Contributed by Cyril Habougit, MD1; Fabien Forest, MD1; Claire Boutet, MD, PhD2; Catherine Douchet, MD1; Jean-Louis Stephan, MD, PhD3; Marie-Laure Stachowicz1; Francois Vassal, MD4; Michel Péoc'h MD, PhD1
Departments of 1Pathology, 2Radiology, 3Pediatric Oncology, and 4Neurosurgery of Saint Etienne University Hospital. North Hospital Avenue Albert Raimond 42055 Saint Etienne CEDEX 2, FRANCE
An eleven year-old male patient was addressed to our institution with headache, vomiting and right VI cranial nerve paralysis. Clinical examination did not reveal any other neurological deficits. During skin examination multiple congenital melanocytic nevi were observed (Fig 1a). MRI scans showed a leptomeningeal lesion extending from T5 to T11 (Fig 1b). This lesion was hypersignal on T1 sequence enhanced with gadolinium injection and hypointense signal on T2 sequence. At the supratentorial level a dilatation of the lateral and the third ventricle with a wide posterior fossa were found, without tumoral lesion (Fig 1c).
Microscopically, the leptomeningeal lesion was composed of discohesive cells with low N/C ratio. No atypia or mitoses were seen (Fig 1d). Tumor cells contained a brown pigment. No deposit was showed on Perl's iron stain. Immunohistochemical study showed expression of S100 protein, HMB45 (Fig 1e) and Melan-A by tumor cells. Proliferation index evaluated by Ki67 antibody was less than 1%. Molecular analysis of the leptomeningeal tumor revealed a mutation on codon 61 in exon 3 of NRAS (Q61K)(Fig 1f). No mutation of BRAF codon 600 was detected (Snapshot technique). Biopsy of the skin nevus revealed congenital nevus pattern cells in the lower two-thirds of the dermis, with an extension between collagen bundles singly or in Indian file and extension on the adnexa. The same Q61K NRAS mutation was found in the nevi while BRAF V600 screening was negative. What is your diagnosis?