Autopsy case report of intravascular large B-cell lymphoma with neoplastic PD-L1 expression

Abstract

Intravascular large B-cell lymphoma (IVLBCL) is a rare and clinically distinctive entity characterized by the almost exclusive growth of large cells within the lumen of blood vessels in particular capillaries. Reports of this peculiar disease, do not commonly address the PD-L1 expression on IVLBCL tumor cells. Here, we describe a 51-year-old Japanese woman who presented with rapidly progressive cognitive decline and higher brain dysfunction. CT scan and MRI revealed multiple ischemic foci in the cerebral hemispheres, ground-glass opacity in the lungs, and splenomegaly. Random skin biopsy for IVLBCL diagnosis yielded negative results. The patient experienced a rapidly deteriorating clinical course with no treatment, and died from the disease after 3 months of hospitalization. Post-mortem examination revealed systemic intravascular plugging of lymphoma cells, without mass lesions in the central nervous system or in visceral organs such as the lungs, liver, pituitary gland, ovaries, and uterus. The tumor cells were positive for CD10, CD20, BCL2, BCL6, and MUM1, but not other lineage-specific markers. Notably, the tumor cells showed strong PD-L1 expression. Our case was diagnosed as IVLBCL with neoplastic PD-L1 expression. These findings suggest that PD-L1 is associated with immune evasion of IVLBCL and may play a role in the pathogenesis and peculiar biological behavior of this unique disease. Additionally, PD-L1 may represent a possible therapeutic target for immune check-point inhibitors.

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

“…The clinicopathologic findings and prognoses of our patients have been already documented in details as separate case reports and are briefly summarized in Table .…”

“…Intravascular large B‐cell lymphoma (IVLBCL) is a rare variant of extranodal diffuse large B‐cell lymphoma (DLBCL), characterized by the proliferation of large tumor cells within the lumina of small or intermediate‐sized blood vessels and capillaries . This disease is systemic, can potentially involve any organ, and is often widely disseminated .…”

“…Intravascular large B‐cell lymphoma (IVLBCL) is a rare variant of extranodal diffuse large B‐cell lymphoma (DLBCL), characterized by the proliferation of large tumor cells within the lumina of small or intermediate‐sized blood vessels and capillaries . This disease is systemic, can potentially involve any organ, and is often widely disseminated . Recent advances in molecular analyses indicated a high prevalence of the L265P activating mutation in the MYD88 gene and mutations of Y196 in the CD79B gene, resulting in constitutive activation of NFκβ‐signaling.…”

“…We recently reported an autopsy case of IVLBCL with neoplastic PD‐L1 expression using an anti‐PD‐L1 antibody (SP142) . This further prompted us to comprehensively screen for neoplastic PD‐L1 expression in tumor cells from the affected organs and tissues using formalin‐fixed paraffin‐embedded (FFPE) blocks in a series of autopsy cases with IVLBCL.…”

“…We initially surveyed 10 autopsy cases with IVLBCL (male: female = 5:5, a median onset age of 61 years [51–99 years]) by immunostaining the FFPE sections with three anti‐PD‐L1 antibodies (SP142, 1:50, Spring Bioscience, Fremont, CA, USA; E1J2J, 1:50, Cell Signaling Technology, Danvers, MA, USA; and 28‐8, 1:50, Abcam, Cambridge, UK), but only two previously reported cases presented with successful antigen retrieval . The eight remaining cases showed no positivity in the neoplastic cells or cells in the tumor microenvironment probably due to the prolonged formalin fixation.…”