Orbital meningeal melanocytoma: Histological, immunohistochemical and molecular characterization of a case and review of the literature

Aims We provide morphological, immunohistochemical and molecular characterization of the 3rd “intermediate-grade” orbital meningeal melanocytoma, testing for the first time Vysis Melanoma FISH Probe Kit. We reviewed the literature in order to discuss the main differential diagnoses and to provide a better molecular description of these unusual tumors of difficult diagnosis and controversial management. Methods Histochemical stains (Haematoxylin and Eosin, Perls, reticulin), immunohistochemistry (HMB45, p16, Melan-A, S100, EMA, Ki67, CD68), polymerase chain reaction amplification and sequence analysis (BRAF, exon 15; NRAS exons 2 and 3; c-KIT, exons 11, 13, 17, 18; GNAQ, exons 4 and 5; GNA11, exons 4 and 5) and fluorescent in situ hybridization (RREB1, 6p25; MYB, 6q23; CCND1, 11q13; CEP 6, 6p11.1-q11.1) were performed on paraffin-embedded, formalin-fixed material. Results Histological diagnosis of “intermediate-grade” melanocytoma was supported by zonal necrosis and increased Ki67-index (12%). Immunophenotype: HMB45 + (strong, >75%), Melan-A + (strong, >75%), p16 + (∼20%), S100 −/+ (<5%), EMA −/+ (<5%), CD68 − (positive histiocytes). No gene mutations nor copy-number alterations were identified. The patient was asymptomatic and disease-free 3 years after total surgical excision. Conclusions Adequate sampling and accurate immunohistochemical characterization are important for a correct diagnosis. Molecular analysis could provide important additional information (especially for “intermediate-grade” tumors), but further data are needed.