Despite controversial significance, the presence of neck LN metastases in DTC seems more frequently to affect disease prognosis since the affected patients already at surgery may more likely undergo recurrences or metastases in the follow-up. Moreover, a high LN ratio, defined as the number of metastatic LN divided by the number of removed LN, and the presence of LN macro metastases seem to have a significant prognostic value [37]. Thus, it is crucial to correctly evaluate patient staging after thyroidectomy and radioiodine ablation therapy to permit an adequate monitor of patients in a long-term follow-up for re-staging the disease and appropriately changing the therapeutic strategy.
In the last years, ¹³¹I-SPECT/CT proved a reliable diagnostic tool to accurately identify and characterize neck LN metastases in DTC patients in both post-thyroidectomy pre-ablation phase [24, 26, 38], and in post-radioiodine therapy phase [21, 28-33]. The procedure substantially reduced the number of occult and unclear radioiodine avid foci at planar WBS; the latter has been considered for many years the reference imaging method in the diagnostic protocol of DTC after thyroidectomy. SPECT/CT can also determine LN status in the neck more accurately than planar WBS [16, 19, 26-30], also identifying rarer parapharyngeal metastases [39].
In the present study performed in DTC patients already submitted to thyroidectomy and radioiodine ablation and in long-term follow-up, SPECT/CT with diagnostic radioiodine dose proved a reliable tool to better identify, precisely localize and characterize neck ¹³¹I-avid foci compared to planar WBS. SPECT/CT also detected more iodine-avid foci than WBS allowing the identification of additional occult not-suspicious cervical LN metastases not evidenced by WBS and clarified unclear images or wrongly classified foci, as also reported by other authors [16, 40, 41]. Regarding this latter aspect, planar WBS localized foci in thyroid bed classifying these as remnant tissue in some cases, while the foci corresponded to cervical LN because of the poor anatomic information provided by planar procedure; however, image interpretation on SPECT/CT was more accurate, improving WBS diagnostic specificity. Among unclear foci, there were also areas of physiologic uptake, to the interpretation of which SPECT/CT contributed to clarifying false-positive results of WBS; this result was even more important when these foci were single, for avoiding unnecessary treatments.
Thus, the performance of WBS was improved for the diagnosis, staging, and follow-up in patients with neck LN metastases contributing to correctly change patient classification and management, including surgery or radioiodine therapies, and avoiding additional imaging procedures and guiding the decision on long-term follow-up strategy.
In particular, the data obtained in the present study demonstrated that SPECT/CT gave more information on LN staging in an elevated percentage of patients, thus resulting in a completion of TNM staging and risk new stratification. SPECT/CT superiority than planar WBS, that is in agreement with previous results obtained by some authors [16, 19, 27-30], is particularly significant when the latter is inconclusive and thyroglobulin levels are undetectable or very low in VL cases with T1aN0M0, and even more with single LN metastasis. Moreover, SPECT/CT performance was even higher than WBS when the nodes are sited in regions where these can be difficult to be discriminated from thyroid remnants or physiologic structures with elevated iodine uptake; among these, there are those adjacent to sub-mandibular glands that can affect the identification of neoplastic nodes. The latter were detected by SPECT/CT but not by WBS in our patients. However, as a rule, a microscopic disease in LN may escape detection by SPECT/CT like WBS.
The results of this study also confirmed that thyroglobulin levels could remain undetectable or very low in presence of neck LN metastases, particularly when these are single and the neck represents the only site of recurrence, thus suggesting that undetectable thyroglobulin levels cannot exclude a metastasis in an LN. Also in these cases, SPECT/CT proved useful to change risk stratification and treatment.
In the present study, the multifocal disease had been ascertained at the surgery in 40.7 % of PC patients who developed metastases during long-term follow-up suggesting that these cancers have an increased metastatic potential, as reported by other authors (6), also including papillary microcarcinoma (19). Moreover, 24.1 % of PC patients also had lymph node metastases already at surgery as well as 14.8 % of cases had extra-thyroid tumor extension, these disorders representing important risk factors for neck recurrences during follow-up, in particular when cervical nodes are numerous and even of large volume (37, 42-45). Furthermore, the latter two factors were also associated with multifocal disease in some cases and, besides, in 13.5 % of PC patients all three factors were present with a higher possibility of disease progression. Moreover, unlike the results reported by other authors (6), the size of the primary tumors in our cases seems to have a significant effect on neck LN metastasis appearance in the follow-up, 61 % of patients having carcinomas > 10 mm.
Based on the present data on a long-term follow-up of a large series of DTC patients with radioiodine avid foci only in the neck,¹³¹I-SPECT/CT proved to add an important contribution to planar WBS interpretation. These favorable results agree with the data obtained in previous studies [16, 19], also in both pre-ablation and post-therapeutic phases [25-30, 46].
However, a relative limitation due to the retrospective nature of the present study should be considered.
The presence of very small size nodes, which can also be the site of microscopic metastases, could cause problems of identification associating the diagnostic dose of radioiodine with the low spatial resolution of the machine by partial volume effect. However, microscopic metastases do not seem to significantly get worse disease prognosis and only histology could give a correct definition since no imaging procedure can give certain information.
Furthermore, any misregistration defects have been limited by immobilizer systems utilized during exam acquisition, which, however, results in longer duration with possible patient discomfort.
Concerning radiation additional dose from CT to that of radioiodine, there is not an elevated exposure from low energy CT with effective doses for neck/chest of one mSv in average with the machine used in present study and in other studies [47]; such a slight exposure can be considered negligible considering the benefits of SPECT/CT technology.
The results of the present study cannot be generalizable being obtained in only one center, and the experienced nuclear medicine physicians who independently interpreted the SPECT/CT images belonged to the same Department.
The patients submitted to SPECT/CT and WBS have been enrolled in part in hypothyroidism after hormone therapy interruption and in part after rhTSH stimulation. Moreover, some LN metastases detected by SPECT/CT have not confirmed by histopathologic examinations for practical and ethical reasons, but only validated by follow-up with clinical data, thyroglobulin variations and the results of radiologic and nuclear medicine procedures.
Finally, being DTC carcinomas slowly growing malignancies, these can require a more prolonged follow up since some foci classified as benign might prove metastases late as well as eventual micrometastasis in a lymph node, that may be occult at the first examination of SPECT/CT like WBS, might be revealed macrometastasis afterward. A more prolonged follow up might also permit a better evaluation of the outcome of therapeutic strategies.
Despite its limitations, SPECT/CT in this study proved to be a useful diagnostic imaging procedure giving a better characterization of focal areas of uptake excluding malignancy in physiologic sites of tracer uptake. The procedure obtained a more correct anatomic localization of the lesions, thus helping planar WBS interpretation and demonstrated an elevated impact on patient management and therapy planning. SPECT/CT is a simple and non-invasive method that gave in all cases high-quality images that were easy to interpret.