Low Rate of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features in Asian Practice

Dear Editor:

The recent introduction of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) to replace noninvasive encapsulated follicular variant of papillary thyroid carcinoma (eFV-PTC) is expected to have significant implications for patients and clinicians. The authors of the seminal paper estimated that reclassification of noninvasive eFV-PTC to NIFTP could potentially affect >45,000 patients per annum worldwide, who will no longer be labeled as having cancer (1). These projections were based on the findings from several Italian and American institutions, which reported an 18.6% mean incidence of NIFTP among >3400 PTC cases. Independent studies from the United States and Brazil found a 15–25% rate of NIFTP among all PTC (2 –5).

The Asian experience with NIFTP has not yet been reported. We collected data on the NIFTP incidence from the nine institutions (large to midscale tertiary thyroid cancer centers) from six Asian countries. Local databases were searched for all primary PTC over the applicable time period (1–9 years). Cases with recurrent/residual tumors and contralateral cancers on completion thyroidectomy were excluded to avoid duplications. All the slides with diagnoses of FV-PTC were retrieved from the archives and reviewed on-site by pathologists with thyroid expertise. FV-PTC cases were categorized as infiltrative, encapsulated invasive, or encapsulated noninvasive (NIFTP). The latter was applied only under strict diagnostic criteria proposed by Nikiforov et al. (1).

A total of 1070 cases of FV-PTC were identified after screening 26,604 cases of PTC (Table 1). Slide review demonstrated a very low incidence of NIFTP—the mean calculated as an average of particular tumor rates in nine series, regardless of the number of patients, was 1.5% (range 0–4.7%)—more than 10 times less than the Western series. There was a statistically significant variation of NIFTP rate among institutions (p < 0.001). In addition, rates of all forms of FV-PTC (mean 6.3%, range 2.2–9.8%) and its subset eFV-PTC (mean 3.1%, range 0.7–5.5%) were much lower than in the Western experience (e.g., 37.9% and 24% for FV-PTC and eFV-PTC, respectively) (1). Our findings are in the line with a previous study from an independent Japanese institution where noninvasive eFV-PTC accounted for 0.4% of all PTC cases (6).

Such striking differences between Western and Asian series can be attributed to several factors. First, geographic and ethnic differences may influence the type of thyroid tumors (and their mutational profile) that arises in Asian populations (7). Second, differences in histologic interpretation likely contribute to different rates of NIFTP and FV-PTC in general in Asian countries and Western series. In fact, a low rate of inter-observer agreement was previously demonstrated between Japanese and American experts (8). We believe that a variable diagnostic threshold (especially regarding nuclear features) still exists for FV-PTC and may explain the difference in rates of FV-PTC and NIFTP at the two institutions in the same city (Seoul) in the current study. Additional studies are needed to address the above issues.

Our findings may have an important impact for epidemiological studies on thyroid cancer reclassification. According to the GLOBOCAN statistics, 48% of all new thyroid cancer cases are diagnosed in Asia (9). We believe that worldwide estimates of patients affected by NIFTP and cost benefits of the reclassification need to be adjusted with regard to the low NIFTP rate in Asia. The results of our study also have important implications regarding the cytological diagnosis of thyroid nodules. It was reported that the introduction of NIFTP as “non-cancer” substantially decreased the risk of malignancy in indeterminate cytological categories, which may alter clinical decision making (2,4). We expect only a minor impact of NIFTP on risk of malignancy for thyroid nodules in Asian practice. More studies from major Asian countries are highly anticipated to extend our findings and to find a “border” between regions with high (>25%) and low (<10%) incidences of FV-PTC.