Primary Central Nervous System Lymphoma: Understanding End-Stage Symptoms and Disease Progression

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of non-Hodgkin lymphoma that originates within the brain, spinal cord, or eyes. Unlike more common brain tumors such as gliomas or metastatic cancers, PCNSL primarily affects the central nervous system without systemic involvement. One of the hallmark features of this condition is the development of significant peritumoral edema—swelling around the tumor mass—which contributes to a gradual and often relentless increase in intracranial pressure.

Common Neurological Symptoms in Advanced Stages

As the disease progresses, patients typically experience worsening intracranial pressure, leading to persistent and severe headaches, nausea, and projectile vomiting—classic signs of elevated pressure within the skull. These symptoms are not only distressing but also indicate serious underlying neurological compromise. The location of the tumor plays a critical role in determining additional neurological deficits. For instance, lesions in motor regions of the brain may result in progressive limb weakness, eventually progressing to hemiparesis or even full paralysis on one side of the body.

Seizures and Visual Impairment

In addition to motor dysfunction, many individuals suffer from epileptic seizures due to abnormal electrical activity triggered by tumor infiltration. Visual disturbances are also prevalent, with some patients developing partial or complete loss of peripheral vision—known as visual field defects—especially when the occipital lobes or optic pathways are involved.

Cognitive and Psychiatric Manifestations

One of the distinguishing aspects of PCNSL is its early and profound impact on cognitive function. Patients frequently exhibit progressive intellectual decline, memory impairment, confusion, and behavioral changes that resemble dementia. These neuropsychiatric symptoms can emerge earlier and be more pervasive compared to other brain tumors like glioblastoma or metastatic lesions. Mood disturbances, personality shifts, apathy, and even psychosis may occur, often complicating diagnosis and management.

This unique combination of cognitive and psychiatric features, especially when occurring in immunocompetent middle-aged or older adults, should prompt clinicians to consider PCNSL in their differential diagnosis. Early recognition is crucial, although these symptoms often worsen despite treatment, reflecting the infiltrative nature of the disease.

Disease Progression and Terminal Phase

As the tumor advances, neurological deterioration becomes more pronounced. Patients may lapse into stupor and eventually fall into a deep coma. Critical complications such as uncal or transtentorial herniation can develop due to severe brain swelling, leading to fixed and dilated pupils—a sign of brainstem compression. Respiratory irregularities follow, culminating in respiratory arrest, while cardiovascular instability leads to cessation of cardiac activity.

The terminal phase of primary CNS lymphoma is marked by global neurological failure, where multiple brain functions shut down progressively. Palliative care becomes essential during this stage to ensure comfort, manage symptoms, and support both patients and families through end-of-life transitions.

Conclusion and Clinical Implications

While advancements in high-dose chemotherapy, targeted therapies, and radiation techniques have improved outcomes for some patients with PCNSL, prognosis remains guarded, particularly in elderly individuals or those with extensive disease burden. Recognizing the characteristic clinical trajectory—including rising intracranial pressure, focal neurological deficits, cognitive decline, and eventual loss of consciousness—is vital for timely intervention and appropriate palliative planning. Ongoing research into immunotherapy and novel drug delivery systems offers hope for future improvements in survival and quality of life.