Miłosz Badach

TLSs are ectopic, non-encapsulated aggregates of immune cells that develop de novo in non-lymphoid tissues in response to persistent antigenic stimulation and have emerged as clinically relevant features of many solid tumours. However, conventional TLS assessment based on presence/absence, density, or simplified maturation scales does not adequately explain why TLSs are associated with favourable, neutral, or even adverse clinical outcomes across tumour types and treatment settings. In this review, we synthesise the current biological, spatial, and clinical evidence and argue that TLSs should be interpreted not as static histologic findings but as functional immune niches shaped by three interacting axes: structural maturity, spatial localisation, and the functional immune context. We discuss how mature germinal centre-positive TLSs often reflect coordinated B-cell–T-cell cooperation and sustained antigen-driven anti-tumour immunity, whereas partially organised or suppressive TLSs may display transitional or immunoregulatory properties. On this basis, we propose a pragmatic, pathology-oriented conceptual framework that groups TLSs into three simplified functional states: TLS-A, representing mature effector TLSs with germinal centre activity; TLS-B, representing organised but incompletely matured or functionally intermediate TLSs; and TLS-C, representing TLSs dominated by regulatory or suppressive immune programs. We further place these states within recurrent tumour microenvironment archetypes and outline the rationale for a “proposed functional TLS score” integrating histopathologic and molecular readouts. Rather than introducing a definitive biological taxonomy, this framework is intended as a translational model for harmonising TLS interpretation, refining biomarker development, and supporting future studies on prognosis, immunotherapy response, and standardised pathology reporting in solid tumours. Because this framework is derived from a narrative synthesis of published evidence rather than from formal validation, it should be regarded as hypothesis-generating and requires prospective, tumour-specific validation before clinical implementation.

TLS are ectopic, non-encapsulated aggregates of immune cells that develop de novo in non-lymphoid tissues in response to persistent antigenic stimulation, and have emerged as clinically relevant features of many solid tumours. However, conventional TLS assessment based on presence/absence, density, or simplified maturation scales does not adequately explain why TLS are associated with favourable, neutral, or even adverse clinical outcomes across tumour types and treatment settings. In this review, we synthesize current biological, spatial, and clinical evidence and argue that TLS should be interpreted not as static histologic findings, but as functional immune niches shaped by three interacting axes: structural maturity, spatial localization, and functional immune context. We discuss how mature germinal centre-positive TLS often reflect coordinated B-cell–T-cell cooperation and sustained antigen-driven antitumour immunity, whereas partially organised or suppressive TLS may display transitional or immunoregulatory properties. On this basis, we propose a pragmatic, pathology-oriented conceptual framework that groups TLS into three simplified functional states: TLS-A, representing mature effector TLS with germinal centre activity; TLS-B, representing organised but incompletely matured or functionally intermediate TLS; and TLS-C, representing TLS dominated by regulatory or suppressive immune programs. We further place these states within recurrent tumour microenvironment archetypes and outline the rationale for a “functional TLS score” integrating histopathologic and molecular readouts. Rather than introducing a definitive biological taxonomy, this framework is intended as a translational model for harmonising TLS interpretation, refining biomarker development, and supporting future studies on prognosis, immunotherapy response, and standardised pathology reporting in solid tumours.

Micro- and nanoplastics (MNPs) are emerging environmental contaminants of increasing relevance to human health. Growing evidence suggests that, following ingestion, inhalation, or, less convincingly, dermal exposure, MNPs may cross biological barriers, enter lymphatic and vascular compartments, and reach the liver. Owing to portal blood flow, sinusoidal architecture and Kupffer cell activity, the liver appears to be one of the principal sites of early particle sequestration. Human biomonitoring, ex vivo and postmortem studies have detected MNPs in blood and multiple organs, including the liver, although the currently available evidence remains limited and methodologically heterogeneous. Their identification relies on multistep analytical procedures that integrate sample pretreatment with FTIR, Raman spectroscopy, LD-IR, Py-GC-MS and supplementary imaging methods. However, each of these techniques presents significant limitations, particularly in the analysis of nanoplastics. Experimental studies indicate that MNPs may induce hepatic injury through oxidative stress, mitochondrial impairment, endoplasmic reticulum stress, inflammation, DNA damage, dysregulated lipid metabolism and disruption of the gut–liver axis, consequently contributing to steatosis, cholestatic anomalies and fibrosis. Consequently, MNPs should be considered potential contributors to liver pathology, although more comprehensive human data are still required.

Mushroom-related intoxications pose a distinctive challenge for forensic medicine because early manifestations are non-specific, latency may be prolonged, and co-exposures can obscure the mechanism of death. This narrative review summarizes key toxic and psychoactive fungi and their principal compounds, spanning organ-toxic syndromes (amatoxins, orellanine) and functional neuropsychiatric intoxications—acute, predominantly functional effects causing impairment rather than organ failure (psilocybin/psilocin, ibotenic acid/muscimol). We propose an integrated diagnostic workflow combining exposure history, biochemical markers of organ injury, mycological assessment, and confirmatory toxicology. Particular emphasis is placed on postmortem interpretation: toxin instability and biotransformation, conjugation, matrix effects, postmortem redistribution (central vs. femoral blood), and postmortem fungal colonization that may alter analyte profiles or generate misleading metabolites. Because robust lethality thresholds are unavailable for most mushroom toxins, conclusions should rely on a multi-source synthesis of scene information, autopsy/histopathology, and time-dependent matrix selection (urine, gastric contents/vomitus, bile, and selected tissues; kidney for late orellanine confirmation). We review current screening and confirmatory methods—ELISA; LC-MS/MS, LC-HRMS/MS, GC-MS—and highlight pre-analytical requirements (rapid sampling, cold storage) to reduce false negatives. Finally, we discuss emerging directions such as point-of-care tests, portable mass spectrometry, and DNA barcoding for species identification.

Colorectal cancer (CRC) is one of the deadliest and most frequently occurring cancers worldwide. Often diagnosed in advanced stages, it requires more challenging treatment. However, emerging studies highlight the possible role of microRNAs (miRNAs) in the screening, diagnosis, and prognosis of CRC. MiRNAs modulate gene expression and can play both roles in tumor suppressors and oncogenes. In CRC, they influence epithelial–mesenchymal transition (EMT), cell proliferation and migration, apoptosis, autophagy, and patients’ treatment response. In clinical applications, they can be used as predictive and prognostic biomarkers as well as for matching the most suitable treatments. Despite its growing popularity, there is still much to discover about their potential usage in medicine.