Primary Thyroid Cancer Research Articles

Multiple primary thyroid cancer
 in combination with malignant paraganglioma
 of the neck complicated by acute cerebrovascular
 event in the postoperative period:
 Clinical case

Actuality: Paraganglioma originates from the nerve ganglia along a.carotis, the ganglion of n.vagus, and the nerve plexuses around the sigmoid sinus, and has a rich tumor vasculature. Paraganglioma accounts for 0.8% of all CNS tumors and occurs
 most often at 40-60 years. Chemodectoma is located in the common carotid artery bifurcation zone and accounts for 2/3 of all
 glomus tumors.
 Purpose: The article describes a clinical case of multiple primary thyroid cancer in combination with malignant paraganglioma of the neck complicated by acute cerebrovascular event (ACE) in the postoperative period treated at the Head and Neck
 Tumor Department of the Kazakh Institute of Oncology and Radiology.
 Results: The presented clinical case demonstrates the results of the treatment of multiple primary cancer complicated by
 an ACE in the postoperative period. The qualification of doctors, adequate diagnostics contributed to choosing the right ACE
 treatment tactics taking into account all the patient-specific features, the tumor localization, and possible postoperative complications.
 Conclusion: The presented clinical case confirms the available data on the necessity of all diagnostic procedures and their
 effectiveness in the assessment of the prevalence of the process and the involvement of the adjacent anatomical structures in
 the suspected chemodectoma to avoid postoperative consequences that can lead to disability and fatal outcome. A wrong
 choice of the volume of surgical intervention can result in severe postoperative complications. Timely diagnosis and knowledge
 of the clinical course of the ACE helped restore the patient’s general condition and stop signs of cerebral ischemia. Successful
 recovery of a patient depends on the qualifications of the doctors and the prevalence of the tumor process. Adequate symptomatic therapy has a huge impact on the course of a complicated postoperative period.

Multiple Primary Thyroid Cancer
 in combination with Malignant
 Paraganglioma of the Neck
 complicated by Acute Cerebrovascular
 Event in the Postoperative Period:
 Clinical Case

Actuality: Paraganglioma originates from the nerve
 ganglia along a.carotis, the ganglion of n.vagus, and the
 nerve plexuses around the sigmoid sinus, and has a rich
 tumor vasculature. Paraganglioma accounts for 0.8% of all
 CNS tumors and occurs most often at 40-60 years. Chemodectoma is located in the common carotid artery bifurcation zone and accounts for 2/3 of all glomus tumors.
 Purpose: The article describes a clinical case of multiple primary thyroid cancer in combination with malignant
 paraganglioma of the neck complicated by acute cerebrovascular event (ACE) in the postoperative period treated at
 the Head and Neck Tumor Center of the Kazakh Institute of
 Oncology and Radiology.
 Results: The presented clinical case demonstrates the
 results of the treatment of multiple primary cancer complicated by an ACE in the postoperative period. The qualification of doctors, adequate diagnostics contributed to choosing the right ACE treatment tactics taking into account all
 the patient-specific features, the tumor localization, and
 possible postoperative complications.
 Conclusion: The presented clinical case confirms the
 available data on the necessity of all diagnostic procedures
 and their effectiveness in the assessment of the prevalence
 of the process and the involvement of the adjacent anatomical structures in the suspected chemodectoma to avoid
 postoperative consequences that can lead to disability and
 fatal outcome. A wrong choice of the volume of surgical intervention can result in severe postoperative complications.
 Timely diagnosis and knowledge of the clinical course of the
 ACE helped restore the patient’s general condition and stop
 signs of cerebral ischemia. Successful recovery of a patient
 depends on the qualifications of the doctors and the prevalence of the tumor process. Adequate symptomatic therapy
 has a huge impact on the course of a complicated postoperative period.

Cytological diagnosis of a rare synchronous non-small cell lung cancer metastatic to the thyroid gland.

Secondary neoplasms of the thyroid gland are quite uncommon with an estimated incidence rate of 0.1-3% 1,3 , representing either distant metastases or direct extension of tumors from adjacent anatomic structures. Metastases of primary lung cancers to the thyroid are even more unusual but the aggressive nature of lung malignancies often induces to palliative treatment, reasonably underestimating its incidence. In absence of a clinical history of primary tumor, specific symptoms and/or imaging data, the cytological differential diagnosis between primary thyroid cancer and metastatic lung carcinoma could be extremely challenging, especially in light of the overlapping morphological and architectural features.

Germline Mutation in MUS81 Resulting in Impaired Protein Stability is Associated with Familial Breast and Thyroid Cancer.

Multiple primary thyroid cancer (TC) and breast cancer (BC) are commonly diagnosed, and the lifetime risk for these cancers is increased in patients with a positive family history of both TC and BC. Although this phenotype is partially explained by TP53 or PTEN mutations, a significant number of patients are negative for these alterations. We judiciously recruited patients diagnosed with BC and/or TC having a family history of these tumors and assessed their whole-exome sequencing. After variant prioritization, we selected MUS81 c.1292G>A (p.R431H) for further investigation. This variant was genotyped in a healthy population and sporadic BC/TC tissues and investigated at the protein level and cellular models. MUS81 c.1292G>A was the most frequent variant (25%) and the strongest candidate due to its function of double-strand break repair. This variant was confirmed in four relatives from two families. MUS81 p.R431H protein exhibited lower expression levels in tumors from patients positive for the germline variant, compared with wild-type BC, and normal breast and thyroid tissues. Using cell line models, we showed that c.1292G>A induced protein instability and affected DNA damage response. We suggest that MUS81 is a novel candidate involved in familial BC/TC based on its low frequency in healthy individuals and proven effect in protein stability.

SAT-LB25 A Multi-Omics Analysis of Advanced Papillary Thyroid Cancer

Molecular profiling of papillary thyroid carcinoma has largely been confined to exome sequencing of non-aggressive cancer.1,2 Canonical mutations in BRAF and RAS are significantly represented in thyroid tumors, but these mutations have not resulted in diagnostics and therapeutics for advanced disease. To broadly examine the molecular landscape of advanced disease, we conducted a multi-omic analysis of 34 cases of advanced papillary thyroid carcinoma, including patient-matched lymph node metastases, primary tumor, adjacent-normal thyroid and germline. Our genome-wide multi-omic analysis links the regions of activated chromatin with expressed transcripts and proteins, identifying regulatory elements at primary tumor and nodal metastases stages of thyroid cancer progression. Distal regulatory elements putatively upregulate expression of MAPK-pathway genes in both tumors and metastases (36 genes (p =0.0057) in tumors and 76 genes (p =0.0011) in metastases). Furthermore, tumors and metastases harbor accessible chromatin regions that appear to be bound by MAPK transcription factors, FOS and JUN (p-value <10-150 for tumors and metastases). This study identifies regulatory elements that mediate MAPK activity in tumors and metastases of advanced papillary thyroid carcinoma and may ultimately lead to diagnostics and therapeutics that utilize advanced-thyroid-cancer-specific epigenetic targets. References• Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014• Masoodi T, et al. Whole-Exome Sequencing of Matched Primary and Metastatic Papillary Thyroid Cancer. Thyroid. 2020

Added Value of Computed Tomography to Ultrasonography for Assessing LN Metastasis in Preoperative Patients with Thyroid Cancer: Node-By-Node Correlation.

Diagnostic accuracy of US in the evaluation of lymph node (LN) metastasis for thyroid cancer patients is limited. We investigated the value of CT added to US for characterizing LNs in preoperative thyroid cancer patients by node-by-node correlation. A total of 225 primary thyroid cancer patients who underwent LN biopsy were included. Based on node-by-node correlation, 274 LNs were classified into probably benign, indeterminate, and suspicious categories on US, CT, and combined US/CT. Malignancy risks were calculated for each category and were compared between US/CT concordant and discordant cases. On US, CT, and combined US/CT, malignancy risks were 1.7%, 8.7%, and 0% in the probably benign category, 22.4%, 5.9%, and 8.0% in the indeterminate category, and 77.2%, 82.0%, and 75.6% in the suspicious category, respectively. Malignancy risk of the concordant suspicious category was higher than that of the discordant suspicious category (84.7% vs. 43.2%, p < 0.001). The addition of CT helped correctly detect additional metastasis in 16.4% of the US indeterminate LNs and in 1.7% of the US probably benign LNs. CT may complement US for LN characterization in thyroid cancer patients by suggesting the diagnostic confidence level for the suspicious category and helping correctly detect metastasis in US indeterminate LNs.

SUN-481 A Coexisting Primary Papillary Thyroid Carcinoma in a Case of Malignant Struma Ovarii with Follicular Thyroid Carcinoma: 2 Types of Thyroid Cancer in the Same Patient

Introduction: Struma ovarii is a rare monodermal variant of ovarian teratoma diagnosed when thyroid tissue is more than 50% of the overall tissue. It represents only 1% of all ovarian tumors. The vast majority of struma ovarii are benign (95%); however, malignant tumors have been reported in a small percentage of cases. The most common type is papillary carcinoma(PTC), followed by typical follicular carcinoma found in the pathology after surgical oophorectomy. We report a case of malignant struma ovarii with follicular carcinoma in the setting of additional micro PTC found after total thyroidectomy. Case report: A 48-year-old female presented with right-sided pelvic pain and a mobile pelvic mass. Pelvic MRI showed noted a large complex solid mass with cystic components in the right adnexa. It measured 7.7 x 8.4 x 6.7 cm. Subsequently, the patient underwent a robotic hysterectomy, bilateral salpingo-oophorectomy (TAHBSO), bilateral pelvic and para-aortic lymph node sampling, omentectomy and resection of nodules. Final pathology noted an ovary with struma ovarii with well-differentiated follicular carcinoma, peritoneal nodules containing thyroid tissue and benign lymph nodes. Subsequently, iodine 123 SPECT CT showed physiologic uptake in the thyroid with increased uptake in the pelvis, right perirectal region indicating residual thyroid tissue. The patient underwent total thyroidectomy with radioactive ablation with I131 (154.7 mCi). Pathology detected incidental 0.5mm micro PTC and it was classified as staged pT1aN. 6 months postoperatively, thyroglobulin (Tg) and Tg antibodies were undetectable with no abnormalities found on repeat whole-body scans. The patient has been following up with no new issues for the past 5 years indicating a good prognosis with low risk of recurrence. Discussion and Conclusion: In the literature, Struma ovarii containing thyroid-type carcinoma and papillary or follicular thyroid carcinoma metastasizing to the ovary has been documented. The standard treatment of a patient with malignant struma ovarii is TAHBSO and complete surgical staging, including peritoneal washings for cytology, pelvic and para-aortic lymph node sampling, and omentectomy. In cases with the residual malignant disease after surgery, total thyroidectomy and radioactive ablation are recommended. Our case is a unique case given the presence of 2 different thyroid carcinoma in the same patient. In addition, our patient had multiple risk factors for recurrence including large lesions>4 cm, extra ovarian extension, and the coexisting synchronous primary thyroid cancer, however, she had a good prognosis with no recurrence during the 5 years follow up period.

SUN-479 Metastatic Renal Cell Carcinoma (RCC) to the Thyroid: Case Report and Clinical Lesson

Background: Metastatic neoplasms to the thyroid gland are rare and have been observed more in autopsy series than in clinical series. Case: A 71-year old woman presented for thyroid nodule evaluation which was incidentally noted on CT/PET scan. She was diagnosed with renal cell carcinoma (RCC) stage IV (6.4 cm, left nephrectomy) 4 months prior. She had right hemi-thyroidectomy 30 years prior for a benign nodule. She was clinically and biochemically euthyroid with dysphagia and hoarseness in her voice. Thyroid u/s revealed multiple nodules in the left lobe with a dominant 3.6 x 2.9 x 3.6 cm solid, heterogeneous nodule with grade 3 hypervascularity. History positive for 1 cm right renal mass and multiple pulmonary nodules increasing in size thought to be consistent with metastases. The FNA of the dominant nodule was indeterminate, Bethesda III (AUS), GSC suspicious (Affirma, 50% ROM) with negative malignancy classifiers. Patient underwent completion thyroidectomy, and surgical path was consistent multifocal clear cell renal cell carcinoma (CRCC) with the largest focus of 3 cm based on clear cell features and strong positivity for stains: CK OSCAR, RCC, PAX-8 & CD-10. Patient is currently on Pazopanib post thyroid surgery for 18 months, and is stable with no further increase in the size of lung nodules or right renal mass and negative serial PET scans. Clinical lesson: CRCC represents 3-4% of all adult malignancies and 85% of all primary renal tumors. In clinical series, CRCC is the most frequent source of thyroid metastases and represents 12-34% of all secondary thyroid tumors. About 17% of patients with CRCC have metastatic disease at diagnosis. Metastases can be synchronous or metachronous to the primary tumor. Latency from nephrectomy to diagnosis of thyroid mets varies from 2 months-21.9 years. Metastases can be solitary (more common), multiple or diffuse. Radiological findings typically reveal hypoechoic and vascularized mass on ultrasound and cold on thyroid scan. Metastases to thyroid can pose diagnostic problem and be a source of confusion in cytology interpretation. Metastatic CRCC can simulate morphologically primary thyroid neoplasm such as Hurthle cell neoplasm or thyroid carcinomas with clear cell changes. Metastatic carcinoma within the thyroid gland is negative for thyroglobulin, TTF-1, calcitonin unlike primary thyroid cancer. CRCC is usually positive for periodic acid-Schiff and Oil red O, vimentin, and CD10. The mean survival in patients with CRCC who had thyroidectomy alone or with adjuvant treatment was 3 years. Conclusion: Thyroid metastases should be considered in patients with thyroid nodules and positive history of RCC. The preoperative distinction between primary and secondary tumors is difficult. Immunohistochemistry is a useful method for the evaluation of patients with suspected thyroid nodules.

Thyroid gland metastasis from breast cancer: a case report

Primary cancer metastasis to thyroid gland is rare. The most common metastatic tumors of the thyroid gland are from lung, breast and renal cell carcinoma. In this case report, a patient with breast cancer metastasized to the thyroid gland is presented. A 38-year-old female patient was diagnosed with breast cancer, and positron emission tomography-computed tomography (PET-CT) imaging for breast cancer staging revealed fluoro-2deoxy-D-glucose (FDG) uptake in the thyroid nodule. Fine needle aspiration biopsy (FNAB) of the nodule revealed atypia of undetermined significance (Bethesda III). After neoadjuvant chemotherapy, simultaneous breast conserving surgery and total thyroidectomy were performed. Immunohistochemical staining of the pathological specimens revealed breast cancer that had metastasized to the thyroid gland. Immunohistochemical methods helped distinguishing primary thyroid cancer from metastasis. Also, nodules that showed activity involvement were detected randomly in PET-CT, and had to be evaluated in terms of malignancy.

Global RNA Expression and DNA Methylation Patterns in Primary Anaplastic Thyroid Cancer.

Anaplastic thyroid cancer (ATC) is one of the most malignant tumors, with a median survival of only a few months. The tumorigenic processes of this disease have not yet been completely unraveled. Here, we report an mRNA expression and DNA methylation analysis of fourteen primary ATCs. ATCs clustered separately from normal thyroid tissue in unsupervised analyses, both by RNA expression and by DNA methylation. In expression analysis, enrichment of cell-cycle-related genes as well as downregulation of genes related to thyroid function were seen. Furthermore, ATC displayed a global hypomethylation of the genome but with hypermethylation of CpG islands. Notably, several cancer-related genes displayed a correlation between RNA expression and DNA methylation status, including MTOR, NOTCH1, and MAGI1. Furthermore, TSHR and SLC26A7, encoding the thyroid-stimulating hormone receptor and an iodine receptor highly expressed in normal thyroid, respectively, displayed low expression as well as aberrant gene body DNA methylation. This study is the largest investigation of global DNA methylation in ATC to date. It shows that aberrant DNA methylation is common in ATC and likely contributes to tumorigenesis in this disease. Future explorations of novel treatments should take this into consideration.

Increasing Thyroid Cancer Incidence in Oman: A Joinpoint Trend Analysis.

ObjectivesWe sought to investigate the epidemiology of thyroid cancer and its trends in Oman over a 20-year period.MethodsWe analyzed all cases of primary thyroid cancer reported to the Oman National Cancer Registry between 1996 and 2015. Age-standardized incidence rates (ASR) were calculated using the World Standard Population. Joinpoint regression was used to assess trends and obtain annual percentage changes (APC) in incidence rates with 95% confidence intervals (95% CI) and p-values at the alpha = 0.050 level. Gender-specific APC was used to project thyroid cancer incidence rates in Oman over the next 20 years. Population attributable fraction was calculated for obesity and current non-smoking.ResultsA total of 1285 cases of primary thyroid cancer cases were registered in Oman between 1996 and 2015, with a female to male ratio of 4:1. In men, the ASR was 2.0 per 100 000 while in females it was 7.6 per 100 000 (p < 0.010). Over 80.0% of thyroid tumors were of a papillary type and 19.0% follicular type. Statistically significant trends for thyroid cancer were detected in women from 2008–2015 (APC = 14.3%, 95% CI: 8.0–20.9, p < 0.010) and among both genders (APC = 16.7%, 95% CI: 4.9–29.9, p < 0.010). If current trends continue, thyroid cancer incidence will increase to 3.1, 16.6, and 11.8 per 100 000 by 2040 in men, women, and both genders, respectively. Nearly 10.0% of thyroid cancer can be prevented by controlling obesity in the Omani population.ConclusionsOman has had moderate incidence rates of thyroid cancer with an increasing trend among women. Since projections estimate that the rates of this disease will double in women over the next 20 years, health authorities should consider providing sufficient resources to manage this condition and establish prevention programs that address obesity as part of the strategy for the prevention and control of noncommunicable diseases.

Down-regulation of the human major histocompatibility complex class I chain-related gene A (MICA) and its receptor is mediated by microRNA-146b-5p and is a potential mechanism of immunoediting in papillary thyroid carcinoma

Immune escape is one of the main reasons for the rapid progression of cancer and the poor efficacy of immunotherapy. Papillary thyroid cancer (PTC) is usually accompanied by intra-tumoral lymphocytic infiltration. The mechanisms regulating this tumor associated immune response or its evasion are not well understood. The major histocompatibility complex class I chain-related proteins A (MICA) and its receptor the natural killer group 2 member D (NKG2D) are major executers of the anti-tumor defense. This work aimed to study the expression and regulation of MICA-NKG2D and its association with the lymphocytic infiltration and miRNAs in PTC. Expression of MICA and NKG2D in thyroid tissues, and in cultured primary thyroid cancer cells and lymphocytes transfected with miR-146b-5p inhibitor/mimic was tested by RT-PCR. Results were confirmed by immunofluorescence staining and confocal microscopy. MICA is expressed in malignant and benign thyroid tissues with no association with aggressive behavior. Expression of MICA and NKG2D in PTC is concomitant with the presence of tumor associated lymphocytic response and is regulated by miR-146b-5p. MiR-146b-5p indirectly downregulates NKG2D expression in cancer cells and in lymphocytes. Overexpression of miR-146b-5p in PTC down-regulates MICA expression possibly to reduce the immunogenicity of the tumor cells. Targeting of the MICA-NKG2D axis by miR-146b-5p might be one of the ways adopted by thyroid cancer cells to aid the tumor in evading the immune response. The importance of our findings resides in the potential therapeutic use of MICA, NKG2D and miRNA-146b-5p as targets or modulators to enable the immune response against cancer.

Greetings From the Editor of Clinical Thyroidology

Greetings From the Editor of <i>Clinical Thyroidology</i>

Whole-Exome Sequencing of Matched Primary and Metastatic Papillary Thyroid Cancer.

Background: Distant metastasis is a rare occurrence in thyroid cancer, and it can be associated with poor prognosis. The genomic repertoires of various solid malignancies have previously been reported but remain underexplored in metastatic papillary thyroid cancer (PTC). Furthermore, whether distant metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown.Methods: We performed whole-exome sequencing on 14 matched distant metastases, primary PTC tumors, and normal tissues. Point mutations, copy number alterations, cancer cell fractions, and mutational signatures were defined using the state-of-the-art bioinformatics methods. All likely deleterious variants were validated by orthogonal methods.Results: Genomic differences were observed between primary and distant metastatic deposits, with a median of 62% (range 21–92%) of somatic mutations detected in metastatic tissues, but absent from the corresponding primary tumor sample. Mutations in known driver genes including BRAF, NRAS, and HRAS were shared and preferentially clonal in both sites. However, likely deleterious variants affecting DNA methylation and transcriptional repression signaling genes including SIN3A, RBBP1, and CHD4 were found to be restricted in the metastatic lesions. Moreover, a mutational signature shift was observed between the mutations that are specific or enriched in the metastatic and primary lesions.Conclusions: Primary PTC and distant metastases differ in their range of somatic alterations. Genomic analysis of distant metastases provides an opportunity to identify potentially clinically informative alterations not detected in primary tumors, which might influence decisions for personalized therapy in PTC patients with distant metastasis.

Risk of second primary papillary thyroid cancer among adult cancer survivors in the United States, 2000-2015

BackgroundWhile radiotherapy is a major risk factor for thyroid cancer after childhood cancer, factors contributing to increased thyroid cancer risk after adulthood cancer remain unclear. MethodsWe evaluated second primary papillary thyroid cancer (PTC) risk among 3,175,216 ≥ 1-year adult survivors of non-thyroid malignancies from US population-based cancer registries (2000–2015), using standardized incidence ratios (SIRs). Because heightened surveillance may increase detection of indolent thyroid tumors and earlier detection of advanced tumors, we examined SIRs by PTC stage and time since first cancer (latency). ResultsSIRs for second primary PTC (N = 4333) were statistically-significantly 1.2–3.5-fold elevated overall and after 23/27 first cancer types evaluated, with generally similar risks for localized and regional/distant PTC. SIRs for regional/distant PTC (N = 1501) were highest after pancreatic (SIR = 3.7; 95% confidence interval [CI] = 1.9–6.5) and soft tissue (SIR = 4.2; 95%CI = 2.8–6.2) cancers, followed by melanoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma, and larynx, kidney, and brain/central nervous system (SIRs = 2.0–2.9) cancers. SIRs typically decreased with increasing latency but remained statistically-significantly elevated for regional/distant-PTC ≥5 years after diagnosis of cancers of the rectum, pancreas, lung/bronchus, soft tissue, female breast, uterine corpus, prostate, and kidney, and after melanoma, Hodgkin lymphoma, CLL/SLL, and follicular lymphoma. Neither total nor regional/distant PTC were clearly associated with initial course of radiotherapy or chemotherapy. ConclusionsPTC risk was elevated after a range of first primary adult cancers but was not clearly related to treatment. Although surveillance may contribute to elevated short-term risks of PTC, longer-term elevations in regional/distant PTC may be attributable to shared risk factors.

Functional outcome of operative treatment for pelvic metastatic bone disease from primary thyroid cancer: A case series

BackgroundMetastatic bone disease (MBD) is the most common malignancy of bone. It is estimated that 70 % of all malignant bone tumors are due to metastasis. The functional outcome from pelvic MBD surgical management has been rarely described in the literature contrary to that of the long bones. MethodWe reported three patients that underwent pelvic resection surgery due to pelvic MBD. All of the primary tumors were thyroid cancer. We measure the functional outcome using SF-36 and MSTS (musculoskeletal tumor society) scores after a one-year follow-up. ResultThe SF-36 scoring result was that all of the patients had a remarkable improvement in terms of pain (77.5 %, 100 %, and 100 %). All of the patients also still had proper social functioning (75 %, 100 %, and 100 %) and good emotional well-being (72 %, 92 %, and 88 %). According to the MSTS, the second and third case had an excellent functional outcome; however the first case had poor functional outcome ConclusionSurgery remains the choice of therapy for pelvic MBD that results in alleviation of pain and quality of life improvement.

Clinicopathological features, survival and risk in breast cancer survivors with thyroid cancer: an analysis of the SEER database

BackgroundThe co-occurrence of breast cancer (BC) and thyroid cancer (TC) has been mentioned for several years, researchers observed an increased risk of BC patients to develop TC, but few researches concern about the features, survival of BC patients followed by TC and the influent factors of the incidence risk. The present study aimed to estimate the clinicopathological features, survival of BC survivors who had primary TC and the predictive factors on the risk of BC patients to develop TC.MethodsWomen diagnosed with BC between 1992 and 2011, and then developed TC from the Surveillance, Epidemiology, and End Results Database were included. Standardized incidence ratios (SIRs) was used to perform multiple primary analyses, generated from the multiple primary-SIR program in SEER*Stat.ResultsA total of 842 BC then TC patients were included, the median age was 54 years. Additionally, 78.39% were white, 60.45% had T1 cancer, 62.47% had negative lymph nodes, and more than 75% had infiltrating duct carcinoma, 5-year survival rate was 95.4%. Compared with BC only patients, they were younger, had smaller tumor size and a relatively better prognosis. The risk of developing TC was higher in BC patients than in the general population (SIR 1.22, 95% CI [1.14, 1.31]), especially within 3 years. The influent factors of SIR were black race, BC tumor site, grade and ER/PR positive expression.ConclusionsBC patients followed by TC had its particular clinicopathological features. Compared with the features and survival of BC only patients, they were younger, had a smaller tumor size and a relatively better prognosis. Furthermore, BC patients had a high risk of developing TC, especially within 3 years. Black women, primary tumor located in an upper-outer, central, or overlapping site, high grade tumor and with positive hormone receptor expression were predictive factors to develop TC.

The Precursor for Nerve Growth Factor (proNGF) in Thyroid Cancer Lymph Node Metastases: Correlation with Primary Tumour and Pathological Variables.

Metastases in thyroid cancer are associated with aggressive disease and increased patient morbidity, but the factors driving metastatic progression are unclear. The precursor for nerve growth factor (proNGF) is increased in primary thyroid cancers, but its expression or significance in metastases is not known. In this study, we analysed the expression of proNGF in a retrospective cohort of thyroid cancer lymph node metastases (n = 56), linked with corresponding primary tumours, by automated immunohistochemistry and digital quantification. Potential associations of proNGF immunostaining with clinical and pathological parameters were investigated. ProNGF staining intensity (defined by the median h-score) was significantly higher in lymph node metastases (h-score 94, interquartile range (IQR) 50–147) than in corresponding primary tumours (57, IQR 42–84) (p = 0.002). There was a correlation between proNGF expression in primary tumours and corresponding metastases, where there was a 0.68 (95% CI 0 to 1.2) increase in metastatic tumour h-score for each unit increase in the primary tumour h-score. However, larger tumours (both primary and metastatic) had lower proNGF expression. In a multivariate model, proNGF expression in nodal metastases was negatively correlated with lateral neck disease and being male. In conclusion, ProNGF is expressed in locoregional metastases of thyroid cancer and is higher in lymph node metastases than in primary tumours, but is not associated with high-risk clinical features.

Risk of thyroid cancer after therapeutic irradiation in adult patients: An Age-Based surveillance, epidemiology, and end results analysis.

One risk of radiation therapy exposure (XRTe) is second primary thyroid cancer (SPTC). Previous reports examined this in children, but no population-based studies have explored XRTe and SPTC across all ages or stratified by histological subtypes. Database study. We report patient characteristics of a Surveillance, Epidemiology, and End Results (SEER) dataset of SPTC (n = 4,669) using χ2 and t tests. Odds ratio (OR) for SPTC was determined based on age, histology, and XRTe compared to expected values in the SEER database. Kaplan-Meier survival and Cox proportional hazard ratios were reported to determine factors influencing latent survival (LS; time from initial diagnosis to SPTC) and overall survival in univariate and multivariate models. Extrathyroid extension and node status based on XRTe were similar (P = .684 and P = .776, respectively). XRTe patients were more likely to have smaller tumors (17.6 vs. 19.3 mm, P = .007). XRTe patients were diagnosed with SPTC at younger ages (59.8 vs. 62.7 years, P < .001) without a difference in LS (7.45 vs. 7.50 years, P = .426). Patients aged 1 to 14 years and 15 to 29 years at diagnosis of first cancer are at higher risk of SPTC after XRTe (OR = 1.89, P = .005 and OR = 2.35, P = .001, respectively), unlike patients age 30 to 44 years and 45+ years (OR = 1.03, P = .823 and OR = 0.97, P = .624, respectively). This difference is not present for follicular and medullary SPTC. Patients aged 30+ years receiving radiation therapy (XRT) do not have an increased risk of SPTC. Deliberation is necessary in recommending, planning, and delivering XRT to minimize risk of subsequent malignancy in younger patients. NA Laryngoscope, 130: 2081-2086, 2020.

The anti-cancer effects of phenformin in thyroid cancer cell lines and in normal thyrocytes.

Phenformin is a biguanide drug which, besides the original anti-diabetic effect, also exerts anti-cancer effects. The aim of this study was to further characterize these latter in terms of both cell-viability and modulation of the secretion of the pro-tumorigenic chemokine CXCL8. Normal human thyrocytes in primary cultures (NHT) and thyroid cancer cell lines, TPC-1 and 8505C (RET/PTC and BRAFV600E mutated, respectively) were treated with increasing concentrations of phenformin at different times. Cell-viability was assessed by WST-1 and further characterized by AnnexinV/PI staining and cell proliferation colony-assay. CXCL8 levels were measured in cell supernatants. Phenformin reduced cell-viability in TPC-1 and 8505C and their ability to form colonies. In NHT cells, phenformin affected cell-viability only at the maximal dose but interestingly it inhibited CXCL8 secretion at all the concentrations not affecting cell-viability. Phenformin had no effect on CXCL8 secretion in thyroid cancer cell lines. Thus, phenformin exerts anti-cancer effects on both cancer cells (cell death induction) and surrounding normal cells (inhibition of CXCL8 secretion). These results highlight that the anti-cancer effects of phenformin are multifaceted and effective on both solid and soluble components of the tumor-microenvironment.