Unraveling the Enigma: A Five-Year Comprehensive Analysis of Hurthle Cell Tumors in South India's Tertiary Care Center.

BACKGROUND: Hurthle cell tumors of the thyroid gland constitute a rare and enigmatic group of neoplasms, characterized by the presence of Hurthle cells exhibiting abundant eosinophilic cytoplasm and numerous mitochondria. Despite their low incidence, they pose diagnostic challenges and display diverse clinical outcomes. This study aims to provide a comprehensive analysis of the clinicopathological profile of Hurthle cell tumors within a tertiary care center in South India. METHODS: Through a retrospective approach, we analyzed cases of Hurthle cell tumors diagnosed and treated at a tertiary care center over a five-year period. Clinical, radiological, and histopathological data were meticulously collected and scrutinized. The study focused on examining demographic details, presenting symptoms, imaging features, cytological findings, surgical management, and postoperative outcomes of the patients. RESULTS: A total of 32 cases of Hurthle cell tumors were identified during the study period. The majority of patients were female (84%), with a mean age of 49.6 years for Hurthle cell carcinoma. Thyroid enlargement and neck mass were the most common presenting complaints. Fine-needle aspiration cytology showed characteristic features suggestive of Hurthle cell tumors in 33% of cases. Total thyroidectomy remains the mainstay surgical approach. Histopathological evaluation confirmed 62.5% of cases as benign adenomas and 37.5% as malignant carcinomas. Among malignant cases, 67% showed capsular invasion and 33% demonstrated vascular invasion. Of the patients, 33.3% received adjuvant radiotherapy. The overall survival rate was 100%. In our study, we found that thyroid nodules larger than 3 cm demonstrated a higher propensity for Hurthle cell carcinoma. CONCLUSION: Our findings support the multidisciplinary approach in managing Hurthle cell tumors, with a focus on tailored treatment plans for each patient based on individual characteristics. By recognizing the female predominance, assessing nodule size, and employing a combination of thyroidectomy and ablative therapy, clinicians can optimize patient care and contribute to better long-term prognosis and quality of life for those affected by Hurthle cell tumors. Continued research and collaborative efforts are necessary to advance our understanding and refine treatment strategies, paving the way for improved outcomes and enhanced patient management in the future.

Megaprosthesis for a Rare Case of Bone Metastasis of Thyroid Carcinoma: Case Management and Surgical Approach.

We present the case of a 56-year-old male patient diagnosed with Hürthle cell carcinoma (HCC) that developed widespread metastasis in bone, lung, and lymph nodes with a larger tumor located in the right tibia. The patient was only disturbed by the pain, discomfort, and disability linked to the tibial metastasis. After careful consideration, the best course of action was considered to be the surgical excision of the proximal right tibia with arthroplasty using the C LINK Megaprosthesis tumor revision system. Histological and immunohistochemical analyses were conducted on the tibial resection specimen. In addition, a comprehensive review of prior histological specimens from the primary thyroid tumor, lymph nodes, and lung was undertaken to evaluate the prognosis and provide guidance for the postoperative management of the patient.

Oncocytic carcinoma of the thyroid: Conclusions from a 20-year patient cohort.

BACKGROUND: Oncocytic carcinoma (OCA) was recently reclassified as a distinct differentiated thyroid carcinoma (DTC). Given its rarity, OCA studies are limited. This study describes the characteristics of OCA in a 20-year cohort. METHODS: Retrospective analysis of patients with OCA at a single tertiary care hospital from 2000 to 2021. RESULTS: Fifty-one OCA patients (22M:29F) were identified. The mean age at diagnosis was 60.3 years; 90% presented as palpable mass; 24% had a family history of thyroid cancer. None had vocal fold paresis. On ultrasound, most tumors were solid and hypoechoic. FNA (n = 14) showed Bethesda-4 lesions in 93%. All were treated surgically. Histologically, 63% demonstrated angioinvasion, 35% had lymphovascular invasion, and 15% had extrathyroidal extension. Radioactive iodine was used as adjunct therapy in 77%. CONCLUSION: OCA has distinct features that distinguish it from other DTCs, and additional focused studies will help clarify the aggressive nature, treatment options, and prognosis of the disease.

Surgical management of metastatic Hürthle cell carcinoma to the skull base, cortex, and spine: illustrative case.

BACKGROUND: Hürthle cell carcinoma (HCC) is an unusual and aggressive variant of the follicular type of differentiated thyroid cancer (DTC), accounting for less than 3% of DTCs but posing the highest risk of metastasis. Brain metastases are uncommonly reported in the literature but pose a poor prognosis. The low rate of brain metastases from HCC coupled with ambiguous treatment protocols for the extracranial disease complicate successful disease management and definitive treatment strategy. The authors present the case of a patient with HCC metastasis to the skull base, cortex, and spine with recent tibial metastasis. OBSERVATIONS: Despite the presence of metastasis to the cortex, skull base, and spine, the patient responded very well to radiation therapy, sellar mass resection, and cervical spine decompression and fixation and has made a remarkable recovery. LESSONS: The authors' multidisciplinary approach to the patient's care, including a diverse team of specialists from oncology, neurosurgery, orthopedic surgery, radiology, endocrinology, and collaboration with clinical trial researchers, was fundamental to her successful outcome, demonstrating the utility of intersecting specialties in successful outcomes in neuro-oncological patient care.

Hurthle cell carcinoma: a rare variant of thyroid malignancy - a case report.

Oncocytic/Hurthle cell neoplasm is a rare form of thyroid malignancies, derived from follicular epithelium, presenting with a wide variety having either presenting with features of thyrotoxicosis or no any associated symptoms. Case presentation: The authors present a case of a 49-year-old female with a known case of chronic obstructive pulmonary disease and hypertension who presented to our hospital with anterior neck swelling for 4 months that has gradually increased over the time. Physical examination, laboratory test, various radiological imaging, and cytological study led to the diagnosis of Hurthle cell neoplasm. With prompt diagnosis, she was admitted and surgery was done that include right hemithyroidectomy. Though it is a rare type of thyroid malignancy, early diagnosis and proper treatment has shown a very good prognosis. Clinical discussion: Hurthle cell carcinoma initially presents with a single, painless palpable mass in the thyroid with pressure symptoms in advanced cases including dysphagia, dyspnea, and hoarseness. Pain, rapid growth, or significant compressive symptoms are suggestive of an invasive one. Conclusion: This case highlights on rarity of disease, presentation, and availability of treatment modality.

Immunomorphological Patterns of Chaperone System Components in Rare Thyroid Tumors with Promise as Biomarkers for Differential Diagnosis and Providing Clues on Molecular Mechanisms of Carcinogenesis.

Hurthle cell (HC), anaplastic (AC), and medullary (MC) carcinomas are low frequency thyroid tumors that pose several challenges for physicians and pathologists due to the scarcity of cases, information, and histopathological images, especially in the many areas around the world in which sophisticated molecular and genetic diagnostic facilities are unavailable. It is, therefore, cogent to provide tools for microscopists to achieve accurate diagnosis, such as histopathological images with reliable biomarkers, which can help them to reach a differential diagnosis. We are investigating whether components of the chaperone system (CS), such as the molecular chaperones, can be considered dependable biomarkers, whose levels and distribution inside and outside cells in the tumor tissue could present a distinctive histopathological pattern for each tumor type. Here, we report data on the chaperones Hsp27, Hsp60, and Hsp90. They presented quantitative levels and distribution patterns that were different for each tumor and differed from those of a benign thyroid pathology, goiter (BG). Therefore, the reported methodology can be beneficial when the microscopist must differentiate between HC, AC, MC, and BG.

Lenvatinib as a Promising Treatment Option for Unresectable Hürthle Cell Carcinoma: A Case Report.

Hürthle cell carcinoma (HCC) of the thyroid gland generally has a more aggressive clinical course than other differentiated thyroid cancers (DTCs), and it is associated with a higher rate of distant metastases. In this case report, we highlight the importance of tyrosine kinase inhibitors as a management strategy for unresectable DTCs. Surgical management is challenging if the cancer is locally advanced and invades major neck structures with an increased risk of recurrence. Tyrosine kinase inhibitors (TKIs) are used in the case of advanced disease, especially in unresectable, radio-iodine refractory and with metastatic status. Lenvatinib, a TKI, used as the first line of treatment, plays a key role in improving prognosis and survival rates among patients. A 37-year-old gentleman presented with a locally advanced and widely metastasized case of large Hürthle cell carcinoma encasing the left carotid sheath and the left recurrent laryngeal nerve. Fine needle aspiration cytology (FNAC) was suggestive of HCC and a positron emission tomography-computed tomography (PET-CT) scan revealed metastases to the lungs and spine. In this case, lenvatinib was used to prevent the proliferation of malignant cells and the neovascularization of the tumor. This clinically translated into a good response in a high disease burden scenario. The patient showed positive results with lenvatinib therapy with a progression-free duration of 30 months and a reduction in the size of cancer. This case report describes the use of lenvatinib for the treatment of a large unresectable locally advanced and widely metastasized case of Hürthle cell carcinoma in a young gentleman with a response profile.

Oncocytic Cell Carcinoma of the Thyroid: A Case Report and an Overview of the Diagnosis, Treatment Modalities, and Prognosis.

Cancers of the thyroid gland are uncommon, accounting for 1% of malignant tumors. Oncocytic carcinoma of the thyroid (OCA), previously known as "Hürthle cell" carcinomas, make up 3% to 5% of all thyroid cancers and are extremely rare. In the United States, the incidence of thyroid cancer is approximately 12 per 100,000 per year and increases with age. The prevalence of thyroid cancers in women is estimated to be twice that in men, with the male gender correlating with a worse prognosis. A definitive diagnosis of OCA is confirmed after complete excision and histopathological examination. OCA is an aggressive tumor with an exceedingly low incidence, a high risk of metastasis, and a poor prognosis. The mainstay of therapy for OCA is surgery. In order to recognize and treat the disease as early as possible, healthcare providers must consider the probability of OCA in patients presenting with a thyroid mass. We hereby present a case of OCA identified incidentally status post tracheostomy and subsequent biopsy. We have an opportunity to review this disease with the hope of improving outcomes by raising awareness and with early recognition.

Radioactive Iodine Therapy Does not Improve Cancer-specific Survival in Hürthle Cell Carcinoma of the Thyroid.

CONTEXT: It is unclear whether radioactive iodine (RAI) therapy could improve cancer-specific survival (CSS) in patients with Hürthle cell carcinoma (HCC) of the thyroid. OBJECTIVE: To investigate the effect of RAI on CSS in HCC patients. METHODS: HCC patients who underwent total thyroidectomy (TT) were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018. The Kaplan-Meier method and the Cox proportional hazards regression model were used to evaluate CSS. Propensity score-matched (PSM) analyses were performed to control the influence of potential confounders. RESULTS: A total of 2279 patients were identified. RAI treatment was not significantly associated with improved CSS in overall or PSM cohort. Subgroup analyses indicated similar results, even in patients with aggressive features such as age 55 years or older, tumor size greater than 40 mm, distant disease in SEER staging, extrathyroidal extension, and lymph node metastases (all P > .05). CONCLUSION: RAI has no statistically significant influence on the CSS in HCC patients. This information may aid in decision-making for RAI therapy in these patients.

Hürthle Cell Carcinoma: Single Center Analysis and Considerations for Surgical Management Based on the Recent Literature.

Background: Hürthle cell carcinoma (HCC) of the thyroid is rare. There are contrasting data on its clinical behavior. The aim of this study was to describe clinic-pathological features and outcomes of HCC patients at our institution, in order to adapt our surgical management. Methods: We retrospectively studied 51 cases of HCC treated at the interdisciplinary endocrine center of the University Hospital of Cologne, Germany between 2005 and 2020. Results: Patients median age was 63 years (range 29-78) with 64.7% of cases being female. Primary treatment included surgery and postoperative radioiodine therapy with 3.7 GBq in all patients. Surgery consisted of total thyroidectomy in all cases and additional central lymphadenectomy in 90.2% of cases. The median number of harvested lymph nodes was 11 (range 2-31). Lymph node involvement was found in two (4.3%) pT4a tumors. In all other cases (95.7%), central lymphadenectomy was prophylactic and lymph nodes were free of metastasis in final histopathology. Twelve (23.5%) patients with incomplete biochemical response to primary treatment were diagnosed with structural relapse during the course of disease, for which seven (58.4%) underwent resection of isolated cervical metastasis. Histopathology revealed soft tissue implants in all cases and cervical surgery led to biochemical and radiologic cure in only two (28.5%) cases. Five (41.6%) patients developed metastatic disease, followed by systemic therapy in two patients. Vascular invasion of the primary tumor was significantly associated with relapse (p<0.01). Conclusions: Recurrence of HCC was common in this study. Given the low rate of lymph node metastases both in this study and in recent literature and the nature of relapse (soft tissue instead of nodal metastasis), the benefit of routine prophylactic central lymph node dissection for HCC remains unclear, especially in the absence of vascular invasion from the primary tumor.

Hürthle cell-predominant thyroid fine needle aspiration cytology: A four risk-factor model highly accurate in excluding malignancy and predicting neoplasm.

BACKGROUND: Interpretation of Hürthle cell-predominant cytologies (HCP) is very challenging as a majority is diagnosed as indeterminate. Prior studies have reported various cytologic features to help distinguish non-neoplastic (NN) from neoplastic and malignant lesions but had contradicting results. Our aim was to identify risk factors predictive of neoplasm and/or malignancy by correlating cytologic features with clinical and ultrasound findings. METHODS: Sixty-nine HCP cases with surgical follow-up were identified, including 35 NN, 20 adenomas, and 14 carcinomas. Ultrasound data were recorded utilizing Thyroid Imaging Reporting and Data System (TI-RADS) and American Thyroid Association (ATA) scoring systems. Sixteen cytologic criteria were evaluated and semi-quantitatively scored. Data were assessed by univariable, multivariable and stepwise logistic regression analysis; and statistical significance achieved at P-value <0.05. RESULTS: On univariable analysis, significant predictors of neoplasm were high cellularity, isolated single cells, absent colloid, non-uniform HC population (anisonucleosis), larger nodule size, and higher ATA score. Large-cell dysplasia and transgressing blood vessels were not found to be significant factors. Multivariable analysis identified a combination of four risk factors (high cellularity, anisonucleosis, absent colloid, and size ≥2.9 cm) that was associated with neoplasm in 10/11 patients. None of 15 patients with zero or 1 out of 4 risk factors had malignancy or neoplasm on follow-up. This model also significantly outperformed ATA and TI-RADS scoring systems. CONCLUSION: In the absence of four or three risk factors, the model excluded malignancy and neoplasm in all patients. The presence of all four factors predicted neoplasm and malignancy in 91% and 46% of cases, respectively.

Development and validation of a prognostic nomogram for Hürthle cell thyroid carcinoma: a SEER-based study.

Background: Hürthle cell carcinoma is a rare subtype of thyroid cancer, and its clinical behavior and biological characteristics remain unclear. This study aimed to establish nomogram models for the prognostic evaluation of Hürthle cell thyroid carcinoma (HCTC) in terms of both cancer-specific survival (CSS) and overall survival (OS). Methods: Data for a total of 3,264 patients with HCTC (2004 to 2018) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analysis was performed to identify significant predictors of prognosis and develop a prognostic nomogram. The performance of the model was assessed based on the area under the receiver operating characteristic curve (AUC), concordance index (c-index), and calibration curves. Results: Multivariate Cox regression analysis showed that age, sex, summary stage, tumor size, N stage, M stage, and treatment with thyroidectomy were independent predictors of OS. Moreover, age, summary stage, tumor size, N stage, M stage, AJCC stage, and treatment with thyroidectomy were significantly correlated with CSS. The c-index of the OS and CSS nomograms developed based on these factors was 0.822 (95% CI: 0.803-0.841) and 0.893 (95% CI: 0.866-0.920), respectively. The AUC was 0.888, 0.841, and 0.834 for 1-, 3-, and 5-year OS and 0.970, 0.949, and 0.933 for 1-, 3-, and 5-year CSS, respectively. The calibration curves showed good agreement between observed and predicted values. Moreover, decision curve analysis revealed that the nomogram had a better clinical utility than individual clinicopathological markers. Conclusions: A prognostic nomogram that allows the individualized assessment of OS and CSS in HCTC was developed. This nomogram could be used to guide treatment decisions in patients with HCTC.

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.

Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Positive Patient With Refractory Metastatic Thyroid Hürthle Cell Carcinoma: A Case Report and Literature Review.

Thyroid Hürthle cell carcinoma, known as thyroid eosinophilic carcinoma, is a rare pathological type of differentiated thyroid cancer (DTC), representing 3-4% of all thyroid cancers. However, given the high risk of invasion and metastasis, thyroid Hürthle cell carcinoma has a relatively poor prognosis. Traditional treatment methods have limited effects on patients with metastatic thyroid cancers. Developing a valuable therapy for advanced thyroid carcinomas is an unfilled need, and immunotherapy could represent another choice for these tumors. We herein reported the case of a patient with recurrent advanced thyroid Hürthle cell cancer and positive programmed death-ligand 1 (PD-L1) expression, who suffered tumor progression after re-surgery, radiotherapy, and targeted therapy. It is encouraging that PD-1 inhibitors in combination with GM-CSF and stereotactic body irradiation (SBRT) on metastatic disease have a significant anti-tumor effect.

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.

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

INTRODUCTION AND IMPORTANCE: Thyroid 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 PRESENTATION: A 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. DISCUSSION: Thyroid 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. CONCLUSION: TH can be recognized through supporting examination; however, discrepancy may occur.

Hürthle Cell Carcinoma of the Thyroid Gland: Systematic Review and Meta-analysis.

INTRODUCTION: Hürthle cell carcinoma (HCC) comprises about 5% of thyroid carcinoma cases. Partly because of its rarity there is much we still need to know about HCC as compared to other histological cancer subtypes. METHODS: We conducted a systematic literature review following PRISMA guidelines and meta-analysis, from 2000 to 2020, to investigate the main characteristics of HCC and clarify information concerning tumor behavior and treatment. RESULTS: Our review included data from 9638 patients reported in 27 articles over the past 20 years. This tumor occurred more frequently in women (67.5%). The mean age was 57.6 years, and the mean size of the neoplasm at diagnosis was 30 mm. Extrathyroidal extension was common (24%) but lymph node metastasis was not (9%). Total thyroidectomy was the most common surgical approach, with neck dissection usually performed in cases with clinically apparent positive neck nodes. Radioiodine therapy was frequently applied (54%), although there is no consensus about its benefits. The mean 5- and 10-year overall survival was 91% and 76%, respectively. CONCLUSION: This review serves to further elucidate the main characteristics of this malignancy. HCC of the thyroid is rare and most often presents with a relatively large nodule, whereas lymph node metastases are rare. Given the rarity of HCC, a consensus on their treatment is needed, as doubts remain concerning the role of specific tumor findings and their influence on management.

Recurrent Hurthle cell thyroid carcinoma does not preclude long-term survival: a case report and review of the literature.

BACKGROUND: Follicular thyroid carcinoma is the second most common malignancy of the thyroid gland. In 2016, the so-called Hurthle cell thyroid carcinoma, formerly known as the oxyphilic variant of the follicular thyroid carcinoma, was reclassified by the World Health Organization as a separate pathological entity, which accounts for approximately 3% of all thyroid cancers. Although Hurthle cell thyroid carcinomas are known for their more aggressive tumor biology, metastases are observed in a minority of cases, and long-term survival can be expected. However, disseminated disease is often associated with poor outcome. CASE PRESENTATION: In the presented case, a 63-year-old Caucasian female was incidentally diagnosed with Hurthle cell thyroid carcinoma after undergoing hemithyroidectomy for a nodular goiter. Following completion thyroidectomy, two courses of radioactive iodine therapy were administered. After 4 years of uneventful follow-up, the patient gradually developed metastases in five different organs, with the majority representing unusual sites, such as heart, kidney, and pancreas over a course of 14 years. The lesions were either treated with radioactive iodine therapy or removed surgically, depending on iodine avidity. CONCLUSION: Follicular and Hurthle cell thyroid carcinoma are known to potentially spread hematogenously to typical sites, such as lung or bones, however; unusual metastatic sites as presented in our case can also be observed. A search of the literature revealed only scattered reports on patients with multiple metastases in unusual locations. Furthermore, the observed long-term survival of our patient is contradictory to the existing data. As demonstrated, recurrent disease may appear years after the initial diagnosis, emphasizing the importance of consistent aftercare. Radioactive iodine therapy, extracorporeal radiation therapy, and surgical metastasectomy are central therapeutic components. In summary, our case exemplifies that thorough aftercare and aggressive treatment enables long-term survival even in recurrent Hurthle cell thyroid carcinoma displaying unusual multisite metastases.

Genetics, Diagnosis, and Management of Hürthle Cell Thyroid Neoplasms.

Hürthle cell lesions have been a diagnostic conundrum in pathology since they were first recognized over a century ago. Controversy as to the name of the cell, the origin of the cell, and even which cells in particular may be designated as such still challenge pathologists and confound those treating patients with a diagnosis of "Hürthle cell" anything within the diagnosis, especially if that anything is a sizable mass lesion. The diagnosis of Hürthle cell adenoma (HCA) or Hürthle cell carcinoma (HCC) has typically relied on a judgement call by pathologists as to the presence or absence of capsular and/or vascular invasion of the adjacent thyroid parenchyma, easy to note in widely invasive disease and a somewhat subjective diagnosis for minimally invasive or borderline invasive disease. Diagnostic specificity, which has incorporated a sharp increase in molecular genetic studies of thyroid tumor subtypes and the integration of molecular testing into preoperative management protocols, continues to be challenged by Hürthle cell neoplasia. Here, we provide the improving yet still murky state of what is known about Hürthle cell tumor genetics, clinical management, and based upon what we are learning about the genetics of other thyroid tumors, how to manage expectations, by pathologists, clinicians, and patients, for more actionable, precise classifications of Hürthle cell tumors of the thyroid.

Epigenomics in Hurthle Cell Neoplasms: Filling in the Gaps Towards Clinical Application.

It has been widely described that cancer genomes have frequent alterations to the epigenome, including epigenetic silencing of various tumor suppressor genes with functions in almost all cancer-relevant signalling pathways, such as apoptosis, cell proliferation, cell migration and DNA repair. Epigenetic alterations comprise DNA methylation, histone modification, and microRNAs dysregulated expression and they play a significant role in the differentiation and proliferation properties of TC. In this review, our group assessed the published evidence on the tumorigenic role of epigenomics in Hurthle cell neoplasms (HCN), highlighting the yet limited, heteregeneous and non-validated data preventing its current use in clinical practice, despite the well developed assessment techniques available. The identified evidence gaps call for a joint endeavour by the medical community towards a deeper and more systematic study of HCN, aiming at defining epigenetic markers in early diagnose, allowing for accurate stratification of maligancy and disease risk and for effective systemic treatment.