Aggressive Thyroid Carcinomas Clinical and Molecular Features: A Systematic Review

Abstract

Aggressive thyroid carcinomas are rare malignancies characterized by a high impact on patient's lives and poor prognosis. The available literature is scarce presenting divergent data concerning the clinical outcomes, prognostic factors and variable mutational signature studies. We aim to collect data from the literature and assemble a systematic review. The literature from 2007 until May 2025 was searched using PubMed. Studies bearing data concerning clinical aspects, prognostic outcomes, or molecular characteristics of differentiated high-grade (DHGTC), poorly differentiated (PDTC), and anaplastic thyroid carcinomas (ATC) were retrieved. Original articles in English, ethically conducted on human patients, were selected. From 688 articles, 39 were included. DHGTC has a good 5-year survival rate (5YSR) of 76%, 23.18% metastasis rate, 42.23%, lymph node involvement (LNI), 61.44% extrathyroidal extension (ETE), majority being diagnosed in stage III. PDTC has an intermediate 5YSR of 65.71%, 21.17% distant metastasis, 32.22% LNI, and 55.19% ETE, majority diagnosed in stage III. ATC has a grim 2-year survival rate of 11.15%, 42.15% metastasis, 44.14%, LNI, and 58.51% ETE, majority presented in stage IV-B. Mutational profiling shows that each carcinoma has its unique set of molecular alterations. Most positive prognostic comes for DHGTC, then PDTC, and finally, ATC.

Keywords: ATC; DHGTC; PDTC; aggressive; anaplastic; differentiated high grade; poorly differentiated; thyroid carcinoma.

Figure 1

PRISMA flow chart showing the employed search strategy [59].

Figure 2

Metastasis rates upon initial presentation, lymph node involvement, and extrathyroidal extension values as percentages, represented for each type of cancer. On the vertical axes, we plotted points pertaining to the value provided by each study and the standard deviation. The red horizontal lines provide the weighted average for each parameter, weighted by the number of patients included in the studies. DM distant metastases; LN lymph node involvement; ETE: extrathyroidal extension; DHGTC: differentiated high-grade thyroid carcinoma; PDTC: poorly differentiated thyroid carcinoma; ATC: anaplastic thyroid carcinoma; n: number of patients included in each column.

Figure 3

(A) AJCC Stage at presentation distribution by type of cancer, as weighted averages. (B) Weighted average of mean tumor size by cancer type, vertical bars plot for standard deviation. DHGTC: differentiated high grade thyroid carcinoma; PDTC: poorly differentiated thyroid carcinoma; ATC: anaplastic thyroid carcinoma, n: number of patients included.

Figure 4

Overall survival for each type of cancer. Note the abruptly smaller overall survival in the case of ATC. DHGTC: differentiated high grade thyroid carcinoma. PDTC: poorly differentiated thyroid carcinoma; ATC: anaplastic thyroid carcinoma, n: number of patients included.

Figure 5

Mutation prevalence in percentage, represented for each type of cancer. On the horizontal axis, we plotted the value provided by each study and the standard deviation. The red vertical lines provide the weighted average for each parameter, weighted by the number of patients included in the studies. Only TP53 difference is statistically significant between DHGTC-PDTC and DHGTC-ATC (p < 0.01). DHGTC: differentiated high grade thyroid carcinoma; PDTC: poorly differentiated thyroid carcinoma; ATC: anaplastic thyroid carcinoma, n: number of patients included for each parameter.