Abstract
1. Anaplasia in Wilms Tumour: A 30-Year UK Experience
1Sidra Medicine, Doha, Qatar
2University Hospital of Wales, Cardiff, UK
3UCL Great Ormond Street Institute of Child Health, London, UK
Abstract
Background
Anaplasia is a recognised unfavourable histological feature of Wilms Tumour (WT). It is subclassified into focal (FA) and diffuse (DA), which have different treatment and outcome implications in COG and SIOP studies.
Aim
Investigate the frequency, age and stage distribution, and outcomes of WT with anaplasia (AWT) treated in UK-CCLG centres between 1991 and 2020.
Material and Methods
Retrospective analysis of UKW3, SIOPUK2001 and IMPORT studies.
Results
AWT prevalence was 171/1829 (9.3%), including 148/1691 (8.8%) unilateral WT, 23/138 (16.7%) bilateral WT; FA 43/171 (25.1%), DA 128/171 (74.9%). 33/171 (19.3%) AWT were diagnosed as non-AWT by institutional pathologists. Male-to-female ratios were similar between AWT and non-AWT (1.3 vs. 1.1, p = 0.33). Median age at diagnosis: DA 55 months, FA 39 months, non-AWT 37 months. No AWT were diagnosed before age 1yr, 53.8% were above age 4yr (35.4% non-AWT, p < 0.00001). Stage distribution of FA and non-AWT was similar, whereas DA showed significantly more stage IV&V, and fewer stage I cases. 63/171 (36.8%) AWT relapsed (7/43 16.3% FA vs. 56/128 43.8% DA, p = 0.001), with only 4/63 (6.3%) after 24 months. Event-free and overall survival (EFS) estimates at four years, EFS: DA 51% (95%CI 41-64%), FA 88% (75-100%), non-AWT 85% (83-87%); OS: DA 57% (47-70%), FA 95% (85-100%), non-AWT 94% (92-95%).
Conclusions
AWT still represents a diagnostic challenge with ∼20% of misdiagnosed cases. FA and DA significantly differ in age and stage distributions, and outcomes. FA outcome is not significantly different from non-AWT, whereas DA has significantly worse outcome despite more aggressive treatment.
2. Clinical Exome Versus Conventional Sequencing in the Diagnosis of Fetal Skeletal Dysplasias
1Pathology, Hospital Clinic, Universitat de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
2Obstetrics, Hospital Clinic, Universitat de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
3Genomics
4Pediatrics, Hospital Clínic
Published in Virchows Archiv 2020 vol 477 (supp1) s5 OFP-02-002
3. Differential Phenotype, Density and Distribution of Maternal and Fetal Macrophages in Infected and Non-Infected Preterm Versus Term Deliveries
1PRIME Research Team Academic Unit or Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK
2Department of Obstetrics and Gynaecology, University of Sheffield, Sheffield, UK
Abstract
The heterogeneous pathophysiology of preterm birth (PTB) makes prediction and prevention problematic, however, a causal association between spontaneous PTB and infection and inflammation has been described; up to 40% of preterm births have been identified as showing tissue features of infection/inflammation. A lack of studies on the role of the placenta in the immunological pathomechanisms of PTB means it is unclear whether inflammation leads to PTB through an endogenous placental immune response that prematurely activates inflammatory pathways associated with labour, or whether placental maldevelopment leads to dysregulation of maternal tolerance and rejection of the semiallogeneic fetus. Maternal and fetal macrophages are abundant cell populations in compartments of the placenta and each may have a role in the activation of placental inflammatory processes in response to pathogens or locally-produced inflammatory markers, resulting in PTB.
This study aims to evaluate the location, origin, phenotype and quantity of macrophages in preterm and term control, and preterm and term placentas with features of infection/inflammation, to identify whether alterations contribute to the pathogenesis of PTB. Placentas of preterm and term pregnancies are immunohistochemically stained for macrophage markers CD68(+), CD163(+) and CD80(+). Sequentially a CENY-Q (FITC) FISH probe Y-chromosome marker is used to identify macrophages of fetal origin in placentas from male offspring. Sequential immunohistochemical staining is then employed to assess the gestation and infection status-dependent distribution, phenotype and densities of identified macrophage populations, and to determine the contribution of immunological alterations on timing of labour. This work is ongoing.
4. Morphometric Placental Villous and Vascular Characteristics Differ in Early and Late-Onset Placental Syndrome
1Maastricht University Medical Centre, Maastricht, the Netherlands
Abstract
Materials and Methods
Fifty-seven placentas of various gestational ages (GA) were studied on villus area, vessel- and vessel lumen-area and vessel number with morphometry after CD34-immunohistochemistry in terminal villi. We corrected total vessel area for villus area by dividing them into a capillarisation-index. Placentas were grouped into Early-onset Delivery (<34 weeks GA, n = 29) and Late-onset Delivery (≥34 weeks GA, n = 28). Additionally, groups were based on phenotype: 1) Early-onset PE and/or FGR (PE/FGR), n = 20; 2) Lateonset PE/FGR, n = 18; 3) Early-onset Controls, n = 9; and 4) Late-onset Controls, n = 10. Subanalyses were performed in PE/FGR-cases in relation to umbilical artery (UmbA) Doppler velocimetry.
Results
The effect of PE/FGR on villus area depended on GA (p = 0.029); Late-onset Delivery showed no effect (p = 0.981), whereas in Early-onset PE/FGR villus area was reduced compared to Early-onset Controls (247 µm, 95%CI 77-416; p = 0.006). Early-onset Delivery showed less capillarisation than Late-onset Delivery (capillarisation-index 0.28 vs 0.34, p = 0.005), without interaction for PE/FGR. Interestingly, capillarisation increased with decreasing blood flow in UmbA Doppler.
Conclusion
Abnormal villous growth seemed associated with Early-onset PE/FGR only. However, capillarisation was affected by GA only, independent of PE/FGR and might be related to UmbA Doppler-values. By extending this exploratory study we can further investigate the relationship between capillarisation and villous development in PE/FGR together with UmbA Doppler-values, which may aid in unravelling its pathophysiology.
5. Severe Osteopaenia in a Fetus With Massive Perivillous Fibrin Deposition of the Placenta
1Nottingham University Hospitals NHS Trust, Nottingham, UK
2University Medical Centre Utrecht, Utrecht, the Netherlands
Abstract
A 36 year old, Gravida 5, Para 0 with three first trimester miscarriages, and one midtrimester loss with extreme IUGR. Post mortem following intra-uterine death of a fetus of 27 + 6 weeks gestation with extreme IUGR and intrauterine death.
6. An Unusual Adrenal Tumour in a Neonate
1Hopital Armand Trousseau, Sorbonne University, Paris, France
2University of Caen, Caen, France
3Institute Curie, Paris, France
Abstract
Diagnosis of adrenal lesions in neonates may be challenging. In order to illustrate neonatal adrenal pathology, we report the case of a 4 month old female who presented an antenatal adrenal lesion discovered on the 3rd trimester US. Premature birth occurred at 34WG and neonatal MRI suggested an adrenal haemorrhage. Urinary catecholamines were not elevated. A second MRI at the age of 2 months showed a 5cm adrenal lesion with an heterogeneous solid component and a decrease haemorrhagic component. Needle biopsy showed a S100+ and SOX10+ bland neuroid spindle-cell tumour without neuroblastic cells. A Schwannian component of a peripheral neuroblastic tumor or a neurofibroma were suggested. No predisposing condition was suspected clinically. At the age of 5 months, surgical resection of the adrenal lesions was performed which required total left nephrectomy. Maroscopy showed a 7.8cm multinodular extra-renal mass with 2 components, a bland neuroid spindle cell and a small round cell tumor. Immunostaining showed that both components express CD56, NSE, S100, SOX10 and an heterogeneous lo CD99 expression. A malignant peripheral nerve sheath tumour arising in a neurofibroma was suggested. Genomic profiling showed 1q and 22 losses, 22 isodisomy an 8p gains. Transcriptional analysis revealed an EWSR1/ETV1 fusion. We concluded this was an extra skeletal spindle cell Ewing’s sarcoma with EWSR1/ETV1 fusion. Neonatal adrenal lesions/tumours, along with adrenal cysts, adrenal haemorrhage, neuroblastoma, adrenal cortical adenoma/carcinoma and phaeochromocytoma should include extraskeletal Ewing’s sarcoma.
7. Prognostic Significance of Histopathological Response to Preoperative Chemotherapy in Wilms’ Tumour
1Oslo University Hospital, Rikshospitalet, Oslo, Norway
2Saarland University Hospital, Homburg, Germany
3University Hospital, Bonn, Germany
4UCL Great Ormond Street Institute of Child Health, London, UK
5Sidra Medicine, Doha, Qatar
Abstract
Background
In the SIOP Wilms tumour (WT) trials preoperative chemotherapy has been used as the first line of treatment. Completely necrotic WTs (CN-WTs) are regarded as low risk tumours.
Material and Methods
A retrospective study of 2,117 unilateral, non-anaplastic WTs from the UK and German WT studies (2001-2020).
Results
There were 126 (6.0%) patients with CN-WTs and 773 (36.5%) with RT-WTs, stages I-IV. The 5-year RFS and OS for CN-WTs were 95.3% (±2.1% SE) and 97.3% (±2% SE), and for RT-WTs 86.4% (±1.4% SE, p < 0.01) and 95.2 (±0.9% SE, p = 0.59), respectively. Distribution of chemotherapy induced changes-percentage showed a case clustering around <85%, 90%, 95% and 97-99%. For patients having <90% CIC 5y-RFS of 84.2% (±2.0% SE) was superimposable with those having 90-95% CIC (82.5% ±2.5% SE), while for patients having >95-99% CIC 5y-RFS of 92.9% (±2.6% SE) was significantly superior to 90-95% CIC WTs (p = 0.1). 5y-OS was 96.7% (±1.2% SE), 92.4% (±1.7% SE), 97.8% (±1.5% SE) for <90%, 90-95%, and 96-99% CIC, respectively.
Conclusion
WTs with nearly complete response to pre-operative chemotherapy (>95% CIC) share the same excellent RFS as CN-WTs, but receive significantly more treatment. Treatment reduction should be explored for this subset in a clinically controlled trial.
8. Amperes Neonate Presenting With Seizures, Developmental Delay, Macrocephaly and Diffuse MRI Changes
1Great North Children’s Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
2Wolfson Childhood Cancer Research Centre, Newcastle University, Newcastle upon Tyne, UK
3School of Women’s and Children’s Health, University of New South Wales, Sydney, Australia
4Kids Cancer Centre, Sydney Children’s Hospital Randwick, Sydney, Australia
5Department of Neuroradiology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
6Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
7Northern Genetics Service, Newcastle University, Newcastle upon Tyne, UK
8Great Ormond Street Hospital, London, UK
Abstract
Clinical History
A term-born male neonate presented at age 2 months with developmental delay, macrocephaly and focal seizures. MRI showed disseminated, bilateral white matter changes with frontal sparing, leptomeningeal and brain stem enhancement. In addition, cerebral aqueduct narrowing with lateral and third ventricle hydrocephalus was also present. The clinical presentation, atypical imaging and biopsy findings caused diagnostic uncertainty, leading to a decision to treat as low-grade glioma pending definitive diagnosis. The patient experienced recurrent seizures over 8 weeks, worsening white matter changes and hydrocephalus, requiring a ventriculoperitoneal shunt. He deteriorated further with status epilepticus, requiring anticonvulsants, intubation and ventilation. After extensive team discussion, ventilatory support was withdrawn on the grounds of futility, in consultation with the family.
Conclusion
Alexander disease is an autosomal dominant leukodystrophy caused by a mutation in the GFAP gene, which leads to gain of function and accumulation of abnormal protein that impairs astrocyte function (Johnson and Brenner 2003). Clinicians and pathologists need to consider Alexander disease in cases where a neonate presents with seizures and bilateral widespread white matter changes in association with Rosenthal fibres.
9. Unsuspected Myocarditis Presenting as Sudden Death in Infants and Children
1Sheffield Children’s NHS Foundation Trust, Sheffield, UK
Published in Virchows Archiv 2020 (vol 477 (supp1) S115