a selective use of radioiodine treatment (RAI) for papillary thyroid cancer (PTC). Objective To determine how policy changes affect the use of RAI and the short-term outcomes of patients. Design Retrospective analysis of longitudinal data. Setting Academic referral center. Patients Patients with non-aggressive PTC variants; no extrathyroidal invasion or limited to soft tissues, no distant metastases, and ≤5 central-compartment cervical lymph node metastases. In Cohort 1, standard treatments were total thyroidectomy and RAI (May 2005-June 2011); in Cohort 2 decisions on RAI were deferred for ~12 months after surgery (July 2011-December 2018). Propensity score matching was used to adjust for sex, age, tumor size, lymph node status, and extrathyroidal extension. Intervention Immediate RAI or deferred choice. Main outcome measures Responses to initial treatment in ≥3 years of follow-up. Results In Cohort 1, RAI was performed in 50/116 patients (51.7%), while in Cohort 2, it was far less frequent: immediately in 10/156 (6.4%), and in 3 more patients after the first follow-up data. The frequencies of structural incomplete response were low (1-3%), and there were no differences between the two cohorts at any follow-up visit. Cohort 2 patients had higher rates of “gray-zone responses” (biochemical incomplete or indeterminate response). Conclusions Selective use of RAI increases the rate of patients with “uncertain” status during early follow-up. The rate of structural incomplete responses remains low regardless of whether RAI is used immediately or not. Patients should be made aware of both the advantages and drawbacks of omitting RAI.

BRAFV600E hot spot mutation in thyroid carcinomas: first Moroccan experience from a single-institution retrospective study

Background: The incidence of thyroid cancer is increasing worldwide at an alarming rate. BRAFV600E mutation is described to be associated with a worse prognostic of thyroid carcinomas, as well as extrathyroidal invasion and increased mortality. Objective: To our knowledge, there are no reported studies neither from Morocco nor from other Maghreb countries re- garding the prevalence of BRAFV600E mutation in thyroid carcinomas. Here we aim to evaluate the frequency of BRAFV600E oncogene in Moroccan thyroid carcinomas. Methods: In this Single-Institution retrospective study realized in the Anatomic Pathology and Histology Service in the Mil- itary Hospital of Instruction Mohammed V ‘HMIMV’ in Rabat, we report, using direct genomic sequencing, the assessment of BRAFV600E in 37 thyroid tumors. Results: We detected BRAFV600E mutation exclusively in Papillary Thyroid Carcinomas ‘PTC’ with a prevalence of 28% (8 PTC out 29 PTC). Like international trends, Papillary Thyroid Carcinomas ’PTC’ is more frequent than Follicular Thyroid Carcinomas ‘FTC’ and Anaplastic Thyroid Carcinomas ‘ATC’ (29 PTC, 7 FTC and 1 ATC). Conclusion: Our finding gives to the international community the first estimated incidence of this oncogene in Morocco showing that this prevalence falls within the range of international trends (30% to 90%) reported in distinct worldwide ge- ographic regions. Keywords: Biomarker; BRAFV600E; Thyroid cancer; Morocco.

KIFC1 accelerates the proliferation, migration and invasion of papillary thyroid cancer cells via MAPK signaling

Kinesin family member C1 (KIFC1) acts as a kind of minus end-directed motorized protein and is considered as an oncogene of some cancer types. However, no studies have fully elucidated its biological activity and molecular mechanisms in papillary thyroid cancer (PTC). The study focused on reporting the overexpression of KIFC1 in cell lines and tissues of PTC. Moreover, clinicopathological features analysis showed that KIFC overexpression is significantly correlated with extrathyroidal invasion and lymph node metastasis. Knockdown of KIFC1 significantly reduced cell growth, migration and invasion in PTC cells, and concomitant increased levels of differentiation markers, such as Tg and Nis. Knockdown of KIFC1 markedly increased the expression level of epithelial cell marker (E-cadherin), and decreased the expression levels of epithelial-mesenchymal transition (EMT) related transcriptional factor N-cadherin, Snail and ZEB1. Further study revealed that knockdown of KIFC1 downregulated stemness markers ALDH2 and SOX2, and inhibited the MAPK signaling cascades and downstream signaling, including p-ERK, ERK, p-JNK, JNK, MMP2, and MMP9, which can affect the expression of the EMT associated factors. Taken together, we reported that KIFC1 might promoted the proliferation, migration and invasion of PTC cells and offer a candidate molecular target for therapeutic intervention.

ADDITIONAL SURGERY FOR OCCULT RISK FACTORS AFTER LOBECTOMY IN SOLITARY THYROID NODULES IS PREDICTED BY CYTOPATHOLOGY CLASSIFICATION AND TUMOR SIZE

Objective: Clinical practice for differentiated thyroid cancer is moving towards lobectomy rather than total thyroidectomy in patients at low risk of recurrence. However, recurrence risk assessment depends on post-operative findings, while the surgical decision is based on preoperative factors. We determined the preoperative predictors of occult higher-risk pathology and rates of completion thyroidectomy among surgical candidates with nonbenign thyroid nodules 10 to 40 mm and no evidence of extrathyroidal extension or metastasis on preoperative evaluation. Methods: Thyroid surgery cases at a single institution from 2005–2015 were reviewed to identify those meeting American Thyroid Association (ATA) criteria for lobectomy. ATA-based risk stratification from postoperative surgical pathology was compared to preoperative cytopathology, ultrasound, and clinical findings. Results: Of 1,995 thyroid surgeries performed for nonbenign thyroid nodules 10 to 40 mm, 349 met ATA criteria for lobectomy. Occult high-risk features such as tall cell variant, gross extrathyroidal invasion, or vascular invasion were found in 36 cases (10.7%), while intraoperative lymphadenopathy led to surgical upstaging in 13 (3.7%). Intermediate risk features such as moderate lymphadenopathy or minimal extrathyroidal extension were present in an additional 44 cases. Occult risk features were present twice as often in Bethesda class 6 cases (35%) as in lower categories (12 to 17%). In multivariable analysis, Bethesda class and nodule size, but not age, race, sex, or ultrasound features, were significant predictors of occult higher-risk pathology. Conclusion: Most solitary thyroid nodules less than 4 cm and with cytology findings including atypia of undetermined significance through suspicious for papillary thyroid cancer would be sufficiently treated by lobectomy. Abbreviations: ATA = American Thyroid Association; CND = central neck dissection; DTC = differentiated thyroid cancer; ETE = extrathyroidal extension; FNA = fine needle aspiration; FTC/HCC = follicular thyroid carcinoma/Hurthle cell carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; OR = odds ratio; PTC = papillary thyroid cancer; US = ultrasound

Clinical Outcomes and influence factors of differentiated thyroid carcinoma with negative preablative stimulated thyroglobulin and iodine-positive lymph nodes: A retrospective analysis

Background To investigate the clinical outcome of postoperative differentiated thyroid carcinoma(DTC)patients with negative preablative-stimulated thyroglobulin (ps-Tg) and iodine-positive lymph node after the first radioablation. Methods A total of 136 DTC patients with ps-Tg<2ng/ml and iodine-positive lymph nodeswho were initially treated by 131I at our hospital from May 2015 to February 2018 were enrolled. These patients were followed up for 6-36 months, and then were classified into 3 groups according to the clinical outcomes as follows: excellent response (ER) group, indeterminate response (IDR) group, and structural incomplete response (SIR) group.Univariate and multivariate analyses were performed to assess thedifferences of factors (e.g. age, gender, extraglandular infiltration) between 3 groups. Results The N stage (P=0.001), sizes of the displayed lymph nodes (P<0.001), ps-Tg level (P=0.002), and TgAb level (P=0.001) were significantly different among the 3 groups. The gender (P=0.615), age (P=0.332), the primary tumor size (P=0.311), extrathyroidal invasion (P=0.549), T stage (P=0.944), rate of lymph node metastasis (P=0.170), locations of the displayed lymph nodes (P=0.099), and degree of recurrence risk (P=0.783) were not significantly different among the 3 groups.The corresponding sensitivity, specificity, positive predictive value, and negative predictive values were 93.3%, 82.6%, 86.4%, and 91.3% respectively when the cut-off value of the lymph node size was 7.25 mm. Conclusion For the DTC patients with negative ps-Tg and iodine-positive lymph nodes, postoperative N stage, size of the displayed lymph nodes, and ps-Tg and TgAb levels could be used as sensitive indicators for predicting clinical outcomes.

MiR-155 promotes anaplastic thyroid cancer progression by directly targeting SOCS1

Background Anaplastic thyroid cancer (ATC) is considered to be a rare type of thyroid cancer but takes up the most important proportion of thyroid cancer-related deaths. Therefore, the development of molecular targeted therapy is an exciting strategy in the management of ATC. Methods miR-155 and SOCS1 expression were measured by qRT-PCR as well as western blot analysis. 8305c and FRO cells were transfected and cultured for apoptosis assays, transwell, MTT on miR-155 or SOCS1 suppression and overexpression. Dual-luciferase reporter assays and SOCS1 restoration experimentswas implemented for define the relation between SOCS1 and miR-155. In addition, the correlation between miR-155 expression and patients’ clinicopathological features were also explored. Results Aberrant miR-155 and SOCS1 expression and inverse correlation were found in ATC samples. In addition, it indicated that miR-155 expression correlated with cervical metastasis as well as extrathyroidal invasion. Moreover, we demonstrated that miR-155 inhibited 8305c and FRO cells apoptosis, promoted proliferation, invasion and migration. Furthermore, miR-155 inhibition was associated with a significant overexpression of SOCS1. Additionally, luciferase reporter assays presented that miR-155 could bind to SOCS1 3′-UTR, influencing its stability negatively and finally lowering SOCS1 levels. Moreover, it was illustrated that the impacts of miR-155 suppression were reversed by the inhibition of SOCS1 on cell proliferation, apoptosis as well as invasion. Conclusions Aberrant miR-155/SOCS1 expression has been included in ATC progression: miR-155 overexpression leads to SOCS1 suppression and develops ATC progression. Thus, miR-155 has been considered to be an underlying therapeutic target for ATC.

Active Surveillance in Adults with Low-Risk Papillary Thyroid Microcarcinomas: A Prospective Study

The acceptance and results of active surveillance in patients with low-risk papillary thyroid microcarcinomas (PTMC) are unknown in populations other than the Japanese population. This was the objective of the present prospective study. We selected patients ≥20 years who had thyroid nodules ≤1.2 cm with intermediate or high suspicion for malignancy on ultrasonography (US), not located near the recurrent laryngeal nerve and without extrathyroidal invasion or apparent lymph node metastases, whose cytology was suspicious (Bethesda V) or diagnostic (Bethesda VI) of papillary thyroid carcinoma. Patients who opted for active surveillance were followed up by biannual US. Fifteen patients (18.7%) readily opted for surgery and 12 (15%) for active surveillance. Fifty-three patients (66.2%) delegated the decision or wished to know the doctor’s preference before deciding. After the doctor had declared his/her preference for active surveillance, 50 patients decided to have this management and three to have surgery. Only 1/70 patients exhibited tumor progression (growth associated with a suspicion of extrathyroidal invasion) after 30 months of follow-up. Two patients decided to have surgery during follow-up, although the indication was not defined by the study. A>50% reduction in tumor volume was observed in three patients. The study shows that active surveillance can be well accepted if doctors were convinced that it is the best option for patients with low-risk PTMC. At least the short-term results reproduced those observed in other populations, with tumor progression being uncommon.