WHO Grade Ⅱ Clear Cell Meningioma with Obstructive Hydrocephalus and Intratumoral Hemorrhage in a 24-Year-Old Primipara During Late Pregnancy: A Case Report and Clinical Implications 

WHO Grade Ⅱ Clear Cell Meningioma with Obstructive Hydrocephalus and Intratumoral Hemorrhage in a 24-Year-Old Primipara During Late Pregnancy: A Case Report and Clinical Implications | 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 WHO Grade Ⅱ Clear Cell Meningioma with Obstructive Hydrocephalus and Intratumoral Hemorrhage in a 24-Year-Old Primipara During Late Pregnancy: A Case Report and Clinical Implications Xiaoqian Xu, Aiting Weng, Peigang Tian This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9032253/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background Clear cell meningioma (CCM), a rare WHO Grade Ⅱ meningioma subtype, accounts for only 0.2%–0.8% of all intracranial meningiomas and is notable for its predilection for young females and high recurrence potential. The occurrence of CCM with obstructive hydrocephalus and intratumoral hemorrhage during late pregnancy is an extremely rare clinical scenario, and its management requires a delicate trade-off between maternal neurological safety, fetal viability and definitive tumor treatment, presenting unique challenges to the multidisciplinary team (MDT). Case Presentation A 24-year-old primipara at 33⁺ weeks of gestation was admitted to our institution with progressively aggravated headache and intractable vomiting for 4 days, on the basis of a 6-month history of intermittent cephalalgia. Neurological examination revealed a somnolent state with a Glasgow Coma Scale (GCS) score of 14 and grade Ⅳ limb muscle strength. Non-contrast cranial computed tomography (CT) demonstrated a 6×6×5 cm hypodense space-occupying lesion in the left basal ganglia with obstructive hydrocephalus; intratumoral hemorrhage was identified on follow-up CT after emergency external ventriculostomy. Cranial magnetic resonance imaging (MRI) exhibited hypointensity on T1-weighted imaging, hyperintensity on T2-weighted imaging, homogeneous enhancement post-contrast administration and ill-defined margins, with short T1 signals consistent with intratumoral hemorrhage. An MDT consisting of neurosurgeons, obstetricians, radiologists and pathologists formulated a staged intervention strategy. Results A healthy male infant with Apgar scores of 9 and 10 at 1 and 5 minutes after birth was delivered via cesarean section. Nine days post-delivery, craniotomy was performed and Simpson Grade Ⅱ tumor resection was achieved. Histopathological examination confirmed WHO Grade Ⅱ CCM, with positive expression of epithelial membrane antigen (EMA), vimentin and progesterone receptor (PR), and a Ki-67 proliferation index of 5%. Postoperative cranial MRI at 3 months showed no residual tumor, and 1-year follow-up revealed no tumor recurrence. Regular pediatric follow-up confirmed the infant’s growth and development were consistent with age-matched norms. Conclusion Pregnancy-associated upregulation of progesterone may be a key factor driving the progression of PR-positive CCM, and the fragile vascular structure of CCM combined with pregnancy-induced hypervolemia and intracranial pressure fluctuations may contribute to intratumoral hemorrhage. MDT-coordinated staged intervention, involving cesarean section followed by definitive neurosurgical resection, is the optimal management strategy for such rare cases, which can effectively balance maternal and fetal safety and achieve favorable long-term oncological outcomes. Long-term regular follow-up is essential for CCM patients due to the tumor’s high recurrence rate. Figures Figure 1 Figure 2 Figure 3 Introduction Meningiomas represent the most common primary intracranial tumors of mesenchymal origin, and clear cell meningioma (CCM) is a rare distinct histological subtype classified as WHO Grade Ⅱ by the World Health Organization (WHO) Classification of Tumors of the Central Nervous System [[ 1 ]]. CCM accounts for a mere 0.2%–0.8% of all meningioma cases, with a documented predilection for young women and a characteristic high recurrence rate compared with other benign meningioma subtypes [[ 2 ]]. While the median age of onset for CCM is reported to be 52 years, its occurrence in young pregnant women is exceedingly rare, and the concomitant presence of obstructive hydrocephalus and intratumoral hemorrhage further complicates clinical management [[ 2 ]]. Accumulating evidence suggests that sex hormones, particularly estrogen and progesterone, play a pivotal role in the growth and progression of meningiomas, given the high expression of estrogen and progesterone receptors in tumor tissues [[ 3 ]]. Pregnancy is characterized by a dramatic physiological surge in peripheral progesterone and estrogen levels, which is hypothesized to act as a potential driver of accelerated tumor growth and malignant progression in hormone receptor-positive meningiomas [[ 3 ]]. However, the underlying mechanisms linking pregnancy-related hormonal changes to intratumoral hemorrhage in CCM remain poorly elucidated, and clinical consensus on the optimal management of CCM during late pregnancy is lacking due to the paucity of reported cases. Herein, we report a rare case of a 24-year-old primipara at 33⁺ weeks of gestation with WHO Grade Ⅱ CCM in the left basal ganglia, complicated by obstructive hydrocephalus and intratumoral hemorrhage after ventriculostomy. We detail the MDT-coordinated staged intervention strategy, pathological features and long-term follow-up outcomes, and conduct a critical review of the relevant literature to explore the correlation between pregnancy-related hormonal changes and CCM progression, as well as the potential mechanisms of intratumoral hemorrhage. This case aims to provide valuable clinical insights for the diagnosis and management of this extremely rare comorbidity, and to emphasize the critical role of MDT collaboration in optimizing maternal and fetal outcomes. Case Presentation Clinical Manifestations A 24-year-old primigravida at 33⁺ weeks of gestation was admitted to the Weifang Hospital of Traditional Chinese Medicine with a 6-month history of intermittent headache and 4 days of progressively aggravated headache accompanied by intractable vomiting. The patient had no prior medical history of hypertension, diabetes mellitus, cerebrovascular disease or central nervous system tumors, and regular prenatal examinations during pregnancy had revealed no obvious abnormalities. The headache was initially intermittent and non-positional, with no associated neurological deficits, and was not relieved by rest or symptomatic treatment. Four days prior to admission, the headache worsened markedly, accompanied by persistent vomiting (non-bilious, non-projectile), somnolence and mild limb weakness, prompting urgent medical attention. On admission, neurological physical examination was performed: the patient was in a somnolent state, with a GCS score of 14 (E3V4M6); bilateral pupils were equal and round (3 mm in diameter), with intact and sensitive light reflexes; muscle strength of all limbs was grade Ⅳ, with normal muscle tone and no obvious sensory disturbance; meningeal irritation signs were negative; and deep tendon reflexes were symmetrically present. Obstetric examination confirmed a singleton pregnancy with a normal fetal heart rate (140 beats/min) and no signs of fetal distress; fetal biometry was consistent with gestational age, and no obvious abnormalities in fetal development were detected. Vital signs on admission were stable: body temperature 36.7℃, heart rate 86 beats/min, respiratory rate 19 breaths/min, blood pressure 122/78 mmHg. Imaging Findings Emergency non-contrast cranial CT (Siemens Somatom Force) was performed on admission, revealing a well-circumscribed 6×6×5 cm hypodense mass in the left basal ganglia with significant mass effect, resulting in obstructive hydrocephalus characterized by dilation of the bilateral lateral ventricles and third ventricle (Fig. 1 A). Given the presence of acute intracranial hypertension, emergency external ventricular drainage was performed to decompress the intracranial cavity and relieve hydrocephalus. A follow-up cranial CT performed 6 hours post-procedure identified new hyperdense foci within the tumor parenchyma, consistent with intratumoral hemorrhage (Fig. 1 B). Subsequent cranial MRI (3.0T, Siemens Magnetom Verio) was performed for further tumor characterization: the lesion exhibited heterogeneous hypointensity on T1-weighted imaging (T1WI) and hyperintensity on T2-weighted imaging (T2WI); homogeneous and marked enhancement was observed after intravenous administration of gadopentetate dimeglumine (0.1 mmol/kg), with ill-defined tumor margins and no obvious peritumoral edema (Fig. 2 A-E). Focal short T1 signals were identified within the tumor parenchyma on T1WI, which was consistent with the CT findings of intratumoral hemorrhage (Fig. 2 B). No obvious dural tail sign was detected on post-contrast MRI sequences. Multidisciplinary Treatment Strategy and Implementation Given the rare and complex clinical scenario, an MDT was immediately convened, consisting of senior neurosurgeons, obstetricians and gynecologists, diagnostic radiologists, pathologists, anesthesiologists and neonatologists. The MDT conducted a comprehensive assessment of the patient’s condition, tumor characteristics and fetal status, and deliberated on the optimal treatment strategy, considering two core clinical dilemmas: (1) immediate craniotomy for tumor resection would pose a high risk of fetal distress, intrauterine death and preterm birth due to anesthesia and intraoperative hemodynamic fluctuations; (2) expectant management with continued pregnancy would lead to further aggravation of intracranial hypertension and potential life-threatening neurological complications (e.g., brain herniation) due to tumor growth and intratumoral hemorrhage. After rigorous discussion, the MDT formulated a staged intervention strategy prioritizing maternal and fetal safety: Stage 1: Emergency cesarean section to deliver a viable infant, given the gestational age of 33⁺ weeks (fetal lung maturity was confirmed by amniotic fluid examination); Stage 2: Definitive craniotomy for tumor resection 7–10 days post-delivery, after maternal hemodynamic stability, resolution of acute inflammatory responses and optimization of neurological status. Stage 1: Cesarean Section On the day of admission, elective cesarean section was performed under general anesthesia. A lower transverse abdominal incision and low cervical transverse uterine incision were used, and a healthy male infant was delivered uneventfully. The infant had a birth weight of 2200 g, with Apgar scores of 9 at 1 minute and 10 at 5 minutes after birth, indicating no acute neonatal asphyxia. The infant was transferred to the neonatal intensive care unit (NICU) for routine observation and supportive care, with no obvious abnormalities detected during NICU stay. The patient’s postoperative recovery was uncomplicated, with stable vital signs and no exacerbation of neurological symptoms. Stage 2: Craniotomy for Tumor Resection Nine days post-delivery, the patient’s hemodynamic and neurological status was optimized, and intracranial pressure was controlled within a normal range (8–12 cmH₂O) via external ventricular drainage. Craniotomy for tumor resection was performed under general anesthesia and neurophysiological monitoring. A left frontotemporal craniotomy flap was created, and the dura mater was opened in a curvilinear fashion. Intraoperatively, the tumor was found to be located in the left basal ganglia, with a firm texture, rich vascularity and close adhesion to the tuberculum sellae, internal carotid artery and optic nerve. Meticulous microsurgical dissection was performed to preserve the surrounding vital neural and vascular structures, and Simpson Grade Ⅱ resection was achieved (gross total resection of the tumor mass with residual dural attachment). The operation duration was 3.5 hours, with an intraoperative blood loss of 300 mL; no blood transfusion was required. The tumor specimen was sent for immediate histopathological examination. Postoperatively, the patient was transferred to the neurosurgical intensive care unit (NSICU) for close monitoring, with continuation of intracranial pressure monitoring, anti-infective therapy, dehydration and neuroprotective treatment. Histopathological and Immunohistochemical Findings Formalin-fixed, paraffin-embedded tumor tissue specimens were sectioned (4 µm) and stained with hematoxylin and eosin (H&E) for histopathological examination. Microscopic examination revealed the tumor was composed of sheets and nests of polygonal clear cells with abundant glycogen-rich clear cytoplasm and round to ovoid nuclei with fine chromatin and inconspicuous nucleoli (Fig. 3 A). The mitotic count was 2/10 high-power fields (HPF), with no evidence of necrosis or brain parenchymal invasion. Immunohistochemical staining was performed using the EnVision two-step method, with the following primary antibodies: epithelial membrane antigen (EMA), vimentin, progesterone receptor (PR), estrogen receptor (ER), S-100 protein and Ki-67. The results showed strong and diffuse positive expression of EMA (cytoplasmic), vimentin (cytoplasmic) and PR (nuclear) (Fig. 3 B); ER and S-100 protein were negative. The Ki-67 proliferation index was 5%, limited to scattered tumor cells. Based on the 2021 WHO Classification of Tumors of the Central Nervous System, the histopathological and immunohistochemical findings confirmed the diagnosis of WHO Grade Ⅱ clear cell meningioma. Results Postoperative Maternal Recovery The patient’s postoperative course was uncomplicated, with no severe complications such as intracranial rebleeding, infection, cerebrospinal fluid leakage or neurological deterioration. The external ventricular drainage tube was removed on postoperative day 3, and the intracranial pressure remained stable within the normal range. The patient’s consciousness gradually cleared, and limb muscle strength recovered to grade Ⅴ on postoperative day 5; headache and vomiting symptoms resolved completely. A cranial MRI performed on postoperative day 7 showed no residual tumor mass, significant improvement in obstructive hydrocephalus and no evidence of intratumoral rebleeding. The patient was discharged from the hospital on postoperative day 14 with a normal neurological examination and good general condition. Follow-up Outcomes A standardized follow-up protocol was implemented for the patient, including clinical neurological assessment and cranial MRI (T1WI, T2WI and post-contrast T1WI) at 3, 6 and 12 months postoperatively. Cranial MRI at 3 months postoperatively confirmed complete tumor resection with no residual or recurrent lesions, and the ventricular system returned to normal size and morphology. Follow-up at 6 and 12 months postoperatively revealed no evidence of tumor recurrence on cranial MRI, and the patient remained neurologically intact with no headache, seizures or other neurological deficits; she resumed normal daily activities and work. For the infant, regular pediatric follow-up was performed at 1, 3, 6 and 12 months of age, including physical growth assessment, neurodevelopmental screening and neurological examination. The infant’s weight, height and head circumference were all within the normal range for age; neurodevelopmental milestones (e.g., head control, rolling over, sitting, crawling) were achieved on schedule, and neurological examination revealed no obvious abnormalities. At 12 months of age, the infant’s developmental quotient (DQ) was 98, indicating normal neurodevelopment. Discussion This case reports an extremely rare instance of WHO Grade Ⅱ CCM in the left basal ganglia of a 24-year-old primipara during late pregnancy, complicated by obstructive hydrocephalus and intratumoral hemorrhage after ventriculostomy. The successful management of this case with MDT-coordinated staged intervention and favorable long-term outcomes provides critical clinical insights into three key aspects: the correlation between pregnancy-related hormonal changes and CCM progression, the potential mechanisms of intratumoral hemorrhage in CCM, and the optimal clinical management strategy for CCM during late pregnancy. Pregnancy-Related Hormonal Changes as a Driver of CCM Progression Meningiomas are well-recognized as hormone-sensitive tumors, with high expression of progesterone receptors (PR) in approximately 60%–90% of cases and estrogen receptors (ER) in 20%–40% of cases [[ 3 ]]. A growing body of clinical and preclinical evidence supports a causal role for sex hormones in meningioma growth and progression: exogenous hormone therapy (e.g., oral contraceptives, hormone replacement therapy) is associated with increased meningioma incidence and growth, and pregnancy is a known risk factor for accelerated tumor growth in pre-existing meningiomas [[ 3 ],[ 4 ]]. In this case, the tumor tissue exhibited strong and diffuse PR positivity with negative ER expression, and the patient’s clinical symptoms progressed rapidly in the third trimester of pregnancy—a period characterized by the peak of peripheral progesterone levels (up to 100 times the non-pregnant level). This temporal correlation between progesterone surge and tumor progression strongly supports the hypothesis that pregnancy-associated progesterone upregulation is a key driver of CCM growth. The underlying molecular mechanisms by which progesterone promotes CCM progression are thought to involve the activation of PR-mediated signaling pathways in tumor cells, which induces cell proliferation, migration and angiogenesis [[ 5 ]]. Progesterone binding to nuclear PR in meningioma cells leads to the transcription of target genes associated with cell cycle progression (e.g., cyclin D1) and angiogenesis (e.g., vascular endothelial growth factor, VEGF), thereby promoting tumor cell proliferation and neovascularization [[ 5 ]]. In addition, progesterone may modulate the tumor microenvironment by inhibiting anti-tumor immune responses, further facilitating tumor growth [[ 5 ]]. Given the high recurrence rate of CCM, these findings highlight the need for long-term hormonal monitoring and avoidance of exogenous progesterone therapy in PR-positive CCM patients of childbearing age. Potential Mechanisms of Intratumoral Hemorrhage in CCM During Pregnancy Intratumoral hemorrhage is an uncommon but life-threatening complication of intracranial meningiomas, with an incidence of approximately 1%–2% [[ 6 ]]. For CCM, intratumoral hemorrhage is even rarer, and its occurrence during pregnancy has not been previously reported in the literature. In this case, intratumoral hemorrhage was detected on follow-up CT after emergency ventriculostomy, and the MDT hypothesized that this complication was the result of a combination of three factors, namely tumor-specific vascular abnormalities, pregnancy-induced systemic hemodynamic changes and intracranial pressure fluctuations secondary to ventriculostomy. First, CCM is characterized by inherent vascular structural abnormalities, which are a key intrinsic factor for intratumoral hemorrhage. Histopathological studies have shown that CCM blood vessels exhibit abnormal tight junctions between vascular endothelial cells, disorganized vascular smooth muscle layers and deficient basement membrane formation, resulting in fragile and leaky blood vessels with reduced tensile strength [[ 2 ],[ 6 ]]. These structural abnormalities render CCM blood vessels susceptible to rupture even with minor increases in intravascular pressure. Second, pregnancy is associated with significant systemic hemodynamic changes, including a 30%–40% increase in blood volume, increased cardiac output and elevated systemic blood pressure, which lead to increased cerebral perfusion pressure and intravascular pressure in tumor blood vessels [[ 7 ]]. This pregnancy-induced hypervolemia and increased perfusion pressure place additional mechanical stress on the fragile CCM blood vessels, increasing the risk of rupture. Third, emergency external ventriculostomy for obstructive hydrocephalus resulted in rapid intracranial pressure decompression and abrupt fluctuations in intracranial pressure, which caused shear stress on the tumor blood vessels and further precipitated vascular rupture and intratumoral hemorrhage [[ 7 ]]. Collectively, these three factors constitute a "perfect storm" for intratumoral hemorrhage in CCM during late pregnancy, and this mechanistic insight may guide the prevention and management of this rare complication in clinical practice. Optimal Clinical Management Strategy for CCM During Late Pregnancy The management of intracranial tumors during pregnancy is a complex clinical challenge that requires a delicate balance between maternal neurological safety and fetal viability [[ 8 ]]. For CCM during late pregnancy, the paucity of reported cases means that there is no established clinical guideline or consensus on optimal management. The key principle guiding the management of this case was MDT collaboration and staged intervention, which was proven to be safe and effective with favorable maternal and fetal outcomes. The MDT’s decision to perform cesarean section first followed by craniotomy for tumor resection was based on two critical clinical considerations: (1) gestational age of 33⁺ weeks, with confirmed fetal lung maturity, which ensured fetal viability and reduced the risk of neonatal morbidity and mortality; (2) the presence of acute intracranial hypertension and intratumoral hemorrhage, which posed an immediate life-threatening risk to the mother, necessitating definitive tumor resection after fetal delivery. This staged strategy avoided the dual risks of anesthesia and intraoperative hemodynamic fluctuations to the fetus, and allowed for optimal maternal preparation (e.g., hemodynamic stabilization, intracranial pressure control) prior to craniotomy, thereby reducing the risk of postoperative maternal complications. For the surgical management of CCM, Simpson resection grade is a well-recognized prognostic factor for tumor recurrence, with higher resection grades associated with lower recurrence rates [[ 2 ]]. In this case, Simpson Grade Ⅱ resection was achieved due to the tumor’s close adhesion to vital vascular structures (internal carotid artery) and neural tissue (optic nerve), and the Ki-67 proliferation index was 5% (≤ 5%), which are favorable prognostic factors for CCM [[ 2 ]]. Postoperative adjuvant radiotherapy is a controversial topic for WHO Grade Ⅱ CCM: some studies have suggested that adjuvant radiotherapy may reduce recurrence rates in patients with subtotal resection or high-risk features (e.g., high Ki-67 index), while others have reported no significant benefit [[ 9 ],[ 10 ]]. Given the favorable prognostic factors (Simpson Grade Ⅱ resection, Ki-67 = 5%) and the patient’s young age and reproductive status, the MDT decided against postoperative adjuvant radiotherapy and opted for close regular follow-up, which is consistent with the latest clinical evidence [[ 10 ]]. Prognostic Considerations for CCM CCM is a WHO Grade Ⅱ meningioma with a significantly higher recurrence rate than benign WHO Grade Ⅰ meningiomas, with a reported 5-year recurrence rate of approximately 30%–40% [[ 2 ],[ 10 ]]. The main prognostic factors for CCM include the extent of tumor resection, Ki-67 proliferation index, tumor location and presence of peritumoral brain invasion [[ 2 ],[ 10 ]]. In this case, the patient had two favorable prognostic factors (Simpson Grade Ⅱ resection, Ki-67 = 5%) and no adverse prognostic factors (no brain invasion, no distant metastasis), which may explain the absence of tumor recurrence at 1-year follow-up. However, given the high recurrence rate of CCM, long-term regular follow-up (at least 5 years) with cranial MRI is essential to detect early tumor recurrence and initiate prompt intervention. For PR-positive CCM patients of childbearing age, pre-conceptual counseling is also recommended to inform them of the risk of tumor progression during pregnancy and to formulate a personalized monitoring plan. Data Availability Statement The data supporting the findings of this case report are derived from the clinical, imaging and histopathological records of the patient at the Weifang Hospital of Traditional Chinese Medicine. Due to the sensitive nature of these clinical data and the need to protect patient privacy in accordance with the Declaration of Helsinki, the raw individual patient data cannot be made publicly available. De-identified aggregate data and study materials relevant to this case report are available from the corresponding author (Peigang Tian, E-mail: [email protected] ) upon reasonable written request, with the prior approval of the Medical Research Ethics Committee of Weifang Hospital of Traditional Chinese Medicine (Ethical Lot No: 2025YX409). Conclusion This case describes the extremely rare occurrence of WHO Grade Ⅱ CCM with obstructive hydrocephalus and intratumoral hemorrhage in a 24-year-old primipara during late pregnancy, and highlights the critical role of MDT-coordinated staged intervention in achieving favorable maternal and fetal outcomes. Pregnancy-associated progesterone upregulation is a key driver of progression in PR-positive CCM, and intratumoral hemorrhage is likely the result of a combination of tumor-specific vascular fragility, pregnancy-induced hemodynamic changes and intracranial pressure fluctuations. For such rare cases, staged intervention (cesarean section followed by craniotomy) is the optimal management strategy, prioritizing fetal viability while ensuring definitive tumor treatment for the mother. Given the high recurrence rate of CCM, long-term regular clinical and imaging follow-up is mandatory for all patients, and pre-conceptual hormonal counseling is recommended for PR-positive CCM patients of childbearing age. This case enriches the clinical literature on hormone-sensitive meningiomas during pregnancy and provides valuable practical insights for the diagnosis and management of this challenging comorbidity. Declarations Ethical Approval and accordance This study was approved by the Medical Research Ethics Committee of Weifang Hospital of Traditional Chinese Medicine (Ethical Lot No: 2025YX409). All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Consent to participate Written informed consent to participate in the clinical management, follow-up and related research of this case was obtained from the patient (Yuting Zhou) prior to all clinical interventions and examinations. Consent to publish Written informed consent for the publication of this case report and all accompanying imaging and histopathological figures was obtained from the patient (Yuting Zhou). A copy of the written informed consent is available for review by the Editor-in-Chief of this journal upon request. Author Contributions Xiaoqian Xu: Data curation, imaging analysis, formal analysis, writing – original draft. Aiting Weng: Literature review, case summary, writing – review & editing, visualization. Peigang Tian: Conceptualization, supervision, project administration, clinical guidance, writing – review & editing (final version), corresponding author. All authors have read and agreed to the published version of the manuscript. Conflict of Interest Statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Funding Statement This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Data Availability Statement The data supporting the findings of this case report are derived from the clinical, imaging and histopathological records of the patient at the Weifang Hospital of Traditional Chinese Medicine. Due to the sensitive nature of these clinical data and the need to protect patient privacy in accordance with the Declaration of Helsinki, the raw individual patient data cannot be made publicly available. De-identified aggregate data and study materials relevant to this case report are available from the corresponding author (Peigang Tian, E-mail: [email protected] ) upon reasonable written request, with the prior approval of the Medical Research Ethics Committee of Weifang Hospital of Traditional Chinese Medicine (Ethical Lot No: 2025YX409). References Louis DN, Perry A, Wesseling P, et al. WHO Classification of Tumours of the Central Nervous System. 5th ed. Lyon: IARC; 2021. Rahman M, Dutta P, Agarwala P, et al. Clinical manifestation, management and prognosis of clear cell meningioma: an evidence-based review. Int J Neurosci. 2023;133(6):648–53. Karbhari N, Thomas AA. Clinical management of brain tumors in pregnancy. Curr Opin Oncol. 2022;34(6):691–7. Zhang Y, Li X, Wang H, et al. MRI and Pathological Characteristics of Intracranial Clear Cell Meningioma. Chin J CT MRI. 2024;22(3):45–8. Chen H, Li XM, Chen YC, et al. Intracranial clear cell meningioma: a clinicopathologic study of 15 cases. Acta Neurochir (Wien). 2011;153(9):1769–80. Rath S, Sharma A, Gupta A, et al. Management of brain tumours during pregnancy: a systematic review. Ann Med Surg (Lond). 2024;107:105892. Liang Q, Ge P, Liu Y, et al. Central nervous system clear cell meningioma: a systematic literature review. Neurosurg Rev. 2024;47(1):29–38. Li J, Wang Y, Zhang L, et al. Prognostic factors and treatment outcomes of clear cell meningioma: a systematic review and meta-analysis. J Neurooncol. 2024;168(2):317–26. Sandberg DI, Edgar MA, Resch L, et al. MIB-1 staining index of pediatric meningiomas. Neurosurgery. 2001;48(3):590–5. discussion 595–597. Ren L, Hua L, Deng J, et al. Favorable Long-Term Outcomes of Chordoid Meningioma Compared With the Other WHO Grade 2 Meningioma Subtypes. Neurosurgery. 2023;92(4):745–55. Additional Declarations No competing interests reported. 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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-9032253","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":617695185,"identity":"d7473388-d9e7-4720-9cb6-349264ed64d4","order_by":0,"name":"Xiaoqian Xu","email":"","orcid":"","institution":"Weifang Hospital of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Xiaoqian","middleName":"","lastName":"Xu","suffix":""},{"id":617695188,"identity":"9a30dba1-b779-4d37-ae17-025c1cb40b9b","order_by":1,"name":"Aiting Weng","email":"","orcid":"","institution":"Weifang Hospital of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Aiting","middleName":"","lastName":"Weng","suffix":""},{"id":617695198,"identity":"38bded6e-de83-45d5-a3ff-751e1cf88f82","order_by":2,"name":"Peigang Tian","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA30lEQVRIiWNgGAWjYDACZjApASIYHyRU1BDWwYOkhdngwZljRGhBYrNJPmxhJqzFnp352eOCCgu7/tnt1yoSG9gY+Nu7Ewg4jM3ceMYZieQZd86U3UjcIcMgcebsBgJaGMykedskkhlu5KTdSDzDxmAgkUtIC/s3ad5/EsnyQC0FiW3MxGjhAdrSIGFncCP9GANxWg7zlEnPOCaRYHgjh1ki4cwxHoJ+Ye8/vk26oKbOXu5G+sOPPypq5Pjbe/FrAQFQXCQ2MPAYgK0lqBymxR5o4QOiVI+CUTAKRsHIAwAY4UMCuQ4IywAAAABJRU5ErkJggg==","orcid":"","institution":"Weifang Hospital of Traditional Chinese Medicine","correspondingAuthor":true,"prefix":"","firstName":"Peigang","middleName":"","lastName":"Tian","suffix":""}],"badges":[],"createdAt":"2026-03-04 16:08:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9032253/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9032253/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106288856,"identity":"399c1fa3-e451-458b-b8b6-4d069f74401e","added_by":"auto","created_at":"2026-04-07 07:27:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":237353,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Axial CT showing a left basal ganglia hypodense mass with obstructive hydrocephalus. (B) Post-drainage CT demonstrating intratumoral hemorrhage (hyperdense areas).\u003c/p\u003e","description":"","filename":"20260311202400.png","url":"https://assets-eu.researchsquare.com/files/rs-9032253/v1/531a51d4f39ad23d3d2a5a28.png"},{"id":106288969,"identity":"dd9122fa-29c6-417a-b858-661223e71fed","added_by":"auto","created_at":"2026-04-07 07:27:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":151984,"visible":true,"origin":"","legend":"\u003cp\u003eMRI findings: (A-B) T2 and T1 sequences showing lesion characteristics; (E-F) Post-contrast images highlighting enhancement and dural involvement.\u003c/p\u003e","description":"","filename":"20260311202409.png","url":"https://assets-eu.researchsquare.com/files/rs-9032253/v1/2a8065b06a677ba4fca7228e.png"},{"id":106289026,"identity":"1c9e57ed-a48c-41c5-8ca7-fd6ecbb8c83b","added_by":"auto","created_at":"2026-04-07 07:27:56","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1308313,"visible":true,"origin":"","legend":"\u003cp\u003e(A) H\u0026amp;E staining (×100) showing clear cells; (B) EMA immunopositivity.\u003c/p\u003e","description":"","filename":"20260311202413.png","url":"https://assets-eu.researchsquare.com/files/rs-9032253/v1/743163eb2af4f8eb8d7b0cd6.png"},{"id":106414890,"identity":"b1a452f9-f33a-48aa-abce-b709a8f829d4","added_by":"auto","created_at":"2026-04-08 10:29:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2308535,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9032253/v1/89042c5c-6c1f-492a-b059-7a724f839be2.pdf"},{"id":106289024,"identity":"d8f5e2cb-45c6-42f8-a955-0b64726331a8","added_by":"auto","created_at":"2026-04-07 07:27:55","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":8698,"visible":true,"origin":"","legend":"","description":"","filename":"CAREChecklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-9032253/v1/fc67822fc1527ac8d8c1f239.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"WHO Grade Ⅱ Clear Cell Meningioma with Obstructive Hydrocephalus and Intratumoral Hemorrhage in a 24-Year-Old Primipara During Late Pregnancy: A Case Report and Clinical Implications ","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMeningiomas represent the most common primary intracranial tumors of mesenchymal origin, and clear cell meningioma (CCM) is a rare distinct histological subtype classified as WHO Grade Ⅱ by the World Health Organization (WHO) Classification of Tumors of the Central Nervous System [[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e]]. CCM accounts for a mere 0.2%–0.8% of all meningioma cases, with a documented predilection for young women and a characteristic high recurrence rate compared with other benign meningioma subtypes [[\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]]. While the median age of onset for CCM is reported to be 52 years, its occurrence in young pregnant women is exceedingly rare, and the concomitant presence of obstructive hydrocephalus and intratumoral hemorrhage further complicates clinical management [[\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]].\u003c/p\u003e \u003cp\u003eAccumulating evidence suggests that sex hormones, particularly estrogen and progesterone, play a pivotal role in the growth and progression of meningiomas, given the high expression of estrogen and progesterone receptors in tumor tissues [[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]]. Pregnancy is characterized by a dramatic physiological surge in peripheral progesterone and estrogen levels, which is hypothesized to act as a potential driver of accelerated tumor growth and malignant progression in hormone receptor-positive meningiomas [[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]]. However, the underlying mechanisms linking pregnancy-related hormonal changes to intratumoral hemorrhage in CCM remain poorly elucidated, and clinical consensus on the optimal management of CCM during late pregnancy is lacking due to the paucity of reported cases.\u003c/p\u003e \u003cp\u003eHerein, we report a rare case of a 24-year-old primipara at 33⁺ weeks of gestation with WHO Grade Ⅱ CCM in the left basal ganglia, complicated by obstructive hydrocephalus and intratumoral hemorrhage after ventriculostomy. We detail the MDT-coordinated staged intervention strategy, pathological features and long-term follow-up outcomes, and conduct a critical review of the relevant literature to explore the correlation between pregnancy-related hormonal changes and CCM progression, as well as the potential mechanisms of intratumoral hemorrhage. This case aims to provide valuable clinical insights for the diagnosis and management of this extremely rare comorbidity, and to emphasize the critical role of MDT collaboration in optimizing maternal and fetal outcomes.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e "},{"header":"Case Presentation","content":"\u003cp\u003eClinical Manifestations\u003c/p\u003e\u003cp\u003eA 24-year-old primigravida at 33⁺ weeks of gestation was admitted to the Weifang Hospital of Traditional Chinese Medicine with a 6-month history of intermittent headache and 4 days of progressively aggravated headache accompanied by intractable vomiting. The patient had no prior medical history of hypertension, diabetes mellitus, cerebrovascular disease or central nervous system tumors, and regular prenatal examinations during pregnancy had revealed no obvious abnormalities. The headache was initially intermittent and non-positional, with no associated neurological deficits, and was not relieved by rest or symptomatic treatment. Four days prior to admission, the headache worsened markedly, accompanied by persistent vomiting (non-bilious, non-projectile), somnolence and mild limb weakness, prompting urgent medical attention.\u003c/p\u003e\u003cp\u003eOn admission, neurological physical examination was performed: the patient was in a somnolent state, with a GCS score of 14 (E3V4M6); bilateral pupils were equal and round (3 mm in diameter), with intact and sensitive light reflexes; muscle strength of all limbs was grade Ⅳ, with normal muscle tone and no obvious sensory disturbance; meningeal irritation signs were negative; and deep tendon reflexes were symmetrically present. Obstetric examination confirmed a singleton pregnancy with a normal fetal heart rate (140 beats/min) and no signs of fetal distress; fetal biometry was consistent with gestational age, and no obvious abnormalities in fetal development were detected. Vital signs on admission were stable: body temperature 36.7℃, heart rate 86 beats/min, respiratory rate 19 breaths/min, blood pressure 122/78 mmHg.\u003c/p\u003e\u003cp\u003eImaging Findings\u003c/p\u003e\u003cp\u003eEmergency non-contrast cranial CT (Siemens Somatom Force) was performed on admission, revealing a well-circumscribed 6×6×5 cm hypodense mass in the left basal ganglia with significant mass effect, resulting in obstructive hydrocephalus characterized by dilation of the bilateral lateral ventricles and third ventricle (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eA). Given the presence of acute intracranial hypertension, emergency external ventricular drainage was performed to decompress the intracranial cavity and relieve hydrocephalus. A follow-up cranial CT performed 6 hours post-procedure identified new hyperdense foci within the tumor parenchyma, consistent with intratumoral hemorrhage (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eB).\u003c/p\u003e\u003cp\u003eSubsequent cranial MRI (3.0T, Siemens Magnetom Verio) was performed for further tumor characterization: the lesion exhibited heterogeneous hypointensity on T1-weighted imaging (T1WI) and hyperintensity on T2-weighted imaging (T2WI); homogeneous and marked enhancement was observed after intravenous administration of gadopentetate dimeglumine (0.1 mmol/kg), with ill-defined tumor margins and no obvious peritumoral edema (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA-E). Focal short T1 signals were identified within the tumor parenchyma on T1WI, which was consistent with the CT findings of intratumoral hemorrhage (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eB). No obvious dural tail sign was detected on post-contrast MRI sequences.\u003c/p\u003e\u003cp\u003eMultidisciplinary Treatment Strategy and Implementation\u003c/p\u003e\u003cp\u003eGiven the rare and complex clinical scenario, an MDT was immediately convened, consisting of senior neurosurgeons, obstetricians and gynecologists, diagnostic radiologists, pathologists, anesthesiologists and neonatologists. The MDT conducted a comprehensive assessment of the patient’s condition, tumor characteristics and fetal status, and deliberated on the optimal treatment strategy, considering two core clinical dilemmas: (1) immediate craniotomy for tumor resection would pose a high risk of fetal distress, intrauterine death and preterm birth due to anesthesia and intraoperative hemodynamic fluctuations; (2) expectant management with continued pregnancy would lead to further aggravation of intracranial hypertension and potential life-threatening neurological complications (e.g., brain herniation) due to tumor growth and intratumoral hemorrhage.\u003c/p\u003e\u003cp\u003eAfter rigorous discussion, the MDT formulated a staged intervention strategy prioritizing maternal and fetal safety: Stage 1: Emergency cesarean section to deliver a viable infant, given the gestational age of 33⁺ weeks (fetal lung maturity was confirmed by amniotic fluid examination); Stage 2: Definitive craniotomy for tumor resection 7–10 days post-delivery, after maternal hemodynamic stability, resolution of acute inflammatory responses and optimization of neurological status.\u003c/p\u003e\u003cp\u003eStage 1: Cesarean Section\u003c/p\u003e\u003cp\u003eOn the day of admission, elective cesarean section was performed under general anesthesia. A lower transverse abdominal incision and low cervical transverse uterine incision were used, and a healthy male infant was delivered uneventfully. The infant had a birth weight of 2200 g, with Apgar scores of 9 at 1 minute and 10 at 5 minutes after birth, indicating no acute neonatal asphyxia. The infant was transferred to the neonatal intensive care unit (NICU) for routine observation and supportive care, with no obvious abnormalities detected during NICU stay. The patient’s postoperative recovery was uncomplicated, with stable vital signs and no exacerbation of neurological symptoms.\u003c/p\u003e\u003cp\u003eStage 2: Craniotomy for Tumor Resection\u003c/p\u003e\u003cp\u003eNine days post-delivery, the patient’s hemodynamic and neurological status was optimized, and intracranial pressure was controlled within a normal range (8–12 cmH₂O) via external ventricular drainage. Craniotomy for tumor resection was performed under general anesthesia and neurophysiological monitoring. A left frontotemporal craniotomy flap was created, and the dura mater was opened in a curvilinear fashion. Intraoperatively, the tumor was found to be located in the left basal ganglia, with a firm texture, rich vascularity and close adhesion to the tuberculum sellae, internal carotid artery and optic nerve. Meticulous microsurgical dissection was performed to preserve the surrounding vital neural and vascular structures, and Simpson Grade Ⅱ resection was achieved (gross total resection of the tumor mass with residual dural attachment). The operation duration was 3.5 hours, with an intraoperative blood loss of 300 mL; no blood transfusion was required. The tumor specimen was sent for immediate histopathological examination. Postoperatively, the patient was transferred to the neurosurgical intensive care unit (NSICU) for close monitoring, with continuation of intracranial pressure monitoring, anti-infective therapy, dehydration and neuroprotective treatment.\u003c/p\u003e\u003cp\u003eHistopathological and Immunohistochemical Findings\u003c/p\u003e\u003cp\u003eFormalin-fixed, paraffin-embedded tumor tissue specimens were sectioned (4 µm) and stained with hematoxylin and eosin (H\u0026amp;E) for histopathological examination. Microscopic examination revealed the tumor was composed of sheets and nests of polygonal clear cells with abundant glycogen-rich clear cytoplasm and round to ovoid nuclei with fine chromatin and inconspicuous nucleoli (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eA). The mitotic count was 2/10 high-power fields (HPF), with no evidence of necrosis or brain parenchymal invasion.\u003c/p\u003e\u003cp\u003eImmunohistochemical staining was performed using the EnVision two-step method, with the following primary antibodies: epithelial membrane antigen (EMA), vimentin, progesterone receptor (PR), estrogen receptor (ER), S-100 protein and Ki-67. The results showed strong and diffuse positive expression of EMA (cytoplasmic), vimentin (cytoplasmic) and PR (nuclear) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eB); ER and S-100 protein were negative. The Ki-67 proliferation index was 5%, limited to scattered tumor cells. Based on the 2021 WHO Classification of Tumors of the Central Nervous System, the histopathological and immunohistochemical findings confirmed the diagnosis of WHO Grade Ⅱ clear cell meningioma.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003ePostoperative Maternal Recovery\u003c/p\u003e \u003cp\u003eThe patient\u0026rsquo;s postoperative course was uncomplicated, with no severe complications such as intracranial rebleeding, infection, cerebrospinal fluid leakage or neurological deterioration. The external ventricular drainage tube was removed on postoperative day 3, and the intracranial pressure remained stable within the normal range. The patient\u0026rsquo;s consciousness gradually cleared, and limb muscle strength recovered to grade Ⅴ on postoperative day 5; headache and vomiting symptoms resolved completely. A cranial MRI performed on postoperative day 7 showed no residual tumor mass, significant improvement in obstructive hydrocephalus and no evidence of intratumoral rebleeding. The patient was discharged from the hospital on postoperative day 14 with a normal neurological examination and good general condition.\u003c/p\u003e \u003cp\u003eFollow-up Outcomes\u003c/p\u003e \u003cp\u003eA standardized follow-up protocol was implemented for the patient, including clinical neurological assessment and cranial MRI (T1WI, T2WI and post-contrast T1WI) at 3, 6 and 12 months postoperatively. Cranial MRI at 3 months postoperatively confirmed complete tumor resection with no residual or recurrent lesions, and the ventricular system returned to normal size and morphology. Follow-up at 6 and 12 months postoperatively revealed no evidence of tumor recurrence on cranial MRI, and the patient remained neurologically intact with no headache, seizures or other neurological deficits; she resumed normal daily activities and work.\u003c/p\u003e \u003cp\u003eFor the infant, regular pediatric follow-up was performed at 1, 3, 6 and 12 months of age, including physical growth assessment, neurodevelopmental screening and neurological examination. The infant\u0026rsquo;s weight, height and head circumference were all within the normal range for age; neurodevelopmental milestones (e.g., head control, rolling over, sitting, crawling) were achieved on schedule, and neurological examination revealed no obvious abnormalities. At 12 months of age, the infant\u0026rsquo;s developmental quotient (DQ) was 98, indicating normal neurodevelopment.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case reports an extremely rare instance of WHO Grade Ⅱ CCM in the left basal ganglia of a 24-year-old primipara during late pregnancy, complicated by obstructive hydrocephalus and intratumoral hemorrhage after ventriculostomy. The successful management of this case with MDT-coordinated staged intervention and favorable long-term outcomes provides critical clinical insights into three key aspects: the correlation between pregnancy-related hormonal changes and CCM progression, the potential mechanisms of intratumoral hemorrhage in CCM, and the optimal clinical management strategy for CCM during late pregnancy.\u003c/p\u003e \u003cp\u003ePregnancy-Related Hormonal Changes as a Driver of CCM Progression\u003c/p\u003e \u003cp\u003eMeningiomas are well-recognized as hormone-sensitive tumors, with high expression of progesterone receptors (PR) in approximately 60%\u0026ndash;90% of cases and estrogen receptors (ER) in 20%\u0026ndash;40% of cases [[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]]. A growing body of clinical and preclinical evidence supports a causal role for sex hormones in meningioma growth and progression: exogenous hormone therapy (e.g., oral contraceptives, hormone replacement therapy) is associated with increased meningioma incidence and growth, and pregnancy is a known risk factor for accelerated tumor growth in pre-existing meningiomas [[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e],[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]]. In this case, the tumor tissue exhibited strong and diffuse PR positivity with negative ER expression, and the patient\u0026rsquo;s clinical symptoms progressed rapidly in the third trimester of pregnancy\u0026mdash;a period characterized by the peak of peripheral progesterone levels (up to 100 times the non-pregnant level). This temporal correlation between progesterone surge and tumor progression strongly supports the hypothesis that pregnancy-associated progesterone upregulation is a key driver of CCM growth.\u003c/p\u003e \u003cp\u003eThe underlying molecular mechanisms by which progesterone promotes CCM progression are thought to involve the activation of PR-mediated signaling pathways in tumor cells, which induces cell proliferation, migration and angiogenesis [[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]]. Progesterone binding to nuclear PR in meningioma cells leads to the transcription of target genes associated with cell cycle progression (e.g., cyclin D1) and angiogenesis (e.g., vascular endothelial growth factor, VEGF), thereby promoting tumor cell proliferation and neovascularization [[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]]. In addition, progesterone may modulate the tumor microenvironment by inhibiting anti-tumor immune responses, further facilitating tumor growth [[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]]. Given the high recurrence rate of CCM, these findings highlight the need for long-term hormonal monitoring and avoidance of exogenous progesterone therapy in PR-positive CCM patients of childbearing age.\u003c/p\u003e \u003cp\u003ePotential Mechanisms of Intratumoral Hemorrhage in CCM During Pregnancy\u003c/p\u003e \u003cp\u003eIntratumoral hemorrhage is an uncommon but life-threatening complication of intracranial meningiomas, with an incidence of approximately 1%\u0026ndash;2% [[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]]. For CCM, intratumoral hemorrhage is even rarer, and its occurrence during pregnancy has not been previously reported in the literature. In this case, intratumoral hemorrhage was detected on follow-up CT after emergency ventriculostomy, and the MDT hypothesized that this complication was the result of a combination of three factors, namely tumor-specific vascular abnormalities, pregnancy-induced systemic hemodynamic changes and intracranial pressure fluctuations secondary to ventriculostomy.\u003c/p\u003e \u003cp\u003eFirst, CCM is characterized by inherent vascular structural abnormalities, which are a key intrinsic factor for intratumoral hemorrhage. Histopathological studies have shown that CCM blood vessels exhibit abnormal tight junctions between vascular endothelial cells, disorganized vascular smooth muscle layers and deficient basement membrane formation, resulting in fragile and leaky blood vessels with reduced tensile strength [[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e],[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]]. These structural abnormalities render CCM blood vessels susceptible to rupture even with minor increases in intravascular pressure. Second, pregnancy is associated with significant systemic hemodynamic changes, including a 30%\u0026ndash;40% increase in blood volume, increased cardiac output and elevated systemic blood pressure, which lead to increased cerebral perfusion pressure and intravascular pressure in tumor blood vessels [[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]]. This pregnancy-induced hypervolemia and increased perfusion pressure place additional mechanical stress on the fragile CCM blood vessels, increasing the risk of rupture. Third, emergency external ventriculostomy for obstructive hydrocephalus resulted in rapid intracranial pressure decompression and abrupt fluctuations in intracranial pressure, which caused shear stress on the tumor blood vessels and further precipitated vascular rupture and intratumoral hemorrhage [[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]]. Collectively, these three factors constitute a \"perfect storm\" for intratumoral hemorrhage in CCM during late pregnancy, and this mechanistic insight may guide the prevention and management of this rare complication in clinical practice.\u003c/p\u003e \u003cp\u003eOptimal Clinical Management Strategy for CCM During Late Pregnancy\u003c/p\u003e \u003cp\u003eThe management of intracranial tumors during pregnancy is a complex clinical challenge that requires a delicate balance between maternal neurological safety and fetal viability [[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]]. For CCM during late pregnancy, the paucity of reported cases means that there is no established clinical guideline or consensus on optimal management. The key principle guiding the management of this case was MDT collaboration and staged intervention, which was proven to be safe and effective with favorable maternal and fetal outcomes.\u003c/p\u003e \u003cp\u003eThe MDT\u0026rsquo;s decision to perform cesarean section first followed by craniotomy for tumor resection was based on two critical clinical considerations: (1) gestational age of 33⁺ weeks, with confirmed fetal lung maturity, which ensured fetal viability and reduced the risk of neonatal morbidity and mortality; (2) the presence of acute intracranial hypertension and intratumoral hemorrhage, which posed an immediate life-threatening risk to the mother, necessitating definitive tumor resection after fetal delivery. This staged strategy avoided the dual risks of anesthesia and intraoperative hemodynamic fluctuations to the fetus, and allowed for optimal maternal preparation (e.g., hemodynamic stabilization, intracranial pressure control) prior to craniotomy, thereby reducing the risk of postoperative maternal complications.\u003c/p\u003e \u003cp\u003eFor the surgical management of CCM, Simpson resection grade is a well-recognized prognostic factor for tumor recurrence, with higher resection grades associated with lower recurrence rates [[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]]. In this case, Simpson Grade Ⅱ resection was achieved due to the tumor\u0026rsquo;s close adhesion to vital vascular structures (internal carotid artery) and neural tissue (optic nerve), and the Ki-67 proliferation index was 5% (\u0026le;\u0026thinsp;5%), which are favorable prognostic factors for CCM [[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]]. Postoperative adjuvant radiotherapy is a controversial topic for WHO Grade Ⅱ CCM: some studies have suggested that adjuvant radiotherapy may reduce recurrence rates in patients with subtotal resection or high-risk features (e.g., high Ki-67 index), while others have reported no significant benefit [[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e],[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]]. Given the favorable prognostic factors (Simpson Grade Ⅱ resection, Ki-67\u0026thinsp;=\u0026thinsp;5%) and the patient\u0026rsquo;s young age and reproductive status, the MDT decided against postoperative adjuvant radiotherapy and opted for close regular follow-up, which is consistent with the latest clinical evidence [[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]].\u003c/p\u003e \u003cp\u003ePrognostic Considerations for CCM\u003c/p\u003e \u003cp\u003eCCM is a WHO Grade Ⅱ meningioma with a significantly higher recurrence rate than benign WHO Grade Ⅰ meningiomas, with a reported 5-year recurrence rate of approximately 30%\u0026ndash;40% [[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e],[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]]. The main prognostic factors for CCM include the extent of tumor resection, Ki-67 proliferation index, tumor location and presence of peritumoral brain invasion [[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e],[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]]. In this case, the patient had two favorable prognostic factors (Simpson Grade Ⅱ resection, Ki-67\u0026thinsp;=\u0026thinsp;5%) and no adverse prognostic factors (no brain invasion, no distant metastasis), which may explain the absence of tumor recurrence at 1-year follow-up. However, given the high recurrence rate of CCM, long-term regular follow-up (at least 5 years) with cranial MRI is essential to detect early tumor recurrence and initiate prompt intervention. For PR-positive CCM patients of childbearing age, pre-conceptual counseling is also recommended to inform them of the risk of tumor progression during pregnancy and to formulate a personalized monitoring plan.\u003c/p\u003e\u003cp\u003eData Availability Statement\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this case report are derived from the clinical, imaging and histopathological records of the patient at the Weifang Hospital of Traditional Chinese Medicine. Due to the sensitive nature of these clinical data and the need to protect patient privacy in accordance with the Declaration of Helsinki, the raw individual patient data cannot be made publicly available. De-identified aggregate data and study materials relevant to this case report are available from the corresponding author (Peigang Tian, E-mail: [email protected]) upon reasonable written request, with the prior approval of the Medical Research Ethics Committee of Weifang Hospital of Traditional Chinese Medicine (Ethical Lot No: 2025YX409).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case describes the extremely rare occurrence of WHO Grade Ⅱ CCM with obstructive hydrocephalus and intratumoral hemorrhage in a 24-year-old primipara during late pregnancy, and highlights the critical role of MDT-coordinated staged intervention in achieving favorable maternal and fetal outcomes. Pregnancy-associated progesterone upregulation is a key driver of progression in PR-positive CCM, and intratumoral hemorrhage is likely the result of a combination of tumor-specific vascular fragility, pregnancy-induced hemodynamic changes and intracranial pressure fluctuations. For such rare cases, staged intervention (cesarean section followed by craniotomy) is the optimal management strategy, prioritizing fetal viability while ensuring definitive tumor treatment for the mother. Given the high recurrence rate of CCM, long-term regular clinical and imaging follow-up is mandatory for all patients, and pre-conceptual hormonal counseling is recommended for PR-positive CCM patients of childbearing age. This case enriches the clinical literature on hormone-sensitive meningiomas during pregnancy and provides valuable practical insights for the diagnosis and management of this challenging comorbidity.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthical Approval and accordance\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Medical Research Ethics Committee of Weifang Hospital of Traditional Chinese Medicine (Ethical Lot No: 2025YX409). All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003eConsent to participate\u003c/p\u003e\n\u003cp\u003eWritten informed consent to participate in the clinical management, follow-up and related research of this case was obtained from the patient (Yuting Zhou) prior to all clinical interventions and examinations.\u003c/p\u003e\n\u003cp\u003eConsent to publish\u003c/p\u003e\n\u003cp\u003eWritten informed consent for the publication of this case report and all accompanying imaging and histopathological figures was obtained from the patient (Yuting Zhou). A copy of the written informed consent is available for review by the Editor-in-Chief of this journal upon request.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions\u003c/p\u003e\n\u003cp\u003eXiaoqian Xu: Data curation, imaging analysis, formal analysis, writing – original draft.\u003c/p\u003e\n\u003cp\u003eAiting Weng: Literature review, case summary, writing – review \u0026amp; editing, visualization.\u003c/p\u003e\n\u003cp\u003ePeigang Tian: Conceptualization, supervision, project administration, clinical guidance, writing – review \u0026amp; editing (final version), corresponding author.\u003c/p\u003e\n\u003cp\u003eAll authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003eConflict of Interest Statement\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003eFunding Statement\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003eData Availability Statement\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this case report are derived from the clinical, imaging and histopathological records of the patient at the Weifang Hospital of Traditional Chinese Medicine. Due to the sensitive nature of these clinical data and the need to protect patient privacy in accordance with the Declaration of Helsinki, the raw individual patient data cannot be made publicly available. De-identified aggregate data and study materials relevant to this case report are available from the corresponding author (Peigang Tian, E-mail: [email protected]) upon reasonable written request, with the prior approval of the Medical Research Ethics Committee of Weifang Hospital of Traditional Chinese Medicine (Ethical Lot No: 2025YX409).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLouis DN, Perry A, Wesseling P, et al. WHO Classification of Tumours of the Central Nervous System. 5th ed. Lyon: IARC; 2021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRahman M, Dutta P, Agarwala P, et al. Clinical manifestation, management and prognosis of clear cell meningioma: an evidence-based review. Int J Neurosci. 2023;133(6):648\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarbhari N, Thomas AA. Clinical management of brain tumors in pregnancy. Curr Opin Oncol. 2022;34(6):691\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Y, Li X, Wang H, et al. MRI and Pathological Characteristics of Intracranial Clear Cell Meningioma. Chin J CT MRI. 2024;22(3):45\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen H, Li XM, Chen YC, et al. Intracranial clear cell meningioma: a clinicopathologic study of 15 cases. Acta Neurochir (Wien). 2011;153(9):1769\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRath S, Sharma A, Gupta A, et al. Management of brain tumours during pregnancy: a systematic review. Ann Med Surg (Lond). 2024;107:105892.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiang Q, Ge P, Liu Y, et al. Central nervous system clear cell meningioma: a systematic literature review. Neurosurg Rev. 2024;47(1):29\u0026ndash;38.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi J, Wang Y, Zhang L, et al. Prognostic factors and treatment outcomes of clear cell meningioma: a systematic review and meta-analysis. J Neurooncol. 2024;168(2):317\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSandberg DI, Edgar MA, Resch L, et al. MIB-1 staining index of pediatric meningiomas. Neurosurgery. 2001;48(3):590\u0026ndash;5. discussion 595\u0026ndash;597.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRen L, Hua L, Deng J, et al. Favorable Long-Term Outcomes of Chordoid Meningioma Compared With the Other WHO Grade 2 Meningioma Subtypes. Neurosurgery. 2023;92(4):745\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"discover-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)","snPcode":"44337","submissionUrl":"https://submission.springernature.com/new-submission/44337/3","title":"Discover Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-9032253/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9032253/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground\u003c/p\u003e\n\u003cp\u003eClear cell meningioma (CCM), a rare WHO Grade Ⅱ meningioma subtype, accounts for only 0.2%–0.8% of all intracranial meningiomas and is notable for its predilection for young females and high recurrence potential. The occurrence of CCM with obstructive hydrocephalus and intratumoral hemorrhage during late pregnancy is an extremely rare clinical scenario, and its management requires a delicate trade-off between maternal neurological safety, fetal viability and definitive tumor treatment, presenting unique challenges to the multidisciplinary team (MDT).\u003c/p\u003e\n\u003cp\u003eCase Presentation\u003c/p\u003e\n\u003cp\u003eA 24-year-old primipara at 33⁺ weeks of gestation was admitted to our institution with progressively aggravated headache and intractable vomiting for 4 days, on the basis of a 6-month history of intermittent cephalalgia. Neurological examination revealed a somnolent state with a Glasgow Coma Scale (GCS) score of 14 and grade Ⅳ limb muscle strength. Non-contrast cranial computed tomography (CT) demonstrated a 6×6×5 cm hypodense space-occupying lesion in the left basal ganglia with obstructive hydrocephalus; intratumoral hemorrhage was identified on follow-up CT after emergency external ventriculostomy. Cranial magnetic resonance imaging (MRI) exhibited hypointensity on T1-weighted imaging, hyperintensity on T2-weighted imaging, homogeneous enhancement post-contrast administration and ill-defined margins, with short T1 signals consistent with intratumoral hemorrhage. An MDT consisting of neurosurgeons, obstetricians, radiologists and pathologists formulated a staged intervention strategy.\u003c/p\u003e\n\u003cp\u003eResults\u003c/p\u003e\n\u003cp\u003eA healthy male infant with Apgar scores of 9 and 10 at 1 and 5 minutes after birth was delivered via cesarean section. Nine days post-delivery, craniotomy was performed and Simpson Grade Ⅱ tumor resection was achieved. Histopathological examination confirmed WHO Grade Ⅱ CCM, with positive expression of epithelial membrane antigen (EMA), vimentin and progesterone receptor (PR), and a Ki-67 proliferation index of 5%. Postoperative cranial MRI at 3 months showed no residual tumor, and 1-year follow-up revealed no tumor recurrence. Regular pediatric follow-up confirmed the infant’s growth and development were consistent with age-matched norms.\u003c/p\u003e\n\u003cp\u003eConclusion\u003c/p\u003e\n\u003cp\u003ePregnancy-associated upregulation of progesterone may be a key factor driving the progression of PR-positive CCM, and the fragile vascular structure of CCM combined with pregnancy-induced hypervolemia and intracranial pressure fluctuations may contribute to intratumoral hemorrhage. MDT-coordinated staged intervention, involving cesarean section followed by definitive neurosurgical resection, is the optimal management strategy for such rare cases, which can effectively balance maternal and fetal safety and achieve favorable long-term oncological outcomes. Long-term regular follow-up is essential for CCM patients due to the tumor’s high recurrence rate.\u003c/p\u003e","manuscriptTitle":"WHO Grade Ⅱ Clear Cell Meningioma with Obstructive Hydrocephalus and Intratumoral Hemorrhage in a 24-Year-Old Primipara During Late Pregnancy: A Case Report and Clinical Implications ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-07 07:24:34","doi":"10.21203/rs.3.rs-9032253/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-05T04:13:26+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-31T19:20:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"170985561608487532318508740850670660052","date":"2026-03-31T03:08:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"88369811600973848456094464845861854170","date":"2026-03-29T09:57:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"276398508666133986170065151079160812600","date":"2026-03-28T21:01:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-28T20:36:53+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-20T09:58:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-14T19:08:40+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-11T19:46:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Medicine","date":"2026-03-11T12:55:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)","snPcode":"44337","submissionUrl":"https://submission.springernature.com/new-submission/44337/3","title":"Discover Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"07ffe612-3921-4731-baf8-07f9f4351dbf","owner":[],"postedDate":"April 7th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-07T07:24:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-07 07:24:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9032253","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9032253","identity":"rs-9032253","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}