American Thyroid Association Nonclassifiable Thyroid Nodules: A New Perspective

The American Thyroid Association Sonographic Pattern System (ATASPS) cannot categorize as many as 17.9% of thyroid nodules (1), a vexing problem that may hamper its application in clinical practice. In their article in the current issue of Thyroid, Kobaly et al. (2) present a study in which they assessed whether nonhypoechoic solid nodules deemed nonclassifiable (NC) because of certain ultrasound features could be categorized using other grayscale findings without affecting their estimated cancer risk. In particular, the authors focused on nodules containing shadowing macrocalcifications or punctate echogenic foci (PEF), which they collectively termed non-high suspicion calcifications (NHSC).

Out of 728 nodules in this series, 584 nodules were classifiable as ATASPS, while 144 were not. Of the latter, 101 were NC because of NHSC. Notably, when the ATASPS was applied to these nodules using grayscale features other than NHSC, their malignancy risks and cytology findings were not significantly different from the nodules that were classifiable. Nine nodules that contained PEF were predominantly isoechoic, with a 19% cancer prevalence, compared with 10% for the entire low-suspicion group. This difference, which was not statistically significant, was consistent with research showing that PEF in mixed cystic and solid nodules may be less concerning than PEF in solid hypoechoic nodules (3).

Forty-three nodules remained NC after recategorization to exclude NHSC. Of 30 solid nodules that could not be classified because of heterogenous echogenicity, 17 were malignant, which deserves further investigation to determine the significance of this appearance. Thirteen nodules had complete peripheral calcification that concealed their internal architecture. While only two of them were malignant, this conflicts with other published research that demonstrated a much higher cancer rate in rim-calcified nodules (4).

Although most risk stratification systems consider PEF to be suspicious, particularly in solid, predominantly hypoechoic nodules, the significance of other calcifications remains unresolved. The European TIRADS, the Korean TIRADS, and the Chinese TIRADS do not incorporate them in malignancy assessment (5 –7). In contrast, the ACR TI-RADS awards one point for macrocalcifications and two points for rim calcifications (8).

In Kobaly's study, nodules with internal coarse calcifications and peripheral calcifications were grouped for analysis. This contrasts with an evaluation of 3603 nodules by Shin et al. (9), in which they were treated separately. They demonstrated that the likelihood of cancer was greater for macrocalcifications than rim calcifications (33.8% vs. 14.7%). Moreover, nodules with macrocalcifications only were significantly more likely to be malignant than nodules with rim calcifications only (35% vs. 16.7%). Yin et al. (10) assessed 543 patients, of whom 204 had macrocalcifications, which were further subdivided into four morphological subtypes. They found that incomplete rim and layered internal calcifications were associated with malignancy.

If their results can be confirmed, Kobaly et al.'s study will advance the state of the art by informing improvements to the ATASPS that can substantially reduce the proportion of NC nodules. However, further research will be required to evaluate whether there are configurations of macrocalcifications and peripheral calcifications that confer an increased risk of cancer independent of or in addition to other features, especially when they are present in combination. This also highlights the pressing need to reach broad consensus on a universal lexicon for all types of thyroid nodule calcifications, which have been defined differently by various investigators, potentially compounding confusion regarding their significance in cancer risk stratification.