Deep within the intricate architecture of the human brain lie four interconnected cavities known as the ventricles. These essential fluid-filled chambers facilitate the circulation of cerebrospinal fluid (CSF), which cushions neural tissues, removes metabolic waste, and delivers vital nutrients. While these ventricles serve critical physiological roles, they can in rare and alarming instances become the origin of aggressive malignancies. Primary central nervous system lymphoma (PCNSL), a highly malignant tumor typically found in brain parenchyma, has been observed to sporadically infiltrate the ventricular system, presenting unique clinical and pathological challenges. A recent comprehensive analysis led by Professor Xuejun Li from Central South University, China, sheds new light on the elusive characteristics and therapeutic implications of PCNSL when localized within the ventricular compartments.
PCNSL is a subtype of extranodal non-Hodgkin lymphoma that is confined to the brain, spinal cord, leptomeninges, or eyes, without systemic involvement at presentation. Its occurrence in the ventricles is notably rare, leading to limited collective clinical data and a paucity of systematic studies. Recognizing this knowledge gap, Prof. Li and his team embarked on a meticulous retrospective review involving 51 PCNSL cases with ventricular involvement, comprising 29 newly identified patients and 22 cases documented in prior literature. This expansive dataset offers an unprecedented opportunity to decode the clinical presentations, radiological fingerprints, pathological markers, and treatment responses associated with ventricular PCNSL.
Patients affected by ventricular PCNSL exhibited a median age of 53 years and a predominance of male patients. Symptomatically, the clinical picture diverged somewhat from typical PCNSL presentations elsewhere in the brain. The most prevalent complaint was persistent headache, which underscores the impact of mass effect and resultant intracranial pressure fluctuations within the ventricular system. Patients also reported dizziness, nausea, and deficits in vision and memory, along with limb weakness, emphasizing the multifocal neurologic dysfunction caused by tumor invasion or local edema. These symptoms are reflective of the ventricles’ deep midline location and their proximity to critical neuroanatomical structures that govern sensorimotor and cognitive functions.
Magnetic resonance imaging (MRI), a cornerstone in neuro-oncology diagnostics, revealed distinctive yet somewhat variable imaging traits of ventricular PCNSL. On T2-weighted sequences, the lesions predominantly appeared iso- to hypointense, with occasional hyperintensity in rare cases. Contrast-enhanced imaging consistently demonstrated robust enhancement coupled with peritumoral edema, hallmark signs of aggressive neoplastic behavior and disruption of the blood-brain barrier. Strikingly, features such as necrosis, cystic changes, or calcifications commonly seen in other brain tumors were absent, suggesting a relatively uniform tumor pathology. The median tumor size was substantial at 5.21 cm, and consequential obstructive hydrocephalus was identified in multiple patients, owing to tumor-induced blockage of CSF flow pathways.
From a molecular standpoint, immunohistochemical profiling provided critical insights into tumor biology. High positivity rates for BCL-2 and BCL-6 proteins – at 45.45% and 64.29% respectively – indicated active regulation of apoptosis and germinal center B-cell lineage traits, consistent with aggressive large B-cell lymphoma phenotypes. Furthermore, an elevated median Ki-67 proliferation index of 80% confirmed the marked mitotic activity and rapid cellular turnover characteristic of PCNSL, underscoring the tumor’s highly proliferative and invasive nature within the ventricular milieu.
When evaluating prognostic determinants, the study identified patient age exceeding 60 years and female gender as significant predictors of diminished survival outcomes. Remarkably, neither the choice of surgical intervention—ranging from gross tumor resection to stereotactic biopsy—nor the type of chemotherapy administered showed a statistically significant correlation with overall prognosis. This suggests that intrinsic host factors and tumor biology weigh more heavily on disease trajectory than treatment modality alone. Standard therapeutic approaches predominantly involved high-dose methotrexate-based chemotherapy, often preceded by surgical biopsy, reflecting current front-line armamentarium against PCNSL.
The study’s conclusions hold profound clinical implications. Despite the rare occurrence of PCNSL in the ventricles, the tumor’s biological behavior, radiologic characteristics, and pathological hallmarks largely parallel those observed in conventional PCNSL affecting cerebral parenchyma. Hence, treatment strategies applied universally for PCNSL remain applicable and effective for ventricular variants, reaffirming the role of methotrexate-centered chemotherapeutic protocols complemented by carefully considered surgical interventions tailored to individual patient factors.
This investigation not only enriches the scarce literature on ventricular PCNSL but also serves as a pivotal reference point for neuro-oncologists grappling with diagnostic and therapeutic dilemmas posed by these atypical tumor locations. The nuanced understanding of clinical manifestations and MRI features aids in earlier and more precise diagnosis, potentially mitigating the risk of delayed or misdirected treatment. Concurrently, molecular profiling fosters a glimpse into the pathogenetic mechanisms at play, opening avenues for targeted therapies and personalized medicine.
The research underscores the vital necessity for global collaborative efforts to aggregate and analyze rare tumor variants through multicenter studies and registries. Such endeavors can illuminate subtle variations in tumor biology and clinical response, catalyzing advancements in diagnostic accuracy and therapeutic efficacy. As emerging imaging technologies and molecular diagnostics evolve, integrating them into studies of ventricular PCNSL promises to refine prognosis and optimize patient management strategies.
In synthesizing a comprehensive clinical portrait of ventricular PCNSL, Prof. Li’s team provides clinicians with pragmatic evidence that bridges existing gaps, enabling data-driven decision-making for an otherwise elusive and formidable disease entity. Their work reinforces the principle that although anatomical rarity may challenge diagnostic vigilance, it does not necessarily mandate deviation from established oncologic principles. Ultimately, this study exemplifies rigorous scientific inquiry translating into enhanced patient care and underscores the resilience of multidisciplinary approaches in conquering complex neuro-oncological disorders.
As research continues to evolve, ongoing scrutiny of therapeutic outcomes and integration of novel treatment modalities such as immunotherapy and radiotherapy will be essential to improve survival and quality of life for patients facing ventricular PCNSL. Innovations in minimally invasive neurosurgical techniques also promise to ameliorate procedural risks and expand treatment options for these deep-seated tumors. Together, this collective progress offers renewed hope in confronting one of the most challenging facets of central nervous system malignancies.
Subject of Research: People
Article Title: Clinical characteristics and prognosis of ventricular primary central nervous system lymphoma: a case series and literature review
News Publication Date: 10-Oct-2025
Web References:
- DOI link: 10.1186/s41016-025-00410-w
Image Credits: Dr. Xuejun Li from Central South University, China
Keywords: Health and medicine, Clinical medicine, Diseases and disorders, Health care, Human health, Life sciences, Organismal biology, Tumor cells, Brain tumors, Cancer, Lymphoma, Medical treatments
