Lymphoplasmacytic lymphoma associated with diffuse large B-cell lymphoma: Progression or divergent evolution?

Abstract

Aim Lymphoplasmacytic lymphoma (LPL) is an indolent mature B-cell-neoplasm with involvement of the bone marrow. At least 90% of LPLs carry MYD88-L265P mutation and some of them (~10%) transform into diffuse large B-cell-lymphoma (DLBCL). Material and methods Over the past 15 years we have collected 7 cases where the both LPL and DLBCL were diagnosed in the same patient. Clinical records, analytical data and histopathological specimens were reviewed. FISH studies on paraffin-embedded tissue for MYC, BCL2 and BCL6 genes were performed, as well as MYD88-L265P mutation and IGH rearrangement analysis by PCR. A mutational study was done by massive next generation sequencing (NGS). Results There were 4 women and 3 men between 36–91 years of age. Diagnoses were made simultaneously in 4 patients. In two cases the LPL appeared before the DLBCL and in the remaining case the high-grade component was discovered 5 years before the LPL. In 6 cases both samples shared the MYD88-L265P mutation. IGH rearrangement analysis showed overlapping features in two of 6 cases tested. Mutational study was evaluable in three cases for both samples showing shared and divergent mutations. Conclusions These data suggest different mechanisms of DLBCL development in LPL patients.

Hemophagocytic lymphohistiocytosis as an onset of diffuse large B‑cell lymphoma: A case report

“…However, LPL is indolent, and transformation may occur only at a frequency of 5–13% ( 32 ). Furthermore, the prognosis of DLBCL transformed from LPL appears to be worse than that of de novo DLBCL, with a survival time of ~2 years after transformation ( 33 ). Although the most frequent somatic mutation in LPL is MYD88 L265P, this mutation is also common in ABC DLBCL.…”

Clonal Relationship and Mutation Analysis in Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia Associated With Diffuse Large B-cell Lymphoma

“…[3][4][5][6] Here, different models of clonal evolution have been proposed, including linear and divergent clonal evolution. 7,8 DLBCL presentations in antecedent LPL/WM are often localized at extranodal sites, frequently with an activated B-cell phenotype. 5,6 Extranodal DLBCL includes cutaneous involvement, and lymphomas located at immune-privileged (IP) sites, such as central nervous system (CNS) and testis.…”

“…However, in 2%–10% of LPL/WM patients development of diffuse large B‐cell lymphoma (DLBCL) is observed, often resulting from LPL transformation, and associated with a poor prognosis 3–6 . Here, different models of clonal evolution have been proposed, including linear and divergent clonal evolution 7 , 8 . DLBCL presentations in antecedent LPL/WM are often localized at extranodal sites, frequently with an activated B‐cell phenotype 5 , 6 .…”

“…Besides transformation, the occurrence of clonally unrelated DLBCL has been reported in LPL/WM. [7][8][9][10][11] Clonotypic V(D)J analysis has also demonstrated biclonality in a subset of LPL/WM, [12][13][14] but it is still unclear whether these patients are at increased risk of DLBCL development.…”

“…Extranodal DLBCL includes cutaneous involvement, and lymphomas located at immune‐privileged (IP) sites, such as central nervous system (CNS) and testis. Besides transformation, the occurrence of clonally unrelated DLBCL has been reported in LPL/WM 7–11 . Clonotypic V(D)J analysis has also demonstrated biclonality in a subset of LPL/WM, 12–14 but it is still unclear whether these patients are at increased risk of DLBCL development.…”