Placental assessment following a stillbirth is a crucial investigation. It helps identify possible causes or contributing factors to stillbirth. It can help evaluate the risk of recurrence in future pregnancies and may indicate whether further tests are needed. It also provides guidance for managing subsequent pregnancies. In this review, we discuss practical considerations in placental assessment following stillbirth, including how both pre-analytical and analytical factors can influence the assessment. We outline the changes that occur in the placenta after stillbirth and explain how to distinguish these changes from antemortem placental pathology known to cause stillbirth. In addition, we highlight incidental findings and artefacts in the placenta that can be confused with true pathology. Finally, we address current controversies, identify areas for future research, and propose a practical approach to assessing the placenta in cases of stillbirth.

A rapid method for triaging febrile patients by aetiology (e.g., viral or bacterial infection) using gene expression in peripheral blood (PB) is an intensively researched area. However, gene expression in blood represents a composite sum of gene expression of all the component cell types present in the sample. As a result, numerous genes are measured in most proposed signatures. Herein, we propose a simple ratio-based biomarker (RBB) called direct leukocyte subpopulation-transcript abundance assay (DIRECT LS-TA) that recapitulates gene expressions of a single cell type in PB (i.e., monocytes). Based on single-cell RNA sequencing (scRNAseq) data and bulk expression data, IFI27 and SIGLEC1 are found as interferon-stimulated genes (ISGs) predominantly expressed by monocytes. The DIRECT LS-TA method can use a simple ratio of two genes measured in PB as an RBB to represent the target gene expression in monocytes without the need for monocyte purification. Both scRNAseq and bulk RNA sequencing datasets were used to evaluate the correlation between ISG expression in monocytes and PB, with a particular focus on monocyte expression of IFI27. An iceberg plot of bulk transcriptome data was used to identify genes that were predominantly expressed by monocytes in PB. DIRECT LS-TA RBBs of the three genes (IFI27, IFI44L and SIGLEC1) were evaluated by group-wise comparison, receiver operating characteristic and meta-analysis. In addition, the conventional interferon (IFN) score was evaluated for comparison of diagnostic performance. In viral infection datasets, DIRECT LS-TA of IFI27 (IFI27/PSAP or IFI27/CTSS) was most intensely activated (p value by t test <1e-9) and had the best area under the curve (0.94) among the three potential monocyte ISGs analysed. DIRECT LS-TA SIGLEC1 was also another monocyte biomarker but showed a lower activation (p<9e-5). IFI27/PSAP showed better diagnostic performance than the conventional IFN score. On the other hand, IFI44L was not a predominant monocyte expression gene. DIRECT LS-TA of IFI27 (IFI27/PSAP or IFI27/CTSS) measured in PB was the best biomarker of viral infection and IFN activation among ISGs predominantly expressed by monocytes. It performed even better than the conventional IFN score which required quantification of eight genes. The results suggest that DIRECT LS-TA of IFI27 is a monocyte-informative biomarker which is easy to determine in PB without the need for cell sorting.

Hydrops fetalis is defined by abnormal fluid accumulation in at least two fetal compartments, resulting from a range of underlying pathological processes, and with a high mortality at the severe end of the spectrum. Identifying the specific cause is crucial for managing both current and future pregnancies. Despite comprehensive antenatal investigations, including obstetric imaging, serology and genetic testing, many cases of non-immune hydrops fetalis (NIHF) remain unexplained at delivery. Some diagnostic features may not be apparent on ultrasound, with perinatal autopsy providing additional valuable information, particularly when structural fetal anomalies are absent. In this review, a structured, phenotype-based approach to autopsy has been developed for cases of indeterminate aetiology, with categories including NIHF with bilateral cystic hygromas, the pale hydropic baby, NIHF associated with cardiovascular system abnormalities, NIHF with no obvious structural abnormality, and NIHF with prominent ascites. Both genetic and non-genetic causes are considered across all groups, with a particular focus on recently described entities and newly identified underlying aetiologies. Placental examination is also vital and may offer key diagnostic clues; though certain pitfalls must be avoided. Comprehensive evaluation by specialist perinatal pathologists can provide crucial diagnostic information in investigation of NIHF.

Transcription factor 12 (TCF12) is a basic helix-loop-helix transcription factor implicated in tissue differentiation and pathogenesis in many types of cancer. Its role in breast and ovarian cancer remains poorly understood. TCF12 protein expression was assessed by immunohistochemistry in 1,514 primary breast tumours and 423 ovarian tumours. TCF12 mRNA expression was analysed in the Molecular Taxonomy of Breast Cancer International Consortium cohort (n=1,980). Associations between protein expression with clinicopathological variables and patient survival were evaluated. In breast cancer, TCF12 was predominantly expressed in the nucleus with low nuclear expression observed in 32% of cases. Both TCF12 protein and mRNA expression were significantly associated with adverse clinicopathological features, including larger tumour size, higher Nottingham Prognostic Index category, and oestrogen receptor-negative tumours. Low nuclear TCF12 expression was associated with adverse breast cancer-specific survival, particularly in oestrogen receptor-positive tumours; it remained an independent adverse prognostic factor in the multivariate analysis. Similar findings were observed when assessing TCF12 mRNA. No association was observed between TCF12 expression and survival of ovarian cancer patients. Low TCF12 expression identified a biologically aggressive subset of breast cancers with poor prognosis. These findings highlight the potential of TCF12 as a prognostic biomarker in breast cancer. No association between TCF12 expression and survival was observed in ovarian cancer patients, suggesting tumour-specific roles.

Rearrangements involving MECOM at chromosome 3q26.2 are recurrent in myeloid neoplasms, classically represented by inv(3)(q21q26.2) and t(3;3)(q21;q26.2), which reposition the GATA2-distal haematopoietic enhancer and drive aberrant EVI1 overexpression. However, the full structural and mechanistic diversity of MECOM rearrangements (MECOM-r) is yet to be explored. We retrospectively analysed 97 cases with cytogenetically defined MECOM-r and identified 12 with complex rearrangements using GTG-banded karyotyping and tri-colour interphase/metaphase fluorescence in situ hybridisation analyses. These 12 cases demonstrated remarkable structural heterogeneity. The abnormalities encompassed translocations, inversions, insertions, duplications, and deletions, which often coexisted within the same specimen as multiple rearranged subclones. Insertional events emerged as a distinct mechanism of MECOM activation. These encompassed insertions of MYNN and/or MECOM into chromosomes 1 and 6, insertion of chromosome 8 segment into MECOM, and inverted insertions between homologous chromosome 3 segments. Recurrent breakpoints at 3q21 across multiple cases, together with localised copy number imbalances frequently involving the MYNN and GOLIM4 loci at 3q26.2, underscore the architectural fragility of these two regions. Co-occurring abnormalities such as -5/del(5q), -7/del(7q), and TP53 loss were common, reflecting a permissive genomic background for chromosomal reassembly. Our findings expand the mechanistic landscape of MECOM-r beyond canonical inv(3)/t(3;3), establishing 3q21 and 3q26.2 as structural 'hotspots' and genomic instability hubs. Distinct from fusion-driven oncogenes such as KMT2A, MECOM activation results from enhancer hijacking and regional structural remodelling, leading to EVI1 overexpression and clonal evolution in myeloid malignancies.

Accurate grading of bone marrow fibrosis is essential for the diagnosis and prognostication of myeloproliferative neoplasms (MPNs). The 2017 World Health Organization (WHO) Classification recommends a trichrome stain be performed to evaluate collagen fibrosis when reticulin fibrosis grade is >1, but the inter-observer concordance in assessing collagen fibrosis in a routine diagnostic laboratory and the utility of this stain are unclear. This study assesses the inter-observer agreement in the grading of reticulin fibrosis and collagen fibrosis, and the concordance between reticulin and collagen fibrosis. Two pathologists assessed 174 consecutive bone marrow trephine biopsies with a diagnosis of an MPN at a tertiary referral centre. Reticulin fibrosis by silver impregnation and collagen fibrosis by Masson's trichrome stain were independently graded by the pathologists while blinded to clinical information. Discordant scores were reviewed to establish a final grade by consensus. Substantial inter-observer concordance was obtained for both reticulin [83%; Cohen's kappa 0.756, 95% confidence interval (CI) 0.69-0.84] and collagen fibrosis grading (81%; kappa 0.730, 95% CI 0.64-0.82). Using the final consensus scores, reticulin and collagen fibrosis grades were concordant in 60% of cases. Collagen fibrosis grade was higher than reticulin fibrosis score in 11% of cases. Inter-observer concordance in assessing the degree of collagen fibrosis using the trichrome stain is substantial. Reticulin (silver) staining alone may underestimate the degree of fibrosis. The prognostic significance where the degree of collagen fibrosis is greater than that of reticulin is uncertain and should be investigated in future studies.