Poorly differentiated thyroid cancer: molecular signatures, classification, diagnosis, clinical characteristics, treatment, prognosis

Abstract

Poorly differentiated thyroid cancer is an invasive and aggressive malignant tumor that histologically has a solid, trabecular, or islet-like (or a combination thereof ) growth pattern. More often, they arise as a result of cell dedifferentiation of well-differentiated thyroid carcinomas, which lose their typical features and acquire intermediate characteristics between well-differentiated and anaplastic carcinoma. Poorly differentiated thyroid carcinoma (РDTC) was first described in 1907, but it still remains a significant problem for clinicians due to the difficulties associated with the diagnostic process, the need for complex thyroidectomy, high recurrence rate (despite appropriate treatment), and significant mortality. This is why it was important to recognize РDTC as a separate type of malignant tumor, both from an oncological and clinical point of view, but this only happened in 2004. In 2006, the so-called «the Turin criteria» were published, establishing modern histological features by which РDTC is diagnosed. The literature on РDTC contains conflicting data regarding variable mutational signatures, clinical outcomes, and prognostic factors. Despite extensive research efforts,PDC of the thyroid gland still remains clinically and pathologically complex. Consequently, there is a lack of consensus among clinicians on the criteria for defining РDTC and its treatment, given its low incidence and the difficulty in standardizing diagnostic criteria. These limitations also hinder the comparison of therapeutic modalities, results of recent and previous studies, which are insufficient in number, and in some cases often include different histological types of thyroid tumors, which affects the determination of treatment strategy. There are no clinical signs that allow for an accurate diagnosis of РDTC; only morphological examination methods, and
in recent years, immunohistochemical and, to a certain extent, molecular genetic technologies have become increasingly common. Recent advances in the diagnosis of thyroid tumors have also enriched therapeutic options and improved the prognosis, including for patients with РDTC. The review provides information on the classification, prevalence, pathogenesis, genomic landscape, diagnosis, and clinical characteristics of РDTC, as well as therapeutic strategies (including targeted therapy) and disease prognosis.