Pathology

AI calls MSI/MMR from routine H&E in colorectal cancer with >93% agreement

This multi-centre blinded study evaluated PANProfiler Colorectal, an AI tool inferring MSI/MMR status directly from H&E slides in 1,243 CRC patients. Across 3,576 whole-slide images from three UK institutions, the model gave definitive calls in 86.55% of slides. Among definitive calls, overall agreement with standard MSI/MMR testing was 93.83%, with positive and negative agreement of 92.54% and 94.02%, respectively. These data support using AI H&E analysis as a rapid triage or adjunct, potentially reducing immunohistochemistry or PCR burden and turnaround time. 1

GFPT2 is a high-performance IHC marker for mesothelioma with a DDLPS caveat

In 101 mesotheliomas and 266 histologic mimics, GFPT2 IHC was positive in 85.15% of mesotheliomas. GFPT2 was uniformly negative in reactive mesothelial hyperplasia, WDPMT, NSCLC, HGSOC, SFT, synovial sarcoma, leiomyosarcoma and most other mimics. Specificity was 94.7%, but dedifferentiated liposarcoma showed high GFPT2 positivity (85.7%), representing a critical diagnostic pitfall. GFPT2 helps separate malignant from benign/borderline mesothelial lesions and distinguish epithelioid and sarcomatoid mesothelioma from common mimics, except DDLPS. In practice, GFPT2 appears useful in mesothelial panels, provided lipogenic sarcoma is excluded or appropriately investigated. 2

NGS-based IG clonality clarifies minimal marrow involvement in B-cell lymphoma

This EuroClonality-NGS Working Group study applied NGS IG clonality testing to 49 lymphoma staging bone marrows with paired primary lymphoma tissue. Cases clearly positive or negative by morphology/IHC showed distinct levels of overlapping clonal IG rearrangements, validating assay behaviour. Twelve marrows with 1–5% B-cell infiltrates were morphologically/IHC-indeterminate but yielded binary results by paired NGS clonality analysis. Some equivocal marrows showed minimal or absent primary lymphoma rearrangements, while others showed clear clonal overlap with the primary lymphoma. These findings support adding paired NGS IG clonality in difficult marrow staging biopsies to discriminate reactive infiltrates from minimal lymphoma involvement. 3

Melanocytic lesion diagnoses show 33% overall discordance and high variability in indeterminate-risk cases

This retrospective single-institution study analysed 1,491 melanocytic lesions with outside diagnoses re-reviewed in consultation. Overall diagnostic discordance between original and consult readings was 33%, highlighting persistent variability in melanoma-related reporting. Indeterminate-risk lesions with explicit treatment recommendations had 79.2% discordance, most frequently downgraded to benign entities. Academic practice setting and dermatopathology board certification correlated with greater concordance, whereas intent-to-consult correlated with discordance. The data support subspecialty review for ambiguous lesions and underscore the need for better criteria and biomarkers before aggressive management. 4