Poorly differentiated thyroid carcinomas defined on the basis of mitosis and necrosis - A clinicopathologic study of 58 patients

BACKGROUND. Poorly differentiated thyroid carcinomas (PDTC) occupy an intermediate position at the prognostic level on the spectrum of thyroid carcinoma progression. However, their histologic definition is controversial. The objective of the current study was to assess the prognostic significance of PDTC defined on the basis of mitosis and necrosis and search for prognostic markers within this group of tumors that are predictive of overall survival (OS) and progression-free survival (PFS). METHODS. PDTC was defined as thyroid carcinoma with follicular cell differentiation at the histologic and/or immunohistochemical levels and displaying tumor necrosis and/or ! 5 mitoses per 10 high-power fields (X400). Retrospective chart review and microscopic examination identified 58 patients with primary tumors meeting the above criteria and seen at the Memorial Sloan-Kettering Cancer Center between 1992 and 2004. These 58 patients were analyzed for various histologic, clinical, and imaging parameters. Each parameter was correlated with OS and PFS. RESULTS. Of the 58 patients studied, 22 (38%) patients died of disease with a 5-year OS rate of 60%. Forty-three of the 58 patients (74%) developed disease recurrence or disease progression, with a 5-year PFS rate of 25%. The median follow-up for the entire patient population was 42.6 months (range, 4-205 mos). A tumor size > 4 cm was found to be correlated with a decreased PFS time (P < 0.001). Those tumors with a capsule demonstrated a significantly improved OS compared with unencapsulated tumors (P = 0.001). The extent of capsular invasion was found to be a significant adverse factor for PFS (P = 0.05). The presence of extrathyroid extension into perithyroid soft tissue was found to be correlated with a decreased OS (P = 0.001) and PFS (P = 0.004). Of 27 patients with distant metastasis, 19 (70%) had concentrated radioactive iodine (RAI) at their metastatic sites. On multivariate analysis, extrathyroid extension and tumor size emerged as the only significant variables in predicting PFS (P = 0.04 and P = 0.01, respectively) whereas extrathyroid extension was found to be the sole independent prognostic factor for OS (P = 0.01). Growth pattern and cell type did not appear to influence outcome. CONCLUSIONS. PDTC defined on the basis of mitosis and necrosis constitutes a group of tumors that is more aggressive and homogeneous than PDTC defined by growth pattern. Within this group of patients, microstaging (tumor size, the extent of capsular invasion, and, especially, extrathyroid extension), and not growth pattern or cell type, is able to stratify patients into different prognostic categories. RAI uptake occurs in a significant number of patients with PDTC.