Re-Evaluation of 162 Malignant Thyroid Nodules that were Interpreted as Benign Based on Ultrasound Findings

The goal of this study was to estimate the risk of malignant thyroid nodules being interpreted as benign based on ultrasound findings and to clarify the pathological features of these malignant nodules. We retrospectively re-evaluated ultrasound and pathological findings for 162 malignant thyroid nodules that were initially interpreted as benign based on ultrasound findings at Kuma Hospital between April 2012 and June 2015.The incidences of malignancy among “benign” thyroid nodules were 0.5% overall and 6.2% among resected nodules. In addition, 82.7% of thyroid nodules that were originally judged to have low or very low suspicion patterns were subsequently re-categorized as having high or intermediate suspicion patterns. The incidences of irregular margins (63.6%) and low echogenicity (36.4%) were higher than those of punctate microcalcification (17.9%) and the taller-than-wide shape (20.4%). Among microcarcinomas, the incidences were 65.7% for irregular margins and 51.4% for low echogenicity. Rim calcification with small extrusive soft tissue components and extrathyroidal extensions were not observed. After re-evaluation, 40.0% of papillary thyroid carcinomas remained benign based on their variants, such as the encapsulated, follicular, macrofollicular, and oxyphilic cell variants. We conclude that more careful observation, especially for lesions with irregular margins and low echogenicity, can help improve the diagnostic accuracy of thyroid ultrasonography. Furthermore, greater care may decrease the incidence of malignancy among thyroid nodules with low or very low suspicion patterns. Some variants of papillary thyroid carcinoma can have benign ultrasound findings.

Extensive DNA Fragmentation in Oxyphilic Cell Lesions of the Thyroid

The in situ end-labeling (ISEL) method demonstrates DNA fragmentation, commonly regarded as a marker of apoptosis. We investigated by the ISEL procedure a series of 52 thyroid lesions, including 24 lesions of mitochondrion-rich oxyphilic cells, both benign and malignant, and 28 non-oxyphilic control tumors. A high percentage of nuclear ISEL staining (approximating to 100% in most cases) was observed in the vast majority of oxyphilic cells from both adenomas and carcinomas, in the absence of morphological apoptotic changes and with no immunocytochemical evidence of caspase activation. This pattern of DNA fragmentation was not observed in non-oxyphilic lesions and was confirmed in total extracted DNA. Moreover, a peculiar cytoplasmic staining was also observed in oxyphilic cells from both benign and malignant lesions, probably related to abnormal fragmentation of mitochondrial DNA. Similar staining patterns were detected in oxyphilic cell tumors of other organs (parathyroids, salivary glands, and kidneys). These findings are consistent with an extensive DNA fragmentation peculiar to oxyphilic cells, which is not directly related to apoptosis and whose origin and biological significance are presently unknown. (J Histochem Cytochem 49:1003–1011, 2001)