Re-Evaluation of Histopathological Factors Affecting Prognosis of Differentiated Thyroid Carcinoma in an Iodine-Sufficient Country

Poorly differentiated thyroid carcinoma (PDTC) was recognized as an independent clinicohistological entity of thyroid cancer in the 2004 World Health Organization (WHO) classifications, separated from papillary (PTC) and follicular carcinoma (FTC). The Turin proposal provides more specific criteria for the diagnosis of PDTC. However, in an iodine-sufficient country such as Japan, PDTC comprises <1% of all thyroid cancers. In 1983, Sakamoto analyzed pathological characteristics of PTC and FTC that recurred within 5 years after initial surgery and identified solid, trabecular, insular (STI) and scirrhous growth patterns as important predictors of poor prognosis. We re-evaluated the impact of histopathological findings on the clinical course of PTC and FTC.

Specimens from 376 consecutive cases diagnosed as PTC (n = 351) or FTC (n = 25) between 1994 and 2001 were reviewed.

Nine (2%) patients were diagnosed with PDTC according to WHO criteria. Only 1 case (0.3%) met the Turin criteria. In addition, STI components were seen in various specimens as follows: ≥50%, ≥10% but <50%, >0% but <10%, and 0% of specimens for 9 (2%), 31 (8%), 19 (5%), and 317 cases (85%), respectively. As for cause-specific survival, a significant difference was apparent between the ≥50% and ≥10% but <50% groups. Disease-free survival was identical between these groups and was significantly worse than in the >0% but <10% and 0% groups. According to multivariate analysis, histological features of STI ≥10% and squamous metaplasia were significantly related to cause-specific survival, but scirrhous infiltration, necrosis, nuclear atypia, and vascular invasion were not. The presence of STI at a level ≥10% was also a significant risk factor, together with clinical risk factors including large tumor size, large nodal metastasis, and distant metastasis. According to AMES risk-group definition, clinically high-risk patients with STI ≥10% showed the worst 10-year cause-specific survival, at 57%, irrespective of total thyroidectomy with radioactive iodine (RAI) treatment. Ten of 25 PTC patients (40%) with STI ≥10% developed cervical recurrence, whereas 9 of 15 FTC patients (60%) with STI ≥10% showed distant metastasis.

The measurement of STI ≥10% represents a distinctly important risk factor for patient survival. In particular, clinically high-risk patients with STI ≥10% need further therapy beyond RAI. Original histological pattern, as papillary or follicular, affects the site of recurrence.