Sonographic characteristics of diffuse sclerosing variant of papillary thyroid carcinoma with histopathological correlation: a preliminary study

We retrospectively reviewed the preoperative sonograms of 10 lesions in 10 DSVPTC patients related to histopathology compared with 184 leisons in 168 cPTC patients in the same period. Our results demonstrated that although all 10 DSVPTC lesions involved the whole lobe in pathology, only 6 (60%) appeared on sonogram in the form of “snowstorm” pattern. The other 4 (40%) presented as hypoechoic solid nodules with vague borders and abundant microcalcifications (3 were DSVPTC nodules, 1 was a fibrotic nodule). Pathologically, abundant microcalcifications on sonogram were associated with numerous psammoma bodies, and the vague borders of DSVPTC nodules were caused by infiltration into surrounding parenchyma. Additionally, the heterogeneous background (80%) and suspicious metastatic cervical lymph nodes (80%) were also common.

Based on our results, not all DSVPTC lesions with whole lobe encroachment exhibited the “snowstorm” pattern on sonogram. Only 6 DSVPTC lesions pathologically showing diffuse or multifocal tumor cells and psammoma bodies throughout the lobe had that pattern. Lesions in the focal group showed scattered distribution of relatively few psammoma bodies and tumor cells in the parenchyma. Considering that all DSVPTC lesions had pathologically total lobular involvement, we infer that the “snowstorm” pattern can be observed only when psammoma bodies of the lesion are densely distributed, which is consistent with the view of Wang Y et al. that >/= 5 psammoma bodies per ×200 field of microscope might be visible by ultrasound [21]. Previous studies have found that the occurrence rate of the “snowstorm” pattern in DSVPTC was approximately 83%∼100% [12, 13, 22, 23]. In our study, the rate was 60%. We believe the discrepancy is due to the development of ultrasound technology and the improvement of public health awareness, which facilitate the detection of nodular DSVPTC, leading to a decreasing proportion of “snowstorm” patterns.

We found that DSVPTC lesions presenting as hypoechoic solid nodules were aggressive with an ongoing invasion. Among the hypoechoic solid nodules in the focal group, the locations of 3 nodules on sonogram were pathologically consistent with gathering areas of tumor cells and psammoma bodies, and the number of tumor cells decreased with increasing of distance from these areas. 2 lesions in the focal group had lymph vessel tumor emboli, mirroring the invasion of the surrounding parenchyma. The aggressiveness of DSVPTC lesions in the focal group was also reflected in nodular borders and the abundance of microcalcifications on sonogram. On the one hand, the borders of DSVPTC nodules were more poorly defined than cPTCs, corresponding to no capsule structural characteristics of DSVPTC, indicating the infiltrative growth of the tumor [24]. On the other hand, DSVPTC nodules had more microcalcifications than cPTCs, implying numerous psammoma bodies in pathology. Some scholars believed that the extensive psammoma bodies were calcified remnants of necrotic tumor cells in lymphatic vessels due to strong proliferative activity and invasiveness [24]. Nevertheless, the above two points are not enough to distinguish DSVPTC nodules from cPTC nodules and there are still limitations in identifying DSVPTC nodules by conventional ultrasound.

Given the above analysis, DSVPTC could present as the “snowstorm” pattern on sonogram, or hypoechoic solid nodules with vague borders and abundant microcalcifications. Both corresponded to aggressive lesions. Carcangiu ML et al. [25] thought the DSVPTC lesion developed from a localized nodule to the whole lobe scale, which may be linked to our two sonogram appearances. However, this view still needs further study to be confirmed.

The sonogram of DSVPTC can be confused with Hashimoto’s thyroiditis because both share the appearance of heterogeneous background. In our study, 80% of DSVPTC cases had a heterogenous background, while only 33% of cPTC cases had it. From one aspect, stromal fibrosis and lymphocyte infiltration are evident in DSVPTC, leading to a heterogeneous background like Hashimoto’s thyroiditis. On account of this, some scholars believed it was difficult to distinguish DSVPTC from Hashimoto’s thyroiditis on sonograms, resulting in delayed diagnosis of DSVPTC until the lobe was enlarged [26]. For another, DSVPTC is likely to be associated with Hashimoto’s thyroiditis. In a study by Joung JY et al. [27], 60% DSVPTC cases were complicated with Hashimoto’s thyroiditis. Spinelli C et al. [9] found 56% patients had coexistent Hashimoto’s thyroiditis. According to our results, the proportion of DSVPTC patients with pathologically Hashimoto’s thyroiditis was higher than that of cPTC (70.0%: 31.0%). Therefore, attention should be paid to distinguishing these two diseases by ultrasound, and great emphasis should be given to the heterogenous background in unilateral lobe to diagnose DSVPTC since both lobe involvement is common in Hashimoto’s disease.

Notably, in the DSVPTC lesions, 2 sonographically suspicious nodules were verified to be fibrotic nodules by pathology, which increased the risk of misdiagnosis. These 2 fibrotic nodules shared the similar ultrasound appearance, including hypoechogenicity and irregular margins as malignant nodules. One even had a taller-than-wide shape, and the other had microcalcifications. We have never seen such fibrotic nodules in DSVPTC reported before. We speculate that the fibrotic process began after the tumor invasion, as some psammoma bodies were left inside the fibrotic area. In clinical practice, fibrotic nodules in DSVPTC can pose a dilemma when choosing the site of fine needle aspiration. To increase the accuracy, we suggest selecting the parenchyma outside the nodules, especially that with a relatively high concentration of microcalcifications for puncture, in addition to the nodular area for suspicious DSVPTC patients.

All 10 DSVPTC cases in our study had cervical lymph node metastasis, with 80% shown on ultrasound. Previous studies also reported a high incidence of cervical lymph node metastasis of DSVPTC, with a rate of 68% [28] and an average number of 4.5 per case [7]. Kazaure HS et al. [29] found that cervical lymph node metastasis was more common among 261 DSVPTCs than among 42,904 cPTCs (72.2% vs. 56.3%). Some scholars believed that the widespread invasion of the thyroid lymphatic duct led to the propensity of lymph node metastasis [13]. In our study, the sonogram features of metastatic cervical lymph nodes of DSVPTC were similar to those of cPTC, including loss of central hilar echo, cystic change, calcification and cortical hyperechogenicity. Chen CC et al. [10] considered numerous microcalcifications in cervical lymph nodes as a crucial feature to discern DSVPTC. However, only 1 case in our study showed lymph nodes of that kind, which was not statistically significant in comparison with cPTC. One case in our study showed anechoic area in a metastatic cervical lymph node, contradicting the conclusion drawn by Zhu B et al. [30] that cystic change was scarcely seen in metastatic lymph nodes of DSVPTC. Overall, although the metastatic lymph nodes of DSVPTC were more common, the sonogram was not specific.

The study does have some limitations. First of all, it was a retrospective study. The results were inevitably affected by the operator’s preference, although the videos and images were interpreted by two radiologists to avoid intraobserver bias. Second, the sample size was small due to the low incidence of DSVPTC and the insufficient data. A multicenter study covering a larger population is needed. Third, we did not include other conventional variants of PTC, such as follicular variant, in the control group.

In conclusion, DSVPTC can present as the “snowstorm” pattern on sonogram indicating the psammoma bodies diffusely distributed in the lobe, or simply as hypoechoic solid nodules with vague borders and abundant microcalcifications suggesting an ongoing invasion. The lesions of both manifestations are aggressive and require the same attention from the surgeons. Nevertheless, it is difficult to diagnose DSVPTC via conventional ultrasound due to the following reasons: the sonogram of DSVPTC is easily confused with that of Hashimoto’s thyroiditis, the fibrotic nodules in DSVPTC lesions share a similar appearance with malignant thyroid nodules on sonogram, and the metastatic cervical lymph nodes do not have specific sonographic characteristics. Therefore, fine needle aspiration under the guide of ultrasound is necessary.

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