Splenic marginal zone lymphoma (SMZL) is a rare form of non-Hodgkin’s lymphoma (nHL) that often at the time of diagnosis, has spread to the blood and/or bone marrow. Although SMZL survival rates are relatively high (1), up to 30% of SMZL cases advance aggressively, with 5-10% transforming into high-grade diffuse large B-cell lymphoma (1). Due to the rarity of SMZL, there is little clinical information available to predict this progression, in addition to no official treatment plan being available.
To date, SMZL diagnosis heavily relies on conventional 2D imaging, which can be problematic as SMZL is highly heterogeneous and does not account for the 3D environment. Therefore, valuable information about the tumour microenvironment (TME) is lost (2, 3). With the development of the 3D imaging pipeline DIPCO (diagnosing immunolabelled paraffin-embedded cleared organs) (2, 3), this loss in information can be avoided as biopsies are imaged in 3D. In recent years, tumour vascularisation has received increasing attention as a cancer marker due to its established impact in tumour angiogenesis, development, progression, and prognosis (4). However, analysing the vessels of highly vascularised tissue, such as the spleen, has been difficult to date. Here, we utilised the 3D imaging pipeline, DIPCO, to thoroughly analyse CD34, a common vessel marker, in SMZL biopsies. In total, we analysed 12 splenectomy biopsies; within those cases, 7 biopsies remained indolent SMZL, where 5 transformed to diffuse large B-cell lymphoma (DLBCL). We found that vessel mean radius, lumen radius and total vessel volume, were prognostic markers that were positively associated with poorer prognosis. Additionally, we found that vessel tortuosity was negatively associated with poorer prognosis. In summary, we propose that 3D imaging can be a valuable tool to stratify lymphoma progression more accurately, and potentially contribute to therapy outcome, specifically in SMZL cases.