CD20-negative DLBCL transformation after rituximab treatment in follicular lymphoma: a new case report and review of the literature

Abstract

Rituximab is a monoclonal antibody against the CD20 molecule which is used to treat B-cell lymphomas. In 60% of low-grade B lymphomas in which rituximab was effective at first, there was no clinical response in a second treatment and a few cases of follicular lymphomas (FL) with transformation to diffuse large B-cell lymphoma (DLBCL) have been reported. We describe a new case and hypothesize about the mechanisms of transformation: a 52-year-old man, in follow-up during 8 years for FL, who after rituximab treatment and complete remission of FL showed progressive disease involving the liver and duodenal mucosa. Immunohistochemical and molecular studies were performed on paraffin-embedded tissue samples of lymph nodes, the small intestine, and liver tumors. After rituximab treatment, biopsies of a liver lesion and the small bowel both showed CD20-negative large B-cell lymphoma. Molecular study of the initial and relapse specimens shows a CDR2 IgH rearrangement with the same height and t14;18 (MBR). The rapid relapse with the same rearrangement of IgH seems to support the interpretation that the change of grade of lymphoma and loss of CD20 expression occurred before rituximab treatment. The existence of a varying proportion of a CD20-negative cell population in every B-cell lymphoma which does not respond to rituximab should therefore be considered. The reduction of CD20 expression could be a resistance mechanism to rituximab retreatment in DLBCL as a consequence of the progression of low-grade B-cell non-Hodgkin's lymphoma (B-NHL). It is necessary to perform new biopsies to evaluate CD20 expression in relapse or the progression of B-cell lymphoma after rituximab treatment.

Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies: its prevalence and clinical significance

“…Several mechanisms of resistance were predicted as reported previously, including loss of CD20 expression, inhibition of antibody binding, antibody metabolism, expression of complement inhibitors such as CD55/CD59, and membrane/ lipid raft abnormality (reviewed by Smith et al 9 ), [10][11][12][13][14][15][16][17][18][19] but the clinical significance of those mechanisms has remained unclear. In the last 5 years, a CD20-negative phenotypic change in CD20-positive lymphomas after rituximab treatment has been reported by several groups, 16,[20][21][22][23][24][25][26][27][28][29][30][31] indicating that this phenomenon after the use of rituximab may not be rare. Although these reports contain important information from clinical experiences, the frequency of occurrence and detailed molecular biologic information about the CD20-negative phenotype remain to be elucidated.…”

Histiocytic/Dendritic Cell Transformation of B-Cell Neoplasms: Pathologic Evidence of Lineage Conversion in Differentiated Hematolymphoid Malignancies

“…This latter feature can be used to exclude large B-cell transformation in those cases with a history of a primary indolent B-cell neoplasm; however, rare cases could show loss of some of their B-cell-specific antigens during aggressive transformation without acquisition of specific antigen markers for other lineages, particularly after immune-directed therapy. 21 …”

Lineage Determination of CD20- B-Cell Neoplasms: An Immunohistochemical Study

“…7 Of patients with B-cell lymphomas in which rituximab is initially effective, there is no clinical response in a second treatment in about 40% to 60%. 8,9 The resistance to rituximab retreatment in nonresponding recurrent B-cell neoplasms is at least partially attributed to a lack of CD20 expression in these patients 10 ; approximately 20% of patients with B-cell lymphoma treated with rituximab experience relapse with CD20-disease. 11,12 Given the potential benefit of retreatment with rituximab in relapsed B-cell neoplasms, it is important to repeat the tissue biopsy to document the presence or absence of CD20 expression, particularly in the setting of bone marrow involvement.…”