Complement Component 3 Adapts the Cerebrospinal Fluid for Leptomeningeal Metastasis.

We molecularly dissected leptomeningeal metastasis, or spread of cancer to the cerebrospinal fluid (CSF), which is a frequent and fatal condition mediated by unknown mechanisms. We selected lung and breast cancer cell lines for the ability to infiltrate and grow in CSF, a remarkably acellular, mitogen-poor metastasis microenvironment. Complement component 3 (C3) was upregulated in four leptomeningeal metastatic models and proved necessary for cancer growth within the leptomeningeal space. In human disease, cancer cells within the CSF produced C3 in correlation with clinical course. C3 expression in primary tumors was predictive of leptomeningeal relapse. Mechanistically, we found that cancer-cell-derived C3 activates the C3a receptor in the choroid plexus epithelium to disrupt the blood-CSF barrier. This effect allows plasma components, including amphiregulin, and other mitogens to enter the CSF and promote cancer cell growth. Pharmacologic interference with C3 signaling proved therapeutically beneficial in suppressing leptomeningeal metastasis in these preclinical models.

Leptomeningeal metastases: the future is now.

Leptomeningeal metastases (LM) constitute an involvement of cancer which is associated with marked morbidity and mortality. The contemporary diagnostic and therapeutic management of LM from solid tumors is reviewed. Therapeutic modalities including systemic therapies, cerebrospinal fluid (CSF)-directed therapies, and radiation therapy are discussed. This is to provide context for how the field of LM management may evolve in the near term. The future directions currently undergoing investigation for diagnostic, response assessment, and therapeutic purposes are highlighted. This is done within the context of the pathophysiology of the disease. Specifically the role of CSF circulating tumor cells and cell free circulating tumor DNA in diagnosis and response assement are reviewed. Novel therapeutic approaches across a range of modalities are discussed. Numerous ongoing studies which have the potential to alter the management of LM are referenced.

Treatment Options for Leptomeningeal Metastases of Solid Cancers: Literature Review and Personal Experience.

Leptomeningeal metastases (LM) may complicate the clinical course of any solid cancer or hematological malignancy. Diagnosis of such cases requires a multifaceted approach, including careful evaluation of the clinical history, detailed neurological examination, advanced imaging studies, and related laboratory data analysis. Therapeutic options for management of LM have not been standardized yet. Conventional intrathecal chemotherapy with or without involved-field fractionated radiotherapy has only modest efficacy, and the prognosis of most patients remains grim. Therefore, development of new, more aggressive multimodal treatment strategies is definitely needed. Immune checkpoint inhibitors-in particular, molecular targeted therapy-have demonstrated promising results in selected groups of patients. There may be an important role for stereotactic radiosurgery as well. Because organization of prospective randomized multi-institutional trials on treatment of LM of solid cancers may be problematic, practical guidelines for optimal therapeutic strategies in such cases should be established on the basis of integrated results of small-scale prospective and retrospective studies.

Leptomeningeal metastasis from cervical cancer: Report of two cases and a review of the literature.

Leptomeningeal metastases from cervical cancer are extremely rare, with only 24 cases reported in the English-language literature. Leptomeningeal metastasis (LM) is usually a late event, but it can develop at any stage. A 44-year-old woman presented with vertigo, tinnitus, diminution of hearing, and a cervical tumor at the initial visit. She underwent whole brain radiotherapy and systemic chemotherapy. Five months after the initial visit, her condition deteriorated rapidly and she died. A 49-year-old woman underwent surgery and pelvic radiotherapy for cervical cancer. She underwent resection of lung metastases 2 years later and received systemic chemotherapy for lymph node metastases 4 years later. Five years after the initial visit, the patient suddenly presented with diplopia, headache, and vomiting; her clinical course was fulminant and she died. Most patients with LM present with diverse clinical manifestations and deteriorate rapidly despite multiple treatment modalities. Gynecologic oncologists should be aware of this rare complication.

Carcinomatous meningitis from recurrent glassy cell carcinoma of the uterine cervix-A case report.

Carcinomatous meningitis presents with a variety of neurological symptoms and has a poor prognosis. We encountered a case of carcinomatous meningitis from cervical cancer. A 30-year-old patient was diagnosed with cervical cancer (glassy cell carcinoma), stage IIB. She underwent radical hysterectomy and chemoradiotherapy. Nine months later, the disease recurred with iliac lymph node and right lung metastases. The patient received chemotherapy; however, after seven cycles, the lung lesions increased. The patient responded to supportive care; nevertheless, symptoms including headaches developed and were followed by diplopia. A contrast-enhanced magnetic resonance image of the head confirmed the diagnosis of carcinomatous meningitis. She was transferred to the palliative care unit and died approximately 1 week later. Carcinomatous meningitis has a poor prognosis and is difficult to treat; however, early diagnosis may provide meaningful time to patients. Therefore, attention must be paid to meningeal irritation and neurological symptoms.

Current management of central nervous system metastasis from cholangiocarcinoma: the neurosurgical perspective. Literature review.

Purpose: Central nervous system (CNS) metastasis from cholangiocarcinoma (CCA) are extremely rare and associated prognosis is poor. The involvement of the CNS by metastatic CCA may discourage any further treatment; however, data from the literature are discordant, due to recent reports of exceptionally long follow-up after surgical resection of a brain metastasis.Material and Methods: Electronic databases, such as PubMed/MEDLINE and Google Scholar, were analyzed for studies published up to October 2018 using the search term "cholangiocarcinoma and central nervous system metastasis or brain metastasis".Results: We found a total of 18 studies cited in the literature of the 30 year span analyzed, and we added a new case we treated at our Institution, reaching a series of 32 patients. Among these, 7 patients had leptomeningeal dissemination and 25 presented solid CNS metastasis. We analyzed the treatment options and the outcomes, addressing also histopathological insights on tumoral markers possibly involved in the mechanism of metastases of cholangiocarcinomasConclusions: According to the literature data, the outcome remains poor, particularly for those with leptomeningeal diffusion. Nevertheless, long term follow-up is reported in case of surgical resection of CNS metastasis, when there is a good control of the primary tumor. Actually, the majority of patients are often in advanced state of disease at diagnosis and not suitable for initial resective procedure; in these cases neo adjuvant and adjuvant therapies have provided a slight improvement of the outcome.

Episodic Oculomotor Nerve Palsy with Intracranial Hypertension and Carcinomatous Meningitis.

The classically affected cranial nerve from intracranial hypertension is the sixth nerve. Carcinomatous meningitis can cause persistent or progressive cranial nerve palsies by infiltrating them in the subarachnoid space. Here we present a rare case of episodic, short-lasting, and unilateral oculomotor nerve palsy associated with carcinomatous meningitis and intracranial hypertension in a 44-year-old woman diagnosed with metastatic lung adenocarcinoma. As the survival rates enhance for metastatic cancers, neurologists should expect more perplexing neurologic presentations and consider leptomeningeal metastasis and intracranial hypertension in patients who have cancer and present with short episodes of diplopia and unilateral third nerve palsy.

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo - a clinico-pathological case reporT.

BACKGROUND AND PURPOSE: Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose - Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. METHODS: A 56-year-old male patient's interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. RESULTS: During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion - It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the "seed and soil" theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. CONCLUSION: Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Neuroendocrine carcinoma of the colon presenting as acute meningitis.

BACKGROUND: Neuroendocrine tumors represent an expansive group of neoplasms that share an etiology of epithelial origin with neuroendocrine differentiation. Poorly-differentiated neuroendocrine carcinomas behave similarly to their aggressive pulmonary counterpart, small cell lung carcinoma. Most patients with gastroenteropancreatic neuroendocrine tumors present with symptoms of metastasis, most commonly to the liver. There have been no case reports, to our knowledge, until now that demonstrate metastasis to the central nervous system. CASE PRESENTATION: A 72-year-old male with poorly-differentiated stage IIIB neuroendocrine carcinoma of the colon presented with acute altered mental status and right facial droop. Head CT was negative for an acute hemorrhagic process without evidence of suspicious lesions. Several days later, the patient developed fever and neck stiffness suspicious for bacterial meningitis. A lumbar puncture procedure was performed. Cytology of the CSF demonstrated metastatic disease to the central nervous system and the final diagnosis of carcinomatous meningitis secondary to metastatic neuroendocrine carcinoma of the colon was made. CONCLUSIONS: High-grade gastroenteropancreatic neuroendocrine carcinomas most commonly metastasize to the liver, which often corresponds with the patient's initial presentation. When neuroendocrine tumors do metastasize to the central nervous system, the primaries are most commonly of pulmonary origin. When meningeal metastasis does occur, it commonly presents as neurologic deficits or cerebrovascular events, rarely does meningeal metastasis mimic bacterial meningitis with symptoms of fever, photophobia and meningismus. As neuroendocrine carcinomas have been increasing in incidence over the past several decades, it is important to consider varying metastatic presentations when working up a patient with a diagnosis of neuroendocrine tumor.

Leptomeningeal metastasis from systemic cancer: Review and update on management.

Leptomeningeal metastasis is an uncommon and typically late complication of cancer with a poor prognosis and limited treatment options. Diagnosis is often challenging, with nonspecific presenting symptoms ranging from headache and confusion to focal neurologic deficits, such as cranial nerve palsies. Standard diagnostic evaluation involves a neurologic examination, magnetic resonance imaging of the brain and spine with gadolinium, and cytologic evaluation of the cerebral spinal fluid. Therapy entails a multimodal approach focused on palliation with surgery, radiation, and/or chemotherapy, which may be administered systemically or directly into the cerebral spinal fluid. Limited trial data exist to guide treatment, and current regimens are based primarily on expert opinion. Although newer targeted and immunotherapeutic agents are under investigation and have shown promise, an improved understanding of the biology of leptomeningeal metastasis and treatment resistance as well as additional randomized controlled studies are needed to guide the optimal treatment of this devastating disease. Cancer 2018;124:21-35. © 2017 American Cancer Society.

Determinants of prolonged survival for breast cancer patient groups with leptomeningeal metastasis (LM).

The study aimed to assess factors affecting survival of breast cancer patients suffering leptomeningeal metastasis (LM) and to compare survivals in patients with LM as the first and only site of metastases at presentation to patients with LM and metastases in other organs, along with selecting a patient group which had the best survival outcomes. Subject groups consisted of 187 patients consecutively referred during 1999-2015. A Cox proportional hazards model was used to identify factors associated with prolonged survival from LM. The Cox prognostic index was created to identify the group of patients with the most favorable prognosis. Median survival for all patients and for those with LM as the first site of metastases at presentation was 17 weeks and 1 year-survival was 15 and 16%, respectively. Factors beneficially affecting survival were: KPS ≥ 70, older age, biological subtype ER/PR+HER2-, systemic treatment, intrathecal treatment and radiation therapy. Based on these factors, 4 prognostic groups were found, with the most favorable group being 24 LM patients with median survival of 9.6 months. In this group, all patients were treated systemically and all were irradiated, 88% had KPS ≥ 70, about 80% had luminal breast cancer, 75% were treated intrathecally and 58% were more than 53 years old. Out of 4 prognostic groups of patients with LM, the most favorable group was selected. The median survival of breast cancer patients with the leptomeninges as the only site of metastases was comparable to those who had metastases in the leptomeninges and in other organs.

SHP-1 promoter 2 methylation in cerebrospinal fluid for diagnosis of leptomeningeal epithelial-derived malignancy (carcinomatous meningitis).

Current diagnostic methods for leptomeningeal metastasis (LM) from epithelial-derived malignancy (EDM) have limited sensitivity. Here, we explored SHP-1 promoter 2 methylation (SHP1P2)-an epithelial-specific methylation marker previously proven as risk stratification and potential diagnostic marker in non-small cell lung cancer-for EDM with LM. We prospectively recruited 136 patients who were diagnosed EDM with LM (n = 25), EDM without LM (n = 14), non-EDM with LM (n = 8), and benign meningeal diseases (n = 89). The primary cancer sites for EDM with LM were lung (n = 17), breast (n = 5), and colon (n = 3). We performed quantitative analyses of cell-free (cfSHP1P2) and whole fraction (wSHP1P2) from cerebrospinal fluid (CSF); results were correlated with the clinicopathological data, including CSF cytology. Median cfSHP1P2 and wSHP1P2 were 3.08 [range: 0-163.5] and 9.35 [0.69-91.63] ng/ml, respectively, in EDM with LM; 0 [0-0.08] and 0.23 [0-7.84] ng/ml in EDM without LM; and were undetectable in most cases of benign meningeal diseases and non-EDM with LM. The cut-off values of 0.22 ng/ml for methylated cfSHP1P2 and 0.59 ng/ml for wSHP1P2 were the best to discriminate EDM with LM from EDM without LM (sensitivity: 79-100 %; specificity: 83-100 %), as well as from other benign conditions (sensitivity: 85-100 % specificity: 78-100 %). CSF cytology yielded 76 % sensitivity for diagnosing EDM with LM. Further validation of CSF SHP1P2 methylation detection as a role of adjunctive tool for LM from EDM should be interested based on our study.

Leptomeningeal carcinomatosis in esophageal cancer: a case series and systematic review of the literature.

The aim of this study was to more clearly define the clinical course of leptomeningeal carcinomatosis due to esophageal cancer. A single institution retrospective case series was conducted. Additionally, a systematic review of the literature was performed. We present a large case series (n = 7) of leptomeningeal carcinomatosis due to esophageal cancer. Our case series and systematic review of the literature report similar findings. In our series, we report a predominance of male patients (86%) with adenocarcinoma histology (77%). Variable onset of leptomeningeal involvement of esophageal cancer in relation to the original diagnosis of the primary disease (5 months to 3 years and 11 weeks) was noted. Disease progresses quickly and overall survival is poor, measured in weeks (2.5-16 weeks) from the diagnosis of leptomeningeal involvement. Four of our patients initiated whole-brain radiation therapy with only two completing the course prior to clinical deterioration. Our patient with the longest survival (16 weeks) received intrathecal topotecan and oral temozolomide. Leptomeningeal carcinomatosis secondary to esophageal cancer has a poor prognosis. A clearly beneficial treatment modality is lacking.

Demographic profiles and risk factors for mortality in acute meningitis: A nationwide population-based observational study.

Aim: Acute meningitis encompasses bacterial, viral (aseptic), fungal, tuberculous, and carcinomatous meningitis. The rate and risks of mortality in each type remain uncertain. This study aimed to elucidate these aspects in each type of meningitis. Methods: This study utilized Japan's nationwide administrative Diagnosis Procedure Combination (DPC) database. Patients with acute meningitis, treated at 1132 DPC-covered hospitals from 2016 to 2022, were enrolled. Results: Among 47,366,222 cumulative hospitalized patients, 48,758 (0.10%) were hospitalized with acute meningitis. The types of meningitis were as follows: 10,338 with bacterial, 29,486 with viral/aseptic, 965 with fungal, 678 with tuberculous, and 3790 with carcinomatous meningitis. Bacterial and viral meningitis exhibited bimodal age distributions, with the first peak occurring at 0-9 years. The median onset age was below 50 years only in viral meningitis. The mortality rate was the highest in carcinomatous meningitis (39%), followed by fungal meningitis (21%), and the lowest in viral meningitis (0.61%). Mortality rates increased with age across all meningitis types, but this trend was less prominent in carcinomatous meningitis. The duration from admission to mortality was longer in fungal and tuberculous meningitis compared with other types. Staphylococcus aureus in bacterial meningitis (adjusted odds ratio 1.71; p = 0.0016) and herpes simplex virus in viral meningitis (adjusted odds ratio 1.53; p = 0.0467) exhibited elevated mortality rates. Conclusion: Distinct demographic profiles and mortality rates were observed among different meningitis types. The high mortality rates in less common types of meningitis emphasize the necessity to further optimize the required diagnostic and treatment strategies.

Ventriculoperitoneal shunting with an on-off valve for patients with leptomeningeal metastases and intracranial hypertension.

Background: We report our experience with using a ventriculoperitoneal shunt (VPS) with an on-off valve and in-line Ommaya reservoir for the treatment of hydrocephalus or intracranial hypertension in patients with leptomeningeal disease (LMD). Our goal was to determine whether control of intracranial pressure elevation combined with intrathecal (IT) chemotherapy would extend patient survival. Methods: In this IRB-approved retrospective study, we reviewed 58 cases of adult patients with LMD from solid cancers who received a VPS with a reservoir and an on-off valve at M D Anderson Cancer Center from November 1996 through December 2021. Primary tumors were most often melanoma (n = 19) or breast carcinoma (n = 20). Hydrocephalus was diagnosed by clinical symptoms and findings on magnetic resonance imaging (MRI), and LMD by MRI or cerebrospinal fluid analysis. Differences in overall survival (OS) were assessed with standard statistical techniques. Results: Patients who received a VPS and more than 3 IT chemotherapy sessions survived longer (n = 26; OS time from implantation 11.7 ± 3.6 months) than those who received an occludable shunt but no IT chemotherapy (n = 24; OS time from implantation 2.8 ± 0.7 months, P < .018). Peritoneal seeding appeared after shunt insertion in only two patients (3%). Conclusions: This is the largest series reported to date of patients with LMD who had had shunts with on-off valves placed to relieve symptoms of intracranial hypertension. Use of IT chemotherapy and control of hydrocephalus via such shunts was associated with improved survival.

An overview of the therapeutic strategies for neoplastic meningitis due to breast cancer: when and why?

INTRODUCTION: Neoplastic meningitis (NM), also known as leptomeningeal carcinomatosis, is characterized by the infiltration of tumor cells into the meninges, and poses a significant therapeutic challenge owing to its aggressive nature and limited treatment options. Breast cancer is a common cause of NM among solid tumors, further highlighting the urgent need to explore effective therapeutic strategies. This review aims to provide insights into the evolving landscape of NM therapy in breast cancer by collating existing research, evaluating current treatments, and identifying potential emerging therapeutic options. AREAS COVERED: This review explores the clinical features, therapeutic strategies, recent advances, and challenges of managing NM in patients with breast cancer. Its management includes multimodal strategies, including systemic and intrathecal chemotherapy, radiation therapy, and supportive care. This review also emphasizes targeted drug options and optimal drug concentrations, and discusses emerging therapies. Additionally, it highlights the variability in treatment outcomes and the potential of combination regimens to effectively manage NM in breast cancer. EXPERT OPINION: Challenges in treating NM include debates over clinical trial end points and the management of adverse effects. Drug resistance and low response rates are significant hurdles, particularly inHER2-negative breast cancer. The development of more precise and cost-effective medications with improved selectivity is crucial. Additionally, global efforts are needed for infrastructure development and cancer control considering the diverse nature of the disease.

Cranial Nerve III Palsy as the First Sign of Carcinomatous Meningitis From Non-Hodgkin's Lymphoma.

Carcinomatous meningitis (CM) is characterized by the multifocal dissemination of malignant cells into the cerebrospinal fluid (CSF), pia mater, and subarachnoid space. Involvement can occur in the advanced stage of malignancy, causing multifocal involvement and a wide array of symptoms. Diagnosis requires suspicions and a multimodal approach that includes imaging, lumbar puncture, and diagnostic laboratory evaluation. This case represents a female with a history of non-Hodgkin's lymphoma (NHL) and venous thromboembolism on chronic anticoagulation who presented due to acute encephalopathy, hallucinations, and right cranial nerve III palsy for 10 days before arrival. Computed tomography (CT) and angiography of the brain did not show any intracranial abnormalities. Subsequent magnetic resonance imaging (MRI) was without signs of infarction, hemorrhage, or abnormal enhancement, with the MRI of the orbits showing asymmetric linear enhancement anterior to the superior pons and midbrain on the right. Initial differential included a paraneoplastic syndrome, but there was no obvious evidence of pathological enhancement on MRI. Due to progressive bulbar symptoms, a lumbar puncture was performed with cerebrospinal fluid diagnostic workup with cytology showing monoclonal B-cell proliferation consistent with lymphoma. This case illustrates a rare but specific finding of CM as cranial nerve III palsy symptoms in this patient who did not have imaging findings that would reflect her symptoms on the initial MRI of the brain. Furthermore, diagnosing CM is complex and involves a combination of multiple diagnostic and treatment modalities. It is important to recognize the condition early to improve the patient's quality of life, prolong survival, and stabilize neurological deterioration.

Carcinomatous Meningitis and Hydrocephalus in Plasmacytoid Urothelial Carcinoma of the Urinary Bladder With Extremely Elevated CA19-9 Levels.

This case report describes a rare and aggressive presentation of plasmacytoid urothelial carcinoma (PUC) with carcinomatous meningitis, hydrocephalus, extensive organ involvement, and extremely elevated serum CA19-9 levels. Autopsy findings revealed that PUC of the urinary bladder origin caused carcinomatous meningitis and hydrocephalus, with exacerbation of hydrocephalus as the direct cause of death. Immunohistochemical studies confirmed the bladder origin of PUC, and PUC cells were positive for CA19-9, a tumor marker commonly associated with gastrointestinal malignancies, suggesting that the markedly high serum CA19-9 level was related to the tumor-producing mechanism.

The Evolving Landscape of Leptomeningeal Cancer from Solid Tumors: A Systematic Review of Clinical Trials.

Leptomeningeal carcinomatosis (LMC) is a fatal but uncommon complication occurring in 5-15% of patients with stage IV cancer. Current treatment options are ineffective at managing leptomeningeal spread, with a median overall survival (mOS) of 2-6 months. We aimed to conduct a systematic review of the literature to identify past and future therapies for LMC from solid tumors. Forty-three clinical trials (CTs) published between 1982-2022 were identified. Of these, 35 (81.4%) were non-randomized CTs and 8 (18.6%) were randomized CTs. The majority consisted of phase I (16.3%) and phase II CTs (65.1%). Trials enrolled patients with LMC from various primary histology (n = 23, 57.5%), with one CT evaluating LCM from melanoma (2.4%). A total of 21 trials evaluated a single modality treatment. Among CTs, 23.7% closed due to low accrual. Intraventricular (ITV)/intrathecal (IT) drug delivery was the most common route of administration (n = 22, 51.2%) vs. systemic drug delivery (n = 13, 30.3%). Two clinical trials evaluated the use of craniospinal irradiation for LMC with favorable results. LMC continues to carry a dismal prognosis, and over the years, increments in survival have remained stagnant. A paradigm shift towards targeted systemic therapy with continued standardization of efficacy endpoints will help to shed light on promising treatments.

A Case of Leptomeningeal Carcinomatosis Manifesting With Vertigo in the Setting of Intracranial Hypertension.

Leptomeningeal carcinomatosis (LMC) is a rare condition where malignant cells infiltrate the leptomeninges of the central nervous system. We present a case of a 51-year-old male with stage IV adenocarcinoma of the lung who developed recurrent vertigo. The patient initially received a diagnosis of peripheral vertigo, but his symptoms worsened over time and were associated with headache, vomiting, and one episode of seizure. Upon readmission, based on his normal neuroimaging results, normal CSF examination with elevated opening pressure, and papilledema on fundoscopic examination, a diagnosis of pseudotumor cerebri was made. The result of CSF cytology revealed the presence of malignant cells confirming the presence of LMC. This case highlights the importance of considering LMC as a potential cause for unusual neurological symptoms in patients with advanced malignancy, particularly when other conditions like pseudotumor cerebri could obscure its presentation. It is crucial to rule out malignancy through CSF cytology in patients presenting with vertigo and/or other vestibulocochlear symptoms before making an alternative diagnosis that could present similarly.