Advances in Thyroid Pathology: High Grade Follicular Cell-derived Thyroid Carcinoma and Anaplastic Thyroid Carcinoma

Abstract

In the upcoming World Health Organization fifth edition classification of endocrine tumors, there were several major changes related to high grade follicular-derived thyroid carcinoma (HGFCTC) and anaplastic thyroid carcinoma (ATC) based on emerging evidence about the diagnostic criteria clinical behavior, prognostic factors, and molecular signatures of these tumors. In this review, we aim to summarize the major evolutions of HGFCTC and ATC. HGFCTC is a nonanaplastic carcinoma with high grade features (High mitotic count, tumor necrosis). It is subdivided into poorly differentiated thyroid carcinoma diagnosed using the Turin proposal and differentiated high grade thyroid carcinoma. The latter is defined by the presence of the cytoarchitectutal features of well-differentiated thyroid carcinoma (eg, papillae) but harbors elevated mitotic activity and/or tumor necrosis. Poorly differentiated thyroid carcinoma is predominantly RAS-driven and associated with RAI avidity and high propensity for distant metastasis, whereas differentiated high grade thyroid carcinoma is mostly BRAFV600E-driven. ATC may show a wide range of histologic features. Carcinoma of pure squamous phenotype is associated with a high frequency of BRAF V600E mutations and is now considered as a subtype of ATC. There is a stepwise molecular progression from well-differentiated carcinoma to HGFCTC to ATC manifested by 1) early and persistent driver alteration in the MAPK pathway, particularly BRAF V600E and RAS mutations, and 2) gain of secondary aggressive molecular signatures (such as TERT promoter and TP53 mutations) when tumors progress from well-differentiated to high grade to anaplastic carcinoma.

A Non-Invasive Follicular Thyroid Cancer Risk Prediction System Based on Deep Hybrid Multi-feature Fusion Network

“…Follicular thyroid tumours that do not show obvious signs of malignancy currently still require surgical excision and are judged to be benign or malignant based on the presence of envelope, vascularity, extrathyroidal tissue invasion and distant metastases [8]. However, studies have shown that only about 20%-30% of follicular thyroid tumours are proven to be malignant after surgery [9,10], meaning that most patients undergo diagnostic thyroid lobectomy despite the benign nature of the tumour, causing heavy emotional stress and financial burden to the patient. For this reason, it is urgent to have a non-invasive and effective method to predict the risk of benign and malignant thyroid follicular tumours and to guide the clinical diagnosis and treatment process.…”

Special Issue on Neuroendocrine Tumors: Updates on Classification Systems, Streamlining Diagnosis, and Emphasis on Molecular Signatures in Neuroendocrine Neoplasms

“…This special issue of Advances in Anatomic Pathology highlights several hot topics in the realm of neuroendocrine neoplasia of the pituitary, thyroid, adrenal, parathyroid glands, and the pancreas; fundamental for the contemporary practicing pathologist's diagnostic arsenal. [1][2][3][4][5][6][7] These timely reviews will comprise current best practices, including algorithmic approaches to the diagnosis and grading of such entities, along with conveying essential advances at the molecular level. In addition, 1 review focuses solely on the newest updates in familial endocrine tumor syndromes.…”

“…This review also acknowledges many of the pitfalls that we face, particularly in thyroid cytopathology, and highlights the importance of advances in molecular diagnostics that can aid our diagnostic abilities, particularly with limited fine needle aspiration samples that lack complete architectural structure and the presence or absence of invasive features to definitively classify a tumor as malignant or benign 3. Furthermore, Ghossein and Xu deliver a well-written overview detailing the advances in differentiating high-grade follicular carcinoma from anaplastic carcinoma with excellent illustrative examples comparing key histologic, immunohistochemical, and molecular features 4. This review is particularly helpful in demonstrating the key differences between poorly-differentiated and differentiated high-grade carcinomas and the molecular progression starting from a well-differentiated thyroid carcinoma to anaplastic transformation 4…”

“…4 This review is particularly helpful in demonstrating the key differences between poorly-differentiated and differentiated high-grade carcinomas and the molecular progression starting from a well-differentiated thyroid carcinoma to anaplastic transformation. 4 Gambella et al 5 provide a detailed account of the histopathologic features of the uncommon, but aggressive, adrenocortical carcinoma. These tumors pose a unique challenge as there is no reliable way to clinically or radiologically differentiate an adrenal carcinoma from an adenoma; therefore, careful examination by a pathologist is essential.…”

“…3 Furthermore, Ghossein and Xu deliver a well-written overview detailing the advances in differentiating highgrade follicular carcinoma from anaplastic carcinoma with excellent illustrative examples comparing key histologic, immunohistochemical, and molecular features. 4 This review is particularly helpful in demonstrating the key differences between poorly-differentiated and differentiated high-grade carcinomas and the molecular progression starting from a well-differentiated thyroid carcinoma to anaplastic transformation. 4 Gambella et al 5 provide a detailed account of the histopathologic features of the uncommon, but aggressive, adrenocortical carcinoma.…”