Amyloid-β peptide (Aβ) has a key role in the pathogenesis of Alzheimer disease (AD). Immunization with Aβ in a transgenic mouse model of AD reduces both age-related accumulation of Aβ in the brain¹ and associated cognitive impairment^2,3. Here we present the first analysis of human neuropathology after immunization with Aβ (AN-1792). Comparison with unimmunized cases of AD (n = 7) revealed the following unusual features in the immunized case, despite diagnostic neuropathological features of AD: (i) there were extensive areas of neocortex with very few Aβ plaques; (ii) those areas of cortex that were devoid of Aβ plaques contained densities of tangles, neuropil threads and cerebral amyloid angiopathy (CAA) similar to unimmunized AD, but lacked plaque-associated dystrophic neurites and astrocyte clusters; (iii) in some regions devoid of plaques, Aβ-immunoreactivity was associated with microglia; (iv) T-lymphocyte meningoencephalitis was present; and (v) cerebral white matter showed infiltration by macrophages. Findings (i)–(iii) strongly resemble the changes seen after Aβ immunotherapy in mouse models of AD^1,2,3,4,5,6 and suggest that the immune response generated against the peptide elicited clearance of Aβ plaques in this patient. The T-lymphocyte meningoencephalitis is likely to correspond to the side effect seen in some other patients who received AN-1792 (refs. 7,​ 8,​ 9).

Following inguinal orchidectomy, management options for patients with stage I seminoma include initial surveillance or treatment with adjuvant radiotherapy or chemotherapy. The anticipated relapse rate for patients followed by surveillance alone is ∼15%, with adjuvant treatment this risk is reduced to ∼4%–5% at 5 years. After carboplatin treatment, follow-up strategies vary and there are no validated, predictive markers of relapse. We conducted a retrospective analysis of all patients presenting with stage I seminoma who received a single cycle of adjuvant carboplatin in South Central England between 1996 and 2013. We report on outcome and the results of univariate and multivariate analysis evaluating possible risk factors for post carboplatin relapse. A total of 517 eligible patients were identified. All underwent nuclear medicine estimation of glomerular filtration rate before treatment with carboplatin (dosed at area under the curve × 7). With a median follow-up of 47.2 months (range 0.4–214 months), 21/517 patients have relapsed resulting in a 5-year estimated relapse-free survival of 95.0% (95% confidence interval 92.8% to 97.3%). Median time to relapse was 22.7 months (range 12.5–109.5 months). Relapse beyond 3 years was rare (4/517; 0.8%). Twenty of 21 (95%) relapsed patients had retroperitoneal lymph node metastases. The majority (16/21; 76%) of patients had elevated tumour markers at relapse. Twenty of 517 (3.9%) patients developed a new contralateral testicular germ-cell cancer. There were no seminoma-related deaths. Tumour size was the only variable significantly associated with an increased risk of relapse. Overall results for this large cohort of patients confirm an excellent prognosis for these patients with outcomes equivalent to those seen in prospective clinical trials. Increasing tumour size alone appears to be associated with an increased risk of post chemotherapy relapse.

Aims Sentinel lymph node (SLN) biopsy is the preferred surgical technique for staging the axilla in clinically node-negative breast cancer. Accurate intraoperative staging allows for the immediate performance of an axillary clearance in node-positive patients. We assessed the Metasin assay for the intraoperative analysis of SLNs in a prospective evaluation of 250 consecutive patients undergoing intraoperative SLN analysis at the Breast Unit, University Hospital, Southampton, UK. Methods Metasin uses a quantitative reverse transcription PCR to detect two markers of metastasis: cytokeratin 19 (CK19) an epithelial marker and mammaglobin (MGB) a breast specific marker. Metasin results were compared with the results from routine paraffin block histopathology. Results Metasin was robust, with a failure rate of <1%, and demonstrated excellent accuracy and reproducibility. The average turnaround time for the Metasin assay was 42 min, the largest variable being the number of nodes assayed. A total of 533 SLNs were evaluated with 75 patients testing positive for MGB and/or CK19. Based on the analysis of individual SLNs, the overall concordance between Metasin and histology was 92.3% (sensitivity 88.7%, specificity 92.9%). When adjusted for tissue allocation bias, the concordance was 93.8% (sensitivity 89.8%, specificity 94.6%). In this evaluation, 57/250 patients (23%) proceeded to axillary clearance based on Metasin results and were considered spared a second operative procedure. Conclusions Metasin has proven to be an accurate, reproducible and reliable laboratory test. The analysis time is acceptable for intraoperative use, and in comparison to routine histology demonstrates acceptable concordance, sensitivity and specificity.

Primary clear cell microcystic adenoma of the sinonasal cavity is rare. It has previously been described only as a VHL-associated tumour. Von Hippel-Lindau (VHL) syndrome is an inherited cancer syndrome characterised by an elevated risk of neoplasia including clear cell renal cell carcinoma (ccRCC), haemangioblastoma, and phaeochromocytoma. We describe the second reported case of a primary clear cell microcystic adenoma of the sinonasal cavity. The 39-year-old patient with VHL syndrome had previously undergone resection and ablation of ccRCC. He presented with epistaxis. Imaging demonstrated a mass in the ethmoid sinus. Initial clinical suspicion was of metastatic ccRCC. However, tumour morphology and immunoprofile were distinct from the previous ccRCC and supported a diagnosis of primary microcystic adenoma. Analysis of DNA extracted from sinonasal tumour tissue did not show loss of the wild-type allele at the VHL locus. Although this did not support tumour association with VHL disease, it was not possible to look for a loss-of-function mutation. The association of primary microcystic adenoma of the sinonasal cavity with VHL disease remains speculative. These lesions are benign but are likely to require regular surveillance. Such tumours may require repeated surgical excision.

In histopathological image segmentation, existing methods often show low sensitivity to small lesions and indistinct boundaries, leading to missed detections. Since, in clinical diagnosis, the consequences of missed detection are more serious than false alarms, this study proposes ClinSegNet, a recall-oriented and human-centred framework for reliable histopathology screening. ClinSegNet employs a composite optimisation strategy, termed HistoLoss, which balances stability and boundary refinement while prioritising recall. An uncertainty-driven refinement mechanism is further introduced to target high-uncertainty cases with limited fine-tuning cost. In addition, a clinical data processing pipeline was developed, where pixel-level annotations were automatically derived from IHC-to-H&E mapping and combined with public datasets, enabling effective training under limited clinical data conditions. Experiments on the NuInsSeg and NuInsSeg-UHS datasets showed that ClinSegNet achieved recall scores of 0.8803 and 0.8917, further improved to 0.8983 and 0.9053 with HITL refinement, while maintaining competitive Dice and IoU. Comparative and ablation studies confirmed the complementary design of the framework and its advantage in capturing small or complex lesions. In conclusion, ClinSegNet provides a clinically oriented, recall-prioritised framework that enhances lesion coverage, reduces the risk of missed diagnosis, and offers both a methodological basis for future human-in-the-loop systems and a feasible pipeline for leveraging limited clinical data.