Genetics, Diagnosis and Management of Oncocytic (Hürthle Cell) Thyroid Neoplasms

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Background

Traditionally, oncocytic thyroid tumors have been considered to represent a distinctive set of lesions with granular cytoplasmic eosinophilia and striking accumulation of mitochondria because of mitochondrial DNA abnormalities, such as point mutations or deletions. The oncocytic phenotype occurs in a wide range of endocrine neoplasms, being more common in the thyroid. Oncocytic change and tumors with oncocytic cytomorphology encompass a heterogenous group of benign and malignant diagnostic categories. While oncocytic variants of papillary thyroid carcinoma (PTC), poorly differentiated thyroid carcinoma and medullary thyroid carcinomas still remain valid diagnostic considerations in thyroid pathology, advances in molecular biology have questioned the validity of the 2014 WHO classification in which Hürthle cell neoplasms were classified as variants of follicular adenomas (when non-invasive and no PTC nuclei) and follicular thyroid carcinomas (when invasive and no PTC nuclei). Despite the inappropriate terminological designation of “Hürthle cell” for an oncocytic follicular neoplasm lacking PTC nuclei, these tumors are now assigned to a distinct diagnostic category as of the 2017 WHO classification of thyroid neoplasms. However, the proposed classification, and lack of clarity on the classification of tumors in which transition between tumor entities (e.g. some cases classified as Hürthle cell carcinomas can be classified as an oncocytic poorly differentiated thyroid carcinomas) have created complexity and confusions for physicians dealing with these neoplasms.

While the exclusion criteria on how oncocytic poorly differentiated thyroid carcinomas are distinguished from “well differentiated” Hürthle cell carcinoma have not been uniformly used within the 2017 WHO criteria, in general, it is thought that the oncocytic phenotype has been reported to interfere with the response to radioactive iodine therapy (RAI). When a thyroid cancer with an increased risk of structural recurrence is detected, the standard approach has been to perform total thyroidectomy followed by RAI to destroy the remaining thyroid tissue as well as possible metastatic foci. About 10% of these patients show recurrence and around 10 years later metastasized to other organs, and more than 60% of these are oncocytic and tend to manifest with RAI refractory disease. The prognosis of recurrent or metastatic thyroid cancers is poor, with less than 50% survival rate.

A unified AJCC/UICC classification system based on pTNM (tumor, nodes, and metastasis) and age is applied to Hürthle cell carcinomas as well as to all other thyroid carcinomas including those falling into the diagnostic categories of oncocytic papillary thyroid carcinoma and oncocytic poorly differentiated thyroid carcinoma.
In this research topic we are planning to invite experts pathologists, endocrinologists, surgeons, oncologists and scientists to dissect characteristics of oncocytic tumors that will help the reader to explore the pathologic, genomic and proteomic profile of oncocytic thyroid tumors through studies in form of original research, mini reviews, perspective or opinion articles, hypothesis or theory articles etc.

This research topic proposal will review several major advances in our understanding of the pathology of these entities:
o reviewing the morphologic spectrum of oncocytic follicular neoplasms
o the detailed pathological and
o cytological features,
o genomic and
o proteomic profile advancing our understanding the biology of this spectrum will be discussed.

Such a broad and multidisciplinary update in these group of tumors is needed to better understand that characteristics of oncocytic follicular epithelial derived thyroid carcinomas vary depending on the right distinction of diagnostic entities ranging from oncocytic papillary thyroid carcinomas to oncocytic poorly differentiated thyroid carcinomas as well as tumors falling into Hürthle cell carcinomas.

Keywords: Hürthle cell tumor, oncocytic, thyroid, pathology, cytopathology, treatment, molecular biology, genetics, diagnosis

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