title: Severe hydrocephalus caused by diffuse leptomeningeal and neurocutaneous melanocytosis of antenatal onset: a clinical, pathologic, and molecular study of 2 cases.
abstract: Diffuse leptomeningeal melanocytosis (DLM) is a rare nevomelanocytic proliferation arising in the meninges. Despite their lack of morphological features of malignancy, these clonal nevomelanocytic cells are capable of extensive invasion and of malignant behavior. When associated with congenital melanocytic nevi, the disorder is named neurocutaneous melanocytosis (NCM). When symptomatic, DLM is usually revealed during childhood, but some cases remain clinically silent. The aim of this study was to analyze melanocytic proliferation in 2 rare and severe cases of isolated DLM and NCM of prenatal onset by neuropathologic and molecular analysis. We performed neuropathologic examination, comparative genomic hybridization arrays, fluorescence in situ hybridization, BRAF and NRAS pyrosequencing in the 2 cases, and next-generation sequencing in the case of isolated DLM. The neuropathologic examination showed diffuse meningeal melanocytic proliferation involving the whole central nervous system with multiple areas of intraneural invasion, associated with large nevi in 1 case. We did not find any chromosomal imbalances. A NRAS(Q61K) mutation was found in the cutaneous and meningeal lesions from the NCM. No mutation was found within a panel of oncogenes including BRAF, NRAS, HRAS, KIT, GNAQ, and GNA11 concerning the isolated DLM. We report 2 exceptional cases of hydrocephalus of prenatal onset related to DLM and NCM. The molecular mechanisms underlying our case of DLM remain unsolved despite the panel of analysis applied.
authors.affiliation: Inserm, U1078, Brest, F-29200 France; CHRU Brest, Service d'anatomie et cytologie pathologiques, Brest, F-29220 France; Université Européenne de Bretagne, 29238 France. Electronic address: arnaud.uguen@chu-brest.fr.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Uguen
authors.affiliation: CHU Toulouse, Service d'anatomie et cytologie pathologiques, Toulouse, F-31000. Electronic address: laurent.c@chu-toulouse.fr.
authors.forename: Camille
authors.initials: C
authors.lastname: Laurent
authors.affiliation: CHRU Brest, Service d'anatomie et cytologie pathologiques, Brest, F-29220 France; Université Européenne de Bretagne, 29238 France; Université de Brest, Faculté de Médecine et des Sciences de la Santé, EA4685, Brest, F-29200 France. Electronic address: laura.samaison@chu-brest.fr.
authors.forename: Laura
authors.initials: L
authors.lastname: Samaison
authors.affiliation: CRICM, Université Pierre et Marie Curie-Paris 6/Inserm UMR-S975/CNRS UMR 7225, Paris, F-75651 France. Electronic address: boisselierblandine@yahoo.fr.
authors.forename: Blandine
authors.initials: B
authors.lastname: Boisselier
authors.affiliation: CHRU Brest, Service d'anatomie et cytologie pathologiques, Brest, F-29220 France; Université Européenne de Bretagne, 29238 France; Université de Brest, Faculté de Médecine et des Sciences de la Santé, EA4685, Brest, F-29200 France. Electronic address: matthieu.talagas@chu-brest.fr.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Talagas
authors.affiliation: CHRU Brest, Service d'anatomie et cytologie pathologiques, Brest, F-29220 France. Electronic address: sebastian.costa@chu-brest.fr.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Costa
authors.affiliation: CHU Toulouse, Service d'anatomie et cytologie pathologiques, Toulouse, F-31000. Electronic address: aziza.j@chu-toulouse.fr.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Aziza
authors.affiliation: GH Pitié-Salpêtrière, AP-HP, Laboratoire de Neuropathologie, Paris, F-75651 France. Electronic address: karima.mokhtari@psl.aphp.fr.
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.affiliation: Inserm, U1078, Brest, F-29200 France; Université Européenne de Bretagne, 29238 France; CHRU Brest, Laboratoire de Génétique Moléculaire et d'Histocompatibilité, Brest, F-29220 France. Electronic address: cedric.lemarechal@chu-brest.fr.
authors.forename: Cédric
authors.initials: C
authors.lastname: Le Maréchal
authors.affiliation: CHRU Brest, Service d'anatomie et cytologie pathologiques, Brest, F-29220 France; Université Européenne de Bretagne, 29238 France; Université de Brest, Faculté de Médecine et des Sciences de la Santé, EA4685, Brest, F-29200 France. Electronic address: pascale.marcorelles@chu-brest.fr.
authors.forename: Pascale
authors.initials: P
authors.lastname: Marcorelles
mesh_terms: D055028:Comparative Genomic Hybridization; D005260:Female; D005333:Fetus; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D006849:Hydrocephalus / Q000209:etiology*; D017404:In Situ Hybridization, Fluorescence; D008548:Melanosis / Q000150:complications / Q000235:genetics / Q000473:pathology*; D008578:Meninges / Q000473:pathology*; D020752:Neurocutaneous Syndromes / Q000150:complications / Q000235:genetics / Q000473:pathology*; D011247:Pregnancy
keywords: Diffuse meningeal melanocytosis; Hydrocephalus; Molecular study; Neurocutaneous melanocytosis; Prenatal onset