Indian Journal of Cancer Medknow Publications on behalf of Indian Cancer Society ISSN: 0019-509X EISSN: 1998-4774 Vol. 48, Num. 2, 2011, pp. 199-203

Indian Journal of Cancer, Vol. 48, No. 2, April-June, 2011, pp. 199-203

Original Article

Primary central nervous system lymphoma: A study of clinicopathological features and trend in western India

S Pasricha, A Gupta, J Gawande, P Trivedi, D Patel

Department of Pathology, The Gujarat Cancer and Research Institute (M. P. Shah Cancer Hospital), NCH Campus, Asarwa, Ahmedabad 380 016, Gujarat, India

Correspondence Address: S Pasricha Department of Pathology, The Gujarat Cancer and Research Institute (M. P. Shah Cancer Hospital), NCH Campus, Asarwa, Ahmedabad 380 016, Gujarat India drsunilpasricha@yahoo.com

DOI: 10.4103/0019-509X.82890

Abstract

Keywords: Extra nodal non-Hodgkin′s lymphoma, intracranial tumors, primary central nervous system lymphoma

Introduction

Primary central nervous system lymphoma (PCNSL) are rare form of extranodal non-Hodgkin′s lymphoma presenting in the brain, leptomeninges, eye or spinal cord, without evidence of lymphoma in other parts of body sites. ^[1],[2] In early 1970s, PCNSL was a rare neoplasm, comprising of less than 1% of intracranial tumors (ICT). In the ensuing two decades, the incidence of PCNSL increased more than 10-fold, from 2.5 cases per 10 million population in 1973 to 30 cases per 10 million in 1992. ^[3] By 1990, PCNSL comprised nearly 7% of all primary brain tumors. ^[4] This change in the frequency could be attributed to the acquired immunodeficiency syndrome (AIDS) epidemic that began in 1980s. However, of equal concern was the incidence of PCNSL among the patients without AIDS which showed a similar substantial increase over roughly the same period. This increasing disease incidence among immunocompetent individuals remains unexplained. ^[1],[5] Later reports suggested that the annual incidence of PCNSL appeared to be stabilizing or in fact declining slightly. ^[6] Few studies published from India showed that there has been no increase in the incidence of PCNSL. ^{[2],[7],[8],[9]} This study which is second largest study from India was undertaken to determine the clinicopathological characteristics of PCNSL and to analyze the trend of PCNSL over a period of 13 years at our institute which is a referral cancer hospital.

Materials and Methods

The study comprised of all the cases of histologically proven PCNSL diagnosed at the department of histopathology over a period of 13 years (1997-2009). The neurological tumor tissue for diagnosis was obtained either by stereotactic biopsy or craniotomy. Hematoxylin and eosin (H and E) stained slides were reviewed. Immunohistochemistry (IHC) with leukocyte common antigen (LCA) (Neomarkers, clone AB-3, dilution 1:200), CD20 as a B-cell marker (Neomarkers, clone L26, dilution 1:100), and CD3 as a T-cell marker (Neomarkers, clone SP 7, dilution 1:50) were performed on available formalin-fixed paraffin-embedded blocks using Novolink Max Polymer Detection System (RE 7280-K) from Novocastra (UK). These primary antibodies were obtained from United States of America. The complete clinical details were obtained from patient records. Age, sex, radiological findings, immune status, and human immunodeficiency virus (HIV) serology findings were recorded in every case. To exclude the possibility of secondary involvement by a systemic lymphoma, details pertaining to lymphadenopathy, organomegaly, and bone marrow study were also obtained. CSF findings were recorded whenever available. The total numbers of ICT diagnosed during the same period were also obtained to evaluate the relative incidence. The results were analysed using χ²-test.

Results

Incidence

During the study period of 13 years (1997-2009), a total number of 4715 ICT were diagnosed in the department of histopathology. Out of these, 66 cases were diagnosed as PCNSL. Hence, PCNSL accounted for 1.4% of ICT reported at our institute. On dividing our 13-year study period into two equal intervals (six-and-a-half year each), PCNSL cases showed a rising trend from 23 cases in the first half to 43 cases in the second half [Table - 1]. This increase in the PCNSL cases seems to be approximately two-fold. However, this is accompanied by significant and parallel rise of ICT during the same period. Hence on performing the Pearson′s χ²-test, the rise of PCNSL cases are not statistically significant (P = 0.3398).

Clinical features

The age of the patients ranged from 10 to 75 years (median age: 46 years) with equal male-to-female ratio (1:1). The peak incidence was found in fifth to seventh decades [Figure - 1]. The clinical presentation of the patients is shown in [Table - 2]. Eighty-two percent (54 cases) of the patients presented with the symptoms of increased intracranial tension. The lesion was solitary in 85% (56 cases) and multiple in 15% (10 cases). The majority of the lesions were located in the supratentorial region and frontal lobe was most common location [Figure - 2]. HIV serology findings were available in all the cases, and none of the case was positive. All the patients were treated with modified DeAngelis protocol with initial good response and they eventually lost to follow up.

Histopathology and IHC findings

All the cases showed features of NHL in which tumor cells were disposed in a diffuse sheet pattern or dispersed pattern. The cells were large having vesicular nucleus, 1-3 conspicuous nucleoli and moderate amount of pale to eosinophilic cytoplasm. Perivascular arrangement of the tumor cells was observed in the majority of the cases. IHC was performed in 51 cases and the panel comprised of LCA, CD20, CD2, CD3, and GFAP. When there was a differential diagnosis like metastasis or other round cell tumor, additional markers were given. All the cases (100%) were positive for LCA and CD20 [Figure - 3] and hence classified as diffuse large B-cell lymphoma. CD3 positivity was not elicited in any of the case.

Discussion

This study was undertaken to evaluate the clinicopathological profile of patients diagnosed as PCNSL, to determine the frequency of PCNSL among the ICT at our institute and to compare the trend occurring in other parts of India and other countries. Initial studies from western countries have reported an increased incidence of PCNSL in both immunocompromised and immunocompetent patients. ^{[3],[4],[10],[11],[12]} However, recent reports ^[6] suggested that the annual incidence of PCNSL appeared to be stabilizing or in fact slightly declining. Three previous studies published from India [Table - 3] indicate that the frequency of PCNSL is less than 1.5% among the ICT, and there has been no increase in the incidence of PCNSL. Large-case studies in Japan have reported that PCNSL accounted for 2.4% of all ICT. ^[13],[14] In this study, 66 cases of PCNSL have been diagnosed out of 4715 ICT (1.4%) and there is no statistically significant increase in the PCNSL cases at our institute and this finding is similar to previous studies published from India. ^[2],[7],[8] PCNSL can occur at all ages, but a peak in the sixth and seventh decades has been reported in the western countries among the immunocompetent patients. ^{[5],[15],[16]} In our study, all the patients were immunocompetent and peak incidence was found in fifth to seventh decades with almost equal distribution [Figure - 1]. The median age of the patient in our study was 46 years, which is almost similar to those, observed in other parts of India [Table - 3]. However, this a whole decade earlier than those reported in the west. This has been attributed to the demographic pattern of the Indian population. ^[8] A male preponderance has been reported among the immunocompetent population by many authors. ^{[5],[7],[8],[16]} However, in our study male-to-female ratio was equal (33 cases each). Bataille et al.^[15] analyzed 248 cases of PCNSL in immunocompetent patients and the study involved 121 males and 127 female patients (ratio 0.95:1) and the median age was 61 years (range 2-88 years). Fine et al.^[5] analyzed 792 cases of PCNSL in immunocompetent patients and 315 cases of PCNSL in AIDS patients. The median age of patients with and without AIDS was 30.8 and 55.2 years, respectively. The ratio of male-to-female was 7.38 and 1.35 for the patients with and without AIDS, respectively. In our study, the majority of the lesions was located in the supratentorial region and frontal lobe was the most common site. Sarkar et al.^[8] and Paul et al.^[2] have also reported frontal lobe as the most common location in their study [Table - 3]. In our study, all the cases (100%) were classified as high grade, diffuse large B-cell lymphoma which was the predominant histological type in other studies. ^[8],[9],[15] Our study also confirms the rare occurrence of T-cell lymphoma presenting as PCNSL, which indeed is a consistent finding in many reports. ^{[2],[8],[15],[17],[18]} However, a study of 42 cases of PCNSL done by Choi et al.^[19] from Korea reveals an unusual high incidence (16.7%) of T-cell PCNSL. The reporting authors also found that the T-cell PCNSL presented with certain clinical and pathological features that were distinct from B-cell PCNSL and displayed preponderance of CD8 expression. In our study, CSF findings were available in 48 cases. In only one patient, the tumor cells involved CSF and the lesion was located in the corpus callosum with subependymal spread. In the previous studies from India, ^{[2],[7],[8],[9]} the majority of the PCNSL has been reported in immunocompetent patients and in our study all the cases were immunocompetent with no HIV positive case. Sarkar et al.^[8] had one HIV patient and one patient of renal allograft out of total 186 cases. Paul et al.^[2] had only one HIV patient out of 56 cases. A study done by Powari et al.^[7] revealed that except for two renal transplant recipients, none of the patients had any known immunodeficiency state. They also reported the absence of PCNSL in any of the 75 postmortem cases of renal transplant recipients during their study period. Agarwal et al.^[9] had two HIV positive patients out of 26 reported cases. In fact the frequency of PCNSL in HIV positive patients and in renal transplant recipients in India is very low. Autopsy studies conducted at Mumbai (Western India), by Lanjewar et al., ^[20] did not report any case of PCNSL among 85 AIDS patients. A similar observation was reported by Satishchandra et al.^[21] from Bangalore (South India), where there was no case of PCNSL in 100 HIV positive cases with various neurological disorders. Hence, in spite of significant number of HIV positive cases (prevalence of 2.4 million cases in 2007) in India, ^[22] the incidence of PCNSL in these patients is still very low. The most plausible explanation could be that AIDS patients in India die earlier due to opportunistic infections. ^[20],[21] Although, other lymphomas, including those at extranodal sites seems to occur in India in patients with AIDS, PCNLS are still infrequently reported. ^[2]

Studies from western countries have shown a consistent association of PCNSL occurring in immunocompromised patients with EBV (Epstein-Barr virus); however, it is infrequently associated with EBV in immunocompetent individuals. ^[4],[23] In the present series (66 cases), all the patients were immunocompetent and there was no association of PCNSL with other tumors in any individual.

In conclusion, this study which is the second largest study from India reveals that there has been no significant increase in the incidence of PCNSL over the last 13 years which is similar to the findings in the previous studies from India. ^[2],[7],[8] The PCNSL most commonly affects the middle aged and diffuse large B-cell lymphoma is the dominant histological pattern. Unlike the western countries, the association of PCNSL with HIV/AIDS in India is very low in spite of substantial prevalence of HIV/AIDS cases.

Acknowledgments

The authors thank Dr. P. M. Shah, Honorary Director, Dr. K. M. Patel, Dr. S. N. Shukla, Deputy Directors of The Gujarat Cancer & Research Institute to allow us to publish this original article.

References

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