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Archives of Pathology & Laboratory... Jun 2023Thyroid nodules with longitudinal nuclear grooves have been widely regarded as synonymous with papillary thyroid carcinoma (PTC).
CONTEXT.—
Thyroid nodules with longitudinal nuclear grooves have been widely regarded as synonymous with papillary thyroid carcinoma (PTC).
OBJECTIVE.—
To study a series of cases of thyroid nodules that exhibited oncocytic (Hürthle cell) features and contained longitudinal nuclear grooves yet failed to display aggressive behavior or the full features of papillary thyroid carcinoma.
DESIGN.—
The clinicopathologic, immunohistochemical, and molecular genetic features of 15 patients with these features were studied. Next-generation sequencing was performed to examine 161 genes for oncogenic driver alterations associated with thyroid neoplasia.
RESULTS.—
The lesions occurred in 11 women and 4 men aged 27 to 80 years and measured 0.2 to 2.3 cm in diameter (mean, 1.1 cm). The tumors were well circumscribed and noninvasive and showed a proliferation of large cells with abundant granular cytoplasm and centrally placed nuclei displaying scattered longitudinal nuclear grooves. Immunohistochemical stains were negative for HBME-1, galectin-3, and CK19 in all cases. NRAS pQ61R was detected in 6 cases, KRAS p.Q61E in 1 case, and AKT2 p.E17K in 1 case. None of the genetic changes classically associated with conventional PTC or with high-grade thyroid malignant neoplasms were identified. Clinical follow-up in 9 patients showed no evidence of recurrence or metastases between 2 and 13 years (mean, 5.7 years).
CONCLUSIONS.—
Longitudinal nuclear grooves can be occasionally encountered in oncocytic (Hürthle cell) tumors and should not lead to a diagnosis of PTC in the absence of other features supporting that diagnosis.
Topics: Male; Humans; Female; Thyroid Nodule; Oxyphil Cells; Thyroid Neoplasms; Thyroid Cancer, Papillary; Carcinoma, Papillary; Adenoma, Oxyphilic; Molecular Biology
PubMed: 36084253
DOI: 10.5858/arpa.2021-0554-OA -
Frontiers in Endocrinology 2022Hürthle 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...
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.
Topics: Adenocarcinoma; Adult; Aged; Carcinoma, Hepatocellular; Female; Humans; Iodine Radioisotopes; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Oxyphil Cells; Retrospective Studies; Thyroid Neoplasms
PubMed: 35846317
DOI: 10.3389/fendo.2022.904986 -
Science Advances Jun 2022Hürthle cell carcinomas (HCCs) display two exceptional genotypes: near-homoplasmic mutation of mitochondrial DNA (mtDNA) and genome-wide loss of heterozygosity (gLOH)....
Hürthle cell carcinomas (HCCs) display two exceptional genotypes: near-homoplasmic mutation of mitochondrial DNA (mtDNA) and genome-wide loss of heterozygosity (gLOH). To understand the phenotypic consequences of these genetic alterations, we analyzed genomic, metabolomic, and immunophenotypic data of HCC and other thyroid cancers. Both mtDNA mutations and profound depletion of citrate pools are common in HCC and other thyroid malignancies, suggesting that thyroid cancers are broadly equipped to survive tricarboxylic acid cycle impairment, whereas metabolites in the reduced form of NADH-dependent lysine degradation pathway were elevated exclusively in HCC. The presence of gLOH was not associated with metabolic phenotypes but rather with reduced immune infiltration, indicating that gLOH confers a selective advantage partially through immunosuppression. Unsupervised multimodal clustering revealed four clusters of HCC with distinct clinical, metabolomic, and microenvironmental phenotypes but overlapping genotypes. These findings chart the metabolic and microenvironmental landscape of HCC and shed light on the interaction between genotype, metabolism, and the microenvironment in cancer.
Topics: Carcinoma, Hepatocellular; DNA, Mitochondrial; Genotype; Humans; Liver Neoplasms; Mutation; Oxyphil Cells; Thyroid Neoplasms; Tumor Microenvironment
PubMed: 35731870
DOI: 10.1126/sciadv.abn9699 -
Diagnostic Cytopathology Sep 2022Interpretation of Hürthle cell-predominant cytologies (HCP) is very challenging as a majority is diagnosed as indeterminate. Prior studies have reported various...
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.
Topics: Biopsy, Fine-Needle; Colloids; Humans; Oxyphil Cells; Retrospective Studies; Thyroid Neoplasms; Thyroid Nodule
PubMed: 35674254
DOI: 10.1002/dc.25000 -
BMJ Case Reports May 2022Hürthle cell carcinoma (HCC) and medullary thyroid carcinomas (MTC) are uncommon histological subtypes of thyroid cancers, each accounting for around 3% of all thyroid...
Hürthle cell carcinoma (HCC) and medullary thyroid carcinomas (MTC) are uncommon histological subtypes of thyroid cancers, each accounting for around 3% of all thyroid cancers. A septuagenarian woman with a history of multiple primary cancer diagnoses presented with a growing left-sided neck lump. A diagnostic left thyroid lobectomy was performed, and pathological examination found two separate malignant foci: one HCC and an MTC. The patient developed left-sided HCC nodal metastasis, and following several multidisciplinary team discussions, a right completion lobectomy with left lateral neck dissection was performed, revealing further intrathyroidal MTC and extranodal extension of HCC. We present this as the first reported case of a collision tumour of HCC and MTC, and review the available literature regarding collision tumours and their management.
Topics: Carcinoma, Hepatocellular; Carcinoma, Neuroendocrine; Female; Humans; Liver Neoplasms; Oxyphil Cells; Thyroid Neoplasms
PubMed: 35641084
DOI: 10.1136/bcr-2022-248879 -
Cancer Cytopathology Jun 2022The fine-needle aspiration (FNA) diagnosis of thyroid Hürthle cell neoplasms (HCNs) remains challenging. This study explored a possible association of copy number...
BACKGROUND
The fine-needle aspiration (FNA) diagnosis of thyroid Hürthle cell neoplasms (HCNs) remains challenging. This study explored a possible association of copy number variations (CNVs) with Hürthle cell lesions of the thyroid.
METHODS
Thyroid FNA cases that were diagnosed as follicular lesion of undetermined significance (FLUS) or follicular neoplasm (FN)/HCN for which the ThyroSeq version 3 genomic classifier test was performed were retrieved.
RESULTS
A total of 324 thyroid FNA cases (228 FLUS cases, 46 HCN cases, and 50 FN cases) were included in the study. FLUS cases were further classified as Hürthle cell type (follicular lesion of undetermined significance-Hürthle cell type [FLUS-HCT]; 20 cases) or non-Hürthle cell type (follicular lesion of undetermined significance-non-Hürthle cell type [FLUS-NHCT]; 208 cases). HCN and FLUS-HCT cases showed a higher prevalence of CNVs (23 of 66 [35%]) in comparison with those classified as FN or FLUS-NHCT (14 of 258 [5%]; P < .001). A total of 105 patients had histopathologic follow-up. Cases with CNVs were more likely to be neoplastic (18 of 26 [69%]) and associated with Hürthle cell changes (14 of 26 [54%]) in comparison with cases without any molecular alterations (neoplastic, 8 of 24 [33%]; Hürthle cell changes, 2 of 24 [8%]; P < .05). In HCN/FLUS-HCT cases with CNVs (n = 14), Hürthle cell changes (13 of 14 [93%]) and neoplasms (9 of 14 [64%]) were more likely to be seen on surgical follow-up in comparison with the 17 cases without CNVs (Hürthle cell changes, 6 of 17 [35%]; neoplastic, 3 of 17 [18%]; P < .05).
CONCLUSIONS
CNVs identified in thyroid FNA cases are associated with Hürthle cell morphology and are suggestive of a neoplasm with Hürthle cell features in thyroid FNAs classified as FLUS-HCT/HCN. This finding may be helpful in triaging patients who would benefit from surgical management.
Topics: Adenocarcinoma, Follicular; Biopsy, Fine-Needle; DNA Copy Number Variations; Humans; Oxyphil Cells; Thyroid Neoplasms; Thyroid Nodule
PubMed: 35332982
DOI: 10.1002/cncy.22569 -
Cancer Cytopathology Jun 2022
Topics: Adenoma, Oxyphilic; Biopsy, Fine-Needle; Humans; Oxyphil Cells; Thyroid Neoplasms; Thyroid Nodule
PubMed: 35285577
DOI: 10.1002/cncy.22567 -
Thyroid : Official Journal of the... Mar 2022Follicular thyroid carcinoma (FTC) and Hurthle cell carcinoma (HCC) are rare and aggressive thyroid cancers with limited published data comparing their outcomes or...
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). 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. Patients with HCC ( = 111) were more likely to be older than 55 years old (59% vs. 27%, < 0.001) with a tendency to present with more extensive VI (33% vs. 19%, = 0.07) compared with FTC ( = 79). Comparing groups 1, 2, 3, and 4, group 4 patients were more likely to recur (DFS 98%, 93%, 98% vs. 73%, respectively, = 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%, = 0.0025) and had poorer distant control (DRFS: 100%, 95%, 80%, = 0.022), compared with patients absent or focal VI. Accurate assessment of the extent of VI and tumor phenotype (follicular vs. Hurthle) are essential in identifying patients at higher risk of recurrence.
Topics: Adenocarcinoma, Follicular; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Oxyphil Cells; Prognosis; Retrospective Studies; Thyroid Neoplasms
PubMed: 35078345
DOI: 10.1089/thy.2021.0424 -
Endocrinology and Metabolism (Seoul,... Oct 2021Hürthle cell carcinoma (HCC), a type of thyroid carcinoma, is rare in South Korea, and few studies have investigated its prognosis.
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.
Topics: Carcinoma, Hepatocellular; Disease-Free Survival; Female; Humans; Liver Neoplasms; Male; Middle Aged; Oxyphil Cells; Retrospective Studies
PubMed: 34731935
DOI: 10.3803/EnM.2021.1151 -
Journal of Medical Case Reports Aug 2021Follicular 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... (Review)
Review
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.
Topics: Adenoma, Oxyphilic; Female; Humans; Iodine Radioisotopes; Middle Aged; Oxyphil Cells; Thyroid Neoplasms; Thyroidectomy
PubMed: 34376229
DOI: 10.1186/s13256-021-02987-z