Copy number abnormalities in new or progressive ‘neurocutaneous melanosis’ confirm it to be primary CNS melanoma

Excerpt

The term ‘neurocutaneous melanosis’ was coined in 1861 as a post-mortem description of multiple congenital melanocytic naevi (CMN) and fatal diffuse leptomeningeal melanocytosis [5]. The congenital phenotype of this disease is caused by post-zygotic mutations in the gene NRAS in 80% of cases [3], and progression to cutaneous melanoma involves further mutations [1, 3, 6]. We have previously argued that there should be a distinction made between congenital abnormalities of the CNS and acquired primary CNS melanoma [7], a situation which can be considered analogous to the presence of benign congenital naevi on the skin, and the risk of development of cutaneous melanoma. The commonest congenital CNS lesion is intraparenchymal melanosis, which has highly characteristic MRI features, and even if symptomatic does not carry a poor prognosis in terms of life expectancy and does not require biopsy [7]. However, rarer lesions cause more diagnostic uncertainty, and in particular, the term ‘leptomeningeal melanocytosis’ currently includes both stable congenital disease, and either newly acquired or clinically and radiologically progressive fatal disease [4, 7]. The problem with distinguishing benign from malignant leptomeningeal disease other than by clinical outcome has been that histological studies do not always demonstrate malignant morphology or leptomeningeal invasion of the underlying parenchyma, despite being ultimately fatal. Histology, however, continues to form a key part of any assessment, including for distinguishing melanoma from the very rare occurrence of other CNS tumours in this condition. …