Differential Diagnosis for PCNSL (Primary Central Nervous System Lymphoma)

Single Most Likely Diagnosis

• Glioblastoma: This is often considered due to its high prevalence among brain tumors and similar presentation with PCNSL, including rapid onset of neurological deficits and mass effect on imaging. However, glioblastoma typically shows more heterogeneous enhancement and necrosis on MRI compared to PCNSL.

Other Likely Diagnoses

• Metastatic Brain Tumors: These can mimic PCNSL in terms of multiple lesions and rapid progression. However, metastases are more likely to have a clear primary source and may show different enhancement patterns.
• Toxoplasmosis: Especially in immunocompromised patients, toxoplasmosis can present with multiple ring-enhancing lesions, similar to PCNSL. However, the clinical context (e.g., HIV/AIDS) and response to empirical treatment can help differentiate.
• Multifocal Glioma: Though less common, multifocal gliomas can present similarly to PCNSL with multiple lesions. The differentiation often relies on histopathological examination.

Do Not Miss Diagnoses

• Cerebral Vasculitis: This condition can present with multiple lesions and enhancement patterns similar to PCNSL but is often associated with systemic symptoms and can be diagnosed through angiography or biopsy. Missing this diagnosis could lead to inappropriate treatment and poor outcomes.
• Infectious Encephalitis: Certain types of encephalitis, especially those caused by herpes simplex virus, can present with focal lesions and must be treated promptly to avoid severe neurological damage or death.
• Progressive Multifocal Leukoencephalopathy (PML): Seen in immunocompromised patients, PML can mimic PCNSL with white matter lesions but has distinct clinical and radiological features, including a lack of mass effect and enhancement.

Rare Diagnoses

• Lymphomatoid Granulomatosis: A rare condition that can involve the CNS and mimic PCNSL, characterized by angiocentric and angiodestructive lymphoproliferative lesions.
• Germinoma: Though typically found in the pineal or suprasellar regions, germinomas can occasionally present in other areas and may mimic PCNSL, especially in young adults.
• Primary CNS Melanocytic Lesions: Rare, pigmented lesions that can mimic PCNSL on imaging but have distinct histological features.

Each of these diagnoses has unique features that can help differentiate them from PCNSL, emphasizing the importance of comprehensive clinical evaluation, imaging, and often, histopathological confirmation.