Type Of Thyroid Carcinoma Research Articles

B7-H3 and ICAM-1 are potentially therapeutic targets for thyroid carcinoma

Although most differentiated thyroid carcinoma has a clinically favorable prognosis, some of specific types of thyroid cancer (such as anaplastic thyroid carcinoma and advanced papillary thyroid carcinoma) show fatal outcomes and require novel treatments. Immunotherapy is a promising avenue for the treatment of advanced thyroid carcinoma. B7-H3 (B7 homolog 3 protein) and ICAM-1 (intercellular adhesion molecule 1), as two important immune checkpoints (ICPs), is becoming hopeful target spots for immunotherapy. A growing amount of evidence has suggested that B7-H3 and ICAM-1 are upregulated in papillary thyroid carcinoma. However, their expression level in specific types of thyroid cancer remains largely unclear. In the present study, we explored the expression level of B7-H3 and ICAM-1 in different types of thyroid carcinoma. In the groups of the TCGA cohort, both B7-H3 and ICAM-1 mRNA were highly expressed in thyroid carcinoma. Furthermore, the patients with Stage2, 61-80y, Follicular thyroid papillary carcinoma and N0 had lower B7-H3 and ICAM-1 mRNA expression. In the groups of our cohort, PTCs and ATCs showed frequently moderate to strong expression of B7-H3 and ICAM-1 protein expression. The significant relevance of B7-H3 staining score with ICAM-1 staining score was observed in TCGA database and our cohort, which might open avenues for the combination therapy in advanced thyroid cancer.

Comprehensive Review of the Imaging Recommendations for Diagnosis, Staging, and Management of Thyroid Carcinoma.

Thyroid cancer is the most common head and neck cancer (HNC) in the world. In this article, we comprehensively cover baseline, posttreatment, and follow-up imaging recommendations for thyroid carcinomas along with the eighth edition of the tumor, node, metastasis (TNM) staging system proposed by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC). We include characterization and risk stratification of thyroid nodules on ultrasound (US) proposed by various international bodies. Management guidelines (depending upon the type of thyroid carcinoma) based on the international consensus recommendations (mainly by the American Thyroid Association) are also extensively covered in this article, including the role of a radioiodine scan. The management of recurrent disease is also briefly elucidated in this article. In addition, we cover the risk factors and etiopathogenesis of thyroid carcinoma along with the non-imaging diagnostic workup essential for thyroid carcinoma management, including the significance of genetic mutations. US is the diagnostic imaging modality of choice, with US-guided fine needle aspiration (FNA) being the procedure of choice for tissue diagnosis. The roles of computed tomography (CT), magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) in thyroid carcinoma staging are also specified. Through this article, we aim to provide a comprehensive reference guide for the radiologists and the clinicians in the pursuit of optimal care for patients with thyroid carcinoma.

Risk factors for cervical lymph node metastasis in the central or lateral cervical region in medullary thyroid carcinoma: a systematic review and meta-analysis.

Compared with other types of thyroid carcinoma, patients with medullary thyroid carcinoma (MTC) are more likely to develop cervical lymph node metastasis. This study was conducted to clarify the risk factors for cervical lymph node metastasis (central lymph node metastasis or lateral cervical lymph node metastasis) in MTC by meta-analysis, and to provide evidence-based basis for the treatment and prognosis of MTC. The literatures related to cervical lymph node metastasis in medullary thyroid carcinoma were searched in PubMed, Embase, Web of Science, Cochrane, CNKI and Wanfang databases, and statistical analysis was performed using Revman 5.3 and Stata 14.0 software. A total of 28 papers were included in this paper, and meta-analysis showed that the occurrence of central lymph node metastasis (CLNM) in MTC patients was significantly associated with tumor size (OR = 3.07, 95%CI: 2.04-4.63, P < 0.00001), multifocality (OR = 0.29, 95%CI: 0.19-0.44, P < 0.00001), bilaterality (OR = 3.75, 95% CI: 1.95-7.14, P < 0.0001), capsular invasion (OR = 9.88, 95% CI: 5.93-16.45, P < 0.00001) and extrathyroidal extension (OR = 5.48, 95% CI: 2.61-11.51, P < 0.00001). While the occurrence of lateral cervical lymph node metastasis (LLNM) in MTC patients was strongly correlated with gender (OR = 2.97, 95%CI: 2.46-3.58, P < 0.00001), tumor size (OR = 3.88, 95%CI: 1.90-7.92, P = 0.0002 < 0.05), multifocality (OR = 0.43, 95%CI: 0.35-0.51, P < 0.00001), bilaterality (OR = 2.93, 95% CI: 1.72-4.98, P < 0.0001), capsular invasion (OR = 8.44, 95% CI: 6.11-11.64, P < 0.00001), extrathyroidal extension (OR = 7.04, 95% CI: 5.54-8.94, P < 0.00001), margin of the tumor (OR = 4.47, 95% CI: 2.37-8.44, P < 0.00001), shape of the tumor (OR = 6.81, 95% CI: 3.64-12.73, P < 0.00001), preoperative calcitonin level (SMD = 1.39, 95% CI: 0.98-1.80, P < 0.00001), preoperative carcinoembryonic antigen level (SMD = 0.97, 95% CI: 0.74-1.20, P < 0.00001) and CLNM (OR = 19.70, 95% CI: 14.16-27.43, P < 0.00001). Tumor size, multifocality, bilaterality, capsular invasion and extrathyroidal extension are the main risk factors for developing CLNM in MTC patients; And risk factors for developing LLNM in MTC patients include: gender, tumor size, multifocality, bilaterality, capsular invasion, extrathyroidal extension, margin of the tumor, shape of the tumor, preoperative calcitonin level, preoperative carcinoembryonic antigen level and central lymph node metastasis. These risk factors can guide the individualized treatment plan and improve the prognosis of MTC patients.

Role of gene sequencing in classifying struma ovarii: BRAF p.G469A mutation and TERT promoter alterations favour malignant struma ovarii.

Struma ovarii (SO) are rare, accounting for 0.3-1% of ovarian tumours, and include benign and malignant lesions. In most cases, histology is not predictive of clinical outcome and prognosis. The prognosis of histologically malignant thyroid-type carcinomas can indeed be excellent, while SO, composed of normal thyroid tissue, can recur and are designated highly differentiated follicular carcinoma of the ovary. Clearer diagnostic criteria are therefore required. We retrospectively studied 31 SO using DNA and RNA sequencing with pan-cancer gene panels, including eight biologically malignant SO (BMSO) defined based on ovarian serosal or extra-ovarian dissemination at presentation or during follow-up, 10 stage IA histologically malignant SO (HMSO) with thyroid-type carcinoma morphology and 13 biologically and histologically benign SO (BSO), with none of the above-mentioned characteristics. Molecular alterations were observed in 87.5% of BMSO, 70% of HMSO and 7.7% of BSO (P < 0.001). All patients with a peritoneal dissemination at presentation or during follow-up had at least one gene alteration. BRAF mutations (44.5%) were only observed in malignant forms (HMSO and BMSO) and TERT promoter alterations (25%) only in cases of BMSO. The BRAF p.G469A mutation, which is extremely rare in thyroid carcinomas, was the molecular alteration most frequently associated with malignant SO (28.5%). Our results highlight the clinical utility of molecular sequencing in SO, based on this limited number of cases. However, as malignant SO evolve slowly, more extensive molecular studies in SO with more than 10 years' follow-up are required to draw any conclusions on the prognostic value of the associated gene alterations.

The Role of MMP-9 and MMP-9 Inhibition in Different Types of Thyroid Carcinoma.

Matrix metalloproteinase-9 (MMP-9), one of the most investigated and studied biomarkers of the MMPs family, is a zinc-dependent proteolytic metalloenzyme whose primary function is degrading the extracellular matrix (ECM). It has been proved that MMP-9 expression elevates in multiple pathological conditions, including thyroid carcinoma. MMP-9 has a detectable higher level in malignant or metastatic thyroid tumor tissues than in normal or benign tissues and acts as an additional marker to distinguish different tumor stages because of its close correlations with clinical features, such as lymph node metastasis, TNM stage, tumor size and so on. Natural and non-natural MMP-9 inhibitors suppress its expression, block the progression of diseases, and play a role in therapy consequently. MMP-9 inhibitory molecules also assist in treating thyroid tumors by suppressing the proliferation, invasion, migration, metastasis, viability, adhesion, motility, epithelial-mesenchymal transition (EMT), and other risk factors of different thyroid cancer cells. In a word, discovering and designing MMP-9 inhibitors provide great therapeutic effects and promising clinical values in various types of thyroid carcinoma.

Frequency and Type of Thyroid Carcinoma in Patients With Multinodular Goiter.

Background This study aimed to investigate the incidence and subtype of thyroid cancer in multinodular goitre (MNG) patients who underwent total thyroidectomy. Methodology A cross-sectional study was conducted at the Khyber Teaching Hospital, screening 207 MNG patients who received complete thyroidectomies between July and December 2022. The senior consultant diagnosed thyroid cancer based on a complete history, physical examination, and laboratory and radiological studies. Ultrasound-guided fine-needle aspiration cytology was performed by a senior consultant radiologist. Bethesda categories for all lesions were recorded. All patients underwent thyroidectomy, and the diagnosis of thyroid cancer was confirmed on histopathology. Results A total of 207 patients were included in the study, with a mean age of 45.55 ± 8.75 years. Out of 207 patients, 24 (11.59%) were diagnosed with thyroid cancer.Out of 62 male patients, 15 (7.25%) had thyroid cancer. Out of 145 female patients, only nine had cancer (p < 0.001). Nine patients with thyroid cancer had a body mass index (BMI) below 18, compared to only five patients with a BMI of more than 30 kg/m2.The difference in age distribution was not significant in our study (p = 0.102). Conclusion In conclusion, our study sheds light on the frequency and potential risk factors associated with thyroid cancer in patients with multinodular goiter. Our findings reveal that papillary thyroid carcinoma is the most commonly observed form of thyroid cancer in this patient population, with around 12 percent of patients diagnosed with thyroid cancer. Notably, our study highlights that male patients and those with a lower BMI may have a greater risk of developing thyroid cancer in the context of multinodular goiter.The findings of this study have important implications for the care and follow-up of MNG patients who receive total thyroidectomy. Further research is needed to investigate the type and prognosis of thyroid cancer in patients with MNG.

A Case of Papillary Thyroid Carcinoma Arising from Struma Ovarii and Extending into the Bladder

Ovarian goiter is a form of single tissue teratoma of the ovary, accounting for 2% - 3% of mature ovarian teratomas. Malignant transformation may occur in rare cases. Papillary thyroid-type carcinoma represents the most common type of malignant struma ovarii, followed by follicular carcinoma. Malignant struma ovarii is commonly seen in women in the fifth decade. The diagnosis is often made post-operatively after histological examination. Histology also helps assess tumor aggressiveness (mitoses, necrosis, poorly differentiated subtype, etc.). Given the rarity of these lesions, no therapeutic consensus or prognostic value had yet been formally established. We report herein, the case of a 76-year-old woman with a cystic tumor of the right ovary and a nodular lesion of the bladder. The clinical symptomatology is nonspecific, associating abdomino-pelvic pain and a right latero-uterine mass on abdominal palpation. After total hysterectomy with bilateral adnexectomy, the diagnosis of papillary carcinoma arising from struma ovarii and extending into the bladder was made. Through this observation, we suggest to discuss the anatomoclinical particularities of this rare pathological entity.

CACA guidelines for holistic integrative management of thyroid cancer

PurposeIn recent years, thyroid cancer is a common clinical problem. Since guidelines for the diagnosis and treatment of thyroid nodules and differentiated thyroid cancer were revised in 2012, significant scientific advances have occurred in the field. The aim of this guidelines is to inform clinicians, researchers, patients and health policy makers on published evidence and expert consensus relating to the diagnosis and management of thyroid malignancy.MethodsIn order to better promote the clinical management of thyroid cancer in China, Chinese Association of Thyroid Oncology (CATO) organized relevant experts to write these guidelines based on latest relevant literatures and clinical experience of multiple centers.The specific clinical issues and topics addressed in these guidelines were based on published evidence, prior versions of the Chinese guidelines and expert consensus.Results and conclusionThe guidelines provide recommendations for the management of different types of thyroid carcinoma, including papillary, follicular, medullary, and anaplastic carcinomas.

Co-existence of Papillary and Medullary Thyroid Carcinoma: Reports of Three Cases

Medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) are two different types of thyroid carcinoma. They have different features in terms of cellular origin, histopathology, clinical features, prevalence, and prognosis. PTC originates from follicular cells, while MTC from parafollicular cells. MTC and PTC co-existence is a rare phenomenon and occurs in less than 1% of all thyroid tumors. We report three cases with coexistent MTC and PTC in the same thyroid. The papillary component was dominant in two cases and the medullary in one case. While the first case was given radioactive iodine therapy, the third was treated with vandetanib. The second case was followed up postoperatively and did not receive treatment other than levothyroxine replacement. The co-existence of these tumors requires a different clinical approach in treatment and follow-up, depending on which type is dominant. Key Words: Mixed thyroid carcinoma, Papillary thyroid carcinoma, Medullary thyroid carcinoma.

Comparative evaluation of somatostatin and CXCR4 receptor expression in different types of thyroid carcinoma using well-characterised monoclonal antibodies

BackgroundPapillary and follicular thyroid carcinomas can be treated surgically and with radioiodine therapy, whereas therapeutic options for advanced stage IV medullary and for anaplastic tumours are limited. Recently, somatostatin receptors (SSTs) and the chemokine receptor CXCR4 have been evaluated for the treatment of thyroid carcinomas, however, with contradictory results.MethodsThe expression of the five SSTs and of CXCR4 was assessed in 90 samples from 56 patients with follicular, papillary, medullary, or anaplastic thyroid carcinoma by means of immunohistochemistry using well-characterised monoclonal antibodies. The stainings were evaluated using the Immunoreactivity Score (IRS) and correlated to clinical data. In order to further substantiate the immunohistochemistry results, in serial sections of a subset of the samples receptor expression was additionally examined at the mRNA level using qRT-PCR.ResultsOverall, SST and CXCR4 protein expression was low in all four entities. In single cases, however, very high IRS values for SST2 and CXCR4 were observed. SST2 was the most frequently expressed receptor, found in 38% of cases, followed by SST5 and SST4, found in 14 and 9% of tumours, respectively. SST1 and SST3 could not be detected to any significant extent. CXCR4 was present in 12.5% of medullary and 25% of anaplastic carcinomas. Expression SST3, SST4, SST5 and CXCR4 was positively correlated with expression of the proliferation marker Ki-67. Additionally, a negative interrelationship between SST4 or SST5 expression and patient survival and a positive association between SST3 expression and tumour diameter were observed. qRT-PCR revealed a similar receptor expression pattern to that seen at the protein level. However, probably due to the low overall expression, no correlation was found for the SSTs or the CXCR4 between the IRS and the mRNA values.ConclusionsSST- or CXCR4-based diagnostics or therapy in thyroid carcinomas should not be considered in general but may be feasible in single cases with high levels of expression of these receptors.

Proportion of Thyroid Malignancy in Simple Multi-nodular Goiter: A Prospective Observational Study in Rajshahi Medical College Hospital

Background: Thyroid swelling is a common clinical problem throughout the world. Most of the swellings are benign but someare malignant. Epidemiologically ascertained risk factors for thyroid carcinoma are ionizing radiation, presence of thyroidadenoma and multi-nodular goiter. Objectives: To determine the proportion and type of thyroid carcinoma in simple multi-nodular goiter after surgical resectionon histopathological basis.Materials and methods: This prospective observational study was carried out in the Department of Surgery and Otolaryngology and Head neck surgery of Rajshahi Medical College Hospital from January 2015 to December 2016.The studypopulation consisted of 200 patients who were diagnosed as a simple multi-nodular goiter. Among them 60 samples were fromsurgery and 140 samples from Head neck and otolaryngology wards. All the patients were admitted through OPD with routineplus investigations specific to thyroid including thyroid profile, ultrasonography of neck, FNAC of dominant nodule beforebeing subjected to surgery. Results: Among 200 cases which were included in this study 22 (11%) containing foci of malignancy. Incidence of malignancycommonly occurs in females, papillary carcinoma is being the commonest entity. Conclusion: The incidence of malignancy in simple multi-nodular goiter in this study was 11% that is quite high. So, peopleshould be educated and encouraged to attend the thyroid clinics for proper evaluation and early diagnosis of malignancy.

A rare case of highly differentiated follicular carcinoma in ovary with FGFR4 Gly388Arg polymorphism: a case report and literature review

BackgroundHighly differentiated follicular carcinoma (HDFCO) is a rare form of struma-derived thyroid-type carcinoma in ovary, defined as ovarian struma spreading beyond ovary but consisting of benign thyroid tissues. No more than 30 cases of HDFCO have been reported since it was first recognized in 2008. The clinicopathologic and molecular features of HDFCO remain unclear up till now.Case presentationA 38-year-old, para 1 gravida 5 woman has a long history of recurrent right ovarian cysts. Histological evaluation showed the tumor progressed from ovarian mature cystic teratoma (OMCT) to highly differentiated follicular carcinoma (HDFCO) during three relapses. Whole-exome sequencing revealed the germline FGFR4 Gly388Arg polymorphism. Repeated operations were performed to remove lesions for the first two relapses. On the third recurrence, the patient received radical surgery with subsequent thyroidectomy and radioactive iodine ablation. No evidence of disease was observed by February 2022 (8 months).ConclusionsThe germline FGFR4 Gly388Arg polymorphism may accelerate the malignant transformation of HDFCO, probably by working as a second hit in the developing spectrum.

RBM47/SNHG5/FOXO3 axis activates autophagy and inhibits cell proliferation in papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is the main type of thyroid carcinoma. Despite the good prognosis, some PTC patients may deteriorate into more aggressive diseases, leading to poor survival. Molecular technology has been increasingly used in the diagnosis and treatment of thyroid carcinoma. In this study, we identified that RNA Binding Motif Protein 47 (RBM47) was downregulated in PTC tissues and cells, and overexpression of RBM47 could activate autophagy and inhibit proliferation in PTC cells. RBM47 promotes but can not bind directly to Forkhead Box O3 (FOXO3). FOXO3 activates Autophagy Related Gene 3 (ATG3), ATG5, and RBM47 to form a loop and promote autophagy. RBM47 can bind directly to and stabilized lncRNA Small Nucleolar RNA Host Gene 5 (SNHG5) to inhibit PTC cells proliferation and activate autophagy in vitro and in vivo. SNHG5 inhibits ubiquitination and degradation of FOXO3 by recruiting Ubiquitin Specific Peptidase 21 (USP21), then promotes the translocation of FOXO3 from cytoplasm to nucleus. Our study revealed the regulatory mechanism of RBM47/SNHG5/FOXO3 axis on cell proliferation and autophagy in PTC, which may provide valuable insight for the treatment of PTC.

Clinicopathological Profile of Thyroid Carcinoma in Young Patients: An Indonesian Single-Center Study.

Introduction Thyroid cancer is the third most common cancer that occurs in children and adolescents. Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy. Although the mortality rate of thyroid malignancy in children is usually low, the disease recurrence is higher in children with more severe clinical presentation than in adults. This study aimed to determine the demographic and clinicopathological characteristics and outcome of pediatric and adolescent patients with thyroid malignancy in Indonesia. Methods The retrospective study included all patients diagnosed with thyroid carcinoma aged <20 years, from January 1, 2015, to December 31, 2019. Twenty-nine subjects fulfilled the inclusion and exclusion criteria. We retrieved baseline characteristics, pathology features, TSH and fT4 status, radioactive iodine therapy data, and patients' outcomes. Then, data were analyzed using the chi-square or Fisher's exact method. Results We identified 29 eligible subjects, including 3 boys and 26 girls. The most common type of thyroid carcinoma was PTC (96.5%), and follicular type (31%) was the predominant variant of PTC. Lymph node involvement occurred in 24% of patients, while distant metastasis occurred in 17.2% of patients with PTC. Twenty-four (82.7%) patients had stage 1 disease. Disease recurrence was recorded in 31% of patients during the study period with a median follow-up time of 24 months. Conclusion PTC is the most frequent type of thyroid carcinoma among children and adolescents. This malignancy has a low mortality rate, but the recurrence rate remains high among younger patients than adults even during a short-term follow-up analysis. Distant metastasis and lymph node involvement are commonly found in this age group.

Mixed Medullary and Papillary Thyroid Cancer: Case Reports

Introduction: Thyroid cancer is the most common type of endocrine malignancy. Papillary and medullary thyroid carcinomas are two different types of thyroid carcinoma with significant different histology. Synchronous occurrence of these two carcinomas is uncommon.

Clinicopathological Characteristics and Disease-Free Survival in Patients with Hürthle Cell Carcinoma: A Multicenter Cohort Study in South Korea.

Background Hürthle cell carcinoma (HCC), a type of thyroid carcinoma, is rare in South Korea, and few studies have investigated its prognosis.Methods This long-term multicenter retrospective cohort study evaluated the clinicopathological features and clinical outcomes in patients with HCC who underwent thyroid surgery between 1996 and 2009.Results The mean age of the 97 patients included in the study was 50.3 years, and 26.8% were male. The mean size of the primary tumor was 3.2±1.8 cm, and three (3.1%) patients had distant metastasis at initial diagnosis. Ultrasonographic findings were available for 73 patients; the number of nodules with low-, intermediate-, and high suspicion was 28 (38.4%), 27 (37.0%), and 18 (24.7%), respectively, based on the Korean-Thyroid Imaging Reporting and Data System. Preoperatively, follicular neoplasm (FN) or suspicion for FN accounted for 65.2% of the cases according to the Bethesda category, and 13% had malignancy or suspicious for malignancy. During a median follow-up of 8.5 years, eight (8.2%) patients had persistent/recurrent disease, and none died of HCC. Older age, gross extrathyroidal extension (ETE), and widely invasive types of tumors were significantly associated with distant metastasis (all P<0.01). Gross ETE (hazard ratio [HR], 27.7; 95% confidence interval [CI], 2.2 to 346.4; P=0.01) and widely invasive classification (HR, 6.5; 95% CI, 1.1 to 39.4; P=0.04) were independent risk factors for poor disease-free survival (DFS).Conclusion The long-term prognosis of HCC is relatively favorable in South Korea from this study, although this is not a nation-wide data, and gross ETE and widely invasive cancer are significant prognostic factors for DFS. The diagnosis of HCC by ultrasonography and cytopathology remains challenging.

Highly differentiated follicular thyroid-type carcinoma of the ovary reconsidered

More than a decade ago, Roth and Karseladze1 first described the entity of highly differentiated follicular thyroid carcinoma of ovarian origin (HDFCO) and reassessed the previously applied term peritoneal strumosis....

Anaplastic Thyroid Carcinoma: Current Issues in Genomics and Therapeutics.

Anaplastic thyroid carcinoma is a type of thyroid carcinoma with the most aggressive biological behaviour amongst thyroid cancer. Here, we review the current genomic and the impacts of advances in therapies to improve the management of patients with the cancer. Common mutations being identified in anaplastic thyroid carcinoma are p53 and TERT promoter mutations. Other common mutated genes included BRAF, RAS, EIF1AX, PIK3CA, PTEN and AKT1, SWI/SNF, ALK and CDKN2A. Changes in expression of different microRNAs are also involved in the pathogenesis of anaplastic thyroid carcinoma. Curative resection combined with radiotherapy and combination chemotherapies (such as anthracyclines, platins and taxanes) has been shown to have effects in the treatment of some patients with anaplastic thyroid carcinoma. Newer molecular targeted therapies in clinical trials target mostly the cell membrane kinase and downstream proteins. These include targeting the EGFR, FGFR, VEGFR, c-kit, PDGFR and RET on the cell membrane as well as VEGF itself and the downstream targets such as BRAF, MEK and mTOR. Immunotherapy is also being tested in the cancer. Updated knowledge of genomic as well as clinical trials on novel therapies is needed to improve the management of the patients with this aggressive cancer.

A Narrative Review of Genetic Alterations in Primary Thyroid Epithelial Cancer.

Thyroid carcinoma is the most frequent endocrine neoplasia. Different types of thyroid carcinoma are described: well-differentiated papillary thyroid carcinoma (PTC), poorly differentiated thyroid carcinoma (PDTC), follicular thyroid carcinoma (FTC), anaplastic thyroid carcinoma (ATC), and medullary thyroid carcinoma (MTC). MTC is inherited as an autosomal dominant trait in 25% of cases. The genetic landscape of thyroid carcinoma has been largely deciphered. In PTC, genetic alterations have been found in about 95% of tumors: BRAF mutations and RET rearrangements are the main genetic alterations. BRAF and RAS mutations have been confirmed to play an important role also in PDTC and ATC, together with TP53 mutations that are fundamental in tumor progression. It has also been clearly demonstrated that telomerase reverse transcriptase (TERT) promoter mutations and TP53 mutations are present with a high-frequency in more advanced tumors, frequently associated with other mutations, and their presence, especially if simultaneous, is a signature of aggressiveness. In MTC, next-generation sequencing confirmed that mutations in the RET gene are the most common molecular events followed by H-RAS and K-RAS mutations. The comprehensive knowledge of the genetic events responsible for thyroid tumorigenesis is important to better predict the biological behavior and better plan the therapeutic strategy for specific treatment of the malignancy based on its molecular profile.

Malignant struma ovarii: surgical, histopathological and survival outcomes for thyroid-type carcinoma of struma ovarii with recommendations for standardising multi-modal management. A retrospective case series sharing the experience of a single institution over 10years.

Struma ovarii is rare, accounting for 0.3-1% of ovarian tumours. Malignant transformation may occur, most often into papillary thyroid carcinoma. There is a paucity of data pertaining to malignant struma ovarii. This paper shares a decade of experience of a single institution in the management of this rare ovarian cancer, exploring the characteristics of this tumour and suggesting a standardised approach to treatment and follow-up. All patients treated for malignant struma ovarii within a large cancer centre over one decade were identified and data collected retrospectively on presentation, diagnosis, management, follow-up and survival outcomes. A literature review was also undertaken. Eleven cases of malignant struma ovarii were managed in the Oxford Cancer Centre between 2010 and 2019, 6 of which were of papillary thyroid carcinoma sub-type. No cases were correctly diagnosed pre-operatively. All patients had stage I disease and were managed surgically-but with variation in radicality. Patients identified as high-risk based on final histopathology underwent additional thyroidectomy and radio-active iodine ablation therapy. One case of synchronous malignancy of the thyroid gland proper was identified. No disease recurrence occurred. Malignant struma ovarii present a diagnostic challenge. Multi-disciplinary team (MDT) input is essential. Unilateral salpingo-oophrectomy may be adequate if stage I; reserving more radical surgery for advanced disease. Histopathological risk-stratification should be used to identify those most likely to benefit from adjuvant thyroid-targeting therapies. Patients require follow-up, anticipating an overall good prognosis.