Discussion
Palliative radiation or conservative treatment is often selected for ISCM because the disease is associated with a poor prognosis. The main purpose of palliative radiation therapy is to reduce the pain; therefore, radical cure cannot be achieved with only radiation therapy.
Patients expected to respond well to therapeutic intervention are considered candidates for surgical treatment, which can improve the overall survival and neurological functions (2). A few patients with ISCMs of malignant melanoma undergo surgical resection because melanoma tends to be highly resistant to radiation (3). Therefore, the dose of radiation for melanoma is often 4 Gy or more/fraction. In case 1, surgical resection considerably reduced the patient's pain.
Considering the MRI findings, two unique characteristics of ISCMs, rim and flame signs, have been reported (4). Rim signs indicate a more intense thin rim with peripheral enhancement than other tumor areas and flame signs indicate flame-shaped enhancements at the edge of the lesion (above or below). These findings have been reported to be highly specific for ISCMs.
For all ISCMs, the rim sign was detected in 47% cases and the flame sign in 40% cases. Both signs were found in 27% cases and neither sign in 40% cases. Either sign was recognized in 60% cases. Melanoma was detected in five cases in this series but the rim sign was not detected in any (0/5), whereas neither sign was observed in 60% cases (3/5) (4). The authors of the respective studies did not mention these results because of the small number of cases of malignant melanoma.
According to a previous literature review, MRI could not reveal a specific pattern within the tumor owing to a mixture of melanin, intra-tumoral hemorrhage, and fat deposition (5). As a result, no characteristics have been reported so far to aid the diagnosis of ISCM of malignant melanoma.
To the best of our knowledge, 27 cases of ISCM of malignant melanoma (including our two cases) have been reported. In the literature, ISCM of malignant melanoma is described as a small percentage of the ISCMs of all cancer types; thus, it is sometimes not reported in detail.
We examined 12 cases, as the 15 other cases were excepted because there was no description of contrast-enhanced MRI findings (Table I) (5-7). One patient underwent MRI without using a contrast agent, but the characteristics of the lesion was described nonetheless (8).
Moreover, 83.3% (10/12) of these cases showed a single mass by MRI and multiple masses in only two cases (including our case 2). Another case was noted to have intramedullary and intradural extramedullary lesions.
Besides these two cases, a case with multiple masses discovered at autopsy has been reported (9). However, the lesions were not identified by an MRI in this case. Therefore, our case 2 is the first case of ISCM of malignant melanoma with multiple masses localized within the intramedullary area that was detected by MRI.
The rim sign was detected in 33.3% (4/12) and the flame sign was detected in 16.6% patients (2/12). Both signs were found in 8.3% (1/12), either sign in 33.3% (4/12), and neither in 58.3% of patients (7/12). Although the ISCM of malignant melanoma was found in 33.3% patients, the rim sign frequency was slightly lower than that observed in the ISCM of other cancers. Conversely, the flame sign in ISCMs of malignant melanoma was less than that in ISCMs of other cancers.
In the cases of ISCMs of malignant melanoma, the incidence of brain metastasis was as high as 76.4% (13/17). The response rate of intracranial metastases of BRAF V600 mutation-positive malignant melanoma to combination therapy with dabrafenib plus trametinib was 58% and that of extracranial metastases was 55% (10). The response rate of intracranial lesions to the nivolumab plus ipilimumab combination therapy for BRAF V600 mutation-negative malignant melanoma was 57%. Conversely, the response rate of intracranial metastases to immune-checkpoint inhibitor monotherapy was almost 22% (11). Hence, combination therapy was established to be significantly effective. Our cases are unique as patients with ISCMs of malignant melanoma are treated by immune-checkpoint inhibitors or molecule-targeted agents.
In conclusion, the rim sign is detected in some ISCMs of malignant melanoma and in ISCMs of other cancers. We believe that the rim sign in MRI is a useful diagnostic clue of ISCM of malignant melanoma. Although ISCM of malignant melanoma is difficult to diagnose accurately and is associated with poor prognosis owing to complications of brain metastases, the prognosis of malignant melanoma has substantially improved because of treatment advances. Therefore, more accurate diagnoses and the development of therapeutic strategies will help improve patients' quality of life in the future.