Lymphoblastic transformation of follicular lymphoma: a clinicopathologic and molecular analysis of 7 patients

Double- and triple-hit lymphomas can present with features suggestive of immaturity, including TdT expression, and create diagnostic challenges

“…Two of the TdT positive cases in this series were classified as B-LBL at the time of diagnosis. On review of the cases for this study, we feel only case 2 qualifies for the diagnosis of B-LBL, and, as it arose in a patient with a history of follicular lymphoma, the case is perhaps better classified as TdT+ B-lymphoblastic transformation of FL, as suggested by Geyer, et al and Loghavi, et al 5,38 .…”

“…Transformation of FL to B-LBL is rare but well documented in the literature, with most cases showing a MYC rearrangement in addition to IGH/BCL2 fusion 4-8,32-36 . Geyer, et al 5 recently published a series of 7 patients with TdT+ B-lymphoblastic transformation of FL. In that series, the authors raise the possibility that patients presenting with de novo double-hit B-LBL may have a pre-existing low-grade FL masked by the higher-grade process.…”

Dramatic increase in gene mutational burden after transformation of follicular lymphoma into TdT+ B-lymphoblastic leukemia/lymphoma

“…The B-ALL/LBL transformation was ultimately followed by the patient's demise within the following year. This aggressive clinical course appears to be typical in the patients with FL-B-ALL/LBL progression (Geyer et al 2015;Slot et al 2016).…”

“…The rearrangement involving MYC, a potent oncogene, most likely played a key role in this transformation. MYC translocations are well-known to contribute to high aggressiveness of lymphomas and are a hallmark of FL-B-ALL/LBL transformation (Voorhees et al 2004;Young et al 2008;Geyer et al 2015;Slot et al 2016;Li et al 2018). Interestingly, single-cell RNA-seq data in murine models have shown that MYC activity can predict reprogramming efficiency across many somatic cell types (Francesconi et al 2019), emphasizing a potential element of "dedifferentiation" in these transformations.…”

“…Most cases of FL transformation result in diffuse large B-cell lymphoma, but, rarely, lymphoblastic lesions comprised of immature rather than mature B cells can arise, typically in younger patients (De Jong et al 1988;Gauwerky et al 1988;Kroft et al 2000;Sun et al 2002;Young et al 2008). Although the mechanisms underlying transformation to diffuse large B-cell lymphoma have been extensively examined (Rossi et al 2006;Pasqualucci et al 2014), molecular characterization of the "dedifferentiation" to Blymphoblastic leukemia/lymphoma (B-ALL/LBL) has been very limited thus far (Geyer et al 2015;Slot et al 2016). Here we present a case of an FL transformed into B-cell B-ALL/LBL with extensive molecular characterization including analysis of the somatic hypermutation (SHM) status of the immunoglobulin (Ig) genes, cytogenetic studies, and whole-exome sequencing (WES) of the patient's normal, FL, and B-ALL/LBL tissues.…”