Aims Neuroendocrine proliferations have been described in gastrointestinal (GI) mucosa associated with chemoradiation and inflammatory bowel disease (IBD) and can also be seen in gastric mucosa in hypergastrinemic conditions. We have encountered small clusters of neuroendocrine cells in the lamina propria, designated herein as neuroendocrine micronodules (NMs), in biopsies taken at and around the gastroesophageal junction (GEJ) in patients without histories of chemoradiation, IBD or autoimmune metaplastic atrophic gastritis (AMAG) and sought to further characterize their clinicopathological features. Methods Nine patients with NMs were identified during routine signout. An additional 66 consecutive patients with GEJ biopsies containing ≥1 fragment of columnar mucosa were prospectively evaluated. NMs were identified on haematoxylin and eosin staining and confirmed with chromogranin A immunohistochemistry. Results NMs were identified in 8% (5/66) of GEJ biopsies in the prospective cohort. Of the 14 total patients with NMs, the median age was 51 years (range 25–78 years) with slight male predominance (1.7:1). 79% reported proton pump inhibitor (PPI) use, 71% had gastroesophageal reflux disease (GERD) and 36% had hiatal hernia. None had IBD, chemoradiation or prior neuroendocrine neoplasia. Associated histological findings included pancreatic metaplasia in 57%, intestinal metaplasia in 7% and linear neuroendocrine cell hyperplasia in 64%. Twelve patients had concurrently sampled oxyntic mucosa and all lacked evidence of AMAG. Conclusions NMs at the GEJ can be found in up to 8% of unselected biopsies and may occur in patients without AMAG. Possible aetiologies include PPI‐associated ECL hyperplasia and/or GERD‐mediated injury; however, definitive characterization requires further studies.
Tumour‐infiltrating lymphocytes (TILs) are recognized as critical components of the colorectal cancer (CRC) immune microenvironment, demonstrating significant prognostic and predictive implications. However, a clear and widely accepted definition of colorectal TILs has not yet been established, and TILs are not systematically used as biomarkers in current oncology practice. This highlights the need for standardized assessment methods and a deeper understanding of the complex role of TILs in CRC, necessitating collaborative work to achieve clinical importance. This report, on behalf of the International Immuno‐Oncology Biomarker Working Group (ITWG), provides a comprehensive overview of TILs in CRC, including a TILs‐assessment method. It details their multifaceted role of TILs within the tumour microenvironment, details current and emerging methods for their assessment and reviews their prognostic and predictive importance. The report also explores the relationship of TILs to other established and emerging biomarkers in CRC. Emerging trends, including AI‐driven analysis for automated TIL quantification, and single‐cell and spatial technologies for in‐depth characterization of the tumour microenvironment (TME), are also highlighted. The report concludes with a discussion of future directions and the ongoing efforts of the ITWG to address the challenges and standardize and advance the clinical application of TIL assessment in CRC.
INTRODUCTION During routine examination of specimens from patients with steatotic liver disease (SLD), we repeatedly observed a peculiar phenomenon characterized by obstruction of the hepatic sinusoids by lipid vacuoles (lipidic obstruction of sinusoids, LOS). These changes were reminiscent of pseudopeliotic steatosis (PPS), a complication following liver transplantation (LT), but notably occurred outside this context. The aim of our study was to identify diagnostic indicators for LOS and to determine its clinical significance. METHODS Liver specimens routinely sent to our institute between 2019 and 2024 with SLD were examined for LOS. The extracellular nature of the fat and the compression of the sinusoids were demonstrated by ancillary stains (Gomori, CD68, collagen IV). The extent of the LOS was quantified by measuring the area and maximum diameter of fat lakes. The clinical course of patients with LOS was retrospectively evaluated and correlated with the histological findings. RESULTS LOS was observed in eight patients, ranging from focal to very extensive extracellular fat. The diagnosis was based on routine histology, supplemented by collagen IV stain highlighting double contours of sinusoids. The morphological findings suggested that lipidic obstruction of the hepatic sinusoids was a key pathophysiological factor. LOS was associated with liver necrosis and activation of macrophages. Patients with LOS exhibited a variable clinical course, ranging from subclinical to severe, including LT or even death. The extent of fat lakes correlated with the severity of the clinical course. CONCLUSIONS We suggest the term LOS for a particular pattern of liver damage that can occur in SLD outside the transplantation setting and may lead to impaired hepatic blood flow. LOS is associated with a variable clinical presentation, ranging from subclinical to fatal. Clinicians and pathologists should be aware of this complication of SLD, which is diagnosed by liver histology.
