Sub-classification of Indeterminate Nodules May Help Improve Diagnostic Capabilities

Sub-classification of indeterminate thyroid nodules may improve diagnostic capabilities and allow a patient’s risk of cancer to be accurately determined, according to a new study presented at the 15th International Thyroid Congress in Lake Buena Vista, FL, hosted by the American Thyroid Association.¹

Researchers from the Moffitt Cancer Center reported that nuclear atypia should be routinely reported and recognized as a highly suspicious feature in thyroid nodules with indeterminate cytology.

The researchers reviewed the biopsy specimens of 271 patients whose thyroid nodules showed indeterminate cytology. They found that the results of molecular marker tests on these samples did not appear to be sufficiently reliable to avoid surgery, nor sufficiently informative to affect the extent of surgery.

Instead, the molecular tests merely added expense and provided little benefit. However, the researchers found that the molecular marker tests might produce more useful diagnostic information in the other types of nodule with indeterminate cytology, potentially avoiding unnecessary diagnostic surgery in those patients.

“About 20% to 30% of thyroid nodules have indeterminate findings on cytology following a biopsy. The chance of cancer in these nodules is about 1 in 3. In the past, these patients needed surgery to figure out whether it was really cancer, with a second surgery needed to complete the treatment, when cancer was confirmed,” said senior study author Bryan McIver, MD, PhD, who is the chair of the Endocrine Program at Moffitt Cancer Center in Tampa, FL.

“Recently, several molecular tests were developed to improve the ability to diagnose these nodules. However, these tests are expensive, and their performance depends on the probability of cancer in the samples being tested.”

The researchers sub-classified thyroid nodules that showed indeterminate cytology into 4 groups. They found that 29% of the nodules had nuclear atypia, 47% were suspicious for a follicular neoplasm without nuclear features, 24% were suspicious for a Hürthle cell neoplasm without nuclear features, and <1% had other atypical features. 

The nodules classified as having nuclear atypia had a significantly higher prevalence of malignancy than the other groups (63% vs 17%).

“We found that classifying these nodules according to the presence or absence of nuclear atypia (oddly shaped or patterned nuclei) was able to split the nodules into 2 groups. Those with nuclear atypia were most likely to be cancer (>60% chance). Those without these changes were much less likely to be cancer (<20% chance),” Dr. McIver told Cancer Therapy Advisor.

“Based on these results, we suggest that nuclear atypia should always be reported on thyroid cytopathology reports.”

He said molecular tests should not be used to avoid surgery in nodules with nuclear atypia due to a high probability of false-negative findings. Dr. McIver said all of the commercially available molecular tests could be used in those nodules without nuclear atypia.