Immune evasion‐related extranodal large B‐cell lymphoma: A report of six patients with neoplastic PD‐L1‐positive extranodal diffuse large B‐cell lymphoma

Suzuki, Yuka; Sakakibara, Ayako; Shimada, Kazuyuki; Shimada, Satoko; Ishikawa, Eri; Nakamura, Shigeo; Kato, Seiichi; Takahara, Taishi; Asano, Naoki; Satou, Akira; Kohno, Kei

doi:10.1111/pin.12742

Cited by 19 publications

(39 citation statements)

References 40 publications

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“…Recently, Suzuki et al . reported expression of PD‐L1 on neoplastic cells in extranodal large B cell lymphomas in a series of six cases, five of which showed complete to partial intravascular pattern . In this study, we found that four cases (44.4%) were PD‐L1‐positive.…”

Section: Discussionsupporting

confidence: 55%

A study of PD‐L1 expression in intravascular large B cell lymphoma: correlation with clinical and pathological features

2019

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Intravascular large B cell lymphoma (IVLBCL) is a rare, aggressive, extranodal large B cell lymphoma characterised by growth of tumour cells within the lumen of vessels, particularly capillaries. Programmed cell death ligand 1 (PD‐L1) is a cell surface glycoprotein that interacts with programmed death 1 (PD‐1) on the T cell surface, leading to modulation of the immune response. PD‐L1 is a targetable immune check‐point molecule that is expressed on neoplastic cells in various cancers, including a subset of lymphomas. We correlated the expression of PD‐L1 with clinical and pathological findings in this rare disease. Eleven cases of IVLBCL were identified in the archives of Laboratory of Pathology at the National Cancer Institute, NIH. A panel of immunostains (CD20, CD3, CD5, PD‐L1) was performed. The cases were classified as the classic form or the variant associated with haemophagocytic syndrome (HPS) based on published 2017 WHO criteria. Three cases (27.3%) were HPS variant and eight cases (72.7%) were the classic form. Five (45.5%) of 11 cases were CD5‐positive; two of three (66%) were HPS variants and three of eight (37.5%) were classic form. Overall, four of nine evaluable cases (44.4%) were positive for PD‐L1, three of which were classic. Only one CD5‐positive case was PD‐L1‐positive, a classic variant. In summary, a subset of IVLBCL express PD‐L1. Although limited, these data suggest that PD‐L1 is expressed in both the so‐called classic form as well as the HPS variant. PD‐L1 is expressed irrespective of CD5 expression. Finally, detection of PD‐L1 expression in a subset of IVLBCL lymphoma cases may identify patients who might benefit from targeted immunotherapy.

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Section: Discussionsupporting

confidence: 55%

A study of PD‐L1 expression in intravascular large B cell lymphoma: correlation with clinical and pathological features

2019

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“…PD‐L1 protein expression (programmed cell death receptor ligand 1) was also found to be more prevalent in extranodal DLBCL disease than the nodal patients 18 . Expression of PD‐L1 protein is linked to poor prognosis in DLBCL patients with extranodal site of disease 19 . Activation of programmed cell death 1 signalling enables DLBCL tumour cells evade from T cell‐mediated immune response, hence, enhances tumour cells survival and promotes disease progression 20 …”

Section: Discussionmentioning

confidence: 99%

Extranodal site of diffuse large B‐cell lymphoma and the risk of R‐CHOP chemotherapy resistance and early relapse

Ting

Gan

Ong

et al. 2020

Int. J. Clin. Pract.

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Background About 20%‐30% of diffuse large B‐cell lymphoma (DLBCL) patients experience early disease progression despite R‐CHOP chemotherapy treatment. Revised international prognostic index (R‐IPI) score could risk stratify DLBCL patients but does not identify exactly which patient will be resistant to R‐CHOP therapy or experience early relapse. Aims of the Study To analyse pre‐treatment clinical features of DLBCL patients that are predictive of R‐CHOP therapy resistance and early disease relapse after R‐CHOP therapy treatment. Methods Used to Conduct the Study A total of 698 lymphoma patients were screened and 134 R‐CHOP‐treated DLBCL patients were included. The Lugano 2014 criteria was applied for assessment of treatment response. DLBCL patients were divided into R‐CHOP resistance/early relapse group and R‐CHOP sensitive/late relapse group. Results of the Study 81 of 134 (60%) were R‐CHOP sensitive/late relapse, while 53 (40%) were R‐CHOP resistance/early relapse. The median follow‐up period was 59 months ± standard error 3.6. Five‐year overall survival rate of R‐CHOP resistance/early relapse group was 2.1%, while it was 89% for RCHOP sensitive/late relapse group. Having more than one extranodal site of DLBCL disease is an independent risk factor for R‐CHOP resistance/early relapse [odds ratio = 5.268 (1.888‐14.702), P = .002]. The commonest extranodal sites were head and neck, gastrointestinal tract, respiratory system, vertebra and bones. Advanced age (>60 years), advanced disease stage (lll‐lV), raised pre‐treatment lactate dehydrogenase level, bone marrow involvement of DLBCL disease high Eastern Cooperative Oncology Group status (2‐4) and high R‐IPI score (3‐5) showed no significant association with R‐CHOP therapy resistance/early disease relapse (multivariate analysis: P > .05). Conclusion and Clinical Implications DLBCL patients with more than one extranodal site are 5.268 times more likely to be R‐CHOP therapy resistance or experience early disease relapse after R‐CHOP therapy. Therefore, correlative studies are warranted in DLBCL patients with more than one extranodal site of disease to explore possible underlying mechanisms of chemoresistance.

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“…Notably, PD‐L1 immunostaining highlighted the diffuse extravascular invasion of IVLBCL in the affected organs, begging the question whether neoplastic PD‐L1 expression is associated with either additional genetic alterations or the loss of the intravascular microenvironment. We recently reported a short series of immune escape‐related extranodal large B‐cell lymphoma cases, featuring exclusively extranodal sites, neoplastic PD‐L1 expression, and often a partially intravascular pattern . These data were obtained from biopsy specimens and not autopsy material.…”

Section: Discussionmentioning

confidence: 99%

Divergence and heterogeneity of neoplastic PD‐L1 expression: Two autopsy case reports of intravascular large B‐cell lymphoma

Sakakibara

Inagaki

Imaoka

et al. 2019

Pathology International

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Intravascular large B‐cell lymphoma (IVLBCL) is a distinct disease, but the neoplastic PD‐L1 expression on tumor cells may vary among cases. We evaluated 10 IVLBCL autopsy cases for neoplastic PD‐L1 expression, and had positive results in two cases. In one case, neoplastic PD‐L1 expression (SP142, 28‐8, and E1J2J clones) was dependent on the organ and anatomical site (capillaries vs. vessels) of the tumor tissue. Neoplastic PD‐L1 expression was found in tumor cells located in capillaries in the central nervous system, pituitary gland, kidneys, lung, and gastrointestinal tract; sinuses/sinusoids of the spleen, liver, bone marrow, and lymph nodes; and an extravascular location. However, this expression was not detected in tumor cells located in the adrenal gland, thyroid gland, pancreas, ovaries, uterus, pleura, and small or larger‐sized vessels of the lung. The other case showed constant neoplastic PD‐L1 expression on the tumor cells, and in addition to the affected organs, capillaries, and vessels with two anti‐PD‐L1 antibodies (28‐8 and E1J2J, but not SP142). The divergence and heterogeneity of neoplastic PD‐L1 expression were clearly demonstrated in our cases. To the best of our knowledge, this is the first description of divergent neoplastic PD‐L1 expression among the affected organs and anatomical sites in IVLBCL.

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Immune evasion‐related extranodal large B‐cell lymphoma: A report of six patients with neoplastic PD‐L1‐positive extranodal diffuse large B‐cell lymphoma

Cited by 19 publications

References 40 publications

A study of PD‐L1 expression in intravascular large B cell lymphoma: correlation with clinical and pathological features

A study of PD‐L1 expression in intravascular large B cell lymphoma: correlation with clinical and pathological features

Extranodal site of diffuse large B‐cell lymphoma and the risk of R‐CHOP chemotherapy resistance and early relapse

Divergence and heterogeneity of neoplastic PD‐L1 expression: Two autopsy case reports of intravascular large B‐cell lymphoma

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