bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malignancy Risk in 18F-FDG-Avid Thyroid Incidentalomas: Controversies and Limitations
Authors: Bukhari Khulood , Haleem Zarah , Munir Kashif 
Published: May 2021

Abstract
Introduction: The prevalence of malignancy in thyroid incidentalomas (TI) discovered on 18F-FDG-PET or PET/CT varies between 0% and 63.6%. The pooled malignancy rate according to three systematic reviews is 33-35%. The 2015 American Thyroid Association (ATA) guidelines recommend that such nodules, when one centimeter or larger in size, should undergo further investigation with thyroid ultrasound (US) and fine-needle aspiration (FNA) cytology. Objectives: The objective of our study was to determine the rate of malignancy amongst TI discovered incidentally on 18F-FDG-PET or PET/CT, examine their clinicopathologic characteristics, and assess the usefulness of maximum standardized uptake values (SUVmax) in differentiating benign and malignant lesions. Methods: We performed an electronic medical record search looking at all 18F-FDG-PET or PET/CT reports during the study period of 12/01/2015 to 05/31/2019 that included the keyword ‘thyroid’ in the impression. Exclusion criteria included a history of thyroid disease or malignancy, known lesion(s) detected on previous clinical or radiological examinations and diffuse radiotracer uptake. Of the 476 reports reviewed, 136 cases were included in the study. Results: Common indications included initial staging or restaging of lymphoma (diffuse large B-cell, mantle-cell, T-cell types) (27.9%), lung adenocarcinoma (18.4%), head and neck cancer (16.9%) and breast cancer (11%). Fifty-eight (42.6%) patients had metabolically inactive lesions; five (8.6%) underwent further investigation with thyroid US and 3 subsequently with FNA (5%). All 3 had benign cytology. Seventy-seven (56.6%) patients had metabolically active lesions and 25 (32.5%) underwent imaging with thyroid US. Twelve (15.6%) had FNA; eight (66.7%) had benign cytology, two (16.7%) revealed atypia of undetermined significance and two (16.7%) were malignant. Biopsy for the two patients with malignant cytology showed follicular cell neoplasm of oncocytic hurtle cell type, and invasive follicular carcinoma with focal insular and papillary features and extensive capsular and vascular invasion. The mean SUVmax in malignant vs benign lesions was 9.05 and 6.41 respectively. Conclusion: The malignancy rate was 2.6% amongst all patients with 18F-FDG-avid TI and 8% amongst patients with metabolically active lesions who were investigated with thyroid US+/- FNA. This is significantly lower than malignancy rates previously reported in the literature. The evident inhomogeneity in the literature is likely multifactorial and may be explained in part by a dissimilarity among studies, and an informed decision by some to avoid invasive testing in the context of poor prognosis from underlying non-thyroidal cancer. Research is needed to determine the cohort of patients who could potentially benefit from further evaluation and treatment.
The Influence of Incidental Detection of Thyroid Nodule on Thyroid Cancer Risk and Prognosis - a Systematic Review
Authors: Chooi Je Ern , Ravindiran Abiramie , Balasubramanian Saba P 
Published: May 2021

Abstract
Clinically unapparent thyroid nodules discovered serendipitously on imaging for non-thyroid indications are termed ‘thyroid incidentalomas’. The increase in the detection of these incidentalomas (which are known to be very common) has been attributed to the widespread use of diagnostic imaging and the increase in sensitivity and resolution of these modalities. It is unclear whether these incidentalomas have a lower prevalence of thyroid cancer or slower tumour progression compared to symptomatic thyroid nodules. This systematic review aimed to determine the risk of malignancy in incidentally detected thyroid nodules and its impact on prognosis in patients with thyroid cancer. PubMed and MEDLINE® on Web of Science databases were searched from inception to March 2020 for English language articles reporting on human studies of thyroid cancer risk and/or prognosis in incidental and non-incidental nodules. Quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). Seventeen observational studies published between 1998 and 2018 were eligible for analysis; 4 studies reported on risk, 8 studies on prognosis and 5 studies on both risk and prognosis. In the risk review, the odds ratios calculated from the six case-control studies (3246 patients) ranged from 0.64 to 2.86 whilst the relative risks calculated from the three cohort studies (489 patients) ranged from 0.13 to 6.27. NOS score for included risk studies (n=9) ranged from 22.2% to 66.7%. A meta-analysis of the eligible case-control studies (n=3) showed a non-significant summated odds ratio of 1.04 (95% CI=0.63-1.70, p=0.88). In the prognosis review of thirteen studies, three direct and thirteen indirect markers of prognosis were compared between the incidental (1923 patients) and non-incidental (2639 patients) groups. NOS score for included prognosis studies ranged from 66.7% to 100%. Incidentally detected thyroid nodules were significantly more likely to be smaller, have lower rates of extra-thyroidal and extra-nodal extension and lymph node metastasis, and interestingly more likely to have advanced disease. Other indirect prognostic markers were not shown to be significantly different between the two groups. A meta-analysis was not possible but incidentally detected thyroid cancer had better progression-free and overall survival; this finding may be affected by ‘lead time’ bias. Current evidence suggests that the investigation and management of thyroid nodules should not be influenced by the mode of detection.
Ultrasound Guided Percutaneous Ethanol Ablation of Benign Thyroid Nodule: A Study From a Tertiary Hospital in Eastern India
Authors: Baidya Arjun , Faiz Saba , Bhadra Ram Chandra 
Published: May 2021

Abstract
Introduction: Ultrasound guided percutaneous ethanol injection (PEI) of benign thyroid nodule is an easy and effective procedure particularly in cystic and predominantly cystic nodule. Aims: To evaluate efficacy and safety of PEI in managing purely cystic and mixed cystic and solid thyroid nodules. Materials and Methods: Patients of either sex presented with solitary purely cystic benign thyroid nodule, solitary benign mixed with predominantly cystic (&gt;50% of total volume) thyroid nodule, solitary benign mixed with predominantly solid (&gt;50% of total volume) thyroid nodule, solitary solid thyroid nodule were included in this study. Patients who had a nodule BETHESDA 3 and above, pregnancy, patients with critical or terminal illness, patients with other malignancies, multinodular lesions of thyroid, patients with raised T3, T4 and/ or suppressed TSH level were excluded from the study. One hundred sixty patients presenting with thyroid nodule were initially evaluated with thyroid function test and USG. Only those patients with euthyroid solitary thyroid nodules are subjected for fine needle aspiration (FNA). Nodules under BETHESDA 2 are considered for US guided percutaneous ethanol injection (PEI). One hundred twenty-three patients were excluded because of various reasons. Finally ethanol ablation was done in 37 patients. Benign, purely cystic and mixed thyroid nodules were aspirated under ultrasonography guidance. Sterile absolute alcohol (99.99%) (50% of volume aspirated/ maximum 10 ml) was injected and reviewed after 2, 5and 7 months. In case of solid nodule alcohol (50% of nodule volume) was injected. A reduction in volume is calculated at each follow up visit. An adequate response is considered as ≥50 percent reduction in size from baseline after 7 months. If the reduction is &lt;50%, then a second session of absolute ethanol injection is given. Again, patients were similarly followed up after 2, 5 and 7 months. Results: Thirty seven patients underwent PEI. Thirty three patients were considered for final analysis (4 lost to follow up). Response rate of PEI for purely cystic nodule was 100.0% and the overall response rate for mixed nodule was 53.57%. None of the solid nodule responded to PEI even after second session. Among the responder in the mixed nodules, 93.33% responded after first session of PEI. Minor complications like headache occurred in 54.1% patients in the first session. Transient pain at injection site were complained by 86.5% and 37.8% patients in the first and second session respectively. Nausea and vomiting were complained by 18.9% and 16.2% patients in the first and second session respectively.
Conclusions: PEI is an effective and safe for purely cystic and mixed thyroid nodules. It is a relatively safe and less invasive procedure from management of benign solitary cystic and mixed thyroid nodules.
A Tale of Three Cases When Thyroid Cancer Does Not Exist but Metastases Do. A Three-Case Series of Metastatic Follicular Thyroid Carcinoma
Authors: Ziganshina Anna , Brar Rupinder Kaur , Amin Ami , Jennings Timothy , Shawa Hassan 
Published: May 2021

Abstract
Background: Follicular and papillary thyroid carcinomas represent the majority of all malignancies of the thyroid gland. However, follicular thyroid carcinoma (FTC) is much more difficult to diagnose and manage than its papillary counterpart. Among other factors this could be explained by changing diagnostic criteria and by FTC potential for remote distant and often unpredictable metastases sites. Clinical Cases: In our high volume major academic referral center we have encountered three intriguing cases of metastatic FTC with negative surgical thyroid pathology. The first patient is a 61-year-old woman, who at age 50 was diagnosed with 5.4x3.5x4.2 cm left thyroid nodule (TN). FNAB reported hyperplastic nodule versus follicular neoplasm, subsequent surgical pathology report after lobectomy showed hyperplastic nodule. At age 58 she developed a pathological fracture of the 5th thoracic vertebra and pathology report indicated follicular carcinoma of thyroid origin. TG level at this time was 577 ng/ml. Pathology report from completion thyroidectomy again showed nodular hyperplasia, but reexamination of previously resected lobe demonstrated minimally invasive FTC. The second patient is an 83-year-old woman who at age 68 underwent lobectomy for left sided-goiter, pathology report showed benign follicular adenoma. At age 77 she was found to have right-sided skull mass which was determined to be a follicular carcinoma of thyroid origin. Pathology report from completion thyroidectomy was consistent with nodular hyperplasia. At age 82 the patient was noticed to have increased RAI uptake in thyroid bed, sternum, kidneys, and gastroesophageal junction. TG level at this time was 2214 ng/ml. The third patient is a 56-year-old woman initially diagnosed with a 3.5x2.8x2.2cm right TN at age 53. Lobectomy, performed for diagnostic and therapeutic purposes, showed benign follicular adenoma. At age 56 she developed a pathological fracture of the 3rd thoracic vertebra, follicular carcinoma of thyroid origin was shown on pathology report. TG level at this time was 1694 ng/ml. The patient underwent completion thyroidectomy demonstrating multinodular hyperplasia. Conclusion: This case series emphasizes on the pitfalls of follicular neoplasms diagnosis and management. We suggest prolonged clinical and biochemical surveillance of the patients with what appears to be follicular adenoma after lobectomy. Following serum thyroglobulin perhaps represents the most cost-effective surveillance approach of those patients.
Most True Adrenal Incidentalomas Lack Proper Evaluation
Authors: Bell Caitlin , Vinovskis Carissa , Kiseljak-Vassiliades Katja , Wierman Margaret E , Fishbein Lauren Michelle 
Published: May 2021

Abstract
Although the majority of true adrenal incidentalomas are benign and non-functional, appropriate workup is critical to rule out cancers as well as metabolic and cardiovascular diseases such as Cushing’s syndrome, primary aldosteronism (PA), and pheochromocytoma (PCC). The AACE/AAES and ENSAT guidelines recommend that all adrenal incidentalomas be evaluated for worrisome radiographic features and that all patients have initial biochemical work up to evaluate for hypercortisolism and pheochromocytoma as well as primary aldosteronism if hypertensive. Despite this, adrenal incidentalomas often are not evaluated properly leading to delayed diagnoses and potential complications from dysregulated hormone production. To determine if true adrenal incidentalomas are managed properly in our hospital system, we conducted a retrospective chart review. All CT scans (chest or abdomen) of adult patients conducted at the University of Colorado Hospital system between August 2011 and December 2016 were assessed (N=86,771). Of these, 305 scans identified true adrenal incidentalomas. CT scans done for patients with genetic conditions predisposing to adrenal nodules or done for an indication suggestive of adrenal disorder were excluded. From the 305 patient scans, 347 adrenal nodules were identified. Most patients (N=263, 86%) had one adrenal nodule; 42 (14%) had multiple nodules. Mean age of the cohort was 60±12.58 years old (range 21–88), and the majority were female (60.7%). The nodules had a mean size of 2.23±1.42 cm, range 0.5–11.2 cm. Most nodules were identified on CT scans with contrast (79%, N=241). Of the 64 scans (21%) done without contrast, 43% of the nodules had non-contrast enhanced (NCE) Hounsfield units (HU) less than 10, suggesting benign adenomas. Thirty-nine nodules (57%) had NCE HU greater than 10; eight of those were surgically removed (4 metastases from other primary cancers; 2 PCC; 2 lipid poor adrenal cortical adenomas). Most nodules were not biochemically evaluated. Only 64 of the 305 patients (21%) were tested for hypercortisolism (1mg ODST in 35; 24hr UFC in 29). Of those, three (0.1%) were diagnosed with Cushing’s syndrome. Only 82 patients (27%) were evaluated for PCC with plasma and/or 24hr urine metanephrines. Of these, 10 were diagnosed with PCC (3.3%). Only 24 patients (7.9%) were screened for PA with serum aldosterone and plasma renin activity, and four (1.3%) were positive. Taken together, of the 305 patients with adrenal incidentalomas, only 29 (9.5%) met guideline recommendations for biochemical work up for both hypercortisolism and PCC. Of those, 10 had a history of hypertension, yet only 5 were evaluated for PA. In summary, less than 10% of true adrenal incidentalomas had the proper biochemical evaluation. This suggests there are likely missed functional nodules leading to delayed or missed diagnosis possibly contributing to cardiovascular and metabolic consequences.
Birt Hogg Dube Syndrome and Thyroid Cancer - Is There an Association?
Authors: Hehar Jaspreet , Bhan Arti 
Published: May 2021

Abstract
A 71-year-old man presented for evaluation of thyroid nodules. Past medical history includes auricular trichodiscoma/fibrofolliculomas and colon cancer at age 39. He underwent genetic testing revealing mutations of the CHEK2 and FLCN gene, conferring a diagnosis of Birt-Hogg-Dube syndrome (BHD). Subsequently, several family members were diagnosed with this syndrome. He was initially seen for evaluation of chronic cough. A neck ultrasound showed suspicious thyroid nodules and fine needle aspiration revealed suspicion for papillary thyroid cancer. He had molecular testing by AFIRMA and was GSC negative. He underwent right hemithyroidectomy and then completion with findings of a right lobe follicular thyroid carcinoma. Given underlying history of BHD, genetic testing was performed to assess for additional mutations that could predispose to thyroid cancer. This may help to raise awareness of screening for the presence of thyroid nodules and possibly thyroid carcinoma in individuals with BHD. Birt-Hogg-Dube (BHD) syndrome is a rare, autosomal dominant syndrome caused by a germline mutation in the FLCN gene, and is characterized by the presence of fibrofolliculomas, pneumothorax, and renal tumors. Thyroid nodules have been associated with BHD, present in 65% of individuals and 90% of families with this syndrome, however connection between BHD and thyroid cancer has not been established. For our patient, the most significant finding after a 170-gene panel analysis was an NRAS Q61R mutation. Mutations in RAS genes may be found in 15-20% of papillary thyroid cancers, 40-50% of follicular cancers, and 20-40% in follicular adenomas, and indicate poor prognosis. A CHEK2 mutation was also identified, which has been associated with an increased risk of multiple cancers, including thyroid. In addition, he had coding variants in the ATR gene on chromosome 3, as well as the IDH2 gene on chromosome 13. IDH2 may have a role in the development of thyroid cancer, however the contribution of these variants to tumor development or progression is currently unknown. For our patient, there is no published data to our knowledge regarding the findings of his coding variants and their possible association to BHD syndrome. More research needs to be done to assess for additional mutational variations present in those with BHD syndrome that may predispose to the development of thyroid cancer. Hara, H et al. “N-ras mutation: an independent prognostic factor for aggressiveness of papillary thyroid carcinoma.” Surgery vol. 116,6 (1994): 1010-6.
Dabrafenib Induced Pancreatitis: A Rare Event During RAI- Refractory Treatment of Metastatic Papillary Thyroid Cancer
Authors: Edwards Khary , McFadden David , Agosto Salgado Sarimar N 
Published: May 2021

Abstract
Dabrafenib, a BRAF selective tyrosine kinase inhibitor (TKI) has been associated with pancreatitis alone, and in combination with trametinib (a MEK pathway inhibitor). We report a case of dabrafenib induced acute pancreatitis in a patient undergoing treatment for metastatic papillary thyroid cancer (PTC). This adverse event has not been previously reported in thyroid cancer patients using dabrafenib. Case: A 61-year-old female with papillary thyroid cancer status post total thyroidectomy with pathology revealing right 7.6cm PTC with extrathyroidal extension and 13/72 metastatic lymph nodes. She received 100mCi of radioactive iodine (RAI). Ten months post-surgery, she underwent revision neck dissection with 3/36 nodes positive for metastatic disease and neck muscle invasion by PTC. Molecular testing demonstrated AKT1 and BRAFV600E mutations. Due to progressive neck and mediastinal tumors, recommendation was to proceed with systemic therapy. Initially started dabrafenib monotherapy; after 3 doses patient developed burning epigastric pain and fever. Examination revealed abdominal tenderness, elevated lipase at 2266 U/L (8-76U/L), mild hyperbilirubinemia and leukocytosis. CT abdomen/pelvis revealed peripancreatic fat stranding consistent with focal acute pancreatitis. No history of alcohol use. Dabrafenib was assessed to be culprit of pancreatitis; with immediate discontinuation of TKI and supportive management patient improved. At present patient is tolerating Lenvatinib therapy. BRAFV600E mutation occurs in 29-83% of thyroid cancers affecting growth, proliferation, survival, migration, and loss of tissue-specific differentiation via the intracellular MEK/ERK pathway1. RAI offers an important treatment modality for thyroid cancer patients, however patients with BRAFV600E are often poor responders or refractory to RAI1. Dabrafenib, a specific BRAFV600E tyrosine kinase inhibitor in combination with trametinib (a MEK inhibitor) is FDA approved for treatment BRAFV600E mutated anaplastic thyroid cancer; furthermore there is evidence on PTC responses including redifferentiation 2. Pancreatitis has been reported in &lt;1% of dabrafenib treated patients as monotherapy and in combination with trametinib in unresectable or metastatic melanoma clinical trials. It was reported in 4% of patients in a NSCLC when used in combination with trametinib. Recurrent pancreatitis when dabrafenib was re-introduced at a lower dose has also been reported3. Furthermore, it was the cause of pancreatitis in a patient with metastatic melanoma 4 months into the treatment in combination with trametinib4. As this treatment option becomes increasingly utilized for metastatic or locally advanced anaplastic/papillary thyroid cancers, endocrinologists should be aware of the potential for dabrafenib induced pancreatitis during monotherapy use or in combination with trametinib.
Glioblastoma Multiforme and Papillary Thyroid Carcinoma: Rare Combination of Primary Malignancies
Authors: Katkar Rujuta Baban , Vaddepally Raju 
Published: May 2021

Abstract
Introduction: Studies have reported thyroid cancer patients are potentially at 30% increased risk of getting second primary cancer when compared to the general population. We are describing a young Caucasian male patient who was diagnosed with two synchronous cancers, papillary thyroid cancer (PTC) and glioblastoma multiforme (GBM). Case Report: A 52 year old Caucasian male with past medical history of hypertension, partial right thyroidectomy in 1999 for thyroid nodular disease, and postsurgical hypothyroidism on levothyroxine. He underwent FNA of left thyroid nodule found on routine monitoring of thyroid nodules showed to be suspicious for malignancy. He underwent left hemi-thyroidectomy in July 2019, revealing PTC, follicular variant, encapsulated, noninvasive type measuring 0.9 x 0.9 x 0.5 cm, completely excised with negative margins; reminder of the right hemi-thyroidectomy performed in February 2020, revealing cystic adenomatoid nodule and no evidence of malignancy. Postoperative thyroglobulin and thyroglobulin antibodies levels were undetectable. A diagnostic whole body iodine scan didn’t show metastasis hence Iodine-131 treatment was not warranted. A week following the right hemi-thyroidectomy he presents to the ER with apraxia, difficulty with concentration, visual difficulty, headaches. CT scan of the brain revealed left occipital region revealed a 3.7 x 2.3 cm lesion concerning for malignancy. A follow up contrast-enhanced MRI brain showing multiple ring-enhancing lesions identified within the left posterior occipital lobe measuring 1.7 x 1.8 cm, additional occipital lobe lesion measuring 2.7 cm, mid and posterior parietal lobe measuring 3.0 cm extending to collateral sulcus measuring 2 x 3 x 1.9 cm compressing the posterior horn of left lateral ventricle. Patient underwent suboccipital craniotomy, pathology revealing glioblastoma NOS, WHO grade IV; further biomarker analysis was not available. CT of the chest, abdomen, pelvis showed no evidence of metastatic disease. Postoperative MRI of the brain revealed postoperative changes with resection of the left occipital portion of the lesion with additional enhancing regions in the left parietal and temporal lobes and splenium unchanged. Patient underwent concurrent, definitive chemo-radiation with temozolomide, now on maintenance temozolomide and levothyroxine. Conclusion: PTC is the most common thyroid malignancy, affecting young patients less than 45 years old. GBM can occur in people of any age, but they are more frequent in older adults. Physicians should maintain high surveillance for second primary cancers at a variety of sites in patients who have been found or treated for primary cancers, especially at a young age. Further evaluation of genetic and environmental factors between papillary thyroid cancer and glioblastoma multiforme will improve our understanding of the etiology of these malignancies.