{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T03:36:05Z","timestamp":1783740965743,"version":"3.55.0"},"reference-count":34,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"6","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cosmet Laser Ther"],"published-print":{"date-parts":[[2025,8,11]]},"abstract":"\n BACKGROUND<\/jats:title>\n Malignant melanoma is a highly aggressive type of cancer that frequently causes brain metastases, leading to poor outcomes. Immune checkpoint inhibitors (ICIs), such as nivolumab, play a crucial role in treating metastatic melanoma, yet intracranial hemorrhage (ICH) is a rare but serious complication. Although pseudoprogression and hyperprogressive disease are recognized phenomena associated with ICIs, the precise mechanisms connecting ICIs to ICH are not yet fully understood.<\/jats:p>\n <\/jats:sec>\n \n OBSERVATIONS<\/jats:title>\n The authors report the case of a 75-year-old man with stage IV malignant melanoma who experienced an ICH 5 days after starting nivolumab monotherapy. Imaging revealed a hemorrhagic brain metastasis in the left temporal lobe, necessitating a craniotomy. Histopathology confirmed melanoma metastasis without signs of pseudoprogression or hyperprogressive disease. The patient received whole-brain radiation therapy after surgery but continued to exhibit persistent aphasia and cognitive decline deficits.<\/jats:p>\n <\/jats:sec>\n \n LESSONS<\/jats:title>\n Early-phase intratumoral hemorrhage can occur shortly after ICI therapy, presenting diagnostic and management challenges. While this complication may result from the tumor\u2019s inherent hemorrhagic potential or ICI-induced changes such as pseudoprogression, hyperprogressive disease, or tumor lysis, its precise cause often remains unclear. Close monitoring during ICI treatment is essential to promptly address these potentially life-threatening events.<\/jats:p>\n \n https:\/\/thejns.org\/doi\/10.3171\/CASE2581<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3171\/case2581","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T23:43:46Z","timestamp":1754955826000},"source":"Crossref","is-referenced-by-count":1,"title":["Intratumoral hemorrhage from brain metastases following nivolumab therapy for malignant melanoma: illustrative case"],"prefix":"10.3171","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8666-1420","authenticated-orcid":true,"given":"Takahiro","family":"Iinuma","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Tokyo Saiseikai Central Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2987-7829","authenticated-orcid":true,"given":"Hiroki","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tokyo Saiseikai Central Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Kusuhara","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tokyo Saiseikai Central Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Funakoshi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tokyo Saiseikai Central Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigemichi","family":"Hirose","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology, Tokyo Saiseikai Central Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Terao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tokyo Saiseikai Central Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"issue":"2","key":"bib1","series-title":"Cancer","first-page":"660","article-title":"Malignant melanoma and central nervous system metastases: incidence, diagnosis, treatment and survival","volume":"42","author":"Amer","year":"1978","unstructured":"Amer MHAl-Sarraf MBaker LHVaitkevicius VK.Malignant melanoma and central nervous system metastases: incidence, diagnosis, treatment and survival. Cancer. 1978;42(2):660-668."},{"issue":"14","key":"bib2","series-title":"J Clin Oncol","first-page":"2865","article-title":"Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System","volume":"22","author":"Barnholtz-Sloan","year":"2004","unstructured":"Barnholtz-Sloan JSSloan AEDavis FGVigneau FDLai PSawaya RE.Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004;22(14):2865-2872."},{"issue":"2","key":"bib3","series-title":"Neuro Oncol","first-page":"199","article-title":"Brain and leptomeningeal metastases from cutaneous melanoma: survival outcomes based on clinical features","volume":"10","author":"Raizer","year":"2008","unstructured":"Raizer JJHwu WJPanageas KSBrain and leptomeningeal metastases from cutaneous melanoma: survival outcomes based on clinical features. Neuro Oncol. 2008;10(2):199-207."},{"issue":"3","key":"bib4","series-title":"Cancer Immunol Res","first-page":"179","article-title":"Melanoma brain metastasis pseudoprogression after pembrolizumab treatment","volume":"4","author":"Cohen","year":"2016","unstructured":"Cohen JVAlomari AKVortmeyer AOMelanoma brain metastasis pseudoprogression after pembrolizumab treatment. Cancer Immunol Res. 2016;4(3):179-182."},{"issue":"3","key":"bib5","series-title":"Cancer Control","first-page":"248","article-title":"Diagnosis and treatment of melanoma brain metastasis: a literature review","volume":"16","author":"Sloan","year":"2009","unstructured":"Sloan AENock CJEinstein DB.Diagnosis and treatment of melanoma brain metastasis: a literature review. Cancer Control. 2009;16(3):248-255."},{"issue":"3","key":"bib6","series-title":"No Shinkei Geka","first-page":"261","article-title":"Case of metastatic malignant melanoma detected by multifocal cerebral hemorrhage","volume":"40","author":"Shinomiya","year":"2012","unstructured":"Shinomiya AOkada MHatakeyama TCase of metastatic malignant melanoma detected by multifocal cerebral hemorrhage. Article in Japanese. No Shinkei Geka. 2012;40(3):261-269."},{"issue":"11","key":"bib7","series-title":"Curr Oncol Rep","first-page":"91","article-title":"Pseudoprogression of melanoma brain metastases","volume":"20","author":"Simard","year":"2018","unstructured":"Simard JLSmith MChandra S.Pseudoprogression of melanoma brain metastases. Curr Oncol Rep. 2018;20(11):91."},{"issue":"2","key":"bib8","series-title":"J Neurooncol","first-page":"339","article-title":"DCE-MRI perfusion predicts pseudoprogression in metastatic melanoma treated with immunotherapy","volume":"146","author":"Umemura","year":"2020","unstructured":"Umemura YWang DPeck KKDCE-MRI perfusion predicts pseudoprogression in metastatic melanoma treated with immunotherapy. J Neurooncol. 2020;146(2):339-346."},{"issue":"8","key":"bib9","series-title":"N Engl J Med","first-page":"722","article-title":"Combined nivolumab and ipilimumab in melanoma metastatic to the brain","volume":"379","author":"Tawbi","year":"2018","unstructured":"Tawbi HAForsyth PAAlgazi ACombined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med. 2018;379(8):722-730."},{"issue":"6","key":"bib10","series-title":"Neurology","first-page":"494","article-title":"Intracerebral and subarachnoid hemorrhage in patients with cancer","volume":"74","author":"Navi","year":"2010","unstructured":"Navi BBReichman JSBerlin DIntracerebral and subarachnoid hemorrhage in patients with cancer. Neurology. 2010;74(6):494-501."},{"issue":"5","key":"bib11","series-title":"Melanoma Res","first-page":"516","article-title":"Acute neurological adverse events during immune checkpoint inhibition therapy in patients with melanoma brain metastases","volume":"29","author":"Gr\u00e4tz","year":"2019","unstructured":"Gr\u00e4tz VLangan EANeumann AZillikens DTerheyden P.Acute neurological adverse events during immune checkpoint inhibition therapy in patients with melanoma brain metastases. Melanoma Res. 2019;29(5):516-521."},{"issue":"8","key":"bib12","series-title":"Clin Cancer Res","first-page":"1920","article-title":"Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1\/PD-L1","volume":"23","author":"Champiat","year":"2017","unstructured":"Champiat SDercle LAmmari SHyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1\/PD-L1. Clin Cancer Res. 2017;23(8):1920-1928."},{"issue":"7","key":"bib13","series-title":"Int J Mol Sci","first-page":"3736","article-title":"Hyperprogressive disease: main features and key controversies","volume":"22","author":"Arasanz","year":"2021","unstructured":"Arasanz HZuazo MBocanegra AHyperprogressive disease: main features and key controversies. Int J Mol Sci. 2021;22(7):3736."},{"issue":"1","key":"bib14","series-title":"Sci Rep","first-page":"10084","article-title":"Nationwide patterns of hemorrhagic stroke among patients hospitalized with brain metastases: influence of primary cancer diagnosis and anticoagulation","volume":"10","author":"Lee","year":"2020","unstructured":"Lee VJairam VYu JBPark HS.Nationwide patterns of hemorrhagic stroke among patients hospitalized with brain metastases: influence of primary cancer diagnosis and anticoagulation. Sci Rep. 2020;10(1):10084."},{"issue":"1","key":"bib15","series-title":"BMC Cancer","first-page":"549","article-title":"Unmasking of intracranial metastatic melanoma during ipilimumab\/nivolumab therapy: case report and literature review","volume":"18","author":"McDonald","year":"2018","unstructured":"McDonald MASanghvi PBykowski JDaniels GA.Unmasking of intracranial metastatic melanoma during ipilimumab\/nivolumab therapy: case report and literature review. BMC Cancer. 2018;18(1):549."},{"issue":"2","key":"bib16","series-title":"Cancer","first-page":"306","article-title":"Temozolomide in advanced malignant melanoma with small brain metastases: can we withhold cranial irradiation?","volume":"109","author":"Boogerd","year":"2007","unstructured":"Boogerd Wde Gast GCDalesio O.Temozolomide in advanced malignant melanoma with small brain metastases: can we withhold cranial irradiation? Cancer. 2007;109(2):306-312."},{"issue":"10","key":"bib17","series-title":"Cancers (Basel)","first-page":"2391","article-title":"Factors associated with hemorrhage of melanoma brain metastases after stereotactic radiosurgery in the era of targeted\/immune checkpoint inhibitor therapies","volume":"14","author":"Zoga","year":"2022","unstructured":"Zoga EWolff RAckermann HFactors associated with hemorrhage of melanoma brain metastases after stereotactic radiosurgery in the era of targeted\/immune checkpoint inhibitor therapies. Cancers (Basel). 2022;14(10):2391."},{"issue":"2","key":"bib1","series-title":"Cancer","first-page":"660","article-title":"Malignant melanoma and central nervous system metastases: incidence, diagnosis, treatment and survival","volume":"42","author":"Amer","year":"1978","unstructured":"Amer MHAl-Sarraf MBaker LHVaitkevicius VK.Malignant melanoma and central nervous system metastases: incidence, diagnosis, treatment and survival. Cancer. 1978;42(2):660-668."},{"issue":"14","key":"bib2","series-title":"J Clin Oncol","first-page":"2865","article-title":"Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System","volume":"22","author":"Barnholtz-Sloan","year":"2004","unstructured":"Barnholtz-Sloan JSSloan AEDavis FGVigneau FDLai PSawaya RE.Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004;22(14):2865-2872."},{"issue":"2","key":"bib3","series-title":"Neuro Oncol","first-page":"199","article-title":"Brain and leptomeningeal metastases from cutaneous melanoma: survival outcomes based on clinical features","volume":"10","author":"Raizer","year":"2008","unstructured":"Raizer JJHwu WJPanageas KSBrain and leptomeningeal metastases from cutaneous melanoma: survival outcomes based on clinical features. Neuro Oncol. 2008;10(2):199-207."},{"issue":"3","key":"bib4","series-title":"Cancer Immunol Res","first-page":"179","article-title":"Melanoma brain metastasis pseudoprogression after pembrolizumab treatment","volume":"4","author":"Cohen","year":"2016","unstructured":"Cohen JVAlomari AKVortmeyer AOMelanoma brain metastasis pseudoprogression after pembrolizumab treatment. Cancer Immunol Res. 2016;4(3):179-182."},{"issue":"3","key":"bib5","series-title":"Cancer Control","first-page":"248","article-title":"Diagnosis and treatment of melanoma brain metastasis: a literature review","volume":"16","author":"Sloan","year":"2009","unstructured":"Sloan AENock CJEinstein DB.Diagnosis and treatment of melanoma brain metastasis: a literature review. Cancer Control. 2009;16(3):248-255."},{"issue":"3","key":"bib6","series-title":"No Shinkei Geka","first-page":"261","article-title":"Case of metastatic malignant melanoma detected by multifocal cerebral hemorrhage","volume":"40","author":"Shinomiya","year":"2012","unstructured":"Shinomiya AOkada MHatakeyama TCase of metastatic malignant melanoma detected by multifocal cerebral hemorrhage. Article in Japanese. No Shinkei Geka. 2012;40(3):261-269."},{"issue":"11","key":"bib7","series-title":"Curr Oncol Rep","first-page":"91","article-title":"Pseudoprogression of melanoma brain metastases","volume":"20","author":"Simard","year":"2018","unstructured":"Simard JLSmith MChandra S.Pseudoprogression of melanoma brain metastases. Curr Oncol Rep. 2018;20(11):91."},{"issue":"2","key":"bib8","series-title":"J Neurooncol","first-page":"339","article-title":"DCE-MRI perfusion predicts pseudoprogression in metastatic melanoma treated with immunotherapy","volume":"146","author":"Umemura","year":"2020","unstructured":"Umemura YWang DPeck KKDCE-MRI perfusion predicts pseudoprogression in metastatic melanoma treated with immunotherapy. J Neurooncol. 2020;146(2):339-346."},{"issue":"8","key":"bib9","series-title":"N Engl J Med","first-page":"722","article-title":"Combined nivolumab and ipilimumab in melanoma metastatic to the brain","volume":"379","author":"Tawbi","year":"2018","unstructured":"Tawbi HAForsyth PAAlgazi ACombined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med. 2018;379(8):722-730."},{"issue":"6","key":"bib10","series-title":"Neurology","first-page":"494","article-title":"Intracerebral and subarachnoid hemorrhage in patients with cancer","volume":"74","author":"Navi","year":"2010","unstructured":"Navi BBReichman JSBerlin DIntracerebral and subarachnoid hemorrhage in patients with cancer. Neurology. 2010;74(6):494-501."},{"issue":"5","key":"bib11","series-title":"Melanoma Res","first-page":"516","article-title":"Acute neurological adverse events during immune checkpoint inhibition therapy in patients with melanoma brain metastases","volume":"29","author":"Gr\u00e4tz","year":"2019","unstructured":"Gr\u00e4tz VLangan EANeumann AZillikens DTerheyden P.Acute neurological adverse events during immune checkpoint inhibition therapy in patients with melanoma brain metastases. Melanoma Res. 2019;29(5):516-521."},{"issue":"8","key":"bib12","series-title":"Clin Cancer Res","first-page":"1920","article-title":"Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1\/PD-L1","volume":"23","author":"Champiat","year":"2017","unstructured":"Champiat SDercle LAmmari SHyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1\/PD-L1. Clin Cancer Res. 2017;23(8):1920-1928."},{"issue":"7","key":"bib13","series-title":"Int J Mol Sci","first-page":"3736","article-title":"Hyperprogressive disease: main features and key controversies","volume":"22","author":"Arasanz","year":"2021","unstructured":"Arasanz HZuazo MBocanegra AHyperprogressive disease: main features and key controversies. Int J Mol Sci. 2021;22(7):3736."},{"issue":"1","key":"bib14","series-title":"Sci Rep","first-page":"10084","article-title":"Nationwide patterns of hemorrhagic stroke among patients hospitalized with brain metastases: influence of primary cancer diagnosis and anticoagulation","volume":"10","author":"Lee","year":"2020","unstructured":"Lee VJairam VYu JBPark HS.Nationwide patterns of hemorrhagic stroke among patients hospitalized with brain metastases: influence of primary cancer diagnosis and anticoagulation. Sci Rep. 2020;10(1):10084."},{"issue":"1","key":"bib15","series-title":"BMC Cancer","first-page":"549","article-title":"Unmasking of intracranial metastatic melanoma during ipilimumab\/nivolumab therapy: case report and literature review","volume":"18","author":"McDonald","year":"2018","unstructured":"McDonald MASanghvi PBykowski JDaniels GA.Unmasking of intracranial metastatic melanoma during ipilimumab\/nivolumab therapy: case report and literature review. BMC Cancer. 2018;18(1):549."},{"issue":"2","key":"bib16","series-title":"Cancer","first-page":"306","article-title":"Temozolomide in advanced malignant melanoma with small brain metastases: can we withhold cranial irradiation?","volume":"109","author":"Boogerd","year":"2007","unstructured":"Boogerd Wde Gast GCDalesio O.Temozolomide in advanced malignant melanoma with small brain metastases: can we withhold cranial irradiation? Cancer. 2007;109(2):306-312."},{"issue":"10","key":"bib17","series-title":"Cancers (Basel)","first-page":"2391","article-title":"Factors associated with hemorrhage of melanoma brain metastases after stereotactic radiosurgery in the era of targeted\/immune checkpoint inhibitor therapies","volume":"14","author":"Zoga","year":"2022","unstructured":"Zoga EWolff RAckermann HFactors associated with hemorrhage of melanoma brain metastases after stereotactic radiosurgery in the era of targeted\/immune checkpoint inhibitor therapies. Cancers (Basel). 2022;14(10):2391."}],"container-title":["Journal of Neurosurgery: Case Lessons"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg-case-lessons\/10\/6\/article-CASE2581.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg-case-lessons\/10\/6\/article-CASE2581.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg-case-lessons\/10\/6\/article-CASE2581.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T11:09:11Z","timestamp":1769684951000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg-case-lessons\/10\/6\/article-CASE2581.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,11]]},"references-count":34,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.3171\/case2581","relation":{},"ISSN":["2694-1902"],"issn-type":[{"value":"2694-1902","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,11]]}}}