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Virchows Archiv : An International... Mar 2023Poorly differentiated thyroid carcinoma (PDTC), defined by Turin criteria, comprises a subset of high-grade follicular-derived thyroid carcinomas with intermediate...
Poorly differentiated thyroid carcinoma (PDTC), defined by Turin criteria, comprises a subset of high-grade follicular-derived thyroid carcinomas with intermediate prognosis. While differentiated oncocytic thyroid carcinomas demonstrate clinicopathologic and genetic differences compared to their non-oncocytic counterparts, similar data is limited in oncocytic (Hurthle) PDTCs (OPDTCs). Here, we assessed the impact of various oncocytic cut-offs in PDTCs on clinical, histologic and survival parameters.Our bi-institutional cohort comprised 210 primary PDTCs with available slides reviewed by at least one pathologist. Histologic features, including oncocytic fraction, were recorded. Clinicopathologic data were obtained, including overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), locoregional recurrence free survival (LRRFS), and distant metastasis-free survival (DMFS). Radioactive iodine avidity data was available for 125 PDTCs based on postoperative whole-body scanning.Within our cohort, 39.0% PDTCs had any oncocytic component with 24.8% meeting the 75% World Health Organization (WHO) oncocytic definition. Any oncocytic component and > 25% oncocytic cut-off correlated with decreased DSS and LRRFS, respectively, compared to non-oncocytic PDTCs (NOPDTCs) on univariate and multivariate analysis. The 100% oncocytic cut-off was significant for DSS on univariate analysis but a non-significant trend on multivariate analysis. Any oncocytic cut-off (100%, > 75%, > 50%, > 25%, or > 0%) conferred higher radioactive iodine (RAI)-refractoriness to OPDTCs compared to NOPDTCs. NF1 and PTEN alterations were enriched in OPDTCs (40% vs. 0%, and 60% vs 8%, respectively), whereas NRAS mutations were frequent in NOPDTCs (47% vs. 7%).Among PDTCs, the presence of oncocytes led to downward trend in all outcome parameters, especially for DSS and LRRFS. OPDTCs were enriched in NF1 and PTEN mutations. Consistently, all oncocytic cut-offs were associated with RAI-refractoriness. Accordingly, additional studies are needed to reassess the current 75% cut-off used to define oncocytic thyroid lesions.
Topics: Humans; Thyroid Neoplasms; Oxyphil Cells; Iodine Radioisotopes; Adenocarcinoma, Follicular
PubMed: 36346459
DOI: 10.1007/s00428-022-03422-4 -
European Archives of... Jun 2006Oncocytic neoplasms are tumors composed of oncocytes (i.e., epithelial cells with a large cytoplasm that is rich in mitochondria). Most cases are benign and originate...
Oncocytic neoplasms are tumors composed of oncocytes (i.e., epithelial cells with a large cytoplasm that is rich in mitochondria). Most cases are benign and originate from the major salivary glands, while the minor salivary glands are rarely involved. Occurrence of oncocytic carcinoma (or malignant oncocytoma) within the sinonasal tract is an unusual event. We report a rare case of maxillary sinus oncocytic carcinoma occurring in a 45-year-old male. Biopsy was consistent with an unspecified salivary gland neoplasm. The patient underwent total maxillectomy through a lateral rhinotomic approach; hard palate reconstruction with temporal myofascial flap was performed. Definitive histology was consistent with oncocytic carcinoma. Due to the local extension of the lesion, postoperative radiotherapy (60 Gy) was delivered. Three years after surgery, the patient is free from disease. A brief analysis of the literature was also accomplished in order to discuss treatment options and prognosis of this unusual neoplasm.
Topics: Adenoma, Oxyphilic; Humans; Magnetic Resonance Imaging; Male; Maxillary Sinus Neoplasms; Middle Aged; Rare Diseases; Tomography, X-Ray Computed
PubMed: 16474973
DOI: 10.1007/s00405-005-0004-8 -
Cancer Discovery Aug 2023Oncocytic (Hürthle cell) carcinoma of the thyroid (HCC) is genetically characterized by complex I mitochondrial DNA mutations and widespread chromosomal losses. Here,...
UNLABELLED
Oncocytic (Hürthle cell) carcinoma of the thyroid (HCC) is genetically characterized by complex I mitochondrial DNA mutations and widespread chromosomal losses. Here, we utilize RNA sequencing and metabolomics to identify candidate molecular effectors activated by these genetic drivers. We find glutathione biosynthesis, amino acid metabolism, mitochondrial unfolded protein response, and lipid peroxide scavenging to be increased in HCC. A CRISPR-Cas9 knockout screen in a new HCC model reveals which pathways are key for fitness, and highlights loss of GPX4, a defense against lipid peroxides and ferroptosis, as a strong liability. Rescuing complex I redox activity with the yeast NADH dehydrogenase (NDI1) in HCC cells diminishes ferroptosis sensitivity, while inhibiting complex I in normal thyroid cells augments ferroptosis induction. Our work demonstrates unmitigated lipid peroxide stress to be an HCC vulnerability that is mechanistically coupled to the genetic loss of mitochondrial complex I activity.
SIGNIFICANCE
HCC harbors abundant mitochondria, mitochondrial DNA mutations, and chromosomal losses. Using a CRISPR-Cas9 screen inspired by transcriptomic and metabolomic profiling, we identify molecular effectors essential for cell fitness. We uncover lipid peroxide stress as a vulnerability coupled to mitochondrial complex I loss in HCC. See related article by Frank et al., p. 1884. This article is highlighted in the In This Issue feature, p. 1749.
Topics: Humans; Thyroid Gland; Carcinoma, Hepatocellular; Lipid Peroxides; Fermentation; Oxyphil Cells; Liver Neoplasms; DNA, Mitochondrial
PubMed: 37262067
DOI: 10.1158/2159-8290.CD-22-0976 -
Frontiers in Endocrinology 2021In fine-needle aspirations (FNA) of thyroid, Hürthle cells can be found in a broad spectrum of lesions, ranging from non-neoplastic conditions to aggressive malignant... (Review)
Review
In fine-needle aspirations (FNA) of thyroid, Hürthle cells can be found in a broad spectrum of lesions, ranging from non-neoplastic conditions to aggressive malignant tumors. Recognize them morphologically, frequently represents a challenging for an adequately diagnosis and are associated with a significant interobserver variability. Although the limitations of the morphologic diagnosis still exist, the interpretation of the context where the cells appear and the recent advances in the molecular knowledge of Hürthle cells tumors are contributing for a more precise diagnosis. This review aims to describe the cytology aspects of all Hürthle cells neoplastic and non-neoplastic thyroid lesions, focusing on the differential diagnosis and reporting according to The Bethesda System for Reporting Thyroid Cytology (TBSRTC). New entities according to the latest World Health Organization (WHO) classification are included, as well as an update of the current molecular data.
Topics: Biopsy, Fine-Needle; Cytodiagnosis; Diagnosis, Differential; Humans; Oxyphil Cells; Thyroid Gland; Thyroid Neoplasms; Thyroid Nodule
PubMed: 34248855
DOI: 10.3389/fendo.2021.701877 -
Archives of Pathology & Laboratory... Aug 2008Hürthle cells are eosinophilic, follicular-derived cells that are associated with a variety of nonneoplastic and neoplastic thyroid lesions. The differential diagnosis... (Review)
Review
CONTEXT
Hürthle cells are eosinophilic, follicular-derived cells that are associated with a variety of nonneoplastic and neoplastic thyroid lesions. The differential diagnosis of Hürthle cell lesions is quite broad.
OBJECTIVE
To review the pathologic conditions associated with Hürthle cells in the thyroid and to discuss pathology of thyroid lesions associated with oncocytic cytology.
DATA SOURCES
A variety of thyroid nonneoplastic (autoimmune thyroiditis, multinodular goiter) and neoplastic conditions (Hürthle cell adenoma, Hürthle cell carcinoma) are associated with Hürthle cell cytology. In addition, there are several thyroid neoplasms that should be considered when one observes a Hürthle cell neoplasm in the thyroid (oncocytic variant of medullary carcinoma, several variants of papillary thyroid carcinoma).
CONCLUSIONS
Oncocytic cytology is seen in a variety of thyroid conditions that are associated with a broad differential diagnosis and care must be used for accurate diagnosis. Newer molecular-based techniques may be useful for further classification of thyroid neoplasms with oncocytic pathology.
Topics: Adenocarcinoma; Biopsy, Needle; Diagnosis, Differential; History, 19th Century; Humans; Metaplasia; Oxyphil Cells; Pathology, Surgical; Thyroid Diseases; Thyroid Gland; Thyroid Neoplasms
PubMed: 18684023
DOI: 10.5858/2008-132-1241-TTHOCA -
Virchows Archiv : An International... Jun 2006
Topics: Adenolymphoma; Cell Transformation, Neoplastic; DNA, Mitochondrial; Humans; Mitochondria; Oxyphil Cells; Parotid Neoplasms; Precancerous Conditions
PubMed: 16609912
DOI: 10.1007/s00428-005-0052-x -
Diagnostic Cytopathology Nov 2004The thyroid fine-needle aspiration (FNA) diagnosis of Hürthle-cell neoplasm (HCN)/follicular neoplasm with oncocytic features (FNOF) does not differentiate between...
The thyroid fine-needle aspiration (FNA) diagnosis of Hürthle-cell neoplasm (HCN)/follicular neoplasm with oncocytic features (FNOF) does not differentiate between Hürthle-cell adenoma and carcinoma. A majority of cases diagnosed as HCN undergo surgical excision for definite characterization. The aim of this study was to determine the risk of malignancy in cases diagnosed as HCN and identify clinical features that may help in predicting malignancy in patients with FNA diagnosis of HCN. We reviewed a cohort of 206 cases of thyroid FNA diagnosed as HCN; histological follow-up was available in 169 (82%) cases. The cases were evaluated for patient's age, sex, and size of the nodule and histological diagnosis. One hundred and sixty-six were female patients and 40 were male patients (age range, 12-83 yr). The histological diagnoses were benign in 93 (93/169, 55%) cases and malignant in 76 (76/169, 45%) cases. The malignant histological diagnoses were Hürthle-cell carcinoma (HCC), 53 cases; papillary thyroid carcinoma, 19 cases; follicular carcinoma, 3 cases; and medullary carcinoma, 1 case. The risk of malignancy was greater in nodules measuring > or =2 cm (55% vs. 45%; P value < 0.0001) in patients who were > or =40 yr old (82% vs. 18%, P value < 0.0001) than in patients <40 yr. The risk of malignancy was found greater in male patients than in female patients (61% vs. 43%); however, the difference was not statistically significant. The diagnosis HCN/FNOF carries a higher risk of malignancy as compared with a diagnosis of follicular lesion/neoplasm (20% malignancy rate from previously published studies). Clinical features including size of the nodule, age, and possibly sex of the patient can be a part of the decision analysis in selecting a patient for surgery.
Topics: Adenocarcinoma, Follicular; Adenoma; Adenoma, Oxyphilic; Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Biopsy, Fine-Needle; Child; Female; Humans; Male; Middle Aged; Oxyphil Cells; Retrospective Studies; Thyroid Neoplasms
PubMed: 15468114
DOI: 10.1002/dc.20132 -
HNO Feb 2001Oncocytic neoplasms of the salivary glands are rare. (Review)
Review
BACKGROUND AND OBJECTIVE
Oncocytic neoplasms of the salivary glands are rare.
PATIENTS/METHODS
We report on seven cases of oncocytic neoplasms of the parotid gland (one multifocal nodular oncocytic hyperplasia, five oncocytomas, and one oncocytic carcinoma).
RESULTS
While the history, clinical presentation, and histology of all oncocytic neoplasms showed no characteristic differences, intraoperatively the well-differentiated oncocytic carcinoma displayed an infiltrative, locally aggressive growth pattern. A local carcinoma recurring 7 years later corresponded to the primary tumor. There were no metastases. Immunohistochemistry revealed that all oncocytic neoplasms were positive for markers of cytokeratins (KI-1) and negative for markers of carcinoembryonal antigen (CEA), S-100 protein, and smooth muscle actin (SMA). In contrast to the benign neoplasms, the oncocytic carcinoma showed an increased rate of proliferating cells (MIB-1) and a strongly positive reaction with the antibody MA-903 against high molecular weight cytokeratins.
CONCLUSIONS
In a review of the literature, we could identify a group of locally aggressive, low-grade oncocytic carcinomas with a considerably better prognosis, similar to that of our case. The therapeutic significance of these findings is discussed.
Topics: Adenoma, Oxyphilic; Aged; Biomarkers, Tumor; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Parotid Gland; Parotid Neoplasms
PubMed: 11270192
DOI: 10.1007/s001060050719 -
The Journal of Clinical Endocrinology... Dec 2020Poorly differentiated thyroid cancer (PDTC) is a rare, follicular cell-derived neoplasm with an unfavorable prognosis. The oncocytic variant of PDTC may be associated...
BACKGROUND
Poorly differentiated thyroid cancer (PDTC) is a rare, follicular cell-derived neoplasm with an unfavorable prognosis. The oncocytic variant of PDTC may be associated with even more adverse outcome than classical PDTC cases, but its specific molecular features are largely unknown. Our aim was to explore the immune-related gene expression profile of oncocytic and classical PDTC, in correlation with clinical and pathological characteristics (including programmed death ligand 1 [PD-L1] expression) and outcome, and in comparison with a control group of well-differentiated follicular carcinomas (WDFCs), including conventional follicular carcinomas (FTCs) and Hürthle cell carcinomas (HCCs).
METHODS
A retrospective series of 48 PDTCs and 24 WDFCs was analyzed by means of NanoString technology employing the nCounter PanCancer Immune Profiling panel. Gene expression data were validated using quantitative real-time polymerase chain reaction.
RESULTS
Oncocytic PDTCs showed a specific immune-related gene expression profile, with higher expression of LAIR2, CD274, DEFB1, IRAK1, CAMP, LCN2, LY96, and APOE, and lower expression of NOD1, as compared to conventional PDTCs. This molecular signature was associated with increased intratumoral lymphocytic infiltration, PD-L1 expression, and adverse outcome. Three of these genes, CD274, DEFB1, and IRAK1, as well as PD-L1 expression, were also the hallmarks of HCCs as compared to FTCs. By contrast, the panel of genes differentially regulated in PDTCs as compared to WDFCs was unrelated to the oncocytic phenotype.
CONCLUSIONS
Our results revealed a distinctive immune-related gene expression profile of oncocytic PDTC and confirmed a more aggressive outcome in this cancer subtype. These findings may provide guidance when exploring novel immunotherapeutic options for oncocytic PDTC patients.
Topics: Adenocarcinoma, Follicular; Adenoma, Oxyphilic; Adult; Aged; Aged, 80 and over; Female; Gene Expression Regulation, Neoplastic; Humans; Immunity; Male; Microarray Analysis; Middle Aged; Oxyphil Cells; Retrospective Studies; Thyroid Neoplasms; Transcriptome; Tumor Escape
PubMed: 32936917
DOI: 10.1210/clinem/dgaa655 -
The American Journal of Surgical... Mar 2012Adrenal cortical carcinosarcoma is a rare variant of adrenal cortical carcinoma. Sarcomatous change in adrenal cortical carcinomas is exceptionally rare, with only 9... (Review)
Review
Adrenal cortical carcinosarcoma is a rare variant of adrenal cortical carcinoma. Sarcomatous change in adrenal cortical carcinomas is exceptionally rare, with only 9 cases previously described. Adrenal cortical carcinosarcomas tend to be aggressive tumors, with locoregional recurrence and rapid metastases from the sarcomatoid component. We describe what seems to be the first case of sarcoma arising in oncocytic adrenal cortical carcinoma. The sarcomatous component here was pleomorphic rhabdomyosarcoma. This occurred in a 45-year-old man who had nodal and pulmonary metastases of the rhabdomyosarcomatous component at presentation and who died of progressive disease 11 months later. Here, we discuss the clinical, radiologic, and pathologic findings and review the literature on adrenal cortical carcinosarcomas.
Topics: Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Biopsy; Brain Neoplasms; Carcinosarcoma; Fatal Outcome; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Oxyphil Cells; Rhabdomyosarcoma
PubMed: 22343339
DOI: 10.1097/PAS.0b013e31824517d9