Abortive Plasma Cell Differentiation with Loss of Mature B-Cell Phenotype in a Subset of Patients with De Novo Diffuse Large B-Cell Lymphoma and Transformed Follicular Lymphoma: Relevance of cMYC Rearrangements.
Authors: Cullen Matthew J. , Barrans Sharon L. , Richards Stephen J. , Rawstron Andy C. , O’Connor Sheila J.M. , Tooze Reuben M. , Owen Roger G. , Jack Andrew 
Published: April 2020

The t(8:14) is the characteristic cytogenetic abnormality in Burkitt lymphoma and is found as an additional genetic abnormality in some cases of transformed follicular and DLBCL. Rare cases of de novo precursor B-cell lymphoblastic leukaemia (B-ALL) have also been reported to harbour cMYC translocations. We describe 5 cases referred to our regional haematopathology service that presented some diagnostic difficulties that may represent a previously undescribed phenomenon in Germinal Centre (GC)-derived tumours. 2 patients presented with de novo disease whilst of the other 3, 2 had a preceding history of follicular lymphoma and 1 of DLBCL, with all 3 previously demonstrating a t(14:18). Extranodal disease was the primary presenting feature in all 5 patients, with 2 demonstrating bone marrow involvement, 2 demonstrating soft tissue involvement and 1 involving both. The neoplastic cells displayed lymphoblast-type morphology and flow cytometry demonstrated a CD19+ B-cell phenotype with expression of CD10 and CD38, but absence of surface immunoglobulin, surface CD79b, CD20, and weak CD22. This phenotype was suggestive of a precursor B-cell neoplasm but there was no demonstrable CD34 or Tdt. It was therefore unclear whether these cases represented a precursor B-cell neoplasm or atypical forms of DLBCL. To further characterise these cases we performed FISH studies and investigated the expression of transcription factors involved in B-cell differentiation. Immunocytochemistry revealed a common PAX5+MUM-1+BCL-6− expression profile. This transcription factor profile in conjunction with CD10+ is rare and has previously been demonstrated in only 3/224 cases of de novo DLBCL at our institution. Cases were further evaluated for expression of BLIMP-1 using 2 different antibodies. Expression was noted in all cases but this was not accompanied by CD138 expression. FISH studies demonstrated evidence of a t(8:14) in all cases and a t(14:18) in 4 cases, which was pre-existing in 3. These cases are highly unusual and demonstrate loss of a mature B-cell phenotype and partial or abortive plasma cell differentiation in cells of a germinal centre type. Whilst expression of BLIMP-1 provides an explanation for the partial downregulation of CD20, CD22 and CD79b, the failure to repress PAX5 and CD10 indicates that differentiation was abortive in these cases. Rearrangement of cMYC may play a role in this regard as repression of cMYC is a prerequisite for normal plasma cell differentiation. These cases suggest that abortive plasma cell differentiation occurs in a proportion of de novo GC-derived tumours with a t(8:14) and in a proportion of follicular lymphoma/DLBCL cases which acquire a t(8:14) as a transformation or progressive event. This may lead to the erroneous diagnosis of B-ALL.