Both EBV⁺ and MSI gastric cancers (GCs) have high lymphoid infiltration which is rare in MSS/EBV⁻ cancers. PD-L1/PD-1 interaction leads to a down-regulated immune response and it is one of the most promising targets for gastric cancer immunotherapy. PD-L1/PD-1 and CD8 expression were immunohistochemically investigated in a series of 169 FFPE GCs, including 33 EBV⁺, 59 MSI and 77 MSS/EBV⁻ cases. PD-L1 membrane immunoreactivity in more than 5% of tumor cells was present in 31/169 GCs and was associated with high levels of CD8 intraepithelial lymphocytes (TILs; p < 0.001). PD-L1⁺ cases were mainly poorly differentiated (71%), intestinal type (85%) and high lymphoid response (HLR; 90%) tumors. PD-L1 expression was only present in EBV⁺ (46%), MSI (24%) and rare MSS/EBV⁻ (3%) GCs with high CD8⁺ TILs (p < 0.001). Despite being associated with a better prognosis both in the whole series (p < 0.05) and in the MSI subset, PD-L1 is not an independent prognostic factor. PD-L1 gene amplification was detected in 3/17 cases, including 2/7 EBV⁺ and 1/8 MSI GC. PD-1⁺ TILs were significantly higher in EBV⁺ than MSI and MSS/EBV⁻ cases. PD-L1/PD-1 pathway is selectively activated in HLR GCs and could be considered an emerging therapeutic target, particularly for EBV and MSI GCs.

ChatGPT is an artificial intelligence capable of processing and generating human-like language. ChatGPT’s role within clinical patient care and medical education has been explored; however, assessment of its potential in supporting histopathological diagnosis is lacking. In this study, we assessed ChatGPT’s reliability in addressing pathology-related diagnostic questions across 10 subspecialties, as well as its ability to provide scientific references. We created five clinico-pathological scenarios for each subspecialty, posed to ChatGPT as open-ended or multiple-choice questions. Each question either asked for scientific references or not. Outputs were assessed by six pathologists according to: 1) usefulness in supporting the diagnosis and 2) absolute number of errors. All references were manually verified. We used directed acyclic graphs and structural causal models to determine the effect of each scenario type, field, question modality and pathologist evaluation. Overall, we yielded 894 evaluations. ChatGPT provided useful answers in 62.2% of cases. 32.1% of outputs contained no errors, while the remaining contained at least one error (maximum 18). ChatGPT provided 214 bibliographic references: 70.1% were correct, 12.1% were inaccurate and 17.8% did not correspond to a publication. Scenario variability had the greatest impact on ratings, followed by prompting strategy. Finally, latent knowledge across the fields showed minimal variation. In conclusion, ChatGPT provided useful responses in one-third of cases, but the number of errors and variability highlight that it is not yet adequate for everyday diagnostic practice and should be used with discretion as a support tool. The lack of thoroughness in providing references also suggests caution should be employed even when used as a self-learning tool. It is essential to recognize the irreplaceable role of human experts in synthesizing images, clinical data and experience for the intricate task of histopathological diagnosis.

Lymphoproliferative neoplasms of uncertain biological significance are increasingly encountered due to widespread usage of immunophenotypic and molecular techniques. Considering that clearer biological criteria and patient management have been established for B-cell lymphoproliferative diseases of undetermined significance occurring in the peripheral blood, many issues are still obscure for early lesions detected in lymphoid tissues. Regardless that some categories of lymphoproliferative neoplasms of uncertain biological significance have been recognized by the 4th edition of the WHO, other anecdotal early lymphoproliferative lesions still remain fully undefined. Some early lesions frequently originate from the germinal center, including atypical germinal centers BCL2-negative, an early pattern of large B-cell lymphoma with IRF4 rearrangement, and “in situ” high-grade B lymphomas. Moreover, other early lymphoproliferative lesions arise outside the germinal center and include those developing within the setting of monocytoid B-cell hyperplasia, but they also can be directly or indirectly associated with chronic inflammations. This review aims to summarize the concepts discussed during the IV Workshop organized by the Italian Group of Hematopathology, focus on the state-of-the-art on B-cell lymphoproliferative neoplasms of uncertain biological significance, and offer operative insights to pathologists and clinicians in routine diagnostics.