DLBCL-CNS are all primary intracerebral or intraocular lymphomas. Lymphomas of the dura, intravascular large B-cell lymphoma, lymphoma with evidence of systemic disease or secondary lymphomas, and all immunodeficiency-associated lymphomas are excluded (Swerdlow, et al ,2008).

Expression or absence of chemokines and chemokine receptors or cytokines may contribute to the specific location of DLBCL-CNS. Tumor cells and endothelial cells may interact via activation of IL4 to creats a favourable microenvironment for tumor growth. DLBCL-CNS show a restricted homing to the main immune sanctuaries (brain, eyes and testis) (Swerdlow, et al ,2008). DLBCL-CNS expresses CD20. CD22 or CD79a. CD10 expresses in about 10-20% cases, whereas bcl6 in 60-80% and IRF4/MUM1 in 90%. Approximately 90% of cases show a non-germinal center immunophenotype (CD10-, Bcl6+/-, MUM1+) (Swerdlow, et al ,2008. Bacon, et al.2009).

The incidence of DLBCL-CNS has been increasing and it accounts for 4% of primary brain tumors and only 2-4 % of intracranial neoplasms. The median age is approximately 60 years, and there is a slight preponderance of male patients (Swerdlow, et al ,2008. Patrick, 2015).

DLBCL-CNS commonly presents with either focal neurological deficits (50-80%) or progressive neurocognitive dysfunction (20-30%). In patients who present with acute neurological symptoms, a noncontrast head CT can be unremarkable, and occasionally, hypodense areas can be mistaken for ischemia. The diagnosis of PCNSL is usually not entertained until a contrast- enhanced MRI is performed and reveals a homogenously enhancing mass in the deep white matter or corpus callosum. Typical radiologic features include lesion location adjacent to the cerebrospinal fluid (CSF) space (Swerdlow, et al ,2008. Ferry , 2008. Bacon, et al.2009).

Morphologically, CNS-DLBCL are diffuse infiltrates of centroblasts or immunoblasts, with a tendency to cluster around cerebral blood vessels, often accompanied by small reactive T cells and reactive accessory cells. There is often marked tumour necrosis, especially following the administration of corticosteroids. The Ki67-proliferation fraction is typically high. NS-DLBCL presenting in immunosuppressed individuals is often EBV-positive. CNS-DLBCL must be differentiated from secondary CNS involvement by systemic DLBCL, for which the involvement of multiple extranodal sites or specific extranodal sites such as the testis and sino-nasal cavity is a risk factor.

Although treatment with radiotherapy alone leads to an initial response, disease recurrence is higher when compared to extranodal systemic non- Hodgkin lymphoma .CHOP produces notable imaging responses but no durable disease control .High-dose methotrexate chemotherapy followed by whole brain radiation therapy is regarded as the standard therapy with a response rate of 35-65% (Swerdlow, et al ,2008. Patrick, 2015).

Despite recent advances in treatment and significant improvement in complete remission rates, 35-60 % of PCNSL patients will relapse, usually within the first 2 years from diagnosis; 10-15 % will be refractory to treatment. In primary DLBCL-CNS, there was no significant difference in median overall survival (OS) between the wild type and mutated MYD88 cases, or between methylated and unmethylated MGMT cases. However, a significant difference was noted in median OS between the wild type and mutated CD79B cases (Zheng, et al, 2017. Swerdlow, et al ,2008. Patrick, 2015).