Intrathecal Chemotherapy Through Ommaya Reservoir in Leptomeningeal Metastasis From Cervical Cancer: A Rare Case Report and Literature Review

ABSTRACT

Leptomeningeal metastasis (LM) is a rare complication of cervical cancer associated with a poor prognosis. We report a 61‐year‐old woman with stage IVB cervical squamous cell carcinoma who developed acute headache and diplopia during systemic chemotherapy. Brain magnetic resonance imaging suggested LM, which was confirmed by cerebrospinal fluid (CSF) cytology. An Ommaya reservoir was inserted, and intrathecal methotrexate therapy was initiated. The patient showed rapid neurological improvement, normalization of CSF opening pressure, and sustained clearance of malignant cells on serial CSF cytology. Although systemic disease subsequently progressed, LM‐related neurological symptoms remained well controlled. The patient survived for 8 months after LM diagnosis. This case highlights the importance of considering LM in cervical cancer patients with new neurological symptoms and suggests that intrathecal chemotherapy via an Ommaya reservoir may provide effective neurological control and symptomatic relief.

1. Introduction

Leptomeningeal metastasis (LM) is the dissemination of malignant cells within the leptomeninges and cerebrospinal fluid (CSF), resulting in diverse neurologic manifestations [1]. It is most commonly associated with breast cancer, lung cancer, and melanoma, and is exceedingly rare in gynecologic malignancies, with only limited cases reported in cervical cancer [2, 3, 4, 5, 6, 7, 8, 9, 10, 11]. This rarity contributes to diagnostic delay and uncertainty regarding optimal management.

The diagnosis of LM is challenging because of its nonspecific clinical presentation, including headache, nausea, cranial nerve deficits, and altered mental status. Diagnosis requires an integrated approach combining clinical evaluation, neuroimaging, and CSF cytology, the latter being the gold standard [2].

The prognosis of LM remains poor, with median survival typically limited to weeks to a few months in the absence of treatment [1]. Systemic therapy has limited efficacy in LM due to inadequate penetration across the blood–brain and blood–CSF barriers. Intrathecal (IT) chemotherapy therefore plays a central role by enabling direct drug delivery into the CSF compartment [2]. However, the clinical benefit of IT chemotherapy in cervical cancer–associated LM remains poorly defined, and the use of an Ommaya reservoir for intraventricular administration has rarely been reported [11].

Here, we describe a case of cervical squamous cell carcinoma with LM treated with IT methotrexate via an Ommaya reservoir, which achieved sustained neurological control despite progression of systemic disease.

2. Case Presentation

A 61‐year‐old woman presented to Asan Medical Center with bilateral leg swelling. Computed tomography (CT) venography excluded deep vein thrombosis but revealed a uterine mass with multiple retroperitoneal lymphadenopathies. Laboratory evaluation showed an elevated cancer antigen 125 (CA‐125) level of 3200 U/mL, while squamous cell carcinoma antigen was within the normal range. Histopathological examination following dilatation and curettage with loop electrosurgical excision confirmed invasive squamous cell carcinoma of cervical origin. A supraclavicular lymph node biopsy demonstrated metastatic disease, establishing a diagnosis of stage IVB cervical cancer. The patient subsequently initiated systemic chemotherapy with paclitaxel, cisplatin, and bevacizumab.

After eight cycles of chemotherapy, she presented with acute‐onset headache, vomiting, and diplopia. Ophthalmologic examination demonstrated left fourth and sixth cranial nerve palsies, with left hypertropia, limitation of left eye abduction and infraduction, and subjective binocular oblique diplopia. Funduscopic examination revealed bilateral Grade 2 papilledema, raising concern for elevated intracranial pressure and leptomeningeal involvement. Brain magnetic resonance imaging and CT angiography revealed mild hydrocephalus with periventricular interstitial edema, without intracranial hemorrhage or parenchymal lesions (Figure 1). The radiology report suggested CSF examination because leptomeningeal disease could not be excluded. CSF analysis showed an elevated opening pressure of 36 cmH₂O (normal range, 7.5–20 cmH₂O), a glucose level of 65 mg/dL, a protein level of 31.5 mg/dL, and an increased nucleated cell count of 40/μL. Gram staining revealed no organisms, and bacterial cultures showed no growth. Additional microbiologic studies, including acid‐fast bacilli staining and Mycobacterium tuberculosis DNA testing, were negative. CSF cytology confirmed leptomeningeal metastasis, with malignant cells comprising 73% of nucleated cells (Figure 2). Immunocytochemical staining, including p16 staining, was not performed on the CSF specimen.

FIGURE 1.

Brain MRI findings of leptomeningeal metastasis magnetic resonance imaging (diffusion‐weighted, non‐contrast) demonstrating mild hydrocephalus with periventricular interstitial edema (arrows). No parenchymal mass lesion was identified.

FIGURE 2.

Cytology of cerebrospinal fluid Wright–Giemsa–stained cytospin preparation of cerebrospinal fluid showing clusters of malignant cells. The tumor cells exhibit a high nuclear‐to‐cytoplasmic ratio, irregular nuclei, prominent nucleoli, and variable cytoplasmic vacuolation or blebs (×200, inset ×1000).

Given the need for repeated IT chemotherapy and markedly elevated intracranial pressure, an Ommaya reservoir was placed. In addition to facilitating repeated IT drug administration, the reservoir enabled serial CSF drainage for intracranial pressure control and symptomatic relief. Because the patient presented with severe headache, vomiting, diplopia, bilateral papilledema, and an opening pressure of 36 cmH₂O, intracranial pressure management was initiated before IT chemotherapy. Two days after Ommaya reservoir insertion, 30 mL of CSF was drained to reduce intracranial pressure, and an additional 24 mL was drained on the day of the first IT methotrexate administration. During the treatment course, intracranial pressure was monitored through the reservoir, and further CSF drainage was performed when clinically indicated or when symptoms of intracranial hypertension worsened. IT methotrexate was administered at a dose of 12 mg through the Ommaya reservoir twice weekly for 4 weeks (induction), followed by weekly administration for 4 weeks (consolidation). No corticosteroids were administered for prophylaxis of chemical meningitis, and leucovorin rescue was not used during treatment. Supportive medical management of intracranial hypertension included mannitol, acetazolamide, and topiramate in conjunction with CSF drainage through the Ommaya reservoir. Neurological symptoms improved after induction, with a corresponding reduction in intracranial pressure (Figure 3A). Serial CSF cytology demonstrated a rapid decline in malignant cells, which remained near zero during consolidation (Figure 3B).

FIGURE 3.

Trends in cerebrospinal fluid opening pressure and malignant cell counts. (A) Serial measurements of cerebrospinal fluid opening pressure before and after intrathecal methotrexate therapy, showing progressive reduction following induction treatment. (B) Serial cerebrospinal fluid cytology before and after intrathecal methotrexate therapy, demonstrating a marked decline in malignant cell counts during induction and sustained suppression during consolidation.

Although maintenance IT therapy was planned, systemic chemotherapy with topotecan and cisplatin was resumed due to progression of extraneural disease, including lymphadenopathy and peritoneal carcinomatosis. Despite systemic progression, neurological symptoms remained controlled, with no recurrence of leptomeningeal involvement.

The patient died of progressive systemic disease 8 months after the diagnosis of leptomeningeal metastasis, without recurrence of neurological symptoms.

3. Discussion

Leptomeningeal metastasis (LM) from cervical cancer is an exceptionally rare condition, with only a limited number of cases reported [6, 10, 11]. Consequently, most evidence is derived from small case series, and optimal management strategies remain undefined.

In response to the rarity of this condition, we reviewed previously published reports of LM arising from gynecologic malignancies, including cervical, ovarian, and endometrial cancers (Table S1) [4, 5, 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24]. Among the cervical cancer‐associated cases included in our review, 18 patients were described in individual case reports, in addition to patients included in retrospective series. However, the exact total number of cervical cancer‐associated LM cases and those treated with IT chemotherapy could not be determined because of potential overlap between individual reports and retrospective series. Overall, reported outcomes were poor, with survival generally ranging from several days to a few months after LM diagnosis. Treatment approaches were heterogeneous and included radiotherapy, IT chemotherapy, systemic chemotherapy, and supportive care. These findings indicate that gynecologic cancer‐associated LM is a rare but highly aggressive condition. In the gynecologic cancer series reported by Yano et al., the median survival after LM diagnosis was only 23 days [10].

The pathophysiology of LM in cervical cancer is not fully understood. Proposed mechanisms include hematogenous dissemination, direct extension, and perineural spread, with hematogenous spread considered the most plausible route [10]. Once tumor cells enter the leptomeningeal space, they disseminate through CSF circulation, resulting in multifocal neurological involvement. The central nervous system may also function as a pharmacologic sanctuary site due to limited penetration of systemic therapies across the blood–brain and blood–CSF barriers [2].

The diagnosis of LM is challenging because of nonspecific clinical manifestations and requires integration of clinical findings, neuroimaging, and CSF cytology, the gold standard [2].

Management remains challenging given the lack of standardized treatment protocols and the poor prognosis. IT chemotherapy is a cornerstone of treatment, as it enables direct drug delivery into the CSF and overcomes the limitations of systemic therapy [2, 25]. Among available IT agents, methotrexate remains one of the most commonly used and guideline‐supported treatments for leptomeningeal metastasis from solid tumors. In our review of previously published gynecologic cancer‐associated LM cases across all primary sites, IT chemotherapy was administered in eight cases using agents such as methotrexate, cytarabine, topotecan, thiotepa, and pemetrexed. However, Ommaya reservoir‐facilitated IT therapy was reported in only two cases prior to the present report, highlighting the limited clinical experience with this delivery approach. In previous reports, IT chemotherapy has most commonly been administered via repeated lumbar puncture, often in combination with systemic therapy or radiotherapy [11]. In contrast, an Ommaya reservoir allows repeated intraventricular administration with more consistent drug distribution and improved patient comfort [26], although its use in cervical cancer–associated LM has rarely been reported. In addition to facilitating repeated IT chemotherapy, an Ommaya reservoir may provide clinical benefit in patients with elevated intracranial pressure by allowing serial CSF drainage and pressure monitoring. In the present case, the reservoir served both therapeutic and palliative purposes, contributing to symptom relief from intracranial hypertension while enabling continued IT treatment.

In the present case, IT methotrexate via an Ommaya reservoir resulted in rapid neurological improvement, normalization of intracranial pressure, and sustained cytologic clearance. Notably, this response was maintained despite progression of systemic disease, highlighting a dissociation between systemic and leptomeningeal disease control and supporting the concept of compartmentalized treatment strategies.

The prognosis of LM is generally poor, with median survival measured in weeks without treatment and extending to several months in selected patients [1]. In contrast, our patient achieved durable neurological control for 8 months, suggesting that early IT therapy via an Ommaya reservoir may provide meaningful palliation in selected patients. Although its impact on survival remains uncertain, improved symptom control and reliable IT drug delivery may contribute to prolonged neurological stabilization. Potential complications include infection, catheter obstruction, malposition, and hemorrhage, none of which occurred in the present case.

This study has limitations inherent to a single case report, and the findings cannot be generalized. Further studies are required to define optimal treatment strategies, including patient selection, timing of intervention, and the role of different IT delivery methods. Another limitation is that a whole‐spine MRI was not performed. Although the diagnosis of leptomeningeal metastasis was confirmed by CSF cytology, current clinical guidelines recommend craniospinal MRI evaluation to assess the full extent of neuraxial involvement.

Nevertheless, this case highlights the importance of considering leptomeningeal metastasis in cervical cancer patients presenting with new neurological symptoms. IT methotrexate administered via an Ommaya reservoir achieved durable neurological control despite systemic disease progression, suggesting a potential role for CNS‐directed therapeutic strategies in selected patients.

Author Contributions

Haein Seo: conceptualization, methodology, validation. Seo Woo Chung: writing – review and editing, investigation, visualization. Chery Ahn: conceptualization, methodology, validation, writing – original draft, writing – review and editing, visualization. Sewon Kim: writing – review and editing, investigation, visualization. Byeol Han: conceptualization, writing – original draft, methodology, validation, visualization. Ok‐Ju Kang: conceptualization, methodology, validation, visualization, formal analysis, writing – original draft, writing – review and editing. Dongmin Jo: conceptualization, methodology, validation, visualization. Eunmi Choi: writing – review and editing, investigation, visualization.

Funding

The authors have nothing to report.

Disclosure

An earlier version of this case was presented at the Korean Society of Obstetrics and Gynecology Annual Meeting on October 30, 2025.

Ethics Statement

This study was approved by the Institutional Review Board of Asan Medical Center (IRB no. 2026‐0928). The requirement for informed consent was waived due to the retrospective nature of this report and the use of fully de‐identified clinical data.

Consent

The requirement for informed consent was waived by the Institutional Review Board of Asan Medical Center due to the retrospective nature of this report and the use of fully de‐identified clinical data.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Table S1: Published gynecologic cancer‐associated leptomeningeal metastasis cases.

Data Availability Statement

The data supporting the findings of this study contain potentially identifiable clinical information from a single patient with a rare clinical condition. Because this report is based on an individual case, complete de‐identification cannot be guaranteed, and public sharing of the underlying data may increase the risk of patient re‐identification. Therefore, the data are not publicly available due to patient privacy concerns, institutional regulations, and ethical restrictions. Relevant clinical information supporting the findings of this study is included within the article. Requests for additional de‐identified data may be considered by the corresponding author upon reasonable request and subject to approval by the Institutional Review Board of Asan Medical Center.