The patterns of contrast enhancement have been demonstrated to distinguish between malignant and benign lymph nodes using USPIO-enhanced MR images [
16]. A lymph node with an area of high-signal intensity encompassing the entire node or a portion of it was considered metastatic according to the diagnostic guidelines for USPIO-enhanced MR imaging, which are based on qualitative analysis of the results [
16]. If there is no blackening of the node or if the node is hyperintense to surrounding tissue, or the node has central high-signal with darkening along the peripheral rim, or partial darkening whereby more than 50% of the node has an area of high-singal intensity, a node is diagnosed as metastatic. If less than 50% of the node has high-signal intensity, it is possibly metastatic. If the node has overall dark signal intensity, it is diagnosed as non-metastatic. A larger area of high-signal intensity within the node was reported to be more likely to be metastatic on USPIO-enhanced MR imaging. Lahaye et al. reported that an estimated area of high-signal intensity within the node that was more than 30% was highly predictive of a metastatic node, with a sensitivity of 93% and a specificity of 96% in patients with primary rectal cancer [
21]. They demonstrated that the most accurate and practical predictive criterion is the estimation of the percentage of high-signal intensity within the node on USPIO-enhanced MR imaging. In the present study, we classified the patterns of SPIO uptake for positive sentinel nodes into three; uniform high-signal intensity, partial high-signal intensity involving more than 50% of the node, and partial high-signal intensity involving less than 50% of the node. We demonstrated that high-signal intensity patterns that were uniform or involved more than 50% of the node were observed in nodes with macro-metastases (Figures
2 and
3). High signal intensity patterns involving less than 50% of the node were often observed in nodes with micro-metastases (Figure
4). When the area of high-signal intensity was compared with the pathological size of the metastases, a pathologic > 2 mm sentinel node metastases correlated with the area of high-signal intensity, however, a pathologic ≤ 2 mm sentinel node metastases did not. The size of small metastatic foci could not be assessed because MR imaging had limited resolution in the present setting. It may be difficult to detect micro-metastases with a section thickness of 4 mm at this resolution on 1.5 T MR images. Interstitial administration of SPIO leads to excessive dosage or a high concentration of SPIO, which may conceal some micro-metastatic foci, resulting in underestimation of the size of metastatic foci, while the fatty hilum of a node, which coexists with metastases, may mimic a metastatic deposit, resulting in overestimation of the size of the metastatic foci. In our previous study, MR imaging with interstitial injection of SPIO was evaluated for the detection of metastases in sentinel nodes, which were localized by CT-LG in 102 patients with breast cancer [
13]. The sensitivity, specificity, and accuracy of MR imaging for the diagnosis of sentinel node metastases were 84%, 91%, and 89%, respectively. In 40% of patients with micro-metastases, metastases were not detected, but all patients with macro-metastases were successfully identified. False negatives may be due to micro-metastases. Of the 7 false-positive results, 6 were due to a prominent fatty hilum. False positives may be due to prominent fatty tissue and insufficient transition of SPIO to sentinel nodes. Fat-saturated images, a 3 T MR system and special coil for MR imaging may be needed to clearly identify small metastatic foci.
However, the clinical implication of micro-metastases is debatable. De Boer et al. reported that the presence of both isolated tumor cells and micro-metastases was associated with reduced disease-free survival among patients who did not receive systemic adjuvant therapy [
22]. In patients with isolated tumor cells and micro-metastases who received adjuvant therapy, disease-free survival was improved. In the systematic review, the presence of micro-metastases in axillary lymph nodes detected on single-section examination was associated with poorer disease-free and overall survival [
23], while Hansen et al. reported that patients with micro-metastases do not have a worse disease-free or overall survival than sentinel node-negative patients [
24]. Whether intensive identification of the existence of small disease foci is needed in clinical practice is an urgent problem.
There were some limitations to our study. There was a relatively small number of metastatic nodes in our series. This was due to the selection of patients with T1-2 breast cancers and clinically negative nodes, who do not have many metastatic axillary nodes. In addition, it is unclear whether the 50% cut-off value was appropriate. The 50% cut-off value was applied according to the diagnostic guidelines for USPIO-enhanced MR imaging, and for high-signal intensity in which more than 50% of the node was observed in sentinel nodes with macro-metastases [
16]. A larger study is needed to find the most appropriate cut-off value to confirm the results of our study.