The identification of capsular or vascular invasion is essential for the histological confirmation of EFPTC and the exclusion of NIFTP [3, 5]. We proposed an effective modified gross examination method, which demonstrated a better prediction of malignancy in EFPTNs. In the analysis of EFPTC specimens, capsular invasion was more frequently detected using the modified transverse-vertical method compared with the conventional transverse method. The possibility of identifying capsular invasion was around two times higher in the modified transverse-vertical group than in the conventional transverse group.
In the new WHO classification system, the concept of borderline tumors with UMP was adopted, and follicular carcinoma was categorized into three subgroups [1, 10]. To differentiate malignant tumors from borderline tumors, the accurate assessment of capsular invasion and/or vascular invasion is important. Moreover, the effective gross examination of the entire tumor capsule is an essential first step because of the lack of specific molecular markers for predicting malignancy in EFPTNs, and diagnostic lobectomy is currently the best approach for histological confirmation .
An evaluation of the entire thyroid capsule including the tumor and the adjacent surrounding thyroid parenchyma is ideal for the detection of capsular or vascular invasion in EFPTNs [3, 5,6,7,8]. According to Yamashina, an extensive circumferential dissection of the entire capsule in follicular neoplasms is the ideal gross examination method to avoid tangential sectioning completely . However, Yamashina’s approach has some practical difficulty in obtaining regular thin sections and embedding in paraffin blocks because of the irregular thickness of the sections. A guideline from the Japanese Society of Thyroid Surgery and Kakudo et al. suggested a gross method for examining EFPTNs, which is similar to our method by adding perpendicular cuts to the peripheral slices after making multiple sagittal cuts . However, there is no clear recommendation on how to evaluate effectively the entire tumor capsule or how much is an adequate number of paraffin blocks from these tumors [6, 7]. Several studies have proposed that the submission of at least ten horizontally sectioned blocks with 2–3 sections in each block would likely to be adequate for detecting capsular invasion in EFPTNs [3, 8, 9]. In our modified transverse-vertical method, the additional vertical sections were rendered at the 10% upper and lower ends of the thyroid nodules to examine the entire tumor capsule equally and extensively. We found that these vertical sections accounted for up to 20% of the entire capsular surface area. There might be a risk of under-diagnosis for 4.2% (7/165) of patients, who had only single focus of capsular invasion in the vertical sections of the upper or lower ends of thyroid nodules. If these patients were examined with the conventional transverse method, they might have been misdiagnosed as having benign tumors although the therapeutic plan would not have been different . In addition, the modified method revealed extensive vascular invasion in two patients, and they had a single focus of vascular invasion in the vertical sections of the upper or lower ends of thyroid nodules. The vertical sections effectively demonstrated perpendicular capsular invasion and rare vascular invasion at the tumor-normal interface with the same alignment at the upper or lower ends of thyroid nodules with different diameters.
Previous studies have reported that the sampling number or the extent of gross examination (complete versus incomplete) could be significantly associated with metastatic progression of FTC [14, 15]. This indicated that the first step of histological evaluation (gross examination) might affect both accurate pathological diagnosis and the prediction of the clinical outcomes of patients. However, there is an another study that reported no association between tumor sampling and clinical outcome of the FTC patients . Despite the limited clinical impact, this modified transverse-vertical gross examination method increased the diagnostic rate of FTC and invasive encapsulated FV-PTC by increased detection of definite capsular invasion in EFPTNs.
The number of vascular invasion is important in patients with FTC because it may be directly associated with the clinical outcomes of patients [17,18,19,20,21]. Vascular invasion is considered as an independent risk factor for distant metastasis in FTC [17,18,19, 22]. However, in some cases of minimally invasive FTC without vascular invasion, there may be synchronous distant metastasis [8, 23, 24]. In the present study, three patients (0.9%) had synchronous distant metastasis without vascular invasion. Two of them had only a single focus of capsular invasion by the conventional transverse method, and they might have been under-diagnosed as having follicular adenoma with the conventional transverse method if the tumor capsule had been submitted incompletely.
There are some limitations in the present study. First, it is a single-center and retrospective study; thus, there may be a selection bias. Second, we could not evaluate clinical outcomes with the two different gross examination methods due to the relatively short follow-up duration. Third, we did not evaluate the inter-observer and intra-observer variation in the pathological diagnosis of these thyroid nodules. Furthermore, sampling error cannot be entirely eliminated because only a limited thickness of each paraffin block was confirmed by an endocrine pathologist.
In this study, by adding vertical sections to the upper and lower ends of tumor capsule, we revealed the presence of definite capsular invasion in these areas and suggested this method as an effective even sampling method of the entire tumor capsule. Despite the limited clinical impact, this modified transverse-vertical gross examination method increased the diagnostic rate of FTC and invasive encapsulated FV-PTC by increased detection of definite capsular invasion in EFPTNs.