The first reported case of unclassifiable CD20-negative diffuse large B-cell lymphoma located in the central nervous system (CNS) has been recently published in BMC Neurology.

Primary CNS lymphomas are a rare entity, accounting for less than 2% of non-Hodgkin lymphomas; DLBCL accounts for the great majority of cases. The B-cell antigen marker CD20 is a hallmark of DLBCL, being present in over 98% of cases. The rare CD20-negative DLBCL is characterized by resistance to immunochemotherapy and a poor prognosis.

Read more about DLBCL etiology

“Here, we report the first case of CD20-negative DLBCL originating in the CNS,” the authors wrote.

The case was that of a 54-year-old female who was admitted for a headache lasting 10 days; further questioning revealed the absence of B symptoms. Physical examination was remarkable for poor speech. Complete blood cell count and levels of lactate dehydrogenase and albumin were normal at the time of admission. 

However, computed tomography and magnetic resonance imaging revealed a 3.1×2.7×2-cm mass in the right temporal lobe compressing the right lateral ventricle and the third ventricle. Magnetic resonance spectroscopy indicated malignancy.

The tumor was surgically removed. The macroscopic pathology analysis reported gray-white matter on the surface with an area of broken gray-white tissue. Microscopic examination revealed abundant large lymphoid cells with no lymphoid follicle structures, as well as tumor interstitial microvascular infiltration. The findings led to the diagnosis of lymphoma.

Immunohistochemical analysis was suggestive of B-cell involvement, and further analysis ruled out a germinal origin and astrocytes and oligodendrocytes as possible origins. 

Taking into account these data and the finding of Ki-67 positivity, a diagnosis of DLBCL was made. CD20 negativity was initially assumed to be a technical error. However, a positive control proved the tissue to be CD20 negative. Additional immune indicators were all negative, and the patient was diagnosed with CD20-negative CNS DLBCL.

The disease progressed rapidly despite rounds of chemotherapy, and the patient died 4 months after the initial diagnosis.

“Novel treatment strategies that are based on a comprehensive understanding of the genetic mechanisms of unclassified DLBCLs are urgently required,” the authors concluded. 


Luo S, Huang X, Li Y, Wang J. Primary central nervous system CD20-negative diffuse large B-cell lymphoma: a case report. BMC Neurol. Published online December 29, 2022. doi:10.1186/s12883-022-03031-3