Abstract
I read with interest the article from Rhee et al. entitled “Follicular Variant of Papillary Thyroid Carcinoma: Distinct Biologic Behavior Based on Ultrasonographic Features” (1). In their study, the authors found that patients with a follicular variant of papillary thyroid carcinoma (FVPTC) having malignant ultrasonographic (US) features (taller-than-wide shape, infiltrative margin, marked hypoechogenicity, and micro- or macrocalcifications) have a worse prognosis (e.g., lymph node metastasis, higher stage) than patients with a FVPTC without malignant US features. Thus, they suggest that US can help to predict the behavior of FVPTC.
Those interesting results are in line with several previous clinicopathologic studies, which have shown that the encapsulated or well-circumscribed form of FVPTC very rarely metastasizes, while the infiltrative form of FVPTC is associated with significant risk of lymph node metastasis (2), approaching the rates reported in the classic type of PTC (65%).
However, I would like to point out several additional limitations factors in this retrospective study, from a pathologist's point of view.
Mainly, the histology of FVPTC cases was not reviewed in this study, and important histologic features such as tumor encapsulation or lymphovascular invasion were not recorded. It is well known that the pathologic diagnosis of FVPTC can be very challenging, both preoperatively by fine-needle aspiration biopsy (FNAB) and postoperatively on histology (3,4). FVPTC is subject to exceptionally high rates of interobserver and intraobserver variability even among those considered to be experts in this field (4). In many cases, FVPTC cannot be clearly defined on FNAB and histology, mainly due to the absence of the well-developed nuclear features of PTC (3,4). Therefore, the sensitivity of FNAB for FVPTC is only 25%, and most cases of FVPTC are diagnosed cytologically as “suspicious for PTC,” “suspicious for a follicular neoplasm,” or “atypia of unknown significance” on FNABs, according to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) (3). It would have been very interesting to know the FNAB diagnosis of the FVPTC cases in this study, and to see if there was a correlation with US features (malignant US features group vs. without malignant US features group) and other clinicopathologic parameters. Indeed, it has been shown by VanderLaan et al. that TBSRTC not only conveys malignancy risk, on which recommendation for the management of the patient derives, but also predicts the presence of pathologic risk factors and disease progression when the malignancy is PTC (3). Because a majority of FVPTC end up in one of the indeterminate cytologic categories discussed above, the US characteristics of the tumor may be helpful in order to define the clinical management in this category of patients better, either alone or in conjunction with molecular testing. For example, the clinical management and the prognosis of a FVPTC case diagnosed cytologically as “atypia of unknown significance” without malignant US features are likely to be different from a FVPTC case diagnosed as “suspicious for PTC” with malignant US features.
In addition, because of the inter- and intra-observer variability issue in the diagnosis of FVPTC, it is likely that a subset of encapsulated FVPTCs from this study would have been reclassified either as “follicular adenoma” or as “well differentiated tumor of uncertain malignant potential” by other pathologists. This might explain to some extent the better prognosis of the FVPTC cases without malignant US features, as described by the authors (e.g., no infiltrative margin).
Finally, it would have been very interesting to see if the US features correlate with the histologic (e.g., encapsulated, well defined, infiltrative) and molecular (e.g., BRAF mutation) characteristics of the FVPTC cases.
Therefore, in practice, the US features of FVPTC may prove to be more helpful in guiding the clinical management of patients who have indeterminate cytology, rather than predicting the behavior of FVPTC.
Further studies are required in order to answer those unsolved questions.