Pathology最新文献

Immune checkpoint inhibitor (ICI) therapy has revolutionised oncology, but presents significant diagnostic and therapeutic challenges due to immune-related adverse events, notably ICI-related hepatotoxicity (ICI-H). This study aims to provide insights into the histological manifestations of ICI-H and their impact on clinical decision-making along with follow-up data where available. We retrospectively screened all liver biopsy samples received at statewide tertiary care public pathology laboratories in Western Australia between 2015 and 2024 using the laboratory information system for suspected ICI-H. Patients receiving ICI therapy and those with exposure within 3 months of biopsy were included in the study. Thirteen patients met study criteria. The age range was 29-83 years. All patients had been treated for metastatic malignancy and received steroids at the time of biopsy. ICIs administered included ipilimumab/nivolumab combination therapy (n=5), single-agent pembrolizumab (n=4), single-agent nivolumab (n=2), atezolizumab/bevacizumab combination therapy (n=1), and an experimental bifunctional protein-targeting programmed death ligand 1 (PD-L1) (n=1). The most common pattern of injury was hepatitic injury (nine cases), which was lobular predominant in five cases. These patients were treated with ipilimumab/nivolumab combination therapy or single-agent programmed cell death protein 1 (PD-1) or PD-L1 inhibitors. A pure cholestatic injury pattern was seen in three cases, of which one showed features of ICI-related cholangiopathy, all treated with single-agent pembrolizumab. One case had a mixed hepatitic and cholestatic pattern of injury (treated with atezolezumab). All patients had resolution of ICI-H on being treated with steroids and with or without cessation of ICI. Two patients completed the treatment course while receiving steroids. Four patients tolerated rechallenge with single-agent ICI after the resolution of ICI-H. One patient was rechallenged 4 years later but developed recurrent ICI-H with a similar hepatitic morphology. In conclusion, the hepatitic pattern of injury on biopsy was the most common (nine out of 13 cases), while a pure cholestatic pattern was associated with single-agent PD-1 inhibitor pembrolizumab, including one case with features consistent with ICI-related cholangiopathy. In our limited cohort, there were no patients who developed chronic liver disease after exposure to ICIs.

Flow cytometry immunophenotyping (FCI) and cytogenetic analysis are important diagnostic and prognostic investigations performed on bone marrow biopsy specimens. When particulate aspirate samples are not obtained, trephine samples can be disaggregated to yield cellular material for analysis. In this study, we assessed the performance of mechanical trephine disaggregation for FCI and cytogenetic analysis. Outcomes reported include the underlying pathology leading to suboptimal aspirate material, FCI success rates, sample viability, FCI turnaround time and success of cytogenetic analysis. We performed a retrospective data collection for trephines disaggregated for FCI and cytogenetics between 2019 and 2023 at Royal North Shore Hospital, Sydney, Australia. Results showed that disaggregation of trephine samples for FCI due to suboptimal aspirate material was required in 83 cases, representing 1.3% of all bone marrow biopsies performed during the study period. The most common pathology leading to inadequate aspirate material was primary myelofibrosis in 15 of 83 (18%) cases. Sufficient analytical information to publish an FCI diagnostic report was possible in 56 of 83 (67%) of cases. FCI was successful in 100% of cases of acute leukaemia. Karyotyping was attempted on disaggregated trephine samples in 64 cases. Nineteen of 64 (30%) of cases yielded metaphases to perform a karyotype. Cytogenetic abnormalities with diagnostic or prognostic significance were identified in eight cases (42%). Our study indicates that mechanical disaggregation of bone marrow trephines leads to successful FCI in most cases. Success rates for karyotyping on disaggregated trephines are suboptimal, and the application of alternative cytogenetic techniques should be considered.