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Introduction: Thyroid oncocytic carcinoma, also known as Hürthle cell carcinoma (HCC), is a rare subtype of thyroid cancer with unique characteristics. Radioiodine therapy, while less effective for HCC due to poor radioiodine accumulation in tumor, has shown improved survival rates for tumors larger than 2 cm. Adjuvant radioiodine therapy is recommended in certain cases, particularly for older patients with a worse prognosis. Methods: This study reviewed data from 18 HCC cases compared to the overall patient population (OPP) at our center between 2019 and 2022. Results: The mean age at diagnosis was higher for HCC patients compared to OPP, with varying responses to therapy observed. Assessment of response to therapy after one year revealed 26.7%, 20%, 20%, and 33.3% of HCC patients with excellent, indeterminate, biochemical incomplete, and structural incomplete responses, which were 41.5%, 24.7%, 13%, and 20.7% in OPP, respectively. The Kaplan curve of patient survival showed an average of 100±13.5 months. Conclusion: Approximately 44% of HCC patients showed excellent survival outcomes after radioiodine therapy, highlighting its importance as a treatment option for HCC. Further research is needed to optimize treatment choices and improve patient outcomes in this less common subtype of thyroid cancer. [ABSTRACT FROM AUTHOR]

Background: Oncocytic thyroid carcinoma (OTC) was previously considered a variant of follicular thyroid carcinoma (FTC) but has recently been reclassified as a separate form of thyroid cancer. This study aimed to demonstrate that FTC and OTC are fundamentally distinct entities that can potentially be differentiated preoperatively through cytology and/or molecular testing. Methods: A retrospective chart review of patients diagnosed with FTC and OTC operated upon at two university health centers from January 2016 to September 2023 (n = 3219) was conducted. Molecular testing results were correlated with histopathologic diagnosis. Results: Fifty patients met the inclusion criteria. FTC was identified in 27 (54.0%) patients, and OTC in 23 (46.0%) patients. Patients with OTC were older (61.8 years) than FTC patients (51.2 years) (p = 0.013). Moreover, aggressive tumors were found in 39.1% (9/23) of OTCs compared to 11.1% (3/27) of FTCs (p = 0.021). Amongst Bethesda category III and IV nodules, 17 out of 20 (85.0%) OTC cytology reports demonstrated an oncocytic subtype compared to only 5 out of 24 FTC cytology reports (20.8%) (p = 0.002). On molecular testing, the EIF1AX alteration was exclusively present in OTCs while the PAX8/PPARy and PTEN alterations were exclusively found in FTCs. Copy number alterations (CNAs) were found to be more prevalent in OTC (66.7%) compared to FTC (33.3%), and they were not indicative of tumor aggressiveness. Within the OTC group, all three patients who had a TP53 alteration were diagnosed with aggressive cancer. Lastly, the OTCs exhibited a higher frequency of multiple alterations on molecular testing (66.7%) compared to FTCs (33.3%). Conclusion: To our knowledge, this is the largest study to date comparing the clinical application of abnormalities found on molecular testing for FTC and OTC. It further demonstrates the distinct clinicopathological and molecular characteristics of OTC.

Background: Oncocytic thyroid carcinoma (OTC) was previously considered a variant of follicular thyroid carcinoma (FTC) but has recently been reclassified as a separate form of thyroid cancer. This study aimed to demonstrate that FTC and OTC are fundamentally distinct entities that can potentially be differentiated preoperatively through cytology and/or molecular testing. Methods: A retrospective chart review of patients diagnosed with FTC and OTC operated upon at two university health centers from January 2016 to September 2023 (n = 3219) was conducted. Molecular testing results were correlated with histopathologic diagnosis. Results: Fifty patients met the inclusion criteria. FTC was identified in 27 (54.0%) patients, and OTC in 23 (46.0%) patients. Patients with OTC were older (61.8 years) than FTC patients (51.2 years) (p = 0.013). Moreover, aggressive tumors were found in 39.1% (9/23) of OTCs compared to 11.1% (3/27) of FTCs (p = 0.021). Amongst Bethesda category III and IV nodules, 17 out of 20 (85.0%) OTC cytology reports demonstrated an oncocytic subtype compared to only 5 out of 24 FTC cytology reports (20.8%) (p = 0.002). On molecular testing, the EIF1AX alteration was exclusively present in OTCs while the PAX8/PPARy and PTEN alterations were exclusively found in FTCs. Copy number alterations (CNAs) were found to be more prevalent in OTC (66.7%) compared to FTC (33.3%), and they were not indicative of tumor aggressiveness. Within the OTC group, all three patients who had a TP53 alteration were diagnosed with aggressive cancer. Lastly, the OTCs exhibited a higher frequency of multiple alterations on molecular testing (66.7%) compared to FTCs (33.3%). Conclusion: To our knowledge, this is the largest study to date comparing the clinical application of abnormalities found on molecular testing for FTC and OTC. It further demonstrates the distinct clinicopathological and molecular characteristics of OTC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Differential diagnosis by optical microscopy on biopsies of low-incidence tumors of the same organ can be difficult, hampering patient management, particularly in the many places around the world lacking advanced facilities for cancer diagnosis beyond a histopathology laboratory. Examples of these tumors are the Hurthle cell, anaplastic, and medullary carcinomas of the thyroid. Currently, there are no specific biomarkers detectable by optical microscopy for any of them. We study the Chaperone System of these tumors by immunohistochemistry to determine if its components show distinctive levels and distribution patterns. Here we report that the molecular chaperones Hsp27, Hsp60, and Hsp90, show quantitative levels and distribution patterns different for each tumor and different from those of a benign thyroid pathology, goiter. Therefore, the reported methodology offers a promising tool to diagnose these three malignancies, and for revealing clues about the role of the three chaperones in carcinogenesis of thyroid tissue. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

BackgroundHürthle 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.MethodsWe retrospectively studied 51 cases of HCC treated at the interdisciplinary endocrine center of the University Hospital of Cologne, Germany between 2005 and 2020.ResultsPatients 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

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hurthle cell carcinoma is a rare subtype of follicular thyroid carcinoma. Its aggressive nature and poor prognosis require prompt diagnosis and treatment, which is often challenging. We herein report a case of a woman who complained of lumps on her left and right neck which move with swallowing motion for 15 years, and have gotten bigger in the previous 6 months. Follicular thyroid carcinoma was first suspected based on previous fine needle aspiration biopsy. Total thyroidectomy and selective neck dissection procedure were performed and histopathology examination post-surgery showed Hurthle cell carcinoma. The patient also received thyroid replacement hormone therapy. This case discusses the diagnosis and management of Hurthle cell carcinoma leading to better patient outcome.

The most usual form of the endocrine carcinoma is thyroid cancer (TC). In addition to papillary thyroid carcinoma (PTC), recent studies revealed incidence of RET/PTC rearrangement in other tumors, like Hürthle cell carcinoma (HCC) and even in non-carcinomatous disorders like Hashimoto's thyroiditis. Here, we present a case with concurrence of papillary thyroid carcinoma and Hürthle cell carcinoma. A 60-year-old woman referred to our hospital with a mass in her neck. Physical examinations revealed painful swelling in the thyroid. Ultrasonographic examination showed two hypoechoic nodules in the right lobe. Hürthle cell variant papillary carcinoma was suggested in the cytology report of the fine needle aspiration. Permanent histopathological diagnosis was co-existence of papillary thyroid carcinoma and Hürthle cell carcinoma. The patient was asymptomatic in 14 months follow up. Concurrence of papillary carcinoma and Hürthle cell carcinoma is a rare form of thyroid malignancies, with doubtful cytogenetic findings and biological behaviors. The results showed that it is necessary for the surgeons and pathologists to be aware of lesions for the optimal diagnostic and therapeutic interventions. Also, it is vital to follow up patients with the Hashimot’s thyroiditis who have multiple nodules to detect occult thyroid cancers and decide for better therapeutic programs.

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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hürthle cells (HC) are characterized by abundant granular eosinophilic cytoplasm containing accumulated dysfunctional mitochondria and large nuclei with prominent nucleoli. Based on the distinct clinicopathologic and molecular characteristics of Hürthle cell neoplasms (HCN), the 2017 Endocrine World Health Organization (WHO) moved to categorizing HCN as a separate group of tumors. Hürthle cell carcinomas (HCC) are now subclassified as minimally invasive, encapsulated angioinvasive, and widely invasive. HCC have a low rate of driver mutations associated with follicular thyroid carcinoma. Instead, these neoplasms are characterized by widespread loss of heterozygosity due to whole-chromosome alterations and a high rate of mitochondrial DNA mutations. Increased understanding of the genomic underpinnings of HCC has translated into improvements in molecular testing of HCN. This review will focus on clinical, cytologic, and histopathologic features of HCN, concentrating on diagnostic challenges and prognostic parameters. In addition, the molecular characteristics and molecular testing of HCN will be reviewed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hürthle cell carcinoma (HCC) is a distinct type of thyroid canc er genetically characterized by DNA copy number alterations (CNA), typically of genome haploidization type (GH-type). However, whether CNA also occurs in benign Hürthle cell adenomas (HCA) or Hürthle cell hyperplastic nodules (HCHN), and have diagnostic impact in fine-needle aspiration (FNA) samples, remains unknown. To address these questions, we (1) analyzed 26 HCC, 24 HCA, and 8 HCHN tissues for CNA and other mutations using Th yroSeq v3 (TSv3) next-generation sequencing panel, and (2) determined cancer rate in 111 FNA samples with CNA and known surgical outcome. We identified CNA, more often of the GH-type, in 81% of HCC and in 38% HCA, but not in HCHN. Among four HCC with distant metastasis, all had CNA and three TERT mutations. Overall, positive TSv3 results were obtained in 24 (92%) HCC, including all with ATA high risk of recurrence or me tastasis. Among 111 FNA cases with CNA, 38 (34%) were malignant and 73 (66%) benign. A significant correlation between cancer rate and nodule size was observed, particularly among cases with GH-type CNA, where every additional centimeter of nodule size increased the malignancy odds by 1.9 (95% CI 1.3-2.7; P = 0.001). In summary, the results of this study demonstrate that CNA characteristic of HCC also occur in HCA, although with lower frequency, and probability of cancer in nodules with CNA increases with nodule size. Detection of CNA, in conjunction with other mutations and nodule size, is helpful in predicting malignancy in thyroid nodules. [ABSTRACT FROM AUTHOR]

A paraneoplastic syndrome is the presence of signs and symptoms due to cancer, but it is not a consequence of the mass effect of a tumour. It typically occurs in middle-aged to older patients with solid tumors (lung, breast, and ovaries), and hematological malignancies (leukemia and lymphoma). Autoimmune hemolytic anaemia is also a well-defined paraneoplastic phenomenon in lymphoproliferative disorders and rare solid tumour malignancies such as renal cell carcinoma, ovarian dermoid cysts, thymus cell cancer, Kaposi sarcoma, and cancers of the breast, pancreas, thyroid, and prostate. Most of the time, it is warm and is rarely cold type. We present a case of cold-type autoimmune hemolytic anaemia, presented as paraneoplastic manifestations of a thyroid malignancy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Pandey et al.)

IntroductionHürthle cell carcinoma (HCC) is a rare tumor that tends to metastasize to the lymph nodes. Some studies have correlated size of Hürthle cell tumors with the risk of malignancy. Whether the size of HCC correlates with the risk of lymph node (LN) metastases, to our knowledge has not been addressed.MethodsA retrospective analysis was performed on all patients diagnosed with HCC on final pathology between 1997 and 2008. The tumor size and lymph node status was obtained for each patient. The data were analyzed utilizing Student's t-test and the Fisher's exact test to calculate the two-tailed p-value.ResultsOut of 39 patients diagnosed with HCC 3(8%) had LN metastases; 1 had ipsilateral central LN metastasis and 2 had ipsilateral central and lateral LN metastasis. LN dissection was performed in patients with known metastasis (2 were evident on preoperative ultrasound and 1 intraoperatively). Patients with LN metastasis were older than those without (mean age: 86.7 and 56.4 years, respectively), had larger tumors (mean size: 6 and 4 cm) and were commonly male (2 of 3). No tumor < 5cm presented with lymph node involvement (3/15 with >5cm cancer had node metastasis, 0/24 with

Purpose: There are controversial debates if patients with Hürthle cell carcinoma, also known as oxyphilic or oncocytic cell follicular thyroid carcinoma, have a poorer outcome. In this study, we systematically evaluated the clinical outcome in a large patient cohort following thyroidectomy and initial I-131 radioactive iodine therapy (RIT). Methods: We retrospectively evaluated a total of 378 patients with diagnosed oncocytic follicular Hürthle cell carcinoma (OFTC) (N = 126) or with classical follicular thyroid carcinoma (FTC) (N = 252). Patients received thyroidectomy and complementary I-131 RIT. Clinical data regarding basic demographic characteristics, tumor grade, persistent disease and recurrence during follow-up, and disease-free, disease-specific, and overall survival were collected during follow-up of 6.9 years (interquartile range 3.7; 11.7 years). Univariate and multivariate analyses were used to identify factors associated with disease-related and overall survival. Results: Before and after matching for risk factors, recurrence was significantly more frequently diagnosed in OFTC patients during follow-up (17% vs. 8%; p value 0.037). Likewise, OFTC patients presented with a reduced mean disease-free survival of 17.9 years (95% CI 16.0–19.8) vs. 20.1 years (95% CI 19.0–21.1) in FTC patients (p value 0.027). Multivariate analysis revealed OFTC (HR 0.502; 95% CI 0.309–0.816) as the only independent prognostic factor for disease-free survival. Distant metastases of OFTC patients were significantly less iodine-avid (p value 0.014). Mean disease-specific and overall survival did not differ significantly (p value 0.671 and 0.687) during follow-up of median 6.9 years (3.7; 11.7 years). Conclusions: Our study suggests that recurrence is more often seen in OFTC patients. OFTC patients have a poorer prognosis for disease-free survival. Thus, OFTC and FTC behave differently and should be categorized separately. However, patients suffering from OFTC present with the same overall and disease-specific survival at the end of follow-up indifferent to FTC patients after initial RIT. [ABSTRACT FROM AUTHOR]

Multiple primary malignancies are defined as two or more primary malignant tumors diagnosed in one individual; they are further classified to synchronous or metachronous based on the period between each cancer diagnosis and the other. The diagnosis of four synchronous cancers is exceedingly rare. We report a case of a 72-year-old man, diagnosed with synchronous quadruple cancers, Hurthle cell carcinoma and papillary carcinoma of the thyroid, as well as squamous cell carcinoma and carcinoid tumor of the lung. [ABSTRACT FROM AUTHOR]

Hurthle cell carcinoma is a rare subtype of follicular thyroid carcinoma. Its aggressive nature and poor prognosis require prompt diagnosis and treatment, which is often challenging. We herein report a case of a woman who complained of lumps on her left and right neck which move with swallowing motion for 15 years, and have gotten bigger in the previous 6 months. Follicular thyroid carcinoma was first suspected based on previous fine needle aspiration biopsy. Total thyroidectomy and selective neck dissection procedure were performed and histopathology examination post-surgery showed Hurthle cell carcinoma. The patient also received thyroid replacement hormone therapy. This case discusses the diagnosis and management of Hurthle cell carcinoma leading to better patient outcome. [ABSTRACT FROM AUTHOR]

Abstract Background Hurthle cell carcinoma makes up 3 to 5% of all thyroid cancers and is considered to be a true rarity. The aim of our study was to analyze clinical characteristics and survival rates of patients with Hurthle cell carcinoma. Methods Clinical data regarding basic demographic characteristics, tumor grade, type of surgical treatment and vital status were collected. Methods of descriptive statistics and Kaplan-Meier survival curves were used for statistical analysis. Cox proportional hazards regression was used to identify independent predictors. Results During the period from 1995 to 2014, 239 patients with Hurthle cell carcinoma were treated at our Institution. The average age of the patients was 54.3, with female to male ratio of 3.6:1 and average tumor size was 41.8 mm. The overall recurrence rate was 12.1%, with average time for relapse of 90.74 months and average time without any signs of the disease of 222.4 months. Overall 5-year, 10-year and 20-year survival rates were 89.4%, 77.2%, 61.9% respectively. The 5-year, 10-year and 20-year cancer specific survival rates were 94.6%, 92.5%, 87.4%, respectively. When disease free interval was observed, 5-year, 10-year and 20-year rates were 91.1%, 86.2%, 68.5%, respectively. The affection of both thyroid lobes and the need for reoperation due to local relapse were unfavorable independent prognostic factors, while total thyroidectomy as primary procedure was favorable predictive factor for cancer specific survival. Conclusion Hurthle cell carcinoma is a rare tumor with an encouraging prognosis and after adequate surgical treatment recurrences are rare.

Purpose Radioactive iodine (RAI) is widely used for adjuvant therapy after thyroidectomy, while its value for thyroid cancer has been controversial recently. The primary objectives of this study were to clarify the influence of Radioactive iodine (RAI) on the survival in rare oxyphilic subtype of thyroid cancer (Hürthle cell carcinoma, HCC). Methods Patients diagnosed with oxyphilic thyroid carcinoma from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results Program database. The Kaplan-Meier method was used to compare overall survival (OS) and cancer-specific survival (CSS) among patients who had adjuvant RAI use or not. Univariate and multivariate Cox proportional hazard models were performed for survival analysis, and subsequently visualized by nomogram. Results In all, 2,799 patients were identified, of which 1529 patients had adjuvant RAI use while 1,270 patients had not. Based on multivariate Cox analysis, the RAI therapy confers an improved OS for HCC patients (HR = 0.57, 95% CI [0.44–0.72], P

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Sulaiman et al.)

Purpose: Oncocytic (Hürthle cell) papillary thyroid carcinoma (OPTC) is a rare variant of the papillary thyroid carcinoma (PTC) which comprises approximately 1 to 11 % of PTC cases. Its clinical course and prognosis have not been comprehensively documented and the clinical outcome remains a controversial issue. Therefore, we investigated the long-term prognosis after thyroidectomy and (adjuvant) initial radioactive iodine therapy (RIT) of OPTC compared to PTC. Methods: A total of 563 patients (47 with OPTC and 516 with PTC) with a median follow-up of 9.9 (0.3; 23.5) years were studied. All patients underwent thyroidectomy followed by (adjuvant) initial RIT. Data on the patients' demographics, pathology, laboratory findings, imaging studies, treatment, and follow-up including recurrence, and disease-specific survival were collected. Cox's multivariate regression model was used to identify independent prognostic factors for survival. Results: OPTC patients were significantly older (55.2 ± 12.3 years) than PTC patients (50.3 ± 13.5) at the time of initial diagnosis (p value 0.016). Initial tumor size was larger in the OPTC group (2.8 ± 1.8 cm for OPTC patients, 1.5 ± 1.2 cm for PTC patients, p value < 0.001). Before matching, OPTC patients presented more often with evidence of disease at the last visit of follow-up (p value 0.046). However, this difference was not observed anymore after matching for risk factors (p value 0.637). Disease-specific survival did not differ significantly. Age (HR, 1.183; 95% CI, 1.097–1.276) was identified as an independent prognostic factor for disease-specific survival. OPTC patients predominantly showed a recurrence of distant metastasis within a shorter time despite being not statistically significant. Conclusion: At initial diagnosis, OPTC shows significant differences in terms of age and initial tumor size compared to PTC. Patients suffering from OPTC present with the same clinical long-term outcome indifferent to PTC after (adjuvant) initial RIT after matching. [ABSTRACT FROM AUTHOR]

The most usual form of the endocrine carcinoma is thyroid cancer (TC). In addition to papillary thyroid carcinoma (PTC), recent studies revealed incidence of RET/PTC rearrangement in other tumors, like Hürthle cell carcinoma (HCC) and even in noncarcinomatous disorders like Hashimoto's thyroiditis. Here, we present a case with concurrence of papillary thyroid carcinoma and Hürthle cell carcinoma. A 60-year-old woman referred to our hospital with a mass in her neck. Physical examinations revealed painful swelling in the thyroid. Ultrasonographic examination showed two hypoechoic nodules in the right lobe. Hürthle cell variant papillary carcinoma was suggested in the cytology report of the fine needle aspiration. Permanent histopathological diagnosis was co-existence of papillary thyroid carcinoma and Hürthle cell carcinoma. The patient was asymptomatic in 14 months follow up. Concurrence of papillary carcinoma and Hürthle cell carcinoma is a rare form of thyroid malignancies, with doubtful cytogenetic findings and biological behaviors. The results showed that it is necessary for the surgeons and pathologists to be aware of lesions for the optimal diagnostic and therapeutic interventions. Also, it is vital to follow up patients with the Hashimot's thyroiditis who have multiple nodules to detect occult thyroid cancers and decide for better therapeutic programs. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Petre et al.)

Hürthle cell carcinoma (HCC) is a variant of a follicular carcinoma with a tendency to higher frequency of metastases and a lower survival rate. However, intracavitary cardiac metastases from thyroid HCC are extremely rare. We describe the case of a 57-year-old female with thyroid HCC, 5 years after total thyroidectomy, who presented with dyspnea associated with hypoxia and hypotension. The computed tomography angiogram showed extensive pulmonary embolism and a 6-cm right atrial mass while the lower-extremity deep vein thrombosis studies were negative. This patient received a cardiac thrombectomy using cardiopulmonary bypass support. However, intraoperatively, we found out that the mass was from the mediastinum, directly extending into the heart and clearly unresectable since it effaced at least 1/3 of the right atrial wall. The core biopsy of the mass confirmed that it was metastatic poorly differentiated HCC of thyroidal origin. The patient eventually died of respiratory failure due to a massive pulmonary embolism. For cancer patients with unexplained dyspnea, cardiac metastases should be considered regardless of anticoagulation prophylaxis, especially when there is no deep vein thrombosis in the lower limbs. Early recognition of intracavitary cardiac metastases may help in providing prompt treatment and improving the prognosis.

Background. Hürthle cell neoplasms could be benign (Hürthle cell adenoma) or malignant (Hürthle cell carcinoma). Hürthle cell carcinoma is a rare tumour, representing 5% of all differentiated thyroid carcinomas. The cytological evaluation of Hürthle cell neoplasms by fine needle aspiration biopsy (FNAB) is complicated because of the presence of Hürthle cells in both Hürthle cell adenoma and Hürthle cell carcinoma. Thus, the preoperative distinction between these two entities is very difficult and possible only with pathohistological findings of the removed tumour.