[Combination lymphomas, grey zone lymphomas and future challenges]

Lymphomas are basically divided into Hodgkin and B‑ and T‑cell lymphomas, with diagnosis based on morphological, immunohistochemical and, increasingly, molecular methods. Classic Hodgkin lymphoma is characterised by the presence of Hodgkin-Reed-Sternberg cells, which have a typical marker profile (CD30+, CD15+, Pax5+) and are diagnostically decisive despite their low number. Molecularly, these tumours can be identified as B‑cell lymphomas, with the tumour cells often possessing non-functional immunoglobulin genes.In B‑ and T‑cell lymphomas, the tumour cells in most cases are predominant in terms of numbers; they are classified primarily according to their B‑cell or T‑cell origin. In rare cases, so-called combination lymphomas occur, which combine Hodgkin and B‑ or T‑cell lymphoma components.Grey zone lymphomas exhibit characteristics of both classic Hodgkin's lymphoma and primary mediastinal large B‑cell lymphoma. They are divided into classical Hodgkin lymphoma (cHL)-like and Primary Mediastinal B‑cell lymphoma (PMBCL)-like forms, are difficult to diagnose and sometimes respond poorly to therapy.The future of lymphoma diagnostics lies in combining traditional histological methods with digital techniques and molecular analyses. Modern imaging and single-cell analyses enable more precise determination of both tumour cells and their microenvironment.In addition, novel spatial transcriptomic techniques combine different technologies. 4D techniques allow motility analyses of living tissue sections and thus direct observations of cell interactions. So, it seems possible to characterize localized single cells in tissues using hybridization and sequencing technologies to provide further information of cell-cell interactions and the resulting molecular changes by bioinformatics.These developments open new perspectives for personalised medicine and could help to better predict the success of innovative cell therapies. This article was created to accompany the 62nd IAP Symposium, "Lymph Nodes and Lymphoma Pathology-The Essentials."