BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive malignancy of predominantly B-cell origins. Where tolerated, strong sensitivity is seen with induction regimens containing high-dose methotrexate and rituximab. However, little is known regarding ideal therapy for T-cell variants, especially anaplastic large cell lymphoma.
CASE REPORT: A 20-year-old male with no past medical history developed progressive positional headaches, nausea, and dizziness over several months. Between several hospital visits, he was found to have enhancing lesions of his right caudate, left cerebellum, and right frontal lobe. A lumbar puncture demonstrated pleocytosis (152 WBC, 97% lymphocytes) and a small population of atypical CD5- T-cells on flow cytometry. Preliminary biopsy of the right caudate lesion was inconclusive, significant only for demyelination and a subset of LGL-like T-cells expressing CD3 and TIA-1. Neurology was consulted and he was given high-dose methylprednisolone with significant improvement in his symptoms. However, several months later he returned to the emergency department with new headaches, vomiting, and bilateral nystagmus. A repeat brian MRI showed lesion progression and evidence of hydrocephalus. He received hypertonic saline prior to external ventricular drain placement. Once stabilized, he underwent an uncomplicated left retrosigmoid craniotomy with resection of his cerebellar lesion. Histopathology demonstrated strong CD30 and ALK1 expression, with atypical mature T-cells on flow cytometry (CD4+, CD8+, CD5-). PET/CT imaging, bone marrow biopsy, and an ophthalmologic slit lamp exam were without evidence of systemic disease. He was given a diagnosis of PCNSL of T-cell origin (ALK+ anaplastic large cell subtype) and discharged on a dexamethasone taper. After surgical recovery he was started on induction chemotherapy with high-dose methotrexate, procarbazine, and vincristine (MPV). Interval MR imaging demonstrated marked decrease in the size of his intracranial lesions. He was subsequently transitioned to consolidation with HiDAC with the intent to undergo autologous hematopoietic cell transplant.
CONCLUSIONS: Incidence of ALK-positive anaplastic large cell PCNSL is extremely rare, and thus consensus data regarding optimal treatment is lacking. For younger patients with good functional status and renal clearance, induction therapy containing high-dose methotrexate (i.e. MPV) can provide an effective bridge to consolidation and autologous hematopoietic cell transplant.
