Search Results (5)

Objective: The 2022 WHO classification introduced differentiated high-grade thyroid carcinoma (DHGTC) as a distinct category characterized by high-grade features despite maintained differentiation. Therefore, this study aims to evaluate its clinical characteristics, treatment responses, and the prognostic impact of the Ki-67 proliferation index in this patient population. Methods: We retrospectively reviewed 3100 patients with differentiated thyroid carcinoma (DTC) between 2017 and 2024. From this baseline pool, a total of 56 patients (1.8%) were identified and re-classified as DHGTC based on mitotic count (≥5/2 mm²) and/or tumor necrosis. Additionally, 69 DTC patients (2.2%) with an elevated Ki-67 index (>5%) identified from the same baseline pool—representing an overlapping group with the DHGTC cohort—were analyzed to evaluate its clinical significance. Results: In the DHGTC group, tumor necrosis was present in 87.5% and high mitotic activity in 19.6% of cases. While all DHGTC patients were classified as high-risk under 2025 American Thyroid Association (ATA) guidelines, 42.8% showed biochemical or structural incomplete response at the last follow-up and 28.6% required additional salvage interventions. In the broader DTC cohort, Ki-67 ≥ 15% was significantly associated with older age, larger tumor size, extensive invasion, and poorer treatment response (p < 0.05). However, within the DHGTC subset, Ki-67 ≥ 15% was only significantly associated with increased lymphovascular invasion and more extensive surgery. Conclusions: DHGTC carries a significant burden of aggressive histopathological features and a high risk of structural disease persistence or recurrence. While an elevated Ki-67 index (≥15%) serves as an adverse marker in general DTC, its additional prognostic value within the high-grade DHGTC cohort remains inconclusive, potentially obscured by limited statistical power due to small subgroup sizes. Full article

Thyroid cancer (TC) incidence is rising, necessitating a refined understanding of its complex biology, particularly for advanced forms. This review synthesizes the state-of-the-art knowledge, guided by the WHO 5th Classification (2022), which incorporates molecular findings and introduces categories like Differentiated High-Grade Thyroid Carcinoma (DHGTC) to better stratify prognosis. The review summarizes the molecular changes in thyroid cancer (TC) by establishing a clear link between specific oncogenic alterations and the resulting tumor phenotype, prognosis, risk stratification and therapeutic vulnerabilities. The central importance of the review lies in its comprehensive integration of these molecular changes with the resulting immunological microenvironment and the rationale for novel, personalized therapies. Moreover, high-level genomic instability within aggressive thyroid malignancies promotes an immunosuppressive tumor microenvironment via the selection and recruitment of suppressive immune components, contributing to immune evasion and poor prognosis. This characteristic immunosuppression identifies the aggressive tumors as prime candidates for targeted immunotherapies. The review implicitly argues that understanding the molecular drivers of this immunosuppression is essential for designing effective clinical trials using these novel agents. Diagnostic advancements, including molecular testing for high-risk mutations (BRAF, TERT) and the integration of Artificial Intelligence (AI) for refined risk stratification, are enabling personalized treatment. The evolving molecular and clinical understanding allows for a paradigm shift toward individualized therapies that balance optimal disease control with minimizing morbidity, especially in the context of high-risk disease. Full article

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. Full article

Differentiated high-grade thyroid carcinoma (DHGTC) is a new subset within the spectrum of thyroid malignancies. This review aims to provide a comprehensive overview of DHGTC, focusing on its historical perspective, diagnosis, clinical characteristics, molecular profiles, management, and prognosis. DHGTC demonstrates an intermediate prognosis that falls between well-differentiated thyroid carcinoma and anaplastic thyroid carcinoma. Previously unenumerated, this entity is now recognized for its significant impact. Patients with DHGTC often present at an older age with advanced disease and exhibit aggressive clinical behavior. Molecularly, DHGTC shares similarities with other thyroid malignancies, harboring driver mutations such as BRAFV600E and RAS, along with additional late mutations. The unique behavior and histologic features of DHGTC underscore the necessity of precise classification for prognostication and treatment selection. This highlights the critical importance of accurate diagnosis and recognition by pathologists to enrich future research on this entity further. Full article

In 2022, the new WHO Classification of Endocrine and Neuroendocrine Tumors, Fifth Edition (beta version) (WHO 5th), was published. Large-scale genomic analyses such as The Cancer Genome Atlas (TCGA) have revealed the importance of understanding the molecular genetics of thyroid tumors. Consequently, the WHO 5th was fundamentally revised, resulting in a systematic classification based on the cell of origin of tumors and their clinical risk. This paper outlines the following critical points of the WHO 5th. 1. Genetic mutations in follicular cell-derived neoplasms (FDNs) highlight the role of mutations in the MAP kinase pathway, including RET, RAS, and BRAF, as drivers of carcinogenesis. Differentiated thyroid cancers such as follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) have specific genetic alterations that correlate with morphological classifications: RAS-like tumors (RLTs) and BRAF p.V600E-like tumors (BLTs), respectively. 2. The framework for benign lesions has been revised. The WHO 5th introduces a new category: “developmental abnormalities”. Benign FDNs comprise “thyroid follicular nodular disease”, follicular thyroid adenoma (FTA), FTA with papillary architecture, and oncocytic adenoma (OA). “Hürthle cell adenoma/carcinoma” is renamed oncocytic adenoma/carcinoma of the thyroid (OA/OCA), which can be distinguished from FTA/FTC by its unique genetic background. 3. Low-risk tumors include NIFTP, TT-UMP, and HTT, and they have an extremely low malignant potential or an uncertain malignant potential. 4. PTC histological variants are reclassified as “subtypes” in the WHO 5th. 5. The concept of high-grade carcinomas is introduced, encompassing poorly differentiated thyroid carcinoma (PDTC), differentiated high-grade thyroid carcinoma (DHGTC), and high-grade medullary thyroid carcinoma (MTC). 6. Squamous cell carcinoma is included in anaplastic thyroid carcinoma (ATC) in the WHO 5th due to their shared genetic and prognostic features. 7. Other miscellaneous tumors are categorized as salivary-gland-type carcinomas of the thyroid, thyroid tumors of uncertain histogenesis, thymic tumors within the thyroid, and embryonal thyroid neoplasms. The WHO 5th thus emphasizes the importance of classifying tumors based on both genetic abnormalities and histomorphology. This approach aids in achieving accurate pathological diagnosis and facilitates the early selection of appropriate treatment options, including molecular targeted therapies. Full article