Is Poorly Differentiated Thyroid Cancer Poorly Characterized?

Abstract

Poorly differentiated thyroid cancer (PDTC) has remained a controversial diagnosis. Some clinicians refer to PDTC as thyroid cancers that do not trap radioiodine on radioiodine scans (either initially or during monitoring), and others believe that it is appropriate to refer to rapidly growing thyroid cancers that have apparently not responded to radioactive iodine therapy (1). However, in many instances it is difficult to determine whether radioiodine therapy has been partially effective. We and others had noted that “poorly differentiated thyroid carcinoma is a concept proposed to include carcinomas of follicular thyroid epithelium that retain sufficient differentiation to produce scattered small follicular structures and some thyroglobulin, but generally lack the usual morphologic characteristics of papillary and follicular carcinoma” (2–4). In separate reports, Sakamoto et al (3) in 1983 and Carcangiu et al (5) in 1984 initially pathologically described the discrete category of PDTC. However, these authors used different characteristics to define this entity, resulting in a long-standing dispute regarding the appropriate pathological definition of PDTC. The World Health Organization tumor classification attempted to better define this entity, but this also has been considered controversial (6, 7). Inaneffort toquell thecontroversy,agroupofestablished pathologists and investigators set forth what is referred to as the Turin proposal. This proposal set forth specific histological characteristics toattempt touniversallydefinePDTC(7). These criteria include: 1) the presence of a solid/trabecular/ insular pattern of growth; 2) the absence of the conventional nuclear features of papillary carcinoma; and 3) the presence of at least one of the following features: convoluted nuclei, mitotic activity 3 per 10 high-power fields, and tumor necrosis (7).However,PDTCremainsaclinicallyandpathologically inchoate disorder, and it is not known whether it represents a single clinical or molecular entity. Furthermore, the optimal clinical approach for monitoring and treatment modalities is unknown. Recent articles on the topic of PDTC have assessed and commented upon the diagnostic criteria and have reviewed this entity (8–13). These articles emphasize the variations in the diagnostic criteria and that PDTC is generally considered in the middle of the spectrum between well-differentiated thyroid cancer and undifferentiated or anaplastic thyroid cancer. Asioli et al (14) reported that poorly differentiated carcinoma had a prevalence (in pathological thyroid malignancies) of 1.8% (56 of 3128) in the Unites States (at Mayo Clinic)andof6.7%(96of1442) innorthernItaly (University of Turin). Thyroglobulin immunostaining was positive in 92% (95 of 103) of PDTC cases, and thyroid transcription factor 1 immunostaining was positive in each of 103 PDTC cases. The authors concluded, using univariate analysis, that PDTC was associated with a greater risk of death in patients age 45 or greater and for tumors of 4 cm or larger; multivariate analysis confirmed the age-related finding. The present study by Ibrahimpasic et al (15) from the well-respected Memorial Sloan Kettering group attempts to better define the prognosis of PDTC patients. They retrospectively analyzed 91 patients with PDTC treated at their institution between the years 1986 and 2009. Over a median of 50 months of monitoring, the 5-year overall survival was 62%, and disease-specific survival was 66%. The vast majority of disease-specific deaths were related to the presence of distant, metastatic disease (23 of 27 deaths; 85%). Locoregional control was higher at 81% than was distant control at 59%. Multivariate analysis showed that initial pT4a stage distant metastases (M1) were independently associated with poorer disease-specific survival,