bluuebunny/crossref_metadata_2025_split huggingface dataset:
“High Risk” Features of Differentiated Thyroid Cancer Are Commonly Found in Autopsy Studies: Implications for the ATA Guidelines
Authors: Robenshtok Eyal , Neeman Bar , Reches Liran , Ritter Amit , Bachar Gideon , Shimon Ilan , Mizrachi Aviram 
Published: May 2021

Abstract
Background: While the popularity of lobectomy for differentiated thyroid cancer (DTC) has increased since the 2015 American Thyroid Association guidelines, several recent studies reported that “high risk” histological features may be found in up to half of lobectomy specimens, questioning the validity of this approach. In turn, the actual risk associated with some “high risk” features (multifocality, minimal extra-thyroidal extension (ETE), and small lymph node (LN) metastases) has been questioned in recent years. Aim: To assess the prevalence of “high risk” pathological features in occult DTC detected in autopsy studies. Methods: Meta-analysis of autopsy studies of the thyroid gland in subjects without history of thyroid cancer. Studies with DTC lesions and details on histological features were included. Results: Twenty nine studies including 8,750 subjects fulfilled the inclusion criteria, with incidentally discovered DTC in 740 autopsies (prevalence of 8.5%). Age was reported in 17 studies, with a median age of 61 years (range 41-68 years). Multifocality was reported in 27 studies with a calculated event rate of 28.2% (95%CI 23.1% to 33.8%, random effect), with bilateral involvement in 18% (95%CI 12.6%-25/1%). Minimal ETE was reported in five studies, with an event rate of 24.5% (95%CI 9.3% to 50.7%, random effect), and the presence of LN metastases was reported in 13 studies with an event rate of 11% (95%CI 6.1% to 19.1%, random effect). Vascular invasion was reported in seven studies with an event rate of 16% (95%CI 4% to 47%, random effect). Conclusions: “High risk” histological features are common in occult DTC found in autopsy studies, and do not seem to be markers of aggressive disease. These data support a less aggressive therapeutic approach in patients with microscopic “high risk” features which were not detected on pre-operative ultrasound.
BRAF-Like and RAS-Like Thyroid Cancer is Characterized by Distinct Metabolic Phenotypes
Authors: Kumari Sonam , Adewale Ruth , Thakur Shilpa , Cardenas Stephanie , Klubo-Gwiezdzinska Joanna 
Published: May 2021

Abstract
Background: Next generation sequencing has led to the categorization of thyroid cancer (TC) based on the molecular and transcriptomic profile into the BRAF-like and RAS-like tumors. The BRAF-RAS score (BRS) has been developed to quantify the extent to which the gene expression profile resembles either the BRAFV600E- or RAS-mutant profiles and is utilized as a continuous measure from -1 to +1, respectively. Oncogene-driven signaling pathways have an impact on the intracellular metabolism– glycolysis and oxidative phosphorylation (OXPHOS). There are limited data on the genotype-metabolic phenotype correlation in TC cells. Therefore, the goal of this study was to perform a comprehensive analysis of the association between the BRS and TC cell metabolism. Methods: We analyzed the mRNA expression of key enzymes involved in glycolysis (lactate dehydrogenase LDHA) and OXPHOS (ATP synthase) in 496 BRAF-like and RAS-like human TC tissue samples based on The Cancer Genome Atlas. We performed an in vitro study using 8 TC cell lines– 4 BRAF-like with BRS between -1 and 0, and 4 RAS-like with BRS between 0 and +1. OXPHOS was determined by measuring oxygen consumption rate (OCR) of each cell line using Seahorse XF Cell Mito Stress Test Kit, while Seahorse XF Glycolysis Stress Test Kit was used to measure the extracellular acidification rate (ECAR) due to anaerobic glycolysis The association between the OCR, ECAR and BRS was tested using the Pearson correlation coefficient (r). Student T-test was used to compare the continuous variables between the groups with a p-value of ≤ 0.05 as statistically significant. Results:RAS-like tumors were associated with higher mRNA expression of the OXPHOS marker ATP synthase than BRAF-like lesions, as evidenced by a moderate positive correlation (r = 0.5) between ATP synthase expression and BRS. BRAF-like tumors were characterized by a relatively higher mRNA expression of a glycolytic enzyme LDHA, as documented by a moderate negative correlation (r = -0.6) between LDHA expression and BRS. Consistently, functional in vitro studies revealed that RAS-like cell lines had a higher OXPHOS compared with BRAF-like cell lines (maximum OCR: 2538.4±1601.3 vs 548.5±276.5, p=0.049, respectively). The glycolysis rate was comparable between RAS-like and BRAF-like cell lines (maximum ECAR: 1290.4±520.5 vs 2399.9±1413.1, p=0.19, respectively). There was a strong positive correlation between the BRS and OCR (r=0.78) and a low to negligible negative correlation between BRS and ECAR (r=-0.26) in examined TC cell lines. Conclusions:BRAF-like and RAS-like tumors are characterized by distinct metabolic phenotypes with RAS-like TC more likely to utilize OXPHOS to meet metabolic demands. Therapeutic strategies targeting oncogene-driven signaling pathways and cancer metabolism based on distinct metabolic phenotypes may provide an individualized approach to TC therapy.
Quality of Life in Patients With Low and Very Low Risk Differentiated Thyroid Cancer Who Underwent Thyroidectomy in Quito-Ecuador 2020
Authors: Baquero Stefany A , Hill Dana M 
Published: May 2021

Abstract
Low-risk papillary thyroid cancer (less than one centimeter and entrusting the thyroid) is a common pathology, over-diagnosed and therefore mainly over-treated in young women. Considered a public health problem mainly by two premises: 1) psycho-emotional involvement in people who suffer from it and undergo treatments; 2) and because unnecessary interventions are sometimes carried out that represent a futile cost to the health budget, especially for emerging economies such as the Ecuadorian. Objective: Demonstrate the affectation of the quality of life (QoL) after total thyroidectomy in patients with differentiated thyroid cancer of low and very low risk, who underwent surgery with or without adjuvant radioactive iodine treatment. In addition, to identify if variables such as gender, age, and sequelae of surgery such as hypoparathyroidism and scar influence QoL. M&M: A mixed study (qualitative-quantitative) was carried out, where information was collected electronically (via the whats app) and video call from 25 patients who have been affected by low and very low-risk thyroid cancer, in follow-up in the General Hospital San Francisco de Quito. After approval of the study by the teaching department and the ethics committee, we contacted the patients and asked for demographic data (age, gender); clinical data (use of levothyroxine, calcium); and they were also asked to fill out a self-applicable survey of the quality of life of the University of Washington (UW-Qol v.4). Subsequently, an interview with semi-structured questions was carried out and the participants were asked to make a graph of their neck. Results: In the UW-QoL v.4, it was shown that the physical aspects of quality of life, (chewing, swallowing, shoulder, speech, taste, and saliva) scored 90 points on average, did not present as much impact as the emotional aspects (pain, mood, activity, appearance, recreation, and anxiety) with an average of 83 points. In the interview and in the drawing it is corroborated that the emotional aspect where the appearance with the scar and the decrease in activity is included determine a worse quality of life. Neither gender nor age, nor the appearance of hypoparathyroidism determines a worse QoL. Discussion: The QoL for the WHO has elements that influence the physical and emotional health of a subject, their state of independence, and their social and environmental relationship. The study showed that QoL is affected with low and very low risk thyroid cancer on an emotional level, but not physically. This leads us to raise the possibility that differentiated thyroid cancer due to its low risk of mortality and recurrence in patients could be kept on follow-up and benefit from surgery only in the case that in active follow-up, it increased and became intermediate risk (ATA). Studies with a larger patient population are required to determine if support networks are an important parameter that affects QoL.
Anaplastic Thyroid Cancer Presenting With Brain Metastasis: 17-year Progression Free Survival
Authors: Howard Kathryn Kay , Lapkus Morta , Luehmann Natalie , Nagar Sapna , Czako Peter 
Published: May 2021

Abstract
Anaplastic Thyroid Cancer is the most aggressive thyroid cancer with a median survival of just five months. Long term survival has been reported in locally aggressive cases but has yet to be reported in metastatic disease. This is a report of a 34-year-old male who presented with symptoms of dizziness, confusion, intermittent headaches, and erratic behavior for two weeks found to have metastatic anaplastic thyroid cancer. CT of the head revealed a 1 cm ring enhancing lesion and he was taken to the operating room for a left parietal craniotomy with mass removal. Initial pathology suggested papillary thyroid origin. His neck exam revealed a palpable 3 cm mass in the right thyroid lobe and he subsequently underwent total thyroidectomy. Final pathology revealed anaplastic carcinoma identical to the brain lesion. Post-operatively, he underwent 15 cycles of whole brain radiation therapy. Two additional brain lesions were identified after thyroidectomy and a third was identified after whole brain radiation. He underwent stereotactic radiosurgery of these three lesions less than two months after thyroidectomy. The patient went on to receive modified mantle field irradiation to the neck, thyroid bed, and the upper mediastinum and chemotherapy with doxorubicin for 6-8 weeks and temozolomide for 2 years. Radioactive iodine treatment was not administered. The patient has currently survived 17 years and his persistent, but stable, brain lesions are being followed with serial imaging. He remains clinically and neurologically asymptomatic. This is the first case presenting with long-term survival in a patient with metastatic anaplastic thyroid carcinoma.
Coincidence? - Graves’ Disease & Thyroid Cancer
Authors: Correia Sara , Almeida Lucia Santos , Silva José Diogo , Tavares Patricia , Rocha Gustavo Melo , Oliveira Maria Joao 
Published: May 2021

Abstract
Background: DG coincidently with thyroid carcinoma has been reported as a rare phenomenon. It was thought that DG would be a protective condition in the development of cancer. However, published studies indicate the opposite, reporting an increased prevalence of differentiated thyroid cancer in DG compared to the general population. Some authors even report greater aggressiveness of this type of cancer in the presence of DG, with higher rates of, multifocality, metastatic disease and with a higher risk of recurrence. Clinical Case: Female, 46 years old, smoker 10 U.M.A., sent to the Endocrinology consultation due to symptomatic hyperthyroidism. No history of exposure to cervical radiotherapy, contact with iodinated products or cervical pain. Analytically, TSH &lt;0.008 uUI / mL (0.27-4.2), free T4 4.09 ng/dL(0.93-1.70), free T3&gt;20 pg/mL(2.57-4, 43), high levels of anti-thyroid and anti-TSH receptors 11.4IU/L (N &lt;1.75), diagnosing with Graves’ disease. The thyroid ultrasound revealed a globose and hypervascularized thyroid. In the right hemithyroid, an echogenic nodular area of ​​ill-defined limits of about 12mm was identified, associated with some hyperechogenic elements. Bilateral cervical and submandibular lymph nodes were visualized with a short 8 mm axis, highlighting a ganglion in the right jugular chain, questioning the presence of millimeter echogenic foci. She started metibasol, with improved thyroid function and opted for ultrasound surveillance. Four months later, she repeated the ultrasound of the thyroid, maintaining a hypercogenic area, with ill-defined limits in the right lobe, with a 13mm longest axis. She also maintained adenopathies in the right jugulo-carotid chain, rounded, without hilum, the largest one with 13x9x17mm, and it was performed a fine needle aspiration of the ganglion. There was no measurement of thyroglobulin in the wash. The morphological changes were compatible with ganglion metastasis due to papillary thyroid carcinoma with a predominantly follicular pattern. She started 5% lugol solute, 7 drops every 8 hours for 8 days before surgery and underwent total thyroidectomy and central and lateral lymphadenectomy, with the identification of a mixed, multifocal papillary carcinoma. in the right lobe and isthmus, the microscopic size of the largest focus was 40mm, without invasion of the capsule or vascular invasion, with ganglion metastases in the lateral (9/46) and central district (6/6) (pT2N1b). She underwent treatment with I131 at a dose of 120mCi. Conclusion: This clinical case stands out for its uniqueness, given the simultaneity of Graves’ disease and thyroid cancer. The presence of cervical adenomegaly, which is rare in DG, increased clinical suspicion. Due to the increase of the adenopathy in a short period of time, we decided to perform a biopsy, which in this case was essential for the diagnosis and subsequent treatment.
Not Your Typical “Lipoma”; An Unusual Case of Thyroid Cancer Presenting With a Skull Lesion
Authors: Abdulhadi Basma , Bahl Deepti 
Published: May 2021

Abstract
Background: Bone metastases from thyroid cancers tends to more commonly afflict the long bones, pelvis, ribs, vertebrae and sternum. Skull metastases are exceedingly rare being found in only ~2.5% of patients with thyroid cancer, more commonly in patients with Follicular thyroid carcinomas. We present an unusual case of thyroid cancer presenting with skull metastasis. Clinical Case: A 55 year- old male with a slowly growing skull lesion was referred to our center after an attempt to remove this scalp lesion was aborted as the lesion extended through a calvarial defect. This lesion was noted by the patient 1 year prior to presentation and was slowly growing in size. He opted for watchful monitoring as this was presumed to be a lipoma at the time. Imaging revealed a 6.4 x 4.6 x 6.3 cm lesion in the left parietal region with a large extra-axial and soft tissue components with intervening bone destruction as well as adjacent dural thickening. Differential for the lesion given the radiological appearance included meningioma, hemangiopericytoma, or an osseous/dural metastasis with an unclear primary malignancy. Excision of the extra-axial parietal lesion was consistent with metastatic thyroid carcinoma (follicular variant of papillary carcinoma). Further imaging revealed a multi nodular goiter with a prominent 6 cm left thyroid nodule. Patient had no obstructive symptoms. He underwent a total thyroidectomy with findings of a 6.8 cm minimally invasive follicular carcinoma with multifocal capsular invasion and a focus of vascular invasion. The right lobe revealed 1.5 cm classic PTC. Notably, margins were free of disease and cervical lymph nodes were negative for disease. Imaging revealed no other metastatic lesions. Patient received RAI after his total thyroidectomy and was started on suppressive doses of levothyroxine. He has been followed with annual MRI Brain, USG thyroid and Thyroglobulin levels and remains free of recurrence for the past 36 months. Conclusion: Thyroid cancer can present with skull metastasis without causing significant morbidity. This is a rare manifestation of disease and can be easily misdiagnosed. This case highlights the importance of keeping a broad differential when evaluating skull lesions.
Sarcoidosis-Lymphoma Syndrome Associated With Primary Thyroid Lymphoma: A Case Report
Authors: Yamashita Saori , Matsuda Yayoi , Muta Hiroki , Nagao Toshihiko , Nakao Hiroshi , Haji Shojiro , Nakashima Yasuhiro , Sakamoto Ryuichi , Ogawa Yoshihiro 
Published: May 2021

Abstract
Background: Sarcoidosis is occasionally accompanied by hematologic malignancies, including lymphoma, called sarcoidosis-lymphoma syndrome. Although the mechanism underlying the induction of lymphomas is still unknown, understanding the immunological background of sarcoidosis could help explain the possible mechanisms of the induction of lymphomas. Case Presentation: A 52-year-old woman was diagnosed chronic thyroiditis with normal thyroid function. One year later, she underwent a screening chest radiograph and identified bilateral hilar adenopathy and mediastinum lymphadenopathy. Subsequent mediastinoscopy demonstrated sarcoidosis. Because of the lack of clinical symptoms, steroid treatment was not initiated and regular follow-up was performed. One and a half years after the diagnosis of chronic thyroiditis, she presented with rapid swelling of the thyroid gland. FDG-PET/CT showed intense uptake of FDG in the thyroid gland and multiple lymphadenopathy. Fine-needle aspiration (FNA) cytology of the thyroid gland was only suggestive of a lymphoproliferative disorder and did not provide a definitive diagnosis. Partial thyroidectomy was performed, and the pathology indicated diffuse large B-cell lymphoma (DLBCL) such as high-grade transformation of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma. The results of an examination of a paraffin block histopathology specimen by fluorescence in-situ hybridization (FISH) detected BCL6 rearrangement (3q27), which is the most common chromosomal abnormality in DLBCL. After the treatment with R-EPOCH (rituximab, etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone) chemotherapy, the thyroid gland enlargement has improved markedly, while the lymph nodes remained swelling, that suggested lymph node involvements were due to sarcoidosis. Conclusions: Rapid swelling of the thyroid gland in the setting of chronic thyroiditis should raise suspicion for thyroid lymphoma. Furthermore, our present case might suggest that sarcoidosis accelerate the development and high-grade transformation of thyroid lymphoma. To our knowledge, this is the first reported case of sarcoidosis and primary thyroid lymphoma in the same patient.
The Importance of Lymph Node Dissection in Medullary Thyroid Carcinoma Management
Authors: Villavicencio Camila Alejandra , Franco-Akel Alberto , Belokovskaya Regina 
Published: May 2021

Abstract
Medullary thyroid carcinoma (MTC) is a rare endocrine malignancy that arises from calcitonin (Ct) parafollicular C-cells. Most cases are sporadic with frequent presentation being a solitary thyroid nodule. Total thyroidectomy with central neck dissection of lymph nodes (LN) is the standard treatment for MTC. The need for lateral neck dissection is controversial, with poor efficacy of non-surgical treatments presenting a problem. We present a case of MTC with preoperative Ct &gt;500 pg/mL and negative imaging for metastases who underwent total thyroidectomy without LN exploration with an excellent postoperative biochemical response.
This is a case of a 52-year-old female with a three-year history of anterior neck growth. The repeat fine needle aspiration (FNA) of a, previously negative for malignancy, growing nodule was consistent with MTC. Preoperative Ct and CEA levels were significantly elevated, 834.0 pg/mL and 11.2 ng/dL, respectively; a preoperative pan- CT scan did not reveal any suspicious LN or metastatic lesions and a negative RET oncogene mutation with normal plasma normetanephrines and metanephrines suggested a spontaneous rather than familial MTC. Patient underwent total thyroidectomy without LN exploration. Pathology confirmed MTC stage T1b. The one and three months postoperative follow up showed a significant downtrend with no normalization of Ct and CEA levels, 9.1 – 9.2 and 11.1 – 1.2, respectively. Reoperation for central and lateral neck dissection was considered; however, given the excellent biochemical response as well as the lack of radiographic evidence of disease, it was decided to continue monitoring of Ct and CEA levels for now.
MTC response is monitored by the postoperative serum Ct and CEA levels when compared to the preoperative values. Serum Ct serves as a sensitive tumor marker, which is thought to have correlation with malignancy mass size and its cellular differentiation. The term biochemically cured, refers to the postoperative normalization of CEA and undetectable levels of Ct which carries a 5-year recurrence of 5%. It is believed that the higher the levels and the faster doubling time of these tumor markers the worse is the prognosis. In addition, it is suggested that patient’s age and extent of disease at the time of surgery are proportionally correlated with disease recurrence. However, there are reports of large MTC metastatic deposits with low serum Ct and CEA, rising up the hypothesis that levels reflect cell production potential for tumor markers rather than the number of cells. Reoperation rarely results in biochemical cure, but it may slow disease progression. Normal postoperative Ct levels predict cure; however, the clinical course of those with upper normal limit levels postoperatively is markedly variable. Careful regular biochemical and imaging follow-up will be of the utmost importance for the patient presented in this case.