TO THE EDITOR: We read with great interest the article by Hoffmann and colleagues5(Hoffmann M, Koelsche C, Seiz-Rosenhagen M, et al: TheGNAQin the haystack: intramedullary meningeal melanocytoma of intermediate grade at T9–10 in a 58-year-old woman.J Neurosurg 125:53–56, July 2016). The authors reported an interesting case of an intramedullary intermediate-grade melanocytoma. Histopathological examination revealed a highly cellular tumor composed of epithelioid-shaped tumor cells with scant to moderate cytoplasmic pigmentation and vesicular nuclei with prominent nucleoli. Single mitotic figures and small necrotic areas were present. The proliferation index Ki 67 (MIB1) focally reached 10%. Tumor cells strongly expressed S100 and HMB45, but were negative for BRAF V600E (VE1), pancytokeratin (AE1/3), EMA, and GFAP. Their initial diagnosis was metastatic melanoma, but they changed the diagnosis to melanocytoma after theGNAQmutation was found. We think this diagnosis is incorrect because aGNAQmutation can be found in other tumors such as primary melanoma of the CNS, among others. In addition, they do not mention the possibility of the diagnosis of primary melanoma of the CNS, which we believe is the correct diagnosis in the case presented.
Pigmented (grey, brown, or black) intramedullary tumors are exceedingly rare, with only a few reported cases. When facing a dark intramedullary mass several diagnoses must be considered, including primary melanoma. Other melanin-containing tumors (melanotic ependymoma and melanotic schwannoma) and melanocyte-containing tumors (melanocytoma, melanoma metastasis) are in the differential diagnosis.6,7,9,10,13Melanoma is the third most common cancer-causing brain metastasis,3,8,11but only 12 cases of intramedullary metastases of malignant melanoma have been reported.7
Immunohistochemical markers of melanocytic tumors (such as HMB45, Melan-A, and S100) are not helpful for discerning between pigmented intramedullary tumors because all of them are positive for one or several of these markers.6,12Melanocytoma, primary melanoma, and melanoma metastasis are difficult to differentiate. It is not possible to distinguish between primary melanoma of the CNS and metastatic melanoma by pathological examination. Both are histologically identical, displaying cellular atypia, numerous mitoses, and often demonstrating unequivocal tissue invasion or coagulative necrosis.2We need to exclude melanoma disease elsewhere (skin or mucous melanoma, and visceral metastasis) to make the final diagnosis of primary melanoma of the CNS.4On the other hand, melanocytomas lack cellular atypia, and mitoses are generally absent with a Ki 67 labelling index (a cellular marker of proliferation) of <1%–2% (versus 8% on average in primary melanoma). Similar to melanocytomas, intermediate-grade melanocytoma also lack cellular atypia; however, occasional mitoses, microscopic CNS invasion, and a Ki 67 labelling index ranging from 1% to 4% can be observed.1
In the past decade, much has been learned about the genetic alterations in different subtypes of melanomas. Uveal melanoma and primary melanocytic tumors of the CNS are different from cutaneous melanoma. This is becauseBRAFis the most frequent mutation encountered in melanoma metastasis from the skin (50%), followed byNRASmutation (20%); however,BRAFandNRASare rarely mutated in uveal melanoma (<2%) and primary melanocytic tumors of the CNS (4%).2,9Instead, mutations onGNAQandGNA11are found in 77% of uveal melanomas and 56% of primary melanocytic tumors of the CNS, but mutations inGNAQandGNA11are only present in 1% of cutaneous melanomas.9In other words, aGNAQ-or GNA11-mutated intramedullary melanocytic tumor is probably a primary melanoma of the CNS, melanocytoma, or intermediate-grade melanocytoma, depending on histopathological criteria.
BRAF-mutated melanoma metastases can be treated with BRAF inhibitors. Thus, knowing the mutational status may guide treatment and diagnosis, but is not pathognomonic for any of these tumors. That is, the mutation inGNAQ, found in the case presented by Hoffmann et al.,5不排除原发性黑色素瘤的诊断吗of the CNS. We strongly recommend performing a mutational study in these tumors because very few cases have been analyzed so far, so it is not possible to draw any conclusions. To conclude, even though great advances in molecular aspects of these tumors have been accomplished, a diagnosis based on molecular analysis is not yet possible. Thus, the mainstay of diagnosis should still rest on appropriate histology and the absence of other lesions outside of the CNS.
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YangC,LiG,FangJ,WuL,DengX,XuY:Clinical analysis of primary melanotic ependymoma in the central nervous system: case series and literature review.Acta Neurochir (Wien)155:1839–1847,2015
Disclosures
The authors report no conflict of interest.
