Aggressive Thyroid Carcinomas Clinical and Molecular Features: A Systematic Review

Area of Science:

• Endocrinology and Oncology
• Thyroid Cancer Research
• Molecular Pathology

Background:

• Aggressive thyroid carcinomas, including differentiated high-grade (DHGTC), poorly differentiated (PDTC), and anaplastic thyroid carcinoma (ATC), are rare but devastating malignancies with limited literature on outcomes.
• Existing data on clinical outcomes, prognostic factors, and mutational signatures are often divergent, necessitating a comprehensive review.

Approach:

• A systematic literature review was conducted using PubMed, searching articles from 2007 to May 2025.
• 39 original English articles on human patients, focusing on clinical aspects, prognosis, or molecular characteristics of DHGTC, PDTC, and ATC, were included from 688 retrieved studies.

Key Points:

• Differentiated high-grade thyroid carcinoma (DHGTC) shows a 76% 5-year survival rate, with significant lymph node involvement (42.23%) and extrathyroidal extension (61.44%), predominantly diagnosed in Stage III.
• Poorly differentiated thyroid carcinoma (PDTC) has an intermediate 5-year survival rate of 65.71%, with 32.22% lymph node involvement and 55.19% extrathyroidal extension, also mostly diagnosed in Stage III.
• Anaplastic thyroid carcinoma (ATC) presents a poor 2-year survival rate of 11.15%, with high rates of metastasis (42.15%), lymph node involvement (44.14%), and extrathyroidal extension (58.51%), frequently diagnosed in Stage IV-B. Each subtype exhibits unique molecular alterations.

Conclusions:

• The prognosis for aggressive thyroid carcinomas follows a clear gradient: DHGTC > PDTC > ATC.
• Understanding the distinct clinical and molecular profiles of these aggressive thyroid cancers is crucial for targeted therapeutic strategies and improved patient outcomes.