Hürthle Cell Carcinoma Research Articles

Evaluation of the etiological factors of thyroid gland neoplasms: our clinical experience

Objective: Thyroid cancer (TC), the most common endocrine malignancy worldwide, has a 10-year survival rate of more than 90% and a better prognosis than other malignancies. However, there are still conflicting data on the stimulators of cancer development, and benign thyroid diseases, such as goiter, benign thyroid nodules, Graves’ disease, chronic thyroiditis, breast cancer and various factors including age, gender, consumption of vegetables, fiber food, hypercaloric diet, and tobacco and alcohol use are considered to be responsible. In this study, we aimed to evaluate patients with thyroid neoplasms who underwent surgical treatment in terms of etiological factors discussed in light of the literature.
 Material and Method: In our study, patients who underwent surgery with the diagnosis of thyroid gland neoplasms between 2010 and 2020 were evaluated. A total of 371 patients were included in the study. Statistical analyses were performed using IBM SPSS Statistics v. 22.
 Results: Of the 371 cases included in the study, 78.16% were female and 21.83% were male. The histopathological distribution of diagnoses was as follows: 76.28% papillary thyroid carcinoma (PTC), 4.31% follicular thyroid carcinoma (FTC), 14.29% follicular adenoma (FA), 0.54% Hurthle cell carcinoma (HCC), 3.77% Hurthle cell adenoma (HCA), and 8.08% medullary thyroid carcinoma (MTC). A total of 567 etiological factors were detected in 371 cases, and the highest factors ratio (1.94) being detected in the FTC group and the lowest (1.49) in the FA group. The most common of these factors was chronic lymphocytic thyroiditis (CLT) (35.31%). While the most common etiological factor in the PTC diagnosis group was thyroid and other non-breast cancers and the history of radiotherapy resulting from their treatment, it was a family history of thyroid cancer in the HCA group. Other systematic organ diseases, CLT, and breast cancer were the most common factors. The body mass index was the highest in the MTC group and the lowest in the PTC group.
 Conclusion: Increased human development index, technological developments, greater accessibility of ultrasonography, and better diagnostic sensitivity have led to an increase in the detection of TC. Knowledge of the underlying etiological factors is important for the development of preventive measures and achieving more successful results in terms of diagnosis and treatment.

Mitonuclear Genotype Remodels the Metabolic and Microenvironmental Landscape of Hurthle Cell Carcinoma

Mitonuclear Genotype Remodels the Metabolic and Microenvironmental Landscape of Hurthle Cell Carcinoma

Nomogram Using Host and Tumor Factors to Predict Survival in Individual Patients with Well Differentiated Thyroid Cancer

<h3>Purpose/Objective(s)</h3> Patients with well-differentiated thyroid cancer generally have an excellent outcome. Nonetheless, a subset of patients will do poorly. Traditionally, the TNM system is used to counsel patients on probability of survival. However, this system applies to a population rather than individual patients. In contrast, nomograms utilize several variables to determine outcome in individual patients. The objective of our study was to use tumor and host factors in patients with well differentiated thyroid cancer to develop a nomogram predictive of disease-specific survival (DSS). This would lead to a better guided and personalized assessment of patient's treatment and follow up and would allow us to better counsel patients moving forward. <h3>Materials/Methods</h3> From our departmental thyroid database of 6,259 patients treated with surgery from 1986 to 2015, we excluded patients with incomplete staging data (n=15). Our final cohort consisted in 6,244 patients. Tumor and host variables predictive of survival were identified and used to design a nomogram for DSS. The previously published pretreatment peripheral blood H-index (([Neutrophils x Monocytes]/[Lymphocytes x Hemoglobin X Albumin]) x 100) was used as the surrogate marker for the host status. Multiple imputation was implemented on missing data of the peripheral blood variables. Unadjusted and adjusted HRs were calculated using the Cox proportional hazard model for DSS. A p-value <0.05 was considered significant. Nomograms predictive of 5, 10, 15 and 20-year DSS were created from the model. Statistical analysis was performed using the R software package (http://www.r-project.org). <h3>Results</h3> Median age was 47.4 years (IQR 37.1-58.0), 72% were female. Most cases were Papillary Carcinomas (95.4%), and 2.4% Follicular Carcinomas and 2.2% Hurthle Cell Carcinomas. Following AJCC 8^th Edition, 88.0% were Tx/T1/T2, 68.9% were Nx/N0, and 98.7% M0. H-index values ranged from 0.04 to 18.38 (median 1.17, IQR 0.79-1.75). Increased age, non-papillary carcinoma pathologies, higher TNM, and higher H-index were significantly associated with worse DSS in the multivariable analysis. Based on this model, predictive nomograms were created. Age and distant metastasis were the variables that conferred a higher score in the nomogram and therefore the ones associated with poorer outcomes. H-index incorporated additional stratification of patient's risk by adding information about the host to the generally used tumor factors. <h3>Conclusion</h3> Using tumor and host factors, we have created a nomogram which predicts survival in individual patients with well differentiated thyroid cancer. By having a more precise prediction of each patient's outcomes we can better guide treatment, follow up and counseling.

Neoadjuvant tyrosine kinase inhibitor therapy in locally advanced differentiated thyroid cancer: a series

IntroductionLocally advanced differentiated thyroid cancer (LADTC) management depends on a complex interplay of patient and tumour factors. When primary resection cannot be achieved, neoadjuvant tyrosine kinase inhibitor (TKI) therapy can be considered, but little evidence is available on its success and outcomes. Our aim was to describe a small series of LADTC managed with neoadjuvant TKI therapy.MethodsSuitable patients were prospectively identified in NHS Lothian February 2016 – March 2020.ResultsFour patients were eligible for inclusion, 3 females; 1 male, aged 39–79 years. All were T4a at presentation; three papillary and one Hurthle cell carcinoma. One had pulmonary metastases. Two refused laryngectomy, one was deemed unresectable with extensive tracheal involvement, and one commenced TKI due to COVID-19 related surgical delay. TKI treatment length varied from 1–18 months. There was a marked reduction in tumour volume and local extent in three cases, such that surgical resection without laryngectomy could be achieved. The fourth patient was intolerant of TKI. All ceased TKIs 2 weeks prior to total thyroidectomy, with neck dissection in three, and tracheal resection and re-anastomosis in two. All then had 3700MBq RAI and all patients are currently alive with 14–58 months follow-up. Two patients have no evidence of residual or recurrent disease. The M1 patient has stable low-volume local and distant disease, and one patient has stable low volume indeterminate pulmonary nodules.ConclusionNeoadjuvant TKI therapy in LADTC can be effective in reducing primary tumour extent to potentially facilitate limited surgical resection in a highly selected patient group.

Targeting the mTOR Pathway in Hurthle Cell Carcinoma Results in Potent Antitumor Activity.

Hurthle cell carcinomas (HCCs) are refractory to radioactive iodine and unresponsive to chemotherapeutic agents, with a fatality rate that is the highest among all types of thyroid cancer after anaplastic thyroid cancer. Our previous study on the genomic landscape of HCCs identified a high incidence of disruptions of mTOR pathway effectors. Here, we report a detailed analysis of mTOR signaling in cell line and patient-derived xenograft mouse models of HCCs. We show that mTOR signaling is upregulated and that targeting mTOR signaling using mTOR inhibitors suppresses tumor growth in primary tumors and distant metastasis. Mechanistically, ablation of mTOR signaling impaired the expression of p-S6 and cyclin A2, resulting in the decrease of the S phase and blocking of cancer cell proliferation. Strikingly, mTOR inhibitor treatment significantly reduced lung metastatic lesions, with the decreased expression of Snail in xenograft tumors. Our data demonstrate that mTOR pathway blockade represents a novel treatment strategy for HCC.

Follicular and Hurthle Cell Carcinoma: Comparison of Clinicopathological Features and Clinical Outcomes.

Background: Follicular thyroid carcinoma (FTC) and Hurthle cell carcinoma (HCC) are rare and aggressive thyroid cancers with limited published data comparing their outcomes or regarding their subtypes. The aim of this study was to describe clinicopathological features and compare clinical outcomes of patients with FTC and HCC based on the 2017 World Health Organization definition and extent of vascular invasion (VI). Methods: We retrospectively studied 190 patients with HCC and FTC primarily treated with surgery at Memorial Sloan Kettering Cancer Center between 1986 and 2015. Patients were classified as minimally invasive (MI), encapsulated angioinvasive with focal VI (EA-FVI), encapsulated angioinvasive with extensive VI (EA-EVI), and as widely invasive (WI). To compare clinical outcomes, patients were grouped as follows: group 1 = FTC-MI and FTC EA-FVI, group 2 = FTC EA-EVI and FTC-WI, group 3 = HCC-MI and HCC EA-FVI, group 4 = HCC EA-EVI and HCC-WI. Outcomes of interest were overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), locoregional recurrence-free survival (LRRFS), and distant recurrence-free survival (DRFS). Outcomes were determined using the Kaplan-Meier method and compared with log-rank test. Results: Patients with HCC (n = 111) were more likely to be older than 55 years old (59% vs. 27%, p < 0.001) with a tendency to present with more extensive VI (33% vs. 19%, p = 0.07) compared with FTC (n = 79). Comparing groups 1, 2, 3, and 4, group 4 patients were more likely to recur (DFS 98%, 93%, 98% vs. 73%, respectively, p = 0.0069). There was no statistically significant difference in OS, DSS LRRFS, or DRFS. Stratified by extent of VI (no, focal, and extensive VI), patients with extensive VI were more likely to recur (RFS 100%, 95%, 77%, p = 0.0025) and had poorer distant control (DRFS: 100%, 95%, 80%, p = 0.022), compared with patients absent or focal VI. Conclusions: Accurate assessment of the extent of VI and tumor phenotype (follicular vs. Hurthle) are essential in identifying patients at higher risk of recurrence.

The differences in distant metastatic patterns and their corresponding survival between thyroid cancer subtypes.

This study aimed to systematically elucidate the metastatic patterns and their corresponding survival of each thyroid cancer subtype at time of diagnosis. We accessed the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2018 to search for primary thyroid cancers with DM at presentation (M1). We included 2787 M1 thyroid cancers for statistical analyses and the incidence of DM at presentation was 2.4%. Lung was the most common metastatic site for anaplastic thyroid carcinoma (ATC), poorly differentiated thyroid carcinoma (PDTC), papillary thyroid carcinoma (PTC), and oncocytic (Hurthle) cell carcinoma (HCC) whereas bone is the favorable disseminated site of follicular thyroid carcinoma (FTC) and medullary thyroid carcinoma (MTC). Patients with multi-organ metastases had the worst survival whereas bone metastases were associated with a favorable outcome (p< 0.001). There are significant differences in DM patterns of thyroid cancer subtypes and their corresponding survival.

Comparative Analysis About Clinical Manifestation and Prognostic Factors of Thyroid Follicular and Hurthle Cell Carcinoma

Background and Objectives Follicular thyroid carcinoma (FTC) is the second common thyroid cancer which comprises about 10% of differentiated thyroid carcinoma. Hurthle cell carcinoma (HCC) is a relatively rare disease that has been classified as a subtype of FTC. However, there have been insufficient reports about these two similar thyroid cancers in South Korea due to low incidences. This study aims to present clinical features and evaluate prognostic factors of FTC and HCC.Subjects and Method We reviewed data of 189 FTC and 12 HCC patients who underwent surgery in our center from January 2000 to December 2020. Variables such as clinical characteristics, surgical method, pathologic result, post-operative treatment, survival rate and prognostic factors were included in our study.Results As for age, 67.2% of patients in FTC group and 33.3% of patients in HCC group were older than 55 years-old (&lt;i&gt;p&lt;/i&gt;=0.017). The average tumor sizes of FTC and HCC were 2.98 and 3.1 cm, respectively. The 10-year overall survival rates of FTC and HCC were 96.5% and 100%, respectively. The 10-year disease free survival rates of FTC and HCC were 89.1% and 91.7%, respectively. Subclassification (widely invasive: &lt;i&gt;p&lt;/i&gt;=0.036) and initial distant metastasis (&lt;i&gt;p&lt;/i&gt;&lt;0.001) were significant prognostic factors in FTC.Conclusion This study will be helpful for diagnosis and treatment of FTC and HCC, which are relatively rare.

What&amp;apos;s New in Molecular Targeted Therapies for Thyroid Cancer?

Thyroid cancer refers to various cancers arising from thyroid gland. Differentiated thyroid cancers (DTCs) include papillary, follicular, and Hurthle cell carcinomas and represent cancers retain normal thyroid functions such as iodine uptake. Radioactive iodine (RAI) is generally used for upfront treatment of metastatic DTCs, but RAI refractory DTCs remain to be clinical challenges. Sorafenib and lenvatinib were approved for the treatment of RAI refractory DTCs and more recently, genomics-based targeted therapies have been developed for NTRK and RET gene fusion-positive DTCs. Poorly differentiated and anaplastic thyroid cancers (ATCs) are extremely challenging diseases with aggressive courses. BRAF/MEK inhibition has been proven to be highly effective in BRAF V600E mutation-positive ATCs and immune checkpoint inhibitors have shown promising activities. Medullary thyroid cancers, which arise from parafollicular cells of thyroid, represent a unique subset of thyroid cancer and mainly driven by RET mutation. In addition to vandetanib and cabozantinib, highly specific RET inhibitors such as selpercatinib and pralsetinib have demonstrated impressive activity and are in clinical use.

Using Deep Convolutional Neural Networks for Enhanced Ultrasonographic Image Diagnosis of Differentiated Thyroid Cancer.

Differentiated thyroid cancer (DTC) from follicular epithelial cells is the most common form of thyroid cancer. Beyond the common papillary thyroid carcinoma (PTC), there are a number of rare but difficult-to-diagnose pathological classifications, such as follicular thyroid carcinoma (FTC). We employed deep convolutional neural networks (CNNs) to facilitate the clinical diagnosis of differentiated thyroid cancers. An image dataset with thyroid ultrasound images of 421 DTCs and 391 benign patients was collected. Three CNNs (InceptionV3, ResNet101, and VGG19) were retrained and tested after undergoing transfer learning to classify malignant and benign thyroid tumors. The enrolled cases were classified as PTC, FTC, follicular variant of PTC (FVPTC), Hürthle cell carcinoma (HCC), or benign. The accuracy of the CNNs was as follows: InceptionV3 (76.5%), ResNet101 (77.6%), and VGG19 (76.1%). The sensitivity was as follows: InceptionV3 (83.7%), ResNet101 (72.5%), and VGG19 (66.2%). The specificity was as follows: InceptionV3 (83.7%), ResNet101 (81.4%), and VGG19 (76.9%). The area under the curve was as follows: Incep-tionV3 (0.82), ResNet101 (0.83), and VGG19 (0.83). A comparison between performance of physicians and CNNs was assessed and showed significantly better outcomes in the latter. Our results demonstrate that retrained deep CNNs can enhance diagnostic accuracy in most DTCs, including follicular cancers.

CLINICOPATHOLOGICAL CHARACTERISTICS AND TREATMENT OUTCOME OF PATIENTS WITH METASTATIC DIFFERENTIATED THYROID CANCER

OBJECTIVE: To assess the clinicopathological characteristics and treatment outcomes of metastatic differentiated thyroid cancer (DTC) in our population. METHODS: In this retrospective, real world, single centered study was carried out at Aga Khan University Hospital, Karachi, Pakistan. Data from December 2020 to January 2000 was retrieved about 117 patients with metastatic DTC regarding age at diagnosis, gender, tumor size, extent &amp; spread of tumor and its histological characteristic. The treatment they received and the outcome in terms of status at last follow up was also recorded. RESULTS: Mean age at diagnosis was 46.6±17.2 years with equal male to female ratio (1:1). Most common site of metastasis was lung (n=15; 12.8%) followed by bone (n=11; 9.4%). Papillary carcinoma was the most common subtype (n=105; 89.7%) followed by follicular carcinoma occurring (n=9; 7.7%), hurthle cell carcinoma (n=2; 1.7%) and diffuse sclerosing variant carcinoma (n=1; 0.9%). Tumor size was &lt;4 cm in 54 (46.2%) patients and ≥4 cm in 63 (53.8%) patients. Cervical metastasis was found in 85 (72.6%) patients while extra thyroidal extensions outside the thyroid bed into the surrounding structures was present in 64 (54.7%) patients. The overall survival was 5.6±2.6 years. Ninety-six percent had complete surgical resection followed by radioactive iodine in 107 (91.5%) patients with 65 being given a dose of 150 mCi, 38 given a dose of 100 mCi and 4 given a dose of 50 mCi. CONCLUSION: Most significant factors in predicting outcome in metastatic DTC are age, extra thyroidal extension of primary tumor and distant metastasis.

Large thyroid nodules: should size alone matter?

The management of thyroid nodules ≥ 4cm is controversial due to conflicting evidence on the prevalence of malignancy and diagnostic accuracy of fine-needle aspiration cytology (FNAC). Some literature recommends routine excision of large thyroid nodules due to high cytology false negative rates (FNR). We aim to investigate the diagnostic accuracy of FNAC, prevalence of malignancy in large (≥ 4cm) thyroid nodules compared to nodules < 4cm, and the clinical and ultrasound characteristics of those large nodules with false negative cytology. This was a retrospective case-log review in a tertiary referral hospital. All thyroid nodules subjected to Ultrasound (US)-guided FNAC by the Interventional Radiology department between December 2011 and November 2017 were included. Data on patient demographics, thyroid US features, cytology findings, and surgical histology were collected and analyzed. Sensitivity, specificity, and FNR were calculated based on FNAC results and final post-operative histology. Factors associated with a false negative result were analyzed using univariate and multivariate analyses. A total of 4982 nodules were studied, including 4419 < 4cm and 563 ≥ 4cm. Malignancy rates were similar in both groups. For nodules ≥ 4cm, FNAC sensitivity was 40%, specificity 100%, and FNR 6.6% compared to 4.2% in nodules < 4cm. Within malignant nodules, there was a significantly higher proportion of follicular and Hurthle cell carcinomas in nodules ≥ 4cm. Amongst nodules ≥ 4cm, multivariate analysis revealed male gender to be an independent predictor of FNR (OR 3.32; 95% CI 1.29-8.59). Larger nodules ≥ 4cm have a similar malignancy rate as nodules < 4cm, and FNAC FNR is low at 6.6%. Management of large thyroid nodules should be individualized based on their clinical, sonographic and cytological features rather than routine surgery.

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.

A study of association between serum thyroid stimulating hormone concentration and thyroid cancer and also to assess whether serum thyroid stimulating hormone levels are of value in predicting malignancy in patients with thyroid swelling

Background: Thyroid neoplasm includes both benign and malignant tumors arising in the thyroid gland. Although thyroid cancer accounts for less than 1% of all cancers, the challenge to clinicians is to identify the minority of thyroid nodules that harbor malignancy. There are a number of well-established predictors of malignancy in thyroid nodules. More recently a few studies have suggested that higher concentration of thyroid stimulating hormone (TSH), even within the normal range are associated with subsequent diagnosis of thyroid cancer in patients with thyroid nodules and even higher serum TSH levels have been found associated with advanced stages of thyroid cancer. Methods: A prospective study was conducted on 220 cases without overt thyroid dysfunction attending Department of general surgery, Pushpagiri institute of medical science, Thiruvalla. Results: In our study incidence of malignancy of thyroid carcinoma was highest in patients with serum TSH concentrations, in range of 3.5 mIU/l-5.25 mIU/l, 55 patients out of 220 patients. Individually, incidence of papillary carcinoma (PC) (36/55 patients), follicular carcinoma (FC) (17/55 patients) and Hurthle cell carcinoma (HCC) (2/55 patients) were more in patients with higher TSH. So, from the study it can be clearly state that elevated TSH can be used as an independent predictor of thyroid malignancy. Higher TSH values are associated with papillary thyroid carcinoma.Conclusions: An elevated TSH can be used as an independent predictor of thyroid malignancy, especially for anticipating a probability of papillary carcinoma of thyroid.

Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers.

Simple SummaryThyroid cancer is the most common endocrine malignancy. However, the cytological diagnosis of certain malignant thyroid tumors and their benign counterparts is a challenge for preoperative diagnosis, as nearly 20–30% of biopsied thyroid nodules are classified as having an indeterminate risk of malignancy. Although multigene panels customized for thyroid cancer include most of the known tumor driver genes, many thyroid samples have negative results for the tested genes. To expand our knowledge, driver-negative samples were profiled by RNA-sequencing. Here, we report novel gene variants that might be associated with the pathogenesis of thyroid tumors, and show that driver-negative samples have two distinct expression signatures. We believe that our findings will ultimately impact preoperative diagnosis on thyroid nodules and provide directions for further experimental validation analysis.Thyroid cancer is the most common endocrine malignancy. However, the cytological diagnosis of follicular thyroid carcinoma (FTC), Hürthle cell carcinoma (HCC), and follicular variant of papillary thyroid carcinoma (FVPTC) and their benign counterparts is a challenge for preoperative diagnosis. Nearly 20–30% of biopsied thyroid nodules are classified as having indeterminate risk of malignancy and incur costs to the health care system. Based on that, 120 patients were screened for the main driver mutations previously described in thyroid cancer. Subsequently, 14 mutation-negative cases that are the main source of diagnostic errors (FTC, HCC, or FVPTC) underwent RNA-Sequencing analysis. Somatic variants in candidate driver genes (ECD, NUP98, LRP1B, NCOR1, ATM, SOS1, and SPOP) and fusions were described. NCOR1 and SPOP variants underwent validation. Moreover, expression profiling of driver-negative samples was compared to 16 BRAF V600E, RAS, or PAX8-PPARg positive samples. Negative samples were separated in two clusters, following the expression pattern of the RAS/PAX8-PPARg or BRAF V600E positive samples. Both negative groups showed distinct BRS, ERK, and TDS scores, tumor mutation burden, signaling pathways and immune cell profile. Altogether, here we report novel gene variants and describe cancer-related pathways that might impact preoperative diagnosis and provide insights into thyroid tumor biology.

A CASE OF HÜRTHLE CELL CARCINOMA PRESENTING WITH MALIGNANT PLEURAL EFFUSION

TOPIC: Disorders of the Pleura TYPE: Medical Student/Resident Case Reports INTRODUCTION: Hürthle cell carcinoma (HCC) is uncommon, accounting for 3% of thyroid neoplasms. It is more clinically aggressive compared to other differentiated thyroid cancers. Though thoracic involvement has been reported, it has rarely caused malignant pleural effusion. Here, we describe a case of metastatic HCC presenting with dyspnea and recurrent unilateral pleural effusion. CASE PRESENTATION: A 73-year-old male presented with dyspnea. His past medical history was significant for thyroid HCC diagnosed in 2005. He had undergone thyroidectomy, which was consistent with widely invasive HCC with clear cell change, and radioactive iodine ablation in 2006. He followed with his endocrinologist and oncologist, and was disease free on regular scans. However, his serum thyroglobulin levels continuously rose, prompting a PET scan in 2013 which demonstrated 2 new nodules in the left lower lobe of the lung. Patient had thoracotomy with left lower wedge resection in 2014; pathology was consistent with atypical carcinoid of uncertain source. He remained asymptomatic until he developed dyspnea in 2015; CT chest showed an increase in size of his pulmonary nodules. Biopsy revealed metastatic poorly differentiated thyroid cancer. He underwent right upper lobe radiation and left chest wall mass resection. He continued to have pleuritic chest pain and imaging in 2018 showed a recurrent large left pleural effusion, requiring thoracentesis with symptomatic relief. Cytology was negative at the time. He was then treated with several chemotherapy agents, complicated by side effects. He was diagnosed with left loculated pleural effusion in late 2020, and again pleural fluid was negative for malignancy. He continued to have episodes of desaturation and cardiothoracic surgery was consulted for video-assisted thoracoscopic surgery-guided left indwelling pleural catheter placement. However, he suddenly became hemodynamically unstable and was diagnosed with ST-elevation myocardial infarction. He refused left heart catheterization and continued to deteriorate, ultimately pursuing inpatient hospice. DISCUSSION: Hürthle cell carcinoma is a rare, aggressive form of cancer with high rates of recurrence. Local occurrence and metastatic disease could be found in 30% patients over 20 years after total or subtotal thyroidectomy. Pulmonary metastasis has been reported to be the most common site, though its incidence is significantly less in patients who were treated by total thyroidectomy. Nevertheless, it is imperative to consider HCC recurrence in patients presenting with dyspnea and pleural effusion despite interventions and being disease-free. CONCLUSIONS: Though this patient had negative cytopathologic studies, the recurrence of his unilateral pleural effusion accompanied by progression of his cancer without any other obvious cause cause makes malignant pleural effusion due to HCC the most likely diagnosis. REFERENCE #1: Ahmadi, S., Stang, M., Jiang, X. S., & Sosa, J. A. (2016). Hürthle cell carcinoma: current perspectives. OncoTargets and therapy, 9, 6873–6884. https://doi.org/10.2147/OTT.S119980 REFERENCE #2: Bagherzadegan, N., Feller-Kopman, D., Ernst, A., Haerle, S., & Lunn, W. (2009). An unusual case of hürthle cell carcinoma presenting as metastatic pleural disease 16 years after thyroidectomy. Journal of bronchology & interventional pulmonology, 16(3), 204–206. https://doi.org/10.1097/LBR.0b013e3181b01521 REFERENCE #3: Besic, N., Schwarzbartl-Pevec, A., Vidergar-Kralj, B., Crnic, T., Gazic, B., & Marolt Music, M. (2016). Treatment and outcome of 32 patients with distant metastases of Hürthle cell thyroid carcinoma: a single-institution experience. BMC cancer, 16, 162. https://doi.org/10.1186/s12885-016-2179-3 DISCLOSURES: No relevant relationships by Saloni Goyal, source=Web Response No relevant relationships by Dimitry Petrenko, source=Web Response No relevant relationships by Cleo Zarina Reyes, source=Web Response No relevant relationships by Joseph Schellenberg, source=Web Response

ONCOCYTIC INTRATHYROID PARATHYROID ADENOMA MASQUERADING AS HURTHLE CELL NEOPLASM: FINE NEEDLE ASPIRATION CYTOLOGY OF TWO CASES

Ectopic parathyroid adenomas in thyroid tissue are uncommon (0.7 - 6%), and their oncocytic variants are exceedingly rare. We report two cases of intrathyroid parathyroid adenoma which were diagnosed as Hurthle cell adenoma on cytology. Case 1 is a 49-year-old female with a 2.4 cm hypoechoic nodule in the left lateral neck. Electrochemiluminescent immunoassay of the aspirate revealed PTH level of 422 pg/ml, conrming the presence of hyperfunctional parathyroid tissue. Subsequent resection of the left thyroid lobe revealed an enlarged intrathyroidal parathyroid. Case 2 is a 58-year-old female with a 2.1 cm hypoechoic nodule in the posterior-mid left thyroid lobe. Strong overexpression of parathyroid hormone and Chromogranin A genes and low expression of thyrocyte-related genes suggested parathyroid origin of the cells sampled. MEN1 mutation and multiple copy number alterations indicated the neoplastic nature of the nodule. Parathyroid oxyphil cells and oncocytic thyrocytes share cytomorphological ndings and distinguishing them by cytology alone is challenging, especially when the targeted lesion is intrathyroidal. Distinguishing intrathyroid oncocytic parathyroid adenoma from oncocytic thyroid follicular lesions has signicant clinical implications as Bethesda-IV category lesions have 20%–30% risk of malignancy. While stippled chromatin or intracytoplasmic fat vacuoles may be suggestive of parathyroid origin, these are not specic. Classifying the origin of a nodule as parathyroid vs thyroid rests upon the detection of PTH in aspirate material by ECL, immunocytochemistry or next-generation sequencing. In parathyroid aspirates, PTH level 100 pg/mL is suggestive of the presence of PTH-secre ≥ ting tissue at the site biopsied or along the needle track.

Expanding the spectrum of thyroid carcinoma with somatic DICER1 mutation: a survey of 829 thyroid carcinomas using MSK-IMPACT next-generation sequencing platform.

DICER1 gene encodes an RNaseIII endoribonuclease essential for the cleavage of pre-microRNA to mature microRNA. Germline DICER1 mutation results in DICER syndrome, a cancer predisposition syndrome which manifests in the thyroid gland as early-onset multinodular goiter and increased risk for differentiated thyroid carcinoma. Recently, somatic DICER1 mutations were described in various thyroid neoplasms, including follicular adenoma, papillary thyroid carcinoma, follicular carcinoma, and poorly differentiated thyroid carcinoma. In this study, we identified and described 14 cases (1.7%) with somatic DICER1 mutations from a cohort of 829 patients with thyroid follicular cell-derived thyroid carcinomas which were sequenced using MSK-IMPACT targeted next-generation sequencing platform. We expanded the histologic spectrum of thyroid carcinomas with somatic DICER1 mutations to include Hurthle cell carcinoma, high-grade differentiated thyroid carcinoma, and anaplastic thyroid carcinoma. All patients were adults with a median age of diagnosis of 59years (range: 22-82). Although rare, a subset of thyroid cancers, including the aggressive subtypes, display somatic DICER1 mutations, some of which have oncogenic potential.

Thyroid hemiagenesis associated with Hurthle cell carcinoma: A case report.

Introduction and importanceThyroid hemiagenesis (TH) is a rare congenital anomaly where one lobe fails to develop, especially more frequently occurs on the left lobe. The exact mechanisms for thyroid morphogenesis remain unclear. In this paper, we report a rare case of right lobe TH associated with Hurthle cell carcinoma.Case presentationA 59 years old woman was admitted with a neck lump increasing in size in the last 20 years. There were no symptoms of hyperthyroidism and hypothyroidism. There was a palpable, painless 5 cm mass in the middle of the neck. Initial thyroid ultrasonography (USG) revealed an enlarged left lobe, with hypoechoic lesion with cystic component and calcification (TIRADS 4). However, the right lobe was non-visualized. Fine needle aspiration biopsy result tendency was a malignancy. Hence, isthmolobectomy was conducted. Pathology result was Hurthle cell carcinoma. On the ninth month, USG revealed fibrotic tissue in the right thyroid bed and bilateral lymphadenopathy. Due to discrepancy, the patient was planned for a neck exploration surgery and a right lobe incision. Intraoperatively, the right thyroid was absent. Intraoperative USG also confirmed no right thyroid lobe.DiscussionThyroid hemiagenesis can be visualized by using USG due to its practicality and cost effectiveness reasons. Follow up evaluations consisted of systematic monitoring of thyroid morphology and hormonal functions should follow the diagnosis of TH. Neck exploration surgery might need to be performed to clarify any discrepancy and confirm the diagnosis.ConclusionTH can be recognized through supporting examination; however, discrepancy may occur.

Evaluation of Malignant Cytologic Parameters to Distinguish Hürthle Cell Carcinoma (HCC) from Hürthle Cell Adenoma (HCA) in Thyroid Fine Needle Aspirate (FNA) with Hürthle Cell Lesion (HCL)

Evaluation of Malignant Cytologic Parameters to Distinguish Hürthle Cell Carcinoma (HCC) from Hürthle Cell Adenoma (HCA) in Thyroid Fine Needle Aspirate (FNA) with Hürthle Cell Lesion (HCL)