BRAF Mutant Pulmonary Melanoma with Brain Metastasis in a Young Female: A Case Report

BRAF Mutant Pulmonary Melanoma with Brain Metastasis in a Young Female: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report BRAF Mutant Pulmonary Melanoma with Brain Metastasis in a Young Female: A Case Report Sheilabi Seeburun, Carlos Valladares, Siddhardh Ambula This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7060023/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract We report a case of BRAF-mutant pulmonary melanoma with brain metastasis in an otherwise healthy 30-year-old Caucasian female with no significant past medical or family history. She initially presented with sudden onset right-sided headache, accompanied by nausea, vomiting, neck pain, dizziness, and photophobia. Imaging studies revealed a cyst-like mass in the right frontal parietal lobe and a mass in the left lower lobe with multiple intrapulmonary nodules. Following an extensive workup, the patient was diagnosed with metastatic pulmonary melanoma with a BRAF mutation, prompting a multidisciplinary treatment approach involving neurosurgery, immunotherapy, and radiotherapy. The patient underwent partial surgical resection of the brain lesion and CyberKnife radiosurgery without neurological sequelae. Systemic treatment with ipilimumab/nivolumab was initiated, with close monitoring for immunotherapy-related toxicities. Despite this comprehensive strategy, a subsequent brain MRI at post surgery and after five cycles of immunotherapy showed persistence of the right frontal lobe enhancing mass. This case underscores the challenges of treating BRAF-mutant metastatic pulmonary melanoma and highlights the rarity of metastatic pulmonary melanoma in young females. pulmonary melanoma BRAF-mutant brain metastasis case report Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Primary pulmonary melanoma is a rare form of malignant melanoma that originates in the lung. It is exceedingly uncommon, accounting for only 0.01% of all primary lung tumors ( 1 ) as most cases of melanoma in the lung are metastatic rather than primary. It generally carries a poor prognosis, with most patients surviving less than 18 months ( 2 ). We present a unique case involving a 30-year-old female patient, deviating from the typical demographic profile, which predominantly features a median age of 60 years and male predominance among 76 reported cases worldwide ( 3 ). Case Presentation A 30-year-old Caucasian female with no past medical history presented with a sudden-onset right-sided headache persisting for six days, along with nausea, vomiting, neck pain, dizziness, and photophobia. She denied fever, chills, weight loss, chest pain, shortness of breath, or recent sick contacts. Her surgical history included two low transverse C-sections, and she had no significant family history of malignancy. The patient was an active smoker (0.5 pack per day for 15 years) and denied alcohol abuse or IV drug use. On examination, her vitals were stable, temperature of 97.5°F, blood pressure of 96/53 mm Hg, a pulse rate of 55/min, and a respiratory rate of 16/min. Systemic examinations, including respiratory, cardiovascular, abdominal, and neurological assessments, were unremarkable with a Glasgow Coma Scale score of 15. A non-contrast CT head scan identified a cyst-like mass in the right frontal parietal lobe (Fig. 1 ), confirmed by contrast-enhanced brain MRI (Fig. 2 A-C). A non-contrast CT chest, abdomen and pelvis scan showed a mass in the left lower lobe with multiple intrapulmonary nodules (Fig. 3 ), prompting a CT-guided fine-needle aspiration (FNA) of the lung mass. Immunohistochemistry results indicated melanoma, with positive staining for SOX10 and Melan-A, along with a positive BRAF mutation on genetic sequencing. A PET/CT FDG scan revealed FDG-avid bilateral level 2 lymph nodes of the head and neck, as well as an FDG-avid right submandibular lymph node. A whole-body NM bone scan showed no metastatic disease to bone, and tumor markers (CEA, CA27.29, CA19-9, CA125, AFP) were all negative. The patient was diagnosed with BRAF-mutant metastatic pulmonary melanoma. Treatment and Outcome During hospitalization, the patient was treated with dexamethasone for elevated intracranial pressure and levetiracetam for seizure prophylaxis. One month later, she underwent a right pterional craniotomy with subtotal resection of the right subinsular mass (Fig. 4 ). Histopathologic evaluation confirmed metastatic melanoma, with immunohistochemical staining positive for HMB-45, Melan-A, S100, and SOX10. She subsequently initiated outpatient systemic immunotherapy with combination nivolumab and ipilimumab. A total of five cycles were administered over the following months, with some delays due to steroid use and treatment-related side effects. The patient experienced mild immune-related adverse events including low-grade fevers, intermittent headaches, bilateral lower extremity swelling, pruritus, and a transient maculopapular rash, all of which were managed symptomatically. She also underwent stereotactic radiosurgery to the resection cavity using CyberKnife (8 Gy × 3 fractions), which was completed without neurological complications. Throughout systemic therapy, she was closely monitored for immune-related toxicities—such as pneumonitis, thyroiditis, colitis, cytopenias, and hepatitis—via serial laboratory evaluation including CBC, CMP, liver function tests, and thyroid panels. During treatment, she developed secondary adrenal insufficiency and hypothyroidism, requiring transition from prednisone to maintenance hydrocortisone and later initiation of levothyroxine after discontinuation of methimazole. Three months after craniotomy and two cycles of immunotherapy, a brain MRI revealed a persistent enhancing mass in the right frontal lobe with surrounding vasogenic edema and mild midline shift, but no new intracranial lesions (Fig. 5 ). Following five cycles of immunotherapy, subsequent PET/CT scans showed a decrease in FDG uptake in previously identified lymph nodes, with no signs of new or progressive systemic disease. A follow-up brain MRI performed 10 months later showed a reduction in the size of the right frontal lobe enhancing lesion (24 x 16 mm) and a decrease in surrounding vasogenic edema. Based on the most recent follow-up and imaging, the patient remains clinically stable, and her immunotherapy treatment with nivolumab and ipilimumab was rescheduled accordingly. Discussion The etiology of primary pulmonary melanoma of the lung (PMML) remains uncertain. One hypothesis suggests that cigarette smoke-induced squamous metaplasia may contribute to its development ( 4 ). Other theories propose that melanocytes migrate and transform within the respiratory tract during embryonic development or originate from melanoblasts in the trachea, esophagus, and pharynx ( 5 ). Given our patient's 15-year smoking history, it is possible that smoking played a role in the onset of her pulmonary melanoma. Brain metastases in melanoma are associated with several risk factors, including male sex, age over 60, primary tumors in mucosal areas or specific skin regions, and deeply invasive or ulcerated primary lesions. Additionally, genetic mutations such as BRAF and NRAS, expression of C-C chemokine receptor 4 (CCR4), and activation of the PI3K/AKT signaling pathway have been implicated in the development of brain metastases ( 6 – 11 ). Notably, our patient—a young female without a history of cutaneous or mucosal melanoma—had only one known risk factor: BRAF mutation. The diagnosis of PMML is established through clinical, radiological, and histopathological criteria, necessitating the exclusion of primary melanoma at other sites, including the skin, mucosa, and ocular regions. Additional diagnostic criteria include the presence of a solitary, centrally located lung tumor with immunohistochemical confirmation of melanoma ( 12 ). A definitive diagnosis requires pathological biopsy and immunohistochemical analysis, with key markers such as S-100, HMB-45, and Melan-A confirming the presence of PMML. In our case, fine-needle aspiration biopsy of the left lung mass confirmed the diagnosis of primary pulmonary melanoma with brain metastasis after ruling out cutaneous and mucosal origins. Our patient presented with a symptomatic, solitary brain metastasis measuring approximately 4 cm, accompanied by significant edema and mass effect. A multidisciplinary approach was implemented, beginning with surgical resection of the brain lesion, followed by systemic immunotherapy and stereotactic radiation ( 13 ). Preoperative glucocorticoids were administered to manage vasogenic edema, and postoperative radiotherapy was initiated to address the residual tumor following an incomplete resection. Immunotherapy was planned prior to stereotactic radiosurgery (SRS). While the optimal sequencing of immunotherapy and SRS remains under investigation ( 14 , 15 ), emerging evidence suggests benefits from either concurrent administration or initiating immunotherapy before SRS ( 13 ). To maximize the efficacy of immunotherapy, glucocorticoids were tapered before its initiation. Given the patient's BRAF mutation, immunotherapy-naïve status, and good performance status, we selected combination immunotherapy (CMI) with nivolumab (a PD-1 inhibitor) and ipilimumab (a CTLA-4 inhibitor) as the first-line treatment ( 13 ). Both CMI and combination targeted therapy (TT) using BRAF and MEK inhibitors have demonstrated intracranial efficacy in BRAF-mutant melanomas ( 16 ). However, we prioritized CMI over monotherapy or combination TT, as studies indicate that CMI is associated with improved overall survival (OS) and prolonged progression-free survival (PFS) ( 16 ). Conclusion This case underscores the importance of recognizing PMML as a differential diagnosis for lung masses, particularly in patients without a history of cutaneous melanoma. The young age and female sex of our patient highlight the variability in presentation compared to the previously reported cases, which predominantly feature older male patients. Additionally, this case emphasizes the challenges of treating melanoma brain metastases and the potential for persistent disease despite aggressive multimodal therapy. Given the increasing use of immune checkpoint inhibitors and targeted therapies in melanoma, further studies are needed to optimize treatment strategies, particularly in rare cases like pulmonary melanoma. Strengths The case benefits from a comprehensive, multidisciplinary treatment approach, which included advanced immunotherapy (ipilimumab/nivolumab), surgical resection, and radiosurgery, providing valuable insight into the potential efficacy and challenges of these modalities for treating metastatic pulmonary melanoma. The patient’s detailed diagnostic workup, including imaging, histopathology, and genetic profiling (BRAF mutation), provides a robust foundation for understanding the clinical behavior of BRAF-mutant melanoma and the importance of personalized treatment. Follow-up with serial brain MRIs and PET/CT scans over an extended period allowed for thorough monitoring of treatment response and disease progression, contributing to the literature on how such metastases evolve under therapy. Limitations The rarity of BRAF-mutant pulmonary melanoma limits the generalizability of this case. Limited follow-up data restricts the ability to assess long-term outcomes and the overall efficacy of the treatment regimen, especially regarding the potential for relapse or resistance to immunotherapy. The complex interplay of multiple treatment modalities (surgery, immunotherapy, radiation) makes it difficult to determine the individual contribution of each modality to the patient’s outcome. Patient Perspective When I first started having the headaches and nausea, I never imagined it would lead to a diagnosis of cancer, especially something as rare as melanoma in my lungs and brain. It was terrifying to hear the word ‘cancer’ and 'metastatic.' But I was grateful for how quickly the doctors acted and how they involved me in every decision. The brain surgery and treatments were tough, but I’m thankful I had a team that supported me every step of the way. I hope sharing my story helps in the medical literature. Declarations Acknowledgments The authors would like to acknowledge the neurosurgery, oncology, radiation oncology radiology and pathology teams at Rutgers Health Community Medical Center for their contributions to the patient’s diagnosis and management. Special thanks to the patient and her family for their willingness to share her case to advance medical knowledge Financial Disclosures: None reported Support: None reported Informed Consent: Written informed consent was obtained from the patient relating to the subject matter to appear in the case report. Author Contribution S.S and C.V wrote the main manuscript text and C.V and S.A prepared all figures. All authors reviewed the manuscript. References Xi JM, Wen H, Yan XB, Huang J. Primary pulmonary malignant melanoma diagnosed with percutaneous biopsy tissue: A case report. World J Clin Cases . 2020;8(24):6373–6379. doi: 10.12998/wjcc.v8.i24.6373 Kyriakopoulos C, Zarkavelis G, Andrianopoulou A, et al. Primary Pulmonary Malignant Melanoma: Report of an Important Entity and Literature Review. Case Rep Oncol Med . 2017;2017:8654326. doi: 10.1155/2017/8654326 Paliogiannis P, Fara AM, Pintus G, et al. Primary Melanoma of the Lung: A Systematic Review. Medicina (Kaunas) . 2020;56(11):576. Published 2020 Oct 30. doi: 10.3390/medicina56110576 Wilson RW, Moran CA. Primary melanoma of the lung: a clinicopathologic and immunohistochemical study of eight cases. Am J Surg Pathol . 1997;21(10):1196–1202. doi: 10.1097/00000478-199710000-00010 Yunce M, Selinger S, Krimsky W, Harley DP. Primary malignant melanoma of the lung: a case report of a rare tumor and review of the literature. J Community Hosp Intern Med Perspect . 2018;8(1):29–31. Published 2018 Feb 6. doi: 10.1080/20009666.2018.1424485 Bedikian AY, Wei C, Detry M, et al. Predictive factors for the development of brain metastasis in advanced unresectable metastatic melanoma. Am J Clin Oncol . 2011;34(6):603–610. doi: 10.1097/COC.0b013e3181f9456a El-Osta H, Falchook G, Tsimberidou A, et al. BRAF mutations in advanced cancers: clinical characteristics and outcomes. PLoS One . 2011;6(10):e25806. doi: 10.1371/journal.pone.0025806 Thumar, J., Shahbazian, D., Aziz, S.A. et al. MEK targeting in N-RAS mutated metastatic melanoma. Mol Cancer 13, 45 (2014). https://doi.org/10.1186/1476-4598-13-45 Kotecha R, Miller JA, Venur VA, et al. Melanoma brain metastasis: the impact of stereotactic radiosurgery, BRAF mutational status, and targeted and/or immune-based therapies on treatment outcome. J Neurosurg . 2018;129(1):50–59. doi: 10.3171/2017.1.JNS162797 Klein A, Sagi-Assif O, Meshel T, et al. CCR4 is a determinant of melanoma brain metastasis. Oncotarget . 2017;8(19):31079–31091. doi: 10.18632/oncotarget.16076 Chen G, Chakravarti N, Aardalen K, et al. Molecular profiling of patient-matched brain and extracranial melanoma metastases implicates the PI3K pathway as a therapeutic target. Clin Cancer Res . 2014;20(21):5537–5546. doi: 10.1158/1078-0432.CCR-13-3003 Figueroa Rodriguez F, Uddin A, Nasr J. Primary Pulmonary Malignant Melanoma Found While Evaluating New Onset Cough: A Case Presentation and Literature Review. Case Rep Pulmonol . 2019;2019:3867831. Published 2019 Apr 10. doi: 10.1155/2019/3867831 Flaherty, K.T., Brose, M.S., Schuchter, L.M., Tuveson, D.A., Lee, R.J., Schwartz, B., Lathia, C.D., Weber, B., & O'dwyer, P.J. (2004). Phase I/II trial of BAY 43-9006, carboplatin (C) and paclitaxel (P) demonstrates preliminary antitumor activity in the expansion cohort of patients with metastatic melanoma. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 22 14_suppl , 7507. Amaravadi RK, Schuchter LM, McDermott DF, et al. Phase II Trial of Temozolomide and Sorafenib in Advanced Melanoma Patients with or without Brain Metastases. Clin Cancer Res . 2009;15(24):7711–7718. doi: 10.1158/1078-0432.CCR-09-2074 Eisen T, Marais R, Affolter A, et al. Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies. Br J Cancer 2011; 105:353. Rulli E, Legramandi L, Salvati L, Mandala M. The impact of targeted therapies and immunotherapy in melanoma brain metastases: A systematic review and meta-analysis. Cancer . 2019;125(21):3776–3789. doi: 10.1002/cncr.32375 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 28 Oct, 2025 Reviewers agreed at journal 11 Oct, 2025 Reviewers agreed at journal 22 Aug, 2025 Reviewers invited by journal 13 Jul, 2025 Editor assigned by journal 08 Jul, 2025 Submission checks completed at journal 08 Jul, 2025 First submitted to journal 06 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7060023","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":482015369,"identity":"3550bcb2-5780-49ed-b782-11fd35583cf3","order_by":0,"name":"Sheilabi Seeburun","email":"data:image/png;base64,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","orcid":"","institution":"Rutgers, The State University of New Jersey","correspondingAuthor":true,"prefix":"","firstName":"Sheilabi","middleName":"","lastName":"Seeburun","suffix":""},{"id":482015370,"identity":"ae089da8-4c58-4232-8556-abb21ae00ed3","order_by":1,"name":"Carlos Valladares","email":"","orcid":"","institution":"Jackson Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Carlos","middleName":"","lastName":"Valladares","suffix":""},{"id":482015371,"identity":"73d91f0a-7673-4c4d-8dce-d1b7cdc5baff","order_by":2,"name":"Siddhardh Ambula","email":"","orcid":"","institution":"All India Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Siddhardh","middleName":"","lastName":"Ambula","suffix":""}],"badges":[],"createdAt":"2025-07-06 23:08:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7060023/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7060023/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":86241337,"identity":"5ad81e4d-5cfc-4dc9-b1f9-da04cb3a267f","added_by":"auto","created_at":"2025-07-08 10:39:06","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":32838,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNon contrast CT head illustrating a 35.5x29.5mm cyst-like mass in the right frontal parietal lobe with moderate surrounding vasogenic edema and mass effect upon the frontal horn right lateral ventricle and moderate midline shift of 7mm to the left.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7060023/v1/e5d7cb1ffdae7fe084f38b70.jpg"},{"id":86241700,"identity":"57eb9017-f546-4547-8a69-437e530d2f00","added_by":"auto","created_at":"2025-07-08 10:47:06","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":61669,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDW-MRI at b1000 (A), T2 weighted (B) and core cyberknife imaging (C) showing a 40x33mm cyst-like mass extending along right temporal, frontal and parietal lobe with irregular mixed thin and thick enhancing wall with moderate surrounding edema and mass effect upon right lateral ventricle and 7.7mm midline shift to left.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7060023/v1/62db41949e56f05c80a571e7.jpg"},{"id":86241326,"identity":"32a193cb-dbb2-4b7b-bb9d-d5c620a8889b","added_by":"auto","created_at":"2025-07-08 10:39:04","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":37889,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNon-contrast CT chest, abdomen and pelvis scan showing a mass in the left lower lobe (43.5x31.8mm) with multiple intrapulmonary nodules\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7060023/v1/7261a2a294ff23617a54c6b7.jpg"},{"id":86241330,"identity":"0d744175-4480-4e9f-b873-d1e4098fec5c","added_by":"auto","created_at":"2025-07-08 10:39:04","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":62818,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMRI brain with contrast showing post-surgical changes, with partial resection of enhancing mass lesion (38.5x29.7x44.4mm) with significant vasogenic edema, decreased mass effect, and midline shift.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7060023/v1/73f52ad405eb5b1811d036b5.jpg"},{"id":86241328,"identity":"450c3ee3-7a50-4b23-ac54-1052a5829f7e","added_by":"auto","created_at":"2025-07-08 10:39:04","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":48686,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMRI brain demonstrating an enhancing mass, measuring 37.0x24.1x37.7mm, in right frontal lobe, with surrounding vasogenic edema.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7060023/v1/bb9b79d834e84573dd3f6b8e.jpg"},{"id":86241702,"identity":"37fa9881-186a-4eb8-b251-05cdb6c5c194","added_by":"auto","created_at":"2025-07-08 10:47:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":982500,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7060023/v1/c4d0769b-33da-4ed6-9686-df9384ef8264.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"BRAF Mutant Pulmonary Melanoma with Brain Metastasis in a Young Female: A Case Report","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePrimary pulmonary melanoma is a rare form of malignant melanoma that originates in the lung. It is exceedingly uncommon, accounting for only 0.01% of all primary lung tumors (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) as most cases of melanoma in the lung are metastatic rather than primary. It generally carries a poor prognosis, with most patients surviving less than 18 months (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). We present a unique case involving a 30-year-old female patient, deviating from the typical demographic profile, which predominantly features a median age of 60 years and male predominance among 76 reported cases worldwide (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 30-year-old Caucasian female with no past medical history presented with a sudden-onset right-sided headache persisting for six days, along with nausea, vomiting, neck pain, dizziness, and photophobia. She denied fever, chills, weight loss, chest pain, shortness of breath, or recent sick contacts. Her surgical history included two low transverse C-sections, and she had no significant family history of malignancy. The patient was an active smoker (0.5 pack per day for 15 years) and denied alcohol abuse or IV drug use. On examination, her vitals were stable, temperature of 97.5\u0026deg;F, blood pressure of 96/53 mm Hg, a pulse rate of 55/min, and a respiratory rate of 16/min. Systemic examinations, including respiratory, cardiovascular, abdominal, and neurological assessments, were unremarkable with a Glasgow Coma Scale score of 15.\u003c/p\u003e\u003cp\u003eA non-contrast CT head scan identified a cyst-like mass in the right frontal parietal lobe (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), confirmed by contrast-enhanced brain MRI (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA-C). A non-contrast CT chest, abdomen and pelvis scan showed a mass in the left lower lobe with multiple intrapulmonary nodules (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), prompting a CT-guided fine-needle aspiration (FNA) of the lung mass. Immunohistochemistry results indicated melanoma, with positive staining for SOX10 and Melan-A, along with a positive BRAF mutation on genetic sequencing. A PET/CT FDG scan revealed FDG-avid bilateral level 2 lymph nodes of the head and neck, as well as an FDG-avid right submandibular lymph node. A whole-body NM bone scan showed no metastatic disease to bone, and tumor markers (CEA, CA27.29, CA19-9, CA125, AFP) were all negative. The patient was diagnosed with BRAF-mutant metastatic pulmonary melanoma.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTreatment and Outcome\u003c/b\u003e\u003c/p\u003e\u003cp\u003eDuring hospitalization, the patient was treated with dexamethasone for elevated intracranial pressure and levetiracetam for seizure prophylaxis. One month later, she underwent a right pterional craniotomy with subtotal resection of the right subinsular mass (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Histopathologic evaluation confirmed metastatic melanoma, with immunohistochemical staining positive for HMB-45, Melan-A, S100, and SOX10. She subsequently initiated outpatient systemic immunotherapy with combination nivolumab and ipilimumab. A total of five cycles were administered over the following months, with some delays due to steroid use and treatment-related side effects. The patient experienced mild immune-related adverse events including low-grade fevers, intermittent headaches, bilateral lower extremity swelling, pruritus, and a transient maculopapular rash, all of which were managed symptomatically. She also underwent stereotactic radiosurgery to the resection cavity using CyberKnife (8 Gy \u0026times; 3 fractions), which was completed without neurological complications. Throughout systemic therapy, she was closely monitored for immune-related toxicities\u0026mdash;such as pneumonitis, thyroiditis, colitis, cytopenias, and hepatitis\u0026mdash;via serial laboratory evaluation including CBC, CMP, liver function tests, and thyroid panels. During treatment, she developed secondary adrenal insufficiency and hypothyroidism, requiring transition from prednisone to maintenance hydrocortisone and later initiation of levothyroxine after discontinuation of methimazole.\u003c/p\u003e\u003cp\u003eThree months after craniotomy and two cycles of immunotherapy, a brain MRI revealed a persistent enhancing mass in the right frontal lobe with surrounding vasogenic edema and mild midline shift, but no new intracranial lesions (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Following five cycles of immunotherapy, subsequent PET/CT scans showed a decrease in FDG uptake in previously identified lymph nodes, with no signs of new or progressive systemic disease. A follow-up brain MRI performed 10 months later showed a reduction in the size of the right frontal lobe enhancing lesion (24 x 16 mm) and a decrease in surrounding vasogenic edema. Based on the most recent follow-up and imaging, the patient remains clinically stable, and her immunotherapy treatment with nivolumab and ipilimumab was rescheduled accordingly.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe etiology of primary pulmonary melanoma of the lung (PMML) remains uncertain. One hypothesis suggests that cigarette smoke-induced squamous metaplasia may contribute to its development (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Other theories propose that melanocytes migrate and transform within the respiratory tract during embryonic development or originate from melanoblasts in the trachea, esophagus, and pharynx (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Given our patient's 15-year smoking history, it is possible that smoking played a role in the onset of her pulmonary melanoma.\u003c/p\u003e\u003cp\u003eBrain metastases in melanoma are associated with several risk factors, including male sex, age over 60, primary tumors in mucosal areas or specific skin regions, and deeply invasive or ulcerated primary lesions. Additionally, genetic mutations such as BRAF and NRAS, expression of C-C chemokine receptor 4 (CCR4), and activation of the PI3K/AKT signaling pathway have been implicated in the development of brain metastases (\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Notably, our patient\u0026mdash;a young female without a history of cutaneous or mucosal melanoma\u0026mdash;had only one known risk factor: BRAF mutation.\u003c/p\u003e\u003cp\u003eThe diagnosis of PMML is established through clinical, radiological, and histopathological criteria, necessitating the exclusion of primary melanoma at other sites, including the skin, mucosa, and ocular regions. Additional diagnostic criteria include the presence of a solitary, centrally located lung tumor with immunohistochemical confirmation of melanoma (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). A definitive diagnosis requires pathological biopsy and immunohistochemical analysis, with key markers such as S-100, HMB-45, and Melan-A confirming the presence of PMML. In our case, fine-needle aspiration biopsy of the left lung mass confirmed the diagnosis of primary pulmonary melanoma with brain metastasis after ruling out cutaneous and mucosal origins.\u003c/p\u003e\u003cp\u003eOur patient presented with a symptomatic, solitary brain metastasis measuring approximately 4 cm, accompanied by significant edema and mass effect. A multidisciplinary approach was implemented, beginning with surgical resection of the brain lesion, followed by systemic immunotherapy and stereotactic radiation (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Preoperative glucocorticoids were administered to manage vasogenic edema, and postoperative radiotherapy was initiated to address the residual tumor following an incomplete resection. Immunotherapy was planned prior to stereotactic radiosurgery (SRS). While the optimal sequencing of immunotherapy and SRS remains under investigation (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e), emerging evidence suggests benefits from either concurrent administration or initiating immunotherapy before SRS (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). To maximize the efficacy of immunotherapy, glucocorticoids were tapered before its initiation.\u003c/p\u003e\u003cp\u003eGiven the patient's BRAF mutation, immunotherapy-na\u0026iuml;ve status, and good performance status, we selected combination immunotherapy (CMI) with nivolumab (a PD-1 inhibitor) and ipilimumab (a CTLA-4 inhibitor) as the first-line treatment (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Both CMI and combination targeted therapy (TT) using BRAF and MEK inhibitors have demonstrated intracranial efficacy in BRAF-mutant melanomas (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). However, we prioritized CMI over monotherapy or combination TT, as studies indicate that CMI is associated with improved overall survival (OS) and prolonged progression-free survival (PFS) (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case underscores the importance of recognizing PMML as a differential diagnosis for lung masses, particularly in patients without a history of cutaneous melanoma. The young age and female sex of our patient highlight the variability in presentation compared to the previously reported cases, which predominantly feature older male patients. Additionally, this case emphasizes the challenges of treating melanoma brain metastases and the potential for persistent disease despite aggressive multimodal therapy. Given the increasing use of immune checkpoint inhibitors and targeted therapies in melanoma, further studies are needed to optimize treatment strategies, particularly in rare cases like pulmonary melanoma.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStrengths\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eThe case benefits from a comprehensive, multidisciplinary treatment approach, which included advanced immunotherapy (ipilimumab/nivolumab), surgical resection, and radiosurgery, providing valuable insight into the potential efficacy and challenges of these modalities for treating metastatic pulmonary melanoma.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eThe patient\u0026rsquo;s detailed diagnostic workup, including imaging, histopathology, and genetic profiling (BRAF mutation), provides a robust foundation for understanding the clinical behavior of BRAF-mutant melanoma and the importance of personalized treatment.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eFollow-up with serial brain MRIs and PET/CT scans over an extended period allowed for thorough monitoring of treatment response and disease progression, contributing to the literature on how such metastases evolve under therapy.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLimitations\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eThe rarity of BRAF-mutant pulmonary melanoma limits the generalizability of this case.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eLimited follow-up data restricts the ability to assess long-term outcomes and the overall efficacy of the treatment regimen, especially regarding the potential for relapse or resistance to immunotherapy.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eThe complex interplay of multiple treatment modalities (surgery, immunotherapy, radiation) makes it difficult to determine the individual contribution of each modality to the patient\u0026rsquo;s outcome.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003ePatient Perspective\u003c/b\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eWhen I first started having the headaches and nausea, I never imagined it would lead to a diagnosis of cancer, especially something as rare as melanoma in my lungs and brain. It was terrifying to hear the word \u0026lsquo;cancer\u0026rsquo; and 'metastatic.' But I was grateful for how quickly the doctors acted and how they involved me in every decision. The brain surgery and treatments were tough, but I\u0026rsquo;m thankful I had a team that supported me every step of the way. I hope sharing my story helps in the medical literature.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to acknowledge the neurosurgery, oncology, radiation oncology radiology and pathology teams at Rutgers Health Community Medical Center for their contributions to the patient\u0026rsquo;s diagnosis and management. Special thanks to the patient and her family for their willingness to share her case to advance medical knowledge\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial Disclosures:\u0026nbsp;\u003c/strong\u003eNone reported\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupport:\u0026nbsp;\u003c/strong\u003eNone reported\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent:\u0026nbsp;\u003c/strong\u003eWritten informed consent was obtained from the patient relating to the subject matter to appear in the case report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS.S and C.V wrote the main manuscript text and C.V and S.A prepared all figures. All authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eXi JM, Wen H, Yan XB, Huang J. Primary pulmonary malignant melanoma diagnosed with percutaneous biopsy tissue: A case report. \u003cem\u003eWorld J Clin Cases\u003c/em\u003e. 2020;8(24):6373\u0026ndash;6379. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.12998/wjcc.v8.i24.6373\u003c/span\u003e\u003cspan address=\"10.12998/wjcc.v8.i24.6373\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKyriakopoulos C, Zarkavelis G, Andrianopoulou A, et al. Primary Pulmonary Malignant Melanoma: Report of an Important Entity and Literature Review. \u003cem\u003eCase Rep Oncol Med\u003c/em\u003e. 2017;2017:8654326. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1155/2017/8654326\u003c/span\u003e\u003cspan address=\"10.1155/2017/8654326\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePaliogiannis P, Fara AM, Pintus G, et al. Primary Melanoma of the Lung: A Systematic Review. \u003cem\u003eMedicina (Kaunas)\u003c/em\u003e. 2020;56(11):576. Published 2020 Oct 30. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/medicina56110576\u003c/span\u003e\u003cspan address=\"10.3390/medicina56110576\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWilson RW, Moran CA. Primary melanoma of the lung: a clinicopathologic and immunohistochemical study of eight cases. \u003cem\u003eAm J Surg Pathol\u003c/em\u003e. 1997;21(10):1196\u0026ndash;1202. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/00000478-199710000-00010\u003c/span\u003e\u003cspan address=\"10.1097/00000478-199710000-00010\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYunce M, Selinger S, Krimsky W, Harley DP. Primary malignant melanoma of the lung: a case report of a rare tumor and review of the literature. \u003cem\u003eJ Community Hosp Intern Med Perspect\u003c/em\u003e. 2018;8(1):29\u0026ndash;31. Published 2018 Feb 6. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/20009666.2018.1424485\u003c/span\u003e\u003cspan address=\"10.1080/20009666.2018.1424485\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBedikian AY, Wei C, Detry M, et al. Predictive factors for the development of brain metastasis in advanced unresectable metastatic melanoma. \u003cem\u003eAm J Clin Oncol\u003c/em\u003e. 2011;34(6):603\u0026ndash;610. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/COC.0b013e3181f9456a\u003c/span\u003e\u003cspan address=\"10.1097/COC.0b013e3181f9456a\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEl-Osta H, Falchook G, Tsimberidou A, et al. BRAF mutations in advanced cancers: clinical characteristics and outcomes. \u003cem\u003ePLoS One\u003c/em\u003e. 2011;6(10):e25806. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0025806\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0025806\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eThumar, J., Shahbazian, D., Aziz, S.A. \u003cem\u003eet al.\u003c/em\u003e MEK targeting in N-RAS mutated metastatic melanoma. \u003cem\u003eMol Cancer\u003c/em\u003e 13, 45 (2014). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/1476-4598-13-45\u003c/span\u003e\u003cspan address=\"10.1186/1476-4598-13-45\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKotecha R, Miller JA, Venur VA, et al. Melanoma brain metastasis: the impact of stereotactic radiosurgery, BRAF mutational status, and targeted and/or immune-based therapies on treatment outcome. \u003cem\u003eJ Neurosurg\u003c/em\u003e. 2018;129(1):50\u0026ndash;59. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3171/2017.1.JNS162797\u003c/span\u003e\u003cspan address=\"10.3171/2017.1.JNS162797\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKlein A, Sagi-Assif O, Meshel T, et al. CCR4 is a determinant of melanoma brain metastasis. \u003cem\u003eOncotarget\u003c/em\u003e. 2017;8(19):31079\u0026ndash;31091. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.18632/oncotarget.16076\u003c/span\u003e\u003cspan address=\"10.18632/oncotarget.16076\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen G, Chakravarti N, Aardalen K, et al. Molecular profiling of patient-matched brain and extracranial melanoma metastases implicates the PI3K pathway as a therapeutic target. \u003cem\u003eClin Cancer Res\u003c/em\u003e. 2014;20(21):5537\u0026ndash;5546. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1158/1078-0432.CCR-13-3003\u003c/span\u003e\u003cspan address=\"10.1158/1078-0432.CCR-13-3003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFigueroa Rodriguez F, Uddin A, Nasr J. Primary Pulmonary Malignant Melanoma Found While Evaluating New Onset Cough: A Case Presentation and Literature Review. \u003cem\u003eCase Rep Pulmonol\u003c/em\u003e. 2019;2019:3867831. Published 2019 Apr 10. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1155/2019/3867831\u003c/span\u003e\u003cspan address=\"10.1155/2019/3867831\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFlaherty, K.T., Brose, M.S., Schuchter, L.M., Tuveson, D.A., Lee, R.J., Schwartz, B., Lathia, C.D., Weber, B., \u0026amp; O'dwyer, P.J. (2004). Phase I/II trial of BAY 43-9006, carboplatin (C) and paclitaxel (P) demonstrates preliminary antitumor activity in the expansion cohort of patients with metastatic melanoma. \u003cem\u003eJournal of clinical oncology: official journal of the American Society of Clinical Oncology, 22 14_suppl\u003c/em\u003e, 7507.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAmaravadi RK, Schuchter LM, McDermott DF, et al. Phase II Trial of Temozolomide and Sorafenib in Advanced Melanoma Patients with or without Brain Metastases. \u003cem\u003eClin Cancer Res\u003c/em\u003e. 2009;15(24):7711\u0026ndash;7718. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1158/1078-0432.CCR-09-2074\u003c/span\u003e\u003cspan address=\"10.1158/1078-0432.CCR-09-2074\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEisen T, Marais R, Affolter A, et al. Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies. Br J Cancer 2011; 105:353.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRulli E, Legramandi L, Salvati L, Mandala M. The impact of targeted therapies and immunotherapy in melanoma brain metastases: A systematic review and meta-analysis. \u003cem\u003eCancer\u003c/em\u003e. 2019;125(21):3776\u0026ndash;3789. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/cncr.32375\u003c/span\u003e\u003cspan address=\"10.1002/cncr.32375\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-the-egyptian-national-cancer-institute","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jeci","sideBox":"Learn more about [Journal of the Egyptian National Cancer Institute](http://jenci.springeropen.com)","snPcode":"43046","submissionUrl":"https://submission.springernature.com/new-submission/43046/3","title":"Journal of the Egyptian National Cancer Institute","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"pulmonary melanoma, BRAF-mutant, brain metastasis, case report","lastPublishedDoi":"10.21203/rs.3.rs-7060023/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7060023/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWe report a case of BRAF-mutant pulmonary melanoma with brain metastasis in an otherwise healthy 30-year-old Caucasian female with no significant past medical or family history. She initially presented with sudden onset right-sided headache, accompanied by nausea, vomiting, neck pain, dizziness, and photophobia. Imaging studies revealed a cyst-like mass in the right frontal parietal lobe and a mass in the left lower lobe with multiple intrapulmonary nodules. Following an extensive workup, the patient was diagnosed with metastatic pulmonary melanoma with a BRAF mutation, prompting a multidisciplinary treatment approach involving neurosurgery, immunotherapy, and radiotherapy. The patient underwent partial surgical resection of the brain lesion and CyberKnife radiosurgery without neurological sequelae. Systemic treatment with ipilimumab/nivolumab was initiated, with close monitoring for immunotherapy-related toxicities. Despite this comprehensive strategy, a subsequent brain MRI at post surgery and after five cycles of immunotherapy showed persistence of the right frontal lobe enhancing mass. This case underscores the challenges of treating BRAF-mutant metastatic pulmonary melanoma and highlights the rarity of metastatic pulmonary melanoma in young females.\u003c/p\u003e","manuscriptTitle":"BRAF Mutant Pulmonary Melanoma with Brain Metastasis in a Young Female: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-08 10:38:27","doi":"10.21203/rs.3.rs-7060023/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-10-28T11:49:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"310822379415896223794271561485290175808","date":"2025-10-11T10:26:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"98607087830786491831781315849118213363","date":"2025-08-22T16:06:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-13T09:22:22+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-09T03:43:15+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-09T03:41:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of the Egyptian National Cancer Institute","date":"2025-07-06T22:53:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-the-egyptian-national-cancer-institute","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jeci","sideBox":"Learn more about [Journal of the Egyptian National Cancer Institute](http://jenci.springeropen.com)","snPcode":"43046","submissionUrl":"https://submission.springernature.com/new-submission/43046/3","title":"Journal of the Egyptian National Cancer Institute","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"810fc7d8-216e-4470-b24f-3818f56e3e58","owner":[],"postedDate":"July 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-07-13T09:38:10+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-08 10:38:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7060023","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7060023","identity":"rs-7060023","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}