Primary Leptomeningeal Lymphoma: Clinicopathologic Features of 2 Rare Phenotypes

J Neuropathol Exp Neurol. 2022 Nov 16;81(12):1002-1007. doi: 10.1093/jnen/nlac084.


Primary leptomeningeal lymphoma is exceedingly rare. We describe 2 rare lymphoma cases with exclusive leptomeningeal disease: 1 ALK-positive (ALK+) anaplastic large cell lymphoma (ALCL) and 1 primary effusion lymphoma (PEL). Case 1: A 19-year-old man presented with symptoms concerning for leptomeningitis. Cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis. Spine MRI demonstrated pial enhancement from T10 through the conus medullaris and cauda equina enhancement/thickening. A biopsy showed leptomeningeal involvement by large lymphoma cells with hallmark cells and brisk mitotic activity. By immunohistochemistry, cells were CD7/CD30-positive with cytoplasmic ALK staining. No systemic disease was identified. The diagnosis of primary leptomeningeal ALK+ ALCL was made. Despite 2 CSF relapses requiring systemic therapy and autologous bone marrow transplant, the patient was in complete clinical remission 9 years after the diagnosis. Case 2: A 60-year-old, human immunodeficiency virus-positive man presented with symptoms suggestive of leptomeningitis. Brain MRIs revealed multifocal, supratentorial, and infratentorial leptomeningeal enhancement. A right frontal biopsy demonstrated leptomeningeal involvement by large lymphoma cells negative for B-cell immunostains, but CD138, MUM-1, and HHV8-positive, with aberrant CD3 expression. EBV-encoded RNA in situ hybridization was positive. In absence of solid lesions/extracranial involvement, the diagnosis of leptomeningeal PEL was rendered. Despite initial complete remission after chemotherapy, the patient died 9 months later.

Keywords: ALK-positive anaplastic large cell lymphoma; Central nervous system lymphoma; Immune-privileged sites; Immunodeficiency; Leptomeninges; Primary effusion lymphoma.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Anaplastic Lymphoma Kinase / genetics
  • Humans
  • Lymphoma, Large-Cell, Anaplastic* / diagnosis
  • Lymphoma, Large-Cell, Anaplastic* / genetics
  • Lymphoma, Large-Cell, Anaplastic* / pathology
  • Male
  • Meningeal Neoplasms* / diagnostic imaging
  • Meningeal Neoplasms* / pathology
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Phenotype
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / therapeutic use
  • Young Adult


  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases