{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T05:00:52Z","timestamp":1792299652971,"version":"4.4.0"},"reference-count":35,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T00:00:00Z","timestamp":1705708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Primary meningeal melanomatosis is an extremely rare tumor with very few documented responses to treatment. A 3-year-old male with a complex past medical history, including prematurity and shunted hydrocephalus, was diagnosed with primary meningeal melanomatosis with peritoneal implants. Molecular testing revealed an NRAS Q61R mutation. The patient received proton craniospinal radiation followed by immunotherapy with nivolumab (1 mg\/kg) and ipilimumab (3 mg\/kg) IV every 3 weeks and, upon progression, he was switched to a higher dose of nivolumab (3 mg\/kg IV every 2 weeks) and binimetinib (24 mg\/m2\/dose, twice a day). The patient had significant improvement of CNS disease with radiation therapy and initial immunotherapy but progression of extracranial metastatic peritoneal and abdominal disease. Radiation was not administered to the whole abdomen. After two cycles of nivolumab and treatment with the MEK inhibitor binimetinib, he had radiographic and clinical improvement in abdominal metastasis and ascitis. He ultimately died from RSV infection, Klebsiella sepsis, and subdural hemorrhage without evidence of tumor progression. This is the first report of a child with primary meningeal melanomatosis with extracranial metastatic disease with response to a combination of radiation, immunotherapy and MEK inhibitor therapy.<\/jats:p>","DOI":"10.3390\/curroncol31010041","type":"journal-article","created":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T04:54:01Z","timestamp":1706072041000},"page":"579-587","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Primary Diffuse Leptomeningeal Melanomatosis in a Child with Extracranial Metastasis: Case Report"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2323-5892","authenticated-orcid":false,"given":"Shubin W.","family":"Shahab","sequence":"first","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center, Atlanta, GA 30342, USA"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30322, USA"},{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Winship Cancer Institute, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhumallikarjun","family":"Patil","sequence":"additional","affiliation":[{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30322, USA"},{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason R.","family":"Fangusaro","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center, Atlanta, GA 30342, USA"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30322, USA"},{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Winship Cancer Institute, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke","family":"Patteson","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center, Atlanta, GA 30342, USA"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Goldman-Yassen","sequence":"additional","affiliation":[{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30322, USA"},{"name":"Department of Radiology, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bree R.","family":"Eaton","sequence":"additional","affiliation":[{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30322, USA"},{"name":"Winship Cancer Institute, Atlanta, GA 30322, USA"},{"name":"Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Boydston","sequence":"additional","affiliation":[{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30322, USA"},{"name":"Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Schniederjan","sequence":"additional","affiliation":[{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30322, USA"},{"name":"Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolly","family":"Aguilera","sequence":"additional","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center, Atlanta, GA 30342, USA"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30322, USA"},{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO Classification of Tumors of the Central Nervous System: A summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e1091","DOI":"10.1016\/j.wneu.2019.07.095","article-title":"Primary Malignant Melanoma of the Brain: A Population-Based Study","volume":"130","author":"Puyana","year":"2019","journal-title":"World Neurosurg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"198","DOI":"10.25259\/SNI_743_2020","article-title":"Intradural Extramedullary Primary Central Nervous System Melanoma of the Craniovertebral Junction during Pregnancy: Observations and Outcomes","volume":"12","author":"Valenzuela","year":"2021","journal-title":"Surg. Neurol. Int."},{"key":"ref_4","first-page":"383","article-title":"Primary intracranial melanoma, amelanotic variant: Case report","volume":"33","author":"Iliev","year":"2022","journal-title":"Neurocirugia (Astur. Engl. Ed.)"},{"key":"ref_5","first-page":"293802","article-title":"Primary Intracranial Melanoma with Early Leptomeningeal Spread: A Case Report and Treatment Options Available","volume":"2015","author":"Balakrishnan","year":"2015","journal-title":"Case Rep. Oncol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Baumgartner, A., Stepien, N., Mayr, L., Madlener, S., Dorfer, C., Schmook, M.T., Traub-Weidinger, T., Lotsch-Gojo, D., Kirchhofer, D., and Reisinger, D. (2021). Novel Insights into Diagnosis, Biology and Treatment of Primary Diffuse Leptomeningeal Melanomatosis. J. Pers. Med., 11.","DOI":"10.3390\/jpm11040292"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Angelino, G., De Pasquale, M.D., De Sio, L., Serra, A., Massimi, L., De Vito, R., Marrazzo, A., Lancella, L., Carai, A., and Antonelli, M. (2016). NRAS(Q61K) mutated primary leptomeningeal melanoma in a child: Case presentation and discussion on clinical and diagnostic implications. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2556-y"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/BF00346871","article-title":"Neuroradiological findings in a child with primary leptomeningeal melanoma","volume":"18","author":"Flodmark","year":"1979","journal-title":"Neuroradiology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1002\/(SICI)1097-0142(19990901)86:5<878::AID-CNCR26>3.0.CO;2-Y","article-title":"Leptomeningeal melanoma in childhood","volume":"86","author":"Makin","year":"1999","journal-title":"Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"581.e15","DOI":"10.1016\/j.wneu.2016.06.039","article-title":"Primary Amelanotic Leptomeningeal Melanomatosis in a Child: A Rare but Severe Disease","volume":"92","author":"Szathmari","year":"2016","journal-title":"World Neurosurg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/0887-8994(94)00155-U","article-title":"Primary malignant melanoma of meninges: Atypical presentation of subacute meningitis","volume":"12","author":"Nicolaides","year":"1995","journal-title":"Pediatr. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.2176\/nmc.25.1029","article-title":"Primary melanomas in the central nervous system with peritoneal dissemination through ventriculo-peritoneal shunt. Report of an autopsy case","volume":"25","author":"Tanaka","year":"1985","journal-title":"Neurol. Med. Chir."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e19178","DOI":"10.1097\/MD.0000000000019178","article-title":"Pediatric primary diffuse leptomeningeal melanomatosis: Case report and review of the literature","volume":"99","author":"Xu","year":"2020","journal-title":"Medicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/dc.2840130314","article-title":"Peritoneal implantation of meningeal melanosis via ventriculoperitoneal shunt: A case report and review of the literature","volume":"13","author":"Gattuso","year":"1995","journal-title":"Diagn. Cytopathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"343","DOI":"10.3348\/kjr.2013.14.2.343","article-title":"F-18 fluorodeoxyglucose PET\/CT and post hoc PET\/MRI in a case of primary meningeal melanomatosis","volume":"14","author":"Lee","year":"2013","journal-title":"Korean J. Radiol."},{"key":"ref_16","first-page":"115","article-title":"Primary diffuse meningeal melanomatosis: Radiologic-pathologic correlation","volume":"24","author":"Pirini","year":"2003","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/pcmr.13114","article-title":"Histopathologic abundance of pigmentation correlates with disease-specific survival in malignant melanoma but is not independent of current AJCC pT stage","volume":"36","author":"Aebischer","year":"2023","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1177\/1971400915609348","article-title":"Extracranial, peritoneal seeding of primary malignant brain tumors through ventriculo-peritoneal shunts in children: Case report and review of the literature","volume":"28","author":"Narayan","year":"2015","journal-title":"Neuroradiol. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.wneu.2019.07.046","article-title":"Hydrocephalus Secondary to Intradural Extramedullary Malignant Melanoma of Spinal Cord","volume":"130","author":"Hironaka","year":"2019","journal-title":"World Neurosurg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"102238","DOI":"10.1016\/j.ctrv.2021.102238","article-title":"NRAS mutant melanoma: Towards better therapies","volume":"99","author":"Randic","year":"2021","journal-title":"Cancer Treat. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1158\/2326-6066.CIR-14-0207","article-title":"Impact of NRAS mutations for patients with advanced melanoma treated with immune therapies","volume":"3","author":"Johnson","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMoa1709684","article-title":"Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma","volume":"377","author":"Wolchok","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Eddy, K., and Chen, S. (2020). Overcoming Immune Evasion in Melanoma. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21238984"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1038\/s41388-020-01611-6","article-title":"Is PD-L1 a consistent biomarker for anti-PD-1 therapy? The model of balstilimab in a virally-driven tumor","volume":"40","author":"Grossman","year":"2021","journal-title":"Oncogene"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/S1470-2045(16)30053-5","article-title":"Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: Early analysis of a non-randomised, open-label, phase 2 trial","volume":"17","author":"Goldberg","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1200\/JCO.22.01748","article-title":"Functional Engagement of the PD-1\/PD-L1 Complex but Not PD-L1 Expression Is Highly Predictive of Patient Response to Immunotherapy in Non-Small-Cell Lung Cancer","volume":"41","author":"Gumuzio","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Fejza, A., Polano, M., Camicia, L., Poletto, E., Carobolante, G., Toffoli, G., Mongiat, M., and Andreuzzi, E. (2021). The Efficacy of Anti-PD-L1 Treatment in Melanoma Is Associated with the Expression of the ECM Molecule EMILIN2. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147511"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"187","DOI":"10.2217\/mmt-2016-0013","article-title":"PD-L1 in melanoma: Facts and myths","volume":"3","author":"Mandala","year":"2016","journal-title":"Melanoma Manag."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1158\/2159-8290.CD-12-0464","article-title":"Primary melanoma of the CNS in children is driven by congenital expression of oncogenic NRAS in melanocytes","volume":"3","author":"Pedersen","year":"2013","journal-title":"Cancer Discov."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Knight, A., Karapetyan, L., and Kirkwood, J.M. (2023). Immunotherapy in Melanoma: Recent Advances and Future Directions. Cancers, 15.","DOI":"10.3390\/cancers15041106"},{"key":"ref_31","first-page":"279","article-title":"Treating brain metastases in melanoma: What is the optimal CNS-directed and systemic management?","volume":"7","author":"Wilson","year":"2021","journal-title":"J. Radiosurg. SBRT"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s11060-018-2848-y","article-title":"Pembrolizumab for primary malignant melanoma of the central nervous system","volume":"139","author":"Blechet","year":"2018","journal-title":"J. Neurooncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e22928","DOI":"10.1097\/MD.0000000000022928","article-title":"Primary leptomeningeal melanomatosis successfully treated with PD-1 inhibitor pembrolizumab: A case report","volume":"99","author":"Rakusic","year":"2020","journal-title":"Medicine"},{"key":"ref_34","first-page":"v75","article-title":"Targeted therapy strategies for melanoma brain metastasis","volume":"3","author":"Saberian","year":"2021","journal-title":"Neurooncol. Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1056\/NEJMoa1910836","article-title":"Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma","volume":"381","author":"Larkin","year":"2019","journal-title":"N. Engl. J. Med."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/31\/1\/41\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:46:26Z","timestamp":1760103986000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/31\/1\/41"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,20]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["curroncol31010041"],"URL":"https:\/\/doi.org\/10.3390\/curroncol31010041","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,20]]}}}