Recurrent GTD and GTD coexisting with normal twin pregnancy

Hydatidiform mole (HM) affects around 1/1000 pregnancies, and in such cases the recurrence risk is around 1%, being greater for those with complete HM (CHM). Whilst most cases appear sporadic with unknown mechanisms, there is a distinct subgroup of patients who suffer recurrent pregnancy loss, including multiple recurrent CHM (familial recurrent biparental HM syndrome). The majority of these cases are related to maternal genetic mutations in genes related to the control of imprinting, specifically NALP7 and KHDC3L. Oocyte donation is an effective treatment allowing these patients to have successful pregnancies. Approximately 1 in 50,000 pregnancies are complicated by twin pregnancy comprising normal foetus and HM, the majority of reported cases being CHM. Such pregnancies are at significantly increased risk of complications, including pregnancy loss, early-onset preeclampsia and severe preterm delivery, but when managed conservatively the delivery of a liveborn healthy infant occurs in around one-third of cases. Regardless of management, the risk of persistent GTD in such cases appears similar to that following singleton CHM. Rarely, other conditions mimic prenatal ultrasound appearances of twin pregnancy with HM, CHM mosaicism and placental mesenchymal dysplasia, both of which have distinctive histological and genetic features

p57KIP2 immunostaining for diagnosis of hydatidiform mole.

Accurate diagnosis and sub-classification of hydatidiform moles (HM) and distinction from non-molar (NM) gestations is important, since risk of persistent gestational trophoblastic disease (pGTD) and therefore clinical management differ. P57KIP2 immunostaining has been widely described as an ancillary test to distinguish complete (CHM) and partial (PHM) hydatidiform moles, but cannot discern PHM from non-molar gestations (NM) or identify androgenetic vs biparental CHM, which may be associated with increased recurrence risk. Molecular genotyping (MG) is the gold-standard in these scenarios and also in cases with aberrant/discordant p57KIP2 expression, following which, CHM, PHM and NM can be reliably diagnosed. This article is protected by copyright. All rights reserved

Perinatal pathology reports: A guide for obstetricians

This article will provide the practising obstetrician with a general guide to the structure and interpretation of the histopathology report, with a focus on placental and perinatal autopsy reports. The relevance and readability of a histopathology report is heavily dependent on the quality of clinical information provided by the referring clinician. Walkthroughs of example placental and autopsy reports are provided, along with examples of pathologies and their possible significance to the underlying diagnosis

Characterising Post-mortem Bacterial Translocation Under Clinical Conditions Using 16S rRNA Gene Sequencing in Two Animal Models

Sudden unexpected death in infancy (SUDI) is the sudden and unexpected death of an apparently healthy infant occurring within the first year of life where the cause is not immediately obvious. It is believed that a proportion of unexplained infant deaths are due to an infection that remains undiagnosed. The interpretation of post-mortem microbiology results is difficult due to the potential false-positives, a source of which is post-mortem bacterial translocation. Post-mortem bacterial translocation is the spread of viable bacteria from highly colonised sites to extra-intestinal tissues. We hypothesise that although post-mortem bacterial translocation occurs, when carcasses are kept under controlled routine clinical conditions it is not extensive and can be defined using 16S rRNA gene sequencing. With this knowledge, implementation of the 16S rRNA gene sequencing technique into routine clinical diagnostics would allow a more reliable retrospective diagnosis of ante-mortem infection. Therefore, the aim of this study was to establish the extent of post-mortem bacterial translocation in two animal models to establish a baseline sequencing signal for the post-mortem process. To do this we used 16S rRNA gene sequencing in two animal models over a 2 week period to investigate (1) the bacterial community succession in regions of high bacterial colonisation, and (2) the bacterial presence in visceral tissues routinely sampled during autopsy for microbiological investigation. We found no evidence for significant and consistent post-mortem bacterial translocation in the mouse model. Although bacteria were detected in tissues in the piglet model, we did not find significant and consistent evidence for post-mortem bacterial translocation from the gastrointestinal tract or nasal cavity. These data do not support the concept of significant post-mortem translocation as part of the normal post-mortem process

Current issues in postmortem imaging of perinatal and forensic childhood deaths

Perinatal autopsy practice is undergoing a state of change with the introduction of evidence-based cross-sectional imaging, driven primarily by parental choice. In particular, the introduction of post mortem magnetic resonance imaging (PMMR) has helped to advance less-invasive perinatal autopsy in the United Kingdom (UK) and Europe. However, there are limitations to PMMR and other imaging techniques which need to be overcome, particularly with regard to imaging very small fetuses. Imaging is also now increasingly used to investigate particular deaths in childhood, such as suspected non-accidental injury (NAI) and sudden unexpected death in infancy (SUDI). Here we focus on current topical developments the field, with particular emphasis on the application of imaging to perinatal autopsy, and pediatric forensic deaths. Different imaging modalities and their relative advantages and disadvantages are discussed, together with other benefits of more advanced cross-sectional imaging which currently lie in the research domain. Whilst variations in local imaging service provision and need may determine different practice patterns, and access to machines and professionals with appropriate expertise and experience to correctly interpret the findings may limit current practices, we propose that gold standard perinatal and pediatric autopsy services would include complete PMMR imaging prior to autopsy, with PMCT in suspicious childhood deaths. This approach would provide maximal diagnostic yield to the pathologist, forensic investigator and most importantly, the parents

Whole-tumor apparent diffusion coefficient measurements in nephroblastoma: Can it identify blastemal predominance?

PURPOSE: To explore the potential relation between whole-tumor apparent diffusion coefficient (ADC) parameters in viable parts of tumor and histopathological findings in nephroblastoma. MATERIALS AND METHODS: Children (n = 52) with histopathologically proven nephroblastoma underwent diffusion-weighted magnetic resonance imaging (MRI) (1.5T) before preoperative chemotherapy. Of these, 25 underwent an additional MRI after preoperative chemotherapy, shortly before resection. An experienced reader performed the whole-tumor ADC measurements of all lesions, excluding nonenhancing areas. An experienced pathologist reviewed the postoperative specimens according to standard SIOP guidelines. Potential associations between ADC parameters and proportions of histological subtypes were assessed with Pearson's or Spearman's rank correlation coefficient depending on whether the parameters tested were normally distributed. In case the Mann-Whitney U-test revealed significantly different ADC values in a subtype tumor, this ADC parameter was used to derive a receiver operating characteristic (ROC) curve. RESULTS: The 25(th) percentile ADC at presentation was the best ADC metric correlated with proportion of blastema (Pearson's r = -0.303, P = 0.026). ADC after preoperative treatment showed moderate correlation with proportion stromal subtype at histopathology (r = 0.579, P = 0.002). By ROC analysis, the optimal threshold of median ADC for detecting stromal subtype was 1.362 × 10(-3) mm(2) /s with sensitivity and specificity of 100% (95% confidence interval [CI] 0.65-1.00) and 78.9% (95% CI 0.57-0.92), respectively. CONCLUSION: ADC markers in nephroblastoma are related to stromal subtype histopathology; however, identification of blastemal predominant tumors using whole-tumor ADC measurements is probably not feasible. Level of Evidence 3 J. Magn. Reson. Imaging 2016;00:000-000

Diagnostic accuracy of postmortem ultrasound vs 1.5T postmortem MRI for non-invasive perinatal autopsies

Objectives: To determine the diagnostic accuracy of postmortem magnetic resonance imaging (PM-MRI) and postmortem ultrasound (PM-US) for perinatal autopsy in the same patient cohort, and to determine whether PM-US can provide the same anatomical information as PM-MRI. Methods: In this prospective, 5-year (July 2014–July 2019) single-center study, we performed 1.5-T PM-MRI and PM-US in an unselected cohort of perinatal deaths. The diagnostic accuracies of both modalities were calculated, using autopsy as the reference standard. As a secondary objective, the concordance rates between the two imaging modalities for the overall main diagnosis and for five anatomical regions (brain, spine, thorax, heart and abdomen) were calculated. Results: During the study period, 136 cases underwent both PM-US and PM-MRI, of which 88 (64.7%) also underwent autopsy. There was no significant difference in the rates of concordance with autopsy between the two modalities for overall diagnosis (PM-US, 86.4% (95% CI, 77.7–92.0%) vs PM-MRI, 88.6% (95% CI, 80.3–93.7%)) or in the sensitivities and specificities for individual anatomical regions. There were more non-diagnostic PM-US than PM-MRI examinations for the brain (22.8% vs 3.7%) and heart (14.7% vs 5.1%). If an ‘imaging-only’ autopsy had been performed, PM-US would have achieved the same diagnosis as 1.5-T PM-MRI in 86.8% (95% CI, 80.0–91.5%) of cases, with the highest rates of agreement being for spine (99.3% (95% CI, 95.9–99.9%)) and cardiac (97.3% (95% CI, 92.4–99.1%)) findings and the lowest being for brain diagnoses (85.2% (95% CI, 76.9–90.8%)). Conclusion: Although there were fewer non-diagnostic cases using PM-MRI than for PM-US, the high concordance rate for overall diagnosis suggests that PM-US could be used for triaging cases when PM-MRI access is limited or unavailable

HDR UK supporting mobilising computable biomedical knowledge in the UK

Computable biomedical knowledge (CBK) represents an evolving area of health informatics, with potential for rapid translational patient benefit. Health Data Research UK (HDR UK) is the national Institute for Health Data Science, whose aim is to unite the UK’s health data to enable discoveries that improve people’s lives. The three main components include the UK HDR Alliance of data custodians, committed to making health data available for research and innovation purposes for public benefit while ensuring safe use of data and building public trust, the HDR Hubs, as centres of expertise for curating data and providing expert domain-specific services, and the HDR Innovation Gateway (‘Gateway’), providing discovery, accessibility, security and interoperability services. To support CBK developments, HDR UK is encouraging use of open data standards for research purposes, with guidance around areas in which standards are emerging, aims to work closely with the international CBK community to support initiatives and aid with evaluation and collaboration, and has established a phenomics workstream to create a national platform for dissemination of machine readable and computable phenotypical algorithms to reduce duplication of effort and improve reproducibility in clinical studies

Three-dimensional versus two-dimensional postmortem ultrasound: feasibility in perinatal death investigation

Three- and four-dimensional US techniques in antenatal screening are commonplace, but they are not routinely used for perinatal postmortem US. In this technical innovation, we performed both two-dimensional (2-D) and three-dimensional (3-D) postmortem US on 11 foetuses (mean gestation: 23 weeks; range: 15–32 weeks) to determine whether there was any benefit in 3-D over conventional 2-D methods. In one case of osteogenesis imperfecta, both 2-D and 3-D US images were non-diagnostic because of small foetal size. Of the remaining 10 foetuses, 7 were normal at imaging and autopsy, and 3 had abnormalities detected on both 2-D and 3-D US. There were no false-positive diagnoses by 2-D or 3-D US. Whilst 3-D postmortem US was a feasible technique, it did not provide additional information over 2-D US. Routine 3-D postmortem US cannot therefore be routinely recommended based on our findings

Botryoid Wilms tumor: a non-existent "entity" causing diagnostic and staging difficulties

Wilms tumors growing in a botryoid fashion into the renal pelvis have been reported since the 1960s as a rare tumor type usually associated with stromal histology and a good prognosis. However, the true frequency, association with Wilms tumor subtypes, and stage have never been comprehensively studied. We analyzed all Wilms tumors enrolled into the International Society of Paediatric Oncology (SIOP) United Kingdom 2001 Trial (2001-2011), which showed botryoid growth. In addition, we reviewed published series reporting papers on botryoid Wilms tumors. 77/739 patients (10.4%) showed at least one Wilms tumor with a botryoid pattern, and they were sub-classified according to the SIOP criteria as follows: 28 stromal, 21 mixed, 7 regressive, 3 completely necrotic, 4 blastemal, 2 epithelial, 3 diffuse anaplasia, 1 focal anaplasia, and 10 non-anaplastic type (treated with primary surgery). Stage was as follows: 25 stage I, 21 stage II, 12 stage III, 11 stage IV, and 8 stage V. In six cases, local pathologists incorrectly upstaged the tumor from stage I to stage II based on botryoid growth. The event-free and overall survivals were 90 and 96%, respectively. We concluded that botryoid growth pattern is a common finding in Wilms tumor and that all histological types and stages can share this feature. The botryoid growth itself is not a criterion for stage II. Botryoid Wilms tumor is not an entity but merely represents a pattern of tumor growth; such tumors should be sub-classified according to their overall histological features, which will determine treatment and prognosis