The Oncocytic Variant of Poorly Differentiated Thyroid Carcinoma Shows a Specific Immune-Related Gene Expression Profile

Metović, Jasna; Vignale, Chiara; Annaratone, Laura; Osella‐Abate, Simona; Maletta, Francesca; Rapa, Ida; Cabutti, Francesco; Patriarca, S; Gallo, Marco; Nikiforov, Yuri E.; Volante, Marco; Papotti, Mauro

doi:10.1210/clinem/dgaa655

Cited by 9 publications

(7 citation statements)

References 41 publications

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“…These mutations of the complex I subunit are the only nuclear gene mutations specific to oncocytic tumors reported to date [3]. A distinctive immune-related gene expression profile was found in poorly differentiated HCC, with increased intratumoral lymphocytic infiltration and PDL1 expression and confirmed a more aggressive outcome in this cancer subtype [44].…”

Section: Discussionmentioning

confidence: 88%

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

et al. 2021

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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 metanalysis, 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 9,638 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 5and 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.4 Bullet points 1. Hürthle cell carcinoma is a less frequent differentiated thyroid malignancy, of follicular origin, accounting for only about 5% of all thyroid cancers.2. This type of tumor occurs more frequently in women, at about 60 years of age, and is not usually a large tumor (about 3 cm) when diagnosed.3. It may exhibit extrathyroidal involvement at diagnosis, but lymphatic metastases are infrequent. 4.The main adverse prognostic factors are male gender, higher age and TNM stage. 5.Increasing knowledge about these tumors is important to elucidate their behavior and to be able to adapt treatments, especially to avoid overtreatment by trying to treat them like other histological types.

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Section: Discussionmentioning

confidence: 88%

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

et al. 2021

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“…As in other thyroid tumors, TERT promoter mutation portents a more aggressive clinical course with distant metastatic spread, and reduced iodine uptake. The clinical relevance of recognizing this tumor classification has been highlighted by a recent study showing a distinctive immune-related gene expression profile of oncocytic poorly differentiated thyroid carcinomas, not only confirming that this is a more aggressive cancer subtype but also pointing to a potential role for immunotherapy in the management of these high-grade malignancies ( 53 ).…”

Section: Poorly Differentiated Carcinomamentioning

confidence: 96%

Oncocytic Change in Thyroid Pathology

Sylvia

Mete

2021

Front. Endocrinol.

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Oncocytes are cells that have abundant eosinophilic cytoplasm due to the accumulation of mitochondria; they are also known as oxyphils. In the thyroid they have been called Hürthle cells but this is a misnomer, since Hürthle described C cells; for this reason, we propose the use of “oncocyte” as a scientific term rather than an incorrect eponym. Oncocytic change occurs in nontumorous thyroid disorders, in benign and malignant tumors of thyroid follicular cells, in tumors composed of thyroid C cells, and intrathyroidal parathyroid proliferations as well as in metastatic lesions. The morphology of primary oncocytic thyroid tumors is similar to that of their non-oncocytic counterparts but also is complicated by the cytologic features of these cells that include both abundant eosinophilic cytoplasm and large cherry red nucleoli. The molecular alterations in oncocytic thyroid tumors echo those of their non-oncocytic counterparts but in addition feature mitochondrial DNA mutations as well as chromosomal gains and losses. In this review we emphasize the importance of recognition of the spectrum of oncocytic thyroid pathology. The cell of origin, morphologic features including architecture, nuclear atypia and invasive growth, as well as high grade features such as mitoses and necrosis, enable accurate classification of these lesions. The molecular alterations underlying the pathological entity are associated with genetic alterations associated with oncocytic change. The arbitrary cut-off of 75% oncocytic change to classify a lesion as an oncocytic variant brings another complexity to the classification scheme of tumors that frequently have mixed oncocytic and non-oncocytic components. This controversial and often confusing area of thyroid pathology requires thoughtful and cautious investigation to clarify accurate diagnosis, prognosis and prediction for patients with oncocytic thyroid lesions.

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“…Specific chromosomes appear to undergo gains or losses more frequently than others, suggesting that unique selective pressures are exerted on individual chromosomes. Chrs 1,2,3,4,6,8,9,11,14,15,21,22 exhibited whole chromosome LOH in most cases reported by Gopal et al In contrast, Chrs 5, 7, 12, and 20 exhibited increased copy number relative to other chromosomes. However, it is not clear whether duplication of Chrs 5, 7, 12, and 20 stemmed from positive selection for increased DNA copy number of these chromosomes, or rather originated because these Chrs rarely underwent chromosomal loss prior to WGD.…”

Section: Chromosome Gains and Losses In Hccmentioning

confidence: 87%

“…The presence of a solid, insular, or trabecular growth pattern, not infrequent in Hürthle cell tumors, raises the possibility for transformation to poorly differentiated thyroid carcinoma (PDTC; Figure 3). The original Turin criteria excluded oncocytic/Hürthle cell lesions (11), but this diagnostic line has become blurred more recently (12)(13)(14)(15), a line that warrants molecular sorting rather than subjective histologic review, especially where outcomes and treatment modalities would be modified. These are often widely invasive tumors, with necrosis and mitotic activity, but while the cytoplasm may retain Hürthle cell features, the nuclei may be pleomorphic and lack the distinct prominent, centrally located nucleolus.…”

Section: A B D Cmentioning

confidence: 99%

Genetics, Diagnosis, and Management of Hürthle Cell Thyroid Neoplasms

McFadden

Sadow

2021

Front. Endocrinol.

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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.

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The Oncocytic Variant of Poorly Differentiated Thyroid Carcinoma Shows a Specific Immune-Related Gene Expression Profile

Cited by 9 publications

References 41 publications

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

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

Oncocytic Change in Thyroid Pathology

Genetics, Diagnosis, and Management of Hürthle Cell Thyroid Neoplasms

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