Meningeal melanocytoma is a rare clinical entity. The term was first introduced by Limas and Tio in 1972 to describe a group of benign lesions other than pigmented meningiomas, meningothelial fibroblasts and schwannomas. These benign tumors arise from leptomeningeal melanocytes, and resemble the other melanocytic neoplasms of the central nervous system.6
The etiology and pathogenesis of spinal meningeal melanocytoma remain unclear. Intradural spinal melanocytoma involving S1 nerve root is an extremely rare case. To the best of our knowledge, 13 spinal meningeal melanocytoma cases have been reported.6-18 (Table 1) Among them, three were the meningeal melanocytoma in the dorsal region. The follow-up duration of the present case is by far the longest.
The imaging features of meningeal melanocytoma are still illusive. The degree, distribution of melanin pigment and the presence of hemorrhage of the tumor are often considered in diagnosis. In CT scan, meningeal melanocytoma is manifested as iso- to high-density lesions that can be enhanced by contrast media. In MRI, due to the paramagnetic effect of melanin (PEDDPRE effect), the tumor shows hyper- or iso- intense in T1-weighted images and iso- or slightly hypo- intense in T2-weighted images.15,19,20 But, these radiological manifestations are debatable, usually leading to misdiagnosis of a schwannoma or meningioma. Spinal schwannoma tends to have a signal intensity equal to or less than that of the spinal cord on T1-weighted images. Meningioma usually shows iso- or hyper-intense signals on T2-weighted images, and diffuse enhancement on contrast-enhanced T1-weighted images.21,22 Furthermore, MRI images were sorted into four groups based on putative patterns by Isiklar: (1) melanotic type: hyper-intense in cortex on T1-weighted images, hypo-intense in cortex on T2-weighted images, and iso- or hyper-intense in cortex on proton density-weighted images; (2) amelanotic type: hypo-intense or iso-intense in cortex on T1-weighted images and hyper-intense or iso-intense in cortex on T2-weighted and proton density weighted images; (3) indeterminate, or mixed type: MR imaging characteristics not conforming to those of one of the first two categories; and (4) hematoma type: MR imaging features exhibiting only hematoma.23the meningeal melanocytoma in this case is of melanotic type: hyper-intense in cortex on T1-weighted images, hypo-intense in cortex on T2-weighted images, and iso- or hyper-intense in cortex on proton density-weighted images.
The treatment for spinal meningeal melanocytoma has not been standardized. Complete surgical resection has the best efficacy.12,20,24,25 However, the resectability is sometimes weakened by the involvement of vital structures (such as nerve root). There is little evidence regarding the efficacy of radiotherapy for meningeal melanocytoma. In cases of incomplete resection, adjuvant postoperative radiotherapy is advised. Some scholars hold that the benign melanocytoma with an aggressive course should receive complete surgical resection. Therefore, adjuvant radiotherapy (30–54 Gray) is recommendable for both complete and incomplete resection.26,27 In addition, radiosurgery has been used in special cases.28 Some patients are advised to receive postoperative chemotherapy (DAV) as follows: dacarbazine, 150 mg/day intravenously for 5 days; vincristine, 1 mg/day for 1 day; and ACNU, 100 mg/day for 1 day. This therapy is repeated for three cycles at 1-month intervals. But the benefit of chemotherapy is limited29 and unrecommendable.
Some literatures have discussed the impact of therapeutic options. Rades reviewed 89 intracerebral and spinal melanocytomas recurring within 5 years after surgery. The survival rates were reported as follows: complete resection, 100%; complete resection plus radiotherapy, 100%; incomplete resection plus radiotherapy, 100%; and incomplete resection alone, 46%.30 Roser found that the recurrence rate within two years after complete resection and incomplete resection with radiotherapy was significantly higher than that after incomplete resection alone. So, complete resection was also the best therapeutic option.31
The diagnosis of meningeal melancytoma was confirmed by histopathologic and immunohistochemical tests. Characteristic immunohistochemical properties of meningeal melanocytoma include positive responses to HMB-45, S-100 protein and vimentin. Positive response to HMB-45 favors the tumor of melanocytic origin. S-100 protein can be found not only in cells prone to melanogenesis, but also cells from neuroectoderm. About 10% of malignant melanoma cells are negative for S-100 protein. Therefore, the negativity to S-100 protein cannot exclude the odds of malignant melanoma, and other indicators are needed for diagnosis.15,31 The negativity for epithelial membrane antigen (EMA) can rule out the possibility of meningioma, and the negativity for Leu 7 can rule out schwannoma.10,32 Ki-67 labeling index (>3%) can also assist the diagnosis of meningeal melancytoma. In the present case, immunohistochemical tests revealed that the tumor cells were positive for HMB-45, S-100 protein and Vimentin, and negative for EMA. The Ki-67 labeling index was approximately 5%.33-36
The World Health Organization has classified meningeal melanocytoma into three categories: low grade (melanocytoma), high grade (melanoma), and intermediate-grade.4,37 The present case was diagnosed as low grade melanocytoma. The absence of cellular pleomorphism and rare mitoses often eliminate its malignancy. So the lesion usually has a benign course and a good prognosis. Microscopically, meningeal melanocytoma, usually appears dark-brown or black, nodular and encapsulated, and demonstrates spindle or epithelioid cells with relatively well-defined eosinophilic cytoplasm, centrally-located vesicular nuclei and brown-pigmented granules.1,38-40 Ultrastructurally, the meningeal melanocytoma cells are characterized by of polar cytoplasmic processes, scarce zonula adherens and numerous premelanosomes at different stages of differentiation.41,42 Benign melanocytoma may show an aggressive course to malignancy, and even recur after complete excision.30,43-45 Malignancy has been rarely reported in the literature. Most reported malignant cases develop solitary lesions with slow growth and low infiltration.36,46 Litofsky summarized the characteristics of benign lesions: (1) a history of more than one year; (2) similar imaging characteristics to meningioma; (3) dominant spindle cells with lower mitotic rate.25 Rades reviewed all the reported cases and found that the 5-year local control rate was 78% after complete resection.27 Oruckaptan said that spinal localizations had lower recurrence rates (13%) than cranial lesions (29%).41 In the present case, we performed a gross total resection and the symptoms relieved dramatically after the operation. No signs of local recurrence was seen during the 8-year follow-up.
In conclusion, spinal meningeal melanocytoma inside the nerve root is rare and benign. It is difficult to diagnose and often misdiagnosed as schwannoma or meningioma due to its unspecific clinical manifestations and imaging characteristics. A precise diagnosis could be made based on histopathology. Positive response to HMB-45 favors the tumor of melanocytic origin, so it is suggested as a significant diagnostic marker for meningeal melanocytoma. Complete surgical resection is recommended as the primary treatment. Radiotherapy, chemotherapy and other treatments can be selected as adjuvant therapies, but their effects are controversial. The recurrence and metastasis rates also remain unclear. Accordingly, more treatment choices should be trialed and long-term follow-up undertaken. We believe that enriching clinical documentation and radiological data will polish our understanding on the pathophysiology and behavior of spinal meningeal melanocytoma.