Andrea Palicelli1, Maria Giulia Disanto2, Gabriele Panzarasa3, Claudia Veggiani4, Gabriella Galizia5, Stefano Dal Cin5, Elisa Gruppioni6, Renzo Boldorini7. 1. Department of Health Science, School of Medicine, "Maggiore della Carità" Hospital, University of Eastern Piedmont "Amedeo Avogadro", via Solaroli 17, 28100, Novara, Italy. Electronic address: andreapalicelli@hotmail.it. 2. Department of Health Science, School of Medicine, "Maggiore della Carità" Hospital, University of Eastern Piedmont "Amedeo Avogadro", via Solaroli 17, 28100, Novara, Italy. Electronic address: mariagiuliadisanto@gmail.com. 3. Neurosurgery Unit, "Maggiore della Carità" Hospital, Corso Mazzini 18, 28100, Novara, Italy. 4. Department of Pathology, "Maggiore della Carità" Hospital, University of Eastern Piedmont "Amedeo Avogadro", Corso Mazzini 18, 28100, Novara, Italy. 5. Diagnostic Radiology Unit, "SS Trinità" Hospital, Viale Zoppis 10, 28021, Borgomanero, Italy. 6. Laboratory of Oncologic and Transplantation Molecular Pathology, Department of Pathology, S.Orsola-Malpighi Hospital, University of Bologna, Via Pietro Albertoni, 15,40138, Bologna, Italy. 7. Department of Health Science, School of Medicine, "Maggiore della Carità" Hospital, University of Eastern Piedmont "Amedeo Avogadro", via Solaroli 17, 28100, Novara, Italy; Department of Pathology, "Maggiore della Carità" Hospital, University of Eastern Piedmont "Amedeo Avogadro", Corso Mazzini 18, 28100, Novara, Italy. Electronic address: renzo.boldorini@med.unipmn.it.
Abstract
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.
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.