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. 2023 Mar 28;7(6):893-899.
doi: 10.1182/bloodadvances.2022007360.

Transformation of FL into DLBCL with a PMBL gene expression signature

Tristan Loveday  1 , Gerben Duns  2 , Lisa M Rimsza  3 , Karen L Rech  4 , James R Cook  5 , Ryan S Robetorye  3 , Allison C Rosenthal  6 , Colleen A Ramsower  7 , Tameson K Yip  3 , Catherine L McKinney  7 , Steven H Swerdlow  8 , Shweta Bhavsar  5   8 , Christian Steidl  2 , Sarah E Gibson  3
Affiliations

Transformation of FL into DLBCL with a PMBL gene expression signature

Tristan Loveday et al. Blood Adv. .

Abstract

We investigated the clinicopathologic features of 5 follicular lymphomas (FLs) that transformed (tFL) morphologically to diffuse large B-cell lymphomas (DLBCLs) and had a primary mediastinal large B-cell lymphoma (PMBL)-like gene expression profile (tFL-PMBLsig-pos). None of the tFL-PMBLsig-pos cases arose in the mediastinum, all cases tested had a germinal center B-cell phenotype, 20% were CD30+, 60% CD23+, 80% MAL+, 20% CD200+, and 0% CD273/PDL2+. Whole-exome sequencing detected alterations in genes associated with both FL/DLBCL (CREBBP, KMT2C, KMT2D, ARID1A, HIST1 members, and TNFRSF14) and PMBL (JAK-STAT pathway genes, B2M, and CD58). Copy number (CN) analysis detected gains/amplification of REL and STAT6 in 60%, gains of SOCS1 in 40%, and gains of chromosome 16, including IL4R, in 40% of the cases. CN gains/amplification of BCL6 and MYC and loss of TNFRSF14 and TNFAIP3 were identified in 20% of the cases. Three of 5 cases lacked a BCL2 rearrangement. Despite having some features that are less common in DLBCL (MAL and CD23 expression and JAK-STAT activation), these tFL-PMBLsig-pos cases lack the most characteristic CN alteration seen in PMBL (9p24.1 gain/amplification). This cohort expands the biologic heterogeneity of tFL, illustrating a subset with gene expression and some genetic features reminiscent of PMBL, with potential treatment implications that include the use of novel targeted therapies.

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Conflict of interest statement

Conflict-of-interest disclosure: L.M.R. and C.S. are named inventors on a patent filed by the National Cancer Institute (“Methods for determining lymphoma type”). The remaining authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Morphology and immunophenotype of tFL-PMBLsig-pos cases. (A) The tFL-PMBLsig-pos (case 2) is composed of sheets of large B cells with predominantly centroblastic cytology that coexpress CD20 and CD10 (not shown). (B) CD23 is diffusely positive. (C) CD30 shows prominent background nonspecific staining with only rare strongly positive cells. (D) A large subset of the neoplastic B cells expresses MAL and (E) CD200 but is negative for (F) CD273/PDL2. Original magnifications ×500 (A) and ×200 (B-F); A, hematoxylin and eosin stain and B-F, immunohistochemical stain with hematoxylin counterstain.
Figure 2.
Figure 2.
WES analysis of 5 tFL-PMBLsig-pos cases. (A) Alterations found in a curated list of PMBL and FL/DLBCL-related genes across all 5 tFL-PMBLsig-pos cases. (B) Alterations in the JAK-STAT pathway found among 4 of 5 tFL-PMBLsig-pos cases.
Figure 3.
Figure 3.
CN analysis of 5 tFL-PMBLsig-pos cases. (A) Heatmap showing CN changes by chromosomal location for each tFL-PMBLsig-pos case. (B-D) Graphs showing more detailed CN changes by location in chromosomes 2 (B), 12 (C), and 16 (D). Genes of note are labeled and highlighted with a dotted red line and include REL on chromosome 2 (gains in 3 of 5 cases; case 5/FL1122T2 illustrated), STAT6 on chromosome 12 (gains/amplification in 3 of 5 cases; case 4/FL1179T2 illustrated), and IL4R on chromosome 16 (gains in 2 of 5 cases; case 1/EX00406 illustrated).
See this image and copyright information in PMC

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