J Pathol Transl Med.  2022 Jan;56(1):32-39. 10.4132/jptm.2021.10.05.

Clinicopathologic implication of PD-L1 gene alteration in primary adrenal diffuse large B cell lymphoma

• Lee KR
• Koh J
• Jeon YK
• Kwon HJ
• Lee JO
• Paik JH

• KMID: 2524227
• DOI: http://doi.org/10.4132/jptm.2021.10.05

Abstract

Background
Primary adrenal (PA) diffuse large B cell lymphoma (DLBCL) was previously reported as an aggressive subset of DLBCL, but its genetic features were not sufficiently characterized. From our previous study of DLBCL with programmed death-ligand 1 (PD-L1) gene alterations, we focused on PD-L1 gene alterations in PA-DLBCL with clinicopathologic implications.
Methods
We performed fluorescence in situ hybridization for PD-L1 gene translocation and amplification in PA-DLBCL (n = 18) and comparatively analyzed clinicopathologic characteristics with systemic non-adrenal (NA)-DLBCL (n = 90).
Results
PA-DLBCL harbored distinctive features (vs. NADLBCL), including high international prognostic index score (3–5) (72% [13/18] vs. 38% [34/90], p = .007), poor Eastern Cooperative Oncology Group performance score (≥ 2) (47% [7/15] vs. 11% [10/90], p = .003), elevated serum lactate dehydrogenase (LDH) (78% [14/18] vs. 51% [44/87], p = .035) and MUM1 expression (87% [13/15] vs. 60% [54/90], p = .047). Moreover, PA-DLBCL showed frequent PD-L1 gene alterations (vs. NA-DLBCL) (39% [7/18] vs. 6% [5/86], p = .001), including translocation (22% [4/18] vs. 3% [3/87], p = .016) and amplification (17% [3/18] vs. 2% [2/87], p = .034). Within the PA-DLBCL group, PD-L1 gene–altered cases (vs. non-altered cases) tended to have B symptoms (p = .145) and elevated LDH (p = .119) but less frequent bulky disease (≥ 10 cm) (p = .119). In the survival analysis, PA-DLBCL had a poor prognosis for overall survival (OS) and progression-free survival (PFS) (vs. NA-DLBCL; p = .014 and p = .004). Within the PA-DLBCL group, PD-L1 translocation was associated with shorter OS and PFS (p < .001 and p = .012).
Conclusions
PA-DLBCL is a clinically aggressive and distinct subset of DLBCL with frequent PD-L1 gene alterations. PD-L1 gene translocation was associated with poor prognosis in PA-DLBCL.

Keyword

Malignant lymphoma; Diffuse large B cell lymphoma; Adrenal gland; PD-L1

Figure

• 

  Fig. 1 Fluorescence in situ hybridization analysis of the programmed death-ligand 1 (PD-L1) gene in diffuse large B cell lymphoma. By using a dual-color orange/green break-apart probe, non-split fused signal indicates the absence of translocation (A), while separate orange and green signals indicate the presence of translocation (B). By using a copy number analysis probe, orange (PD-L1 gene) and green (chromosome 9) signals showed a nearly 1:1 ratio in cases with no gain or amplification of the PD-L1 gene (C), in contrast to amplified orange signals indicating PD-L1 gene amplification (D).

• 

  Fig. 2 Kaplan-Meier curves of overall survival (OS) and progression-free survival (PFS) in diffuse large B cell lymphoma (DLBCL) patients. OS (A) and PFS (B) of primary adrenal (PA)- and non-adrenal (NA)-DLBCL patients. OS (C) and PFS (D) of PA-DLBCL patients by the presence of programmed death-ligand 1 (PD-L1) gene alterations. OS (E) and PFS (F) of PA-DLBCL patients by the presence of PD-L1 gene translocation.

Reference

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