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Study Type: Retrospective molecular cohort study (single-centre series, n=89 IVL, with comparator groups of 106 conventional leiomyomas and 83 cellular leiomyomas).

Key Question: What are the molecular drivers of intravenous leiomyomatosis, and how do they differ from conventional and cellular uterine leiomyomas?

Key Findings:

• HMGA2 overexpression by IHC in 87.5% (77/88) of IVLs (strong in 40.9%); about half harboured HMGA2 rearrangements, mainly HMGA2/RAD51B fusion.
• WES (n=10) showed COL gene family mutations in 70% (7/10), all co-occurring with HMGA2 upregulation.
• MED12 exon 2 mutations (2.5%, 2/79) and FH deficiency (2.4%, 2/82) were rare.

Clinical Relevance: HMGA2 IHC may support diagnosis of IVL in difficult cases, and the low FH deficiency rate suggests FH IHC is unlikely to be useful for routine IVL work-up, though this is not a validated diagnostic recommendation.

Limitations: WES was performed in only 10 cases, so the proposed HMGA2-COL cooperation is hypothesis-generating and lacks functional validation.

Study Type: Retrospective case series with molecular profiling (targeted NGS and copy-number analysis); 14 tumours from 13 patients.

Key Question: What are the molecular features of acquired cystic disease-associated renal cell carcinoma (ACD-RCC), and how do they relate to papillary RCC (PRCC)?

Key Findings:

• No recurrent single-gene alterations were identified; occasional variants (KMT2C, SETD2, FANCA, FAT1) have been reported in other series.
• Three copy-number patterns emerged: gain-predominant (n=7; chromosomes 3, 7, 16, 17, 20), loss-predominant (n=4; chromosomes 6, 9, 14, 19, 21), and near-euploid (n=3).
• Gain-predominant tumours overlapped with TCGA-KIRP PRCC (gains of 7, 16, 17, 20). One synchronous ACD-RCC/PRCC pair had near-identical arm-level profiles, differing only by 3q gain in the ACD-RCC.

Clinical Relevance: Copy-number profiling may support classification and diagnostic discrimination of ACD-RCC versus PRCC in end-stage renal disease nephrectomies, though it is not yet a validated diagnostic tool.

Limitations: Very small cohort with no outcome data, so the clinical or prognostic significance of the copy-number subgroups is unknown.

Study Type: Retrospective case series (single-centre, n=9 identified from 3,696 endometrioid carcinomas, 2020–2025)

Key Question: What are the clinicopathologic, immunophenotypic and molecular features of endometrioid carcinoma with malignant squamous differentiation (SqD), and does it carry prognostic significance?

Key Findings:

• Malignant SqD was rare (9/3,696; approximately 0.2%) but associated with deep myometrial invasion, extensive lymphovascular space invasion and frequent nodal metastasis.
• The malignant squamous component localised mainly to invasive fronts and metastatic deposits, with consistent hormone receptor loss. Preoperative biopsy/curettage often underestimated or misclassified it.
• Cases spanned all four TCGA/ProMisE molecular subtypes, with recurrent PI3K/AKT pathway alterations.

Clinical Relevance: Molecular classification alone may not capture this aggressive phenotype, so careful morphological assessment of invasive fronts and nodal disease remains essential in UK endometrial cancer reporting.

Limitations: Very small sample (n=9) with no survival or recurrence outcomes reported in the abstract, limiting conclusions on prognosis and risk stratification.

Study Type: Retrospective diagnostic accuracy study (single-cohort comparison against FISH/molecular reference standard)

Key Question: Which light microscopy-based ancillary tests most accurately identify TFEB-altered renal cell carcinoma and distinguish it from TFE3-rearranged RCC and common renal tumours?

Key Findings:

• TFEB RNA-ISH was positive in all 16 TFEB-altered RCCs (12 rearranged, 4 amplified) and negative in all controls, including TFE3-rearranged tumours.
• Cathepsin K (3F9) and GPNMB were highly sensitive but non-specific, labelling 40% and 50% of TFE3-rearranged tumours respectively, plus subsets of common renal neoplasms. TRIM63 RNA-ISH was positive in all TFEB-altered cases but also in TFE3-rearranged tumours.
• TFEB IHC sensitivity varied by clone; the Bethyl assay was most reliable.

Clinical Relevance: TFEB RNA-ISH could offer UK laboratories without ready FISH access a practical alternative for confirming this rare entity, which often mimics other RCC subtypes.

Limitations: Small TFEB-altered cohort (n=16) and very few TFE3-rearranged (n=5) and FLCN/mTOR-mutated (n=4) controls limit confidence in the reported specificity, which has not been validated prospectively.

Study Type: Interobserver agreement study (five gastrointestinal pathologists, 100 scanned CRC slides)

Key Question: How reproducibly do pathologists grade colorectal adenocarcinoma using AJCC8, WHO5 and WHO6 criteria, and where do the systems diverge?

Key Findings:

• Fleiss kappa showed substantial agreement for all systems: WHO6 0.730, two-tiered AJCC8 0.731, WHO5 0.655 (all P < 0.001), so WHO6 improved on WHO5.
• WHO grading classified far more tumours as high-grade (mean 34.4 cases with WHO6, 33.6 with WHO5) than AJCC8 (11.8 cases) (P < 0.01).
• Reviewers agreed on some scenarios (e.g. discounting invasive front tumour buds under WHO) but diverged on others, notably stroma-rich areas.

Clinical Relevance: WHO-based grading, as used in UK reporting, may upgrade roughly three times as many tumours as AJCC8, with potential consequences for risk stratification and adjuvant treatment decisions.

Limitations: Only five reviewers and 100 cases were assessed, with no outcome data to show which system better predicts prognosis.

Study Type: Multicentre retrospective case series (26 patients; most from Bordeaux, plus international contributors).

Key Question: What is the spectrum and clinical significance of inter-tumour heterogeneity (multiple molecular subtypes within one patient) in hepatocellular adenoma?

Key Findings:

• ITH-HCA was identified in 26 patients (17 women). All women lacked underlying liver disease, whereas 8/9 men had it.
• Inflammatory HCA combined with another subtype was the commonest pattern (22/26), most often with b-catenin exon 3-mutated IHCA (6) or HNF1A-HCA (5). Combinations spanned the full HCA classification.
• Two patients had HNF1A adenomatosis, one with malignant transformation; another patient with b-IHCA exon 3 progressed to HCC. The largest nodule was a 13 cm IHCA, and one sh-HCA presented with haemorrhage.

Clinical Relevance: Sampling a single nodule may miss a high-risk subtype (b-catenin exon 3, sh-HCA), so multinodular HCA warrants subtyping of several lesions and MDT or tertiary referral.

Limitations: Small, selected retrospective series without follow-up data or denominator, so prevalence and malignant transformation risk cannot be estimated.

Study Type: Retrospective case series (n=8), single-centre histopathological analysis.

Key Question: Can a distinct pattern of extracellular fat obstructing hepatic sinusoids be identified in steatotic liver disease outside the post-transplant setting, and does it carry clinical significance?

Key Findings:

• Eight cases identified (2019–2024) showing extracellular fat "lakes" compressing sinusoids, diagnosable on routine histology; collagen IV highlighted double-contoured sinusoids, and Gomori/CD68 confirmed the extracellular fat and macrophage activation.
• LOS was associated with liver necrosis and macrophage activation, mirroring pseudopeliotic steatosis seen after liver transplantation.
• Clinical course ranged from subclinical to liver transplantation or death; fat lake extent correlated with clinical severity (no statistics reported in abstract).

Clinical Relevance: Pathologists reporting steatotic liver biopsies, particularly with the rising MASLD burden in the UK, should recognise this pattern, as it may flag patients at risk of severe deterioration.

Limitations: Very small, selected retrospective series without a comparator group, so incidence, prognostic value, and causality remain unestablished.

Study Type: Retrospective case series (n=10) with molecular and DNA methylation profiling.

Key Question: Is paediatric PLAG1-rearranged fibromyxoid tumour (P-FMT) a distinct entity or part of the lipoblastoma spectrum?

Key Findings:

• All 10 cases (age 3 months–10 years) showed bland spindle cell fibromyxoid morphology with CD34 and desmin positivity; only two contained focal mature adipocytes. PLAG1 rearrangement was confirmed in all, with six different fusion partners (COL1A2 most frequent, n=3).
• On methylation profiling, all P-FMTs clustered with lipoblastoma and separated from other mesenchymal tumours; chromosome 8 gain was significantly enriched in both.
• No recurrence in cases with follow-up (median 22 months).

Clinical Relevance: In paediatric spindle cell or myxoid lesions that are CD34/desmin-positive with little fat, PLAG1 FISH or sequencing may support a diagnosis of lipoblastoma-spectrum tumour, which is relevant to UK specialist sarcoma and paediatric pathology reporting.

Limitations: Small cohort with short follow-up and no stated control or comparator numbers, limiting conclusions on long-term behaviour and the strength of the entity-versus-variant argument.