C-MYCtranslocation in t(14;18) positive follicular lymphoma at presentation: An adverse prognostic indicator?

Abstract

Follicular lymphoma (FL) is a common subtype of low grade B-cell non-Hodgkin lymphoma (NHL). Although this form of lymphoma often pursues an indolent course, in some cases it may behave in a more aggressive manner. Clinical and histological parameters have been shown to correlate with an adverse prognosis but a number of cytogenetic abnormalities may also be associated with aggressive disease. Although, the t(14;18) in itself does not affect outcome in cases of FL, secondary abnormalities that occur in a complex polyploid karyotype may identify cases with a poor prognosis. It is unusual to find both t(14;18) and C-MYC translocation in the same tumour; those cases in which it has been described include examples of high-grade B-cell NHL (either de novo or transformed FL) or B-cell acute lymphoblastic lymphoma. In this report, three cases of FL are described in which both t(14;18) and a C-MYC translocation were identified at presentation. We also summarize four further cases from the literature. This is a small series but one which raises the possibility that the presence of a C-MYC translocations at presentation may identify a particularly aggressive subtype of FL. Further studies are required to investigate the true incidence of this aberration, the impact on C-MYC regulation, clinical course and response to treatment.

Follicular lymphoma grade 3B is a distinct neoplasm according to cytogenetic and immunohistochemical profiles

“…This finding agrees well with the data from other studies, in which MYC translocations were found in up to 13% of cases. 6,[21][22][23][24][25] It is especially interesting to note that the incidence of MYC + cases was the same in the FL/LCC subtype as in the FL3B and DLBCL/FL3B subtypes, making MYC a likely candidate as a progression factor also in "non-transformed" FL. Out of 12 cases of FL with MYC gene translocation, five cases presented with concurrent translocations of either BCL2 or BCL6, while one case of FL3B showed a triple hit of MYC, BCL2 and BCL6.…”

Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival

“…11 These cases may present with variable morphologies, including acute lymphoblastic leukemia/lymphoma (ALL), DLBCL, BCLU, and rarely FL. [13][14][15][16][17][18][19] The primary event in these cases is usually the t(14;18) with the MYC translocation (MYC ϩ ) arising as a secondary genetic event. 13,20 Patients with lymphomas harboring concurrent BCL2 and MYC translocations, hereafter referred to as BCL2 ϩ /MYC ϩ lymphomas, have been described in several small case series as having a very poor overall survival (OS).…”

Can histologic transformation of follicular lymphoma be predicted and prevented?

“…70 Similar to TP53 mutations, MYC translocations are rare at diagnosis but frequently found at transformation. 17,26,29,30,71 The prognostic implication of MYC translocation in FL is unclear, despite these cases typically also harboring a BCL2 translocation and de facto being double-hit lymphomas. It is possible that larger patient cohorts would need to be studied to define whether TP53 and MYC alterations predict transformation.…”