Secondary CNS lymphoma

59-year-old male presenting with first occurrence of generalized tonic-clonic seizure. Patient had a history of mantle cell lymphoma 2-years prior and was on maintenance therapy.

Initial imaging consisted of a CT, which showed an ill-defined, gyriform hyperdense intra-axial lesions in the medial left temporal and occipital lobes with mild midline shift. Delayed postcontrast images demonstrated irregular peripheral enhancement of the hyperdense lesion with some associated white matter hypodensity.

An MRI was performed with multiplanar T2 sequences, followed by FLAIR, diffusion-weighted imaging, and pre- and post-contrast T1 images. The lesion showed T1 hypointensity with leptomeningeal enhancement that extended into the parahippocampal region. T2 and FLAIR imaging showed gyriform heterogeneous hyperintensity in the left occipital, temporal and parahippocampal areas, with associated cortical thickening and an 8mm hyperintense cystic area within the lesion. DWI showed mild signal hyperintensity in the region, with corresponding intermediate values on ADC.

Background

Secondary CNS lymphoma (SCNSL) occurs when primary lymphoma spreads to the leptomeninges, brain parenchyma or spinal cord, and can either be present at the time of initial diagnosis or recurrence. Most cases are due to non-Hodgkin lymphoma, and incidence depends on the aggressiveness of the primary lymphoma, with rates of 3%, 9% or 27% for indolent, aggressive or highly aggressive variants, respectively [1]. SCNSL typically occurs 6-12 months after initial diagnosis [2]. It occurs as an isolated recurrence in 50% of cases, and most develop systemic lymphoma over the next several months [1].

Clinical perspective

Symptoms develop over days to weeks and reflect the location of the underlying lesion. Common presenting symptoms are headache, cranial nerve palsies, altered mental status, and, less frequently, seizures and coma [1]. Hydrocephalus is frequently seen with leptomeningeal disease.

Imaging features

CT appearance of SCNSL is iso/hyperintense, typically located supratentorially abutting an ependymal surface, and can be mainly parenchymal, leptomeningeal, or a combination of both with solitary or multiple lesions [3]. Historically, lesions were thought to be 2/3rds leptomeningeal and 1/3rd parenchymal, but recent studies report parenchymal disease in up to 85% of cases [3]. On contrast CT, there is homogenous enhancement with possible cranial nerve involvement.

Contrast-enhanced MRI is the best modality to evaluate SCNSL, which presents with abnormal homogenous enhancement in immunocompetent patients, and more heterogenous enhancement in immunocompromised patients [2, 4]. The lesions appear as T1WI hypo/isointense. T2WI have variable intensity and are often hypointense to grey matter [2]. T2 FLAIR imaging shows a hyperintense lesion surrounded by oedema, and DWI demonstrates diffusion restriction [2]. MR-spectroscopy can help differentiate SCNSL from other diagnoses with similar appearances, as SCNSL is hypermetabolic with an elevated choline peak [2]. Lumbar punctures are useful for confirming the diagnosis.

Outcome

SCNSL has a poor prognosis, with median survival of 3-5 months without treatment. Most patients either have systemic disease at the time of CNS involvement or will subsequently develop it within months [1, 2]. The mainstay of treatment is chemotherapy with IV methotrexate and cytarabine, which can cross the blood-brain barrier, or intrathecal therapy [1]. Consolidative autologous stem-cell transplants are often performed after induction [5]. If there is systemic disease, typical regiments such as R-CHOP can be added. Radiation can be used for palliative purposes [1]. Novel agents such as BTK inhibitors, Bcl-2 antagonists and CAR-T therapy have been used in refractory cases [5].

All patient data have been completely anonymised throughout the entire manuscript and related files.