J Neurooncol (2015) 125:219–221 DOI 10.1007/s11060-015-1879-x
LETTER TO THE EDITOR
Prevalence of hepatitis B virus in primary central nervous system lymphoma G. Faivre1 • V. Thibault2 • M. L. Tanguy3 • V. Leblond4,5 • S. Choquet4,5 C. Soussain6 • A. Gonzalez-Aguilar1 • M. Sierra del Rio1,7 • C. Houillier1 • K. Hoang-Xuan1,8,9,10,11 • A. Idbaih1,8,9,10,11
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Received: 11 December 2014 / Accepted: 4 August 2015 / Published online: 14 August 2015 Ó Springer Science+Business Media New York 2015
To the Editor, Primary Central Nervous System Lymphoma (PCNSL) is most often non-Hodgkin lymphoma diffuse large B cell lymphoma (NHL-DLBCL) confined exclusively to the central nervous system. Its pathogenesis remains unknown in immunocompromised patients. Recent studies pointed out that systemic NHL, especially B cell NHL, might be associated with Hepatitis B virus (HBV) [1, 2]. We thus reported the prevalence of HBV in immunocompetent patients with PCNSL and search for a possible association. We included 109 patients treated for PCNSL in our department in Paris, France, from 2002 to 2012. The inclusion criteria were: (i) aged C18 years, (ii) pathologically documented diagnosis of ocular or cerebral DLBC-PCNSL, (iii) HIV seronegative and (iv) available HBV serology. The control population included 319 patients treated in the same
Electronic supplementary material The online version of this article (doi:10.1007/s11060-015-1879-x) contains supplementary material, which is available to authorized users. & A. Idbaih
[email protected] G. Faivre
[email protected] 1
2
3
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AP-HP, Groupe Hospitalier Pitie´-Salpeˆtrie`re, Service de Neurologie 2-Mazarin, 47 Boulevard de l’Hoˆpital, 75651 Paris Cedex 13, France AP-HP, Groupe Hospitalier Pitie´-Salpeˆtrie`re, Laboratoire de Virologie, Paris, France AP-HP, Groupe Hospitalier Pitie´-Salpeˆtrie`re Unite´ de recherche clinique, Paris, France
Department, from 1993 to 2011, for other primary brain tumors (PBT) and with available HBV serology. We compared prevalence of HBsAg, anti-HBc and anti-HBs between these populations using a Fischer’s test (STATA 8.0, Woolf test). We also compared prevalence of HBsAg and anti-HBc in the PCNSL group to the French and greater Paris’ area (GPA) populations using an exact test based on binomial probability function [3]. The characteristics of the PCNSL and the PBT populations are reported in Table 1. Prevalence of HBsAg was greater among the PCNSL patients than within the French population (p = 0.01) and the GPA population (p = 0.02). In addition, prevalence of anti-HBc in the PCNSL patients was higher than within the French population (p = 0.01). Although no statistically significant difference was found between PCNSL and PBT patients (p = 0.49 regarding HBsAg, p = 0.10 regarding anti-HBc and p = 0.23 regarding anti-HBs), a trend for a positive association between HBV and PCNSL was highlighted. Regarding active (p = 0.49) and past infections (p = 0.10) and
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UPMC-GRC11-GREChy hoˆpital Pitie´ Salpeˆtrie`re APHP, 75013 Paris, France
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CLCC Hoˆpital Rene´ Huguenin - Institut Curie, Service d’He´matologie, Saint-Cloud, France
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Hospital Regional de Alta Especialidad del Bajio, Leo´n, Guanajuato, Mexico
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Sorbonne Universite´s, UPMC Univ Paris 06, UM 75, 75013 Paris, France
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Inserm, U 1127, ICM, Paris, 75013 Paris, France
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CNRS, UMR 7225, ICM, Paris, 75013 Paris, France
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ICM, 75013 Paris, France
AP-HP, Groupe Hospitalier Pitie´-Salpeˆtrie`re, Service d’He´matologie, Paris, France
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vaccination status (p = 0.11) between the PCNSL and the PBT populations, the results were not statistically significant. Our study points out a potential association between HBV and PCNSL. Similarly to previous studies including systemic NHL, HBsAg prevalence was higher in PCNSL patients than in national or regional populations. Indeed, regarding HBsAg, Marcucci [1] and Wang [2] reported an OR at 3.67 CI 95 % [1.75–7.66] and at 2.3 CI 95 % [1.4–2.6] in NHL-B respectively. Regarding anti-HBc, the OR were 1.28 CI 95 % [0.92–1.78] [1] and 1.8 CI 95 % [1.4–2.2] [2]. Exploring chronic active or chronic inactive infections and carrier status was not conclusive [1]. Note
that only a few of these studies were based on prevalence of HBV in the national population. PCNSL is rare, which may have decreased the power of our study. Indeed, other studies including systemic NHL patients enrolled a larger number of patients, resulting in more significant results [2]. In addition, prevalence of HBV in France is very low, compared to those in Italy or Eastern countries where most relevant studies were conducted [1, 2]: HBsAg prevalence was 5.6 % in the Italian control population [1] compared to 0.65 % in France in 2004 [3]. Interestingly, no difference was found between the PCNSL and the PBT patients. However, when we compared the PBT population to the national and regional populations,
Table 1 Characteristics of PCNSL, Primary Brain Tumor, France and great Paris’ area populations and HBV markers prevalence in those populations PCNSLa (n = 109)
PBT (n = 319)
Franceb (n = 14,416)
GPAb (n = 2225)
Female n (%)
49 (45.0 %)
101 (31.7 %)
7,339 (51 %)
NA
Male n (%)
60 (55.0 %)
218 (68.3 %)
7,077 (49 %)
NA
Sex
Age Median age (Range) \50 years C50 years
62 years (16–84)
49 years (19–83)
NA
NA
16 (14.7 %) 93 (85.3 %)
165 (51.7 %) 154 (48.3 %)
5377 (n = 37 %) 9039 (n = 63 %)
NA NA
Histology DLBCL, n (%)
109 (100 %)
NA
NA
NA
Glioma n (%) [including grade IV, n (%)]
NA
290 (90.9 %) [113 (35.4 %)]
NA
NA
Medulloblastoma, n (%)
NA
10 (3.1 %)
NA
NA
Other PBT, n (%)
NA
19 (6.1 %)
NA
NA
HIV?, n (%)
0 (0.0 %)
0 (0.0 %)
NA
NA
HCV?, n (%)
0 (0.0 %)
5 (1.6 %)
122 (0.84 %)
24 (1.09 %)
HBsAg, n (%)
3 (2.75 %)
7 (2.19 %)
0.65 %
0.8 %
Anti-HBc, n (%)
15 (13.76 %)
28 (8.78 %)
7.3 %
10.77 %
Serology
HBV serology
Anti-HBs, n (%)
31 (28.48 %)
105 (32.92 %)
NA
NA
Active infection
3 (2.75 %)
7 (2.19 %)
NA
NA
Past infection Vaccinated
12 (11.01 %) 23 (21.10 %)
21 (6.58 %) 88 (27.59 %)
NA NA
NA NA
Other PBT included 1 neurocytoma, 2 pinealoblastomas, 1 non specified pineal tumor, 1 neurinoma, 1 germ cell tumor, 7 ependymomas, 2 primitive neuro-ectodermal tumors, 3 ganglioglioma and 1 meningioma; NA, not applicable or not available. Patients suffering from secondary CNS lymphoma or brain metastases were excluded from PBT HBsAg. HBs antigen; anti-HBs, antibodies against HBsAg; anti-HBc, antibodies against a core antigen HBV serologic markers were assessed in the Virology laboratory, using AXSYM or ARCHITECT immunohistochemistry systems (Abbott, Rungis, France) Active infection, HBsAg ?/anti-HBc ?/anti-HBs-; Past infection, HBsAg-/anti-HBc ?/anti-HBs ? or HBsAg-/anti-HBc ?/anti-HBs-; Vaccinated, HBsAg-/anti-HBc-/anti-HBs? PCNSL primary CNS lymphoma, PBT primary brain tumor, n number, GPA greater Paris’ area, DLBCL diffuse large B-cell lymphoma a
Most of our patients come from the greater Paris’ area (GPA) called Ile-de-France
b
Prevalence of Hepatitis B and C in France and in the GPA were calculated based on a sample of the populations [3]
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HBsAg were also higher in the PBT group (2.19 vs. 0.65 %, p = 0.0006 and 2.19 vs. 0.8 %, p = 0.01 respectively), suggesting a selection bias or that these two populations might not have been different. Hepatitis B prevalence varies based on gender and age. Indeed HBsAg and anti-HBc are more common in men (1.1 % versus 0.21 % in women regarding HBsAg; 8.33 % versus 6.33 % in women regarding anti-HBc) [3]. Moreover, HBsAg is more common in young people and antiHBc in the elderly [3]. The PBT population had more men and was younger than the other populations and PCNSL patients were much older, which may have interfered with our results. Besides, most of our patients in PCNSL and PBT populations were on steroids or on chemotherapy, which may have modified the serologic results. CD4? lymphocytes count had been reported to be low in patients with gliomas and treated by radiotherapy and/or chemotherapy and/or steroids. Thus, further larger prospective studies should be conducted to investigate this hypothetic link between HBV and PCNSL. Impact of HBV and antiviral drug effects on PCNSL patients’ outcome could also be reported. Finally, screening HBV by PCR in brain biopsy of PCNSL patients or in the CSF might provide novel insights.
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To conclude, HBsAg and anti-HBc were higher in the PCNSL population than in the French population, and HBsAg was more frequently detected in the PCNSL patients compared to the GPA population. These findings add to the data previously reported regarding HBV and PCNSL but warrant further larger prospective investigations. Acknowledgements LOC network (INCa) and the program ‘‘Investissements d’avenir’’ ANR-10-IAIHU-06T supported this study. Institut Universitaire de Cance´rologie (IUC). Compliance with ethical standards Disclosure
None.
References 1. Marcucci F, Mele A, Spada E et al (2006) High prevalence of hepatitis B virus infection in B-cell non-Hodgkin’s lymphoma. Haematologica 91:554–557 2. Wang F, Xu RH, Han B et al (2007) High incidence of hepatitis B virus infection in B-cell subtype non-Hodgkin lymphoma compared with other cancers. Cancer 109:1360–1364 3. Sanitaire IdV (2004) Prevalence des hepatites B et C en France en 2004
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