Prognostic markers for immunodeficiency-associated primary central nervous system lymphoma

  • Leon D. Kaulen
  • Daniela Galluzzo
  • Pei Hui
  • Frank Barbiero
  • Philipp Karschnia
  • Anita Huttner
  • Robert Fulbright
  • Joachim M. BaehringEmail author
Clinical Study



Immunodeficiency is a major risk factor for primary central nervous system lymphoma (PCNSL), but data on the disease in immunocompromised hosts are scarce. We aimed to define clinical and imaging features and determine prognostic factors for immunodeficiency-associated PCNSL.


All PCNSL cases seen at Yale-New Haven Hospital between 2002 and 2017 were retrospectively screened for immunodeficiency. For patients with immunosuppression, biopsies were evaluated and clinical data were collected. Predictors of survival were identified using Kaplan–Meier survival analysis and log-rank test. p values < 0.05 were considered significant.


23 patients with immunodeficiencies were identified: eleven on immunosuppressants after solid organ transplantation, seven with human immunodeficiency virus infection, and five on immunosuppressive treatment due to various autoimmune disorders. PCNSL cases were largely Epstein-Barr-Virus positive (78%), histologically classified as diffuse large B cell lymphomas (87%), and showed peripheral contrast enhancement (81%) and corresponding heterogeneous diffusion-weighted imaging patterns (DWI) on magnetic resonance imaging (MRI) (71%). Median overall survival was 31 months. Age > 60 years at diagnosis (p < 0.01), peripheral enhancement of the mass on MRI (p = 0.04), heterogeneous DWI patterns (p = 0.04), and clonal immunoglobulin heavy chain gene rearrangement (IgHR) (p = 0.03) were found to be negative prognostic markers.


Immunodeficiency-associated PCNSL presents with similar clinical, pathological and imaging features. Age > 60 years, clonal IgHR, heterogeneous DWI pattern and peripheral enhancement on MRI may serve as predictors of less favorable outcome.


Primary central nervous system (CNS) lymphoma Organ transplantation HIV Autoimmune diseases Immunosuppression Diffusion-weighted imaging Gene rearrangement 



The abstract was previously presented at the 2017 annual meeting of the Society of Neuro-Oncology and was published in Neuro-Oncology, Volume 19, Issue suppl_6, Pages vi212.

Author contributions

LDK and JMB designed the study, analyzed and interpreted data, and drafted the manuscript. LDK and FB acquired patient records. DG carried out ADC measurements. PH conducted immunoglobulin G heavy chain rearrangement analysis. AH provided pathological evaluation and review. RF oversaw ADC measurements and provided radiological review. All authors critically revised, read and approved the final manuscript.

Compliance with ethical standards

Conflict of interests

Authors declare that they have competing interest.

Supplementary material

11060_2019_3208_MOESM1_ESM.docx (18 kb)
Supplementary material 1 (DOCX 17 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeurologyYale School of MedicineNew HavenUSA
  2. 2.Department of PathologyYale School of MedicineNew HavenUSA
  3. 3.Department of Radiology and Biomedical ImagingYale School of MedicineNew HavenUSA
  4. 4.Department of NeurosurgeryYale School of MedicineNew HavenUSA
  5. 5.Departments of Neurology and Neurosurgery, Section of Neuro-OncologyYale School of Medicine, Yale Cancer CenterNew HavenUSA

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