Anke Scharrer

Introduction: Angiosarcomas are very rare, malignant tumors of the endothelial lining of blood vessels and most present cutaneously, while only 10% present as deep soft tissue angiosarcomas. Literature is sparse regarding secondary deep soft tissue angiosarcoma, especially in cases that have formed surrounding a foreign body such as orthopedic implants. Case: A 59-year-old Caucasian male presented with a 1-year history of occasional headaches and non-intentional weight loss. One month prior to consult, he began to experience progressive pelvic pain on weight-bearing, up to 10/10 in severity, with associated swelling of the left leg. Further diagnostics revealed a hypervascular tumor on the anterior left hemipelvis, directly over his initial pelvic injury and orthopedic implants placed 33 years ago. Clinical Discussion: Biopsy revealed a high-grade angiosarcoma surrounding a stainless-steel 316L reconstruction plate adjacent to a titanium alloy (Ti-6Al-4 V) total hip arthroplasty. NextGen Genome sequence analysis done reveals tier II mutations (potential clinical significance) in the HOXB13 p.G84E and RPS6KB1 genes. Conclusion: Few published cases exist regarding secondary deep soft tissue angiosarcoma, and its peculiar presentation in our case arising at the juncture between two orthopedic implants of different compositions suggests a possible effect of galvanic corrosion, and warrants further study.

Brain development and subsequent brain function are highly sensitive to genetic mutations, which can result in severe neurodevelopmental malformations. Alterations in PTEN signaling cause a spectrum of developmental malformations and neurological diseases including epilepsy. To date, a detailed understanding of the neuropathological underpinnings of PTEN ‐associated brain malformations, particularly in fetuses, is missing. We have thus investigated a fetal case of hemimegalencephaly (HME), which is a rare disorder characterized by hemispheric overgrowth, developmental delay, and epileptic seizures. Our assessment of the male fetus includes genetic, radiologic, and histologic features and provides a comprehensive characterization of the cellular alterations in HME together with a genotypic correlation. Genetic analyses uncovered that hemispheric overgrowth was caused by a somatic second hit resulting in biallelic PTEN alteration in the affected brain tissue, although the unaffected hemisphere carried the same PTEN variant as the heterozygous germline variant. Based on the latter, we interpret that the PTEN mutation is not a dominant‐negative variant. Within the outer subventricular zone of the enlarged cortex, we found small nodular heterotopias, which can be origins of focal epileptic seizures. Cell type‐specific marker stainings revealed that the heterotopias consisted exclusively of SATB2 ⁺ glutamatergic projection neurons. Altogether, our analyses and findings contribute to a deeper understanding of the pathomechanisms of a novel PTEN variant driving a severe brain malformation.

Introduction: Soft tissue sarcomas are rare and heterogenous malignancies with a poor prognosis in advanced disease stages. Eribulin is used in metastatic liposarcoma (LPS) patients, who have failed first-line chemotherapy and has been approved for use in patients with LPS in the USA and Europe due to its efficacy in this histological subtype in a phase 3 trial. We have evaluated efficacy and tolerability of eribulin in LPS and leiomyosarcoma (LMS) patients in the routine clinical setting at our department. Methods: In this retrospective single-center analysis, efficacy and safety of eribulin were retrospectively evaluated in advanced LPS and LMS patients at the Division of Oncology, Medical University of Vienna. Results: A total of 32 adult patients treated with eribulin were identified and included in this analysis. Overall response rate was 9.4% for all patients, with one patient with LPS and two patients with LMS showing a partial response. Disease control rate (partial response plus stable disease) for all patients was 50% (LPS: 47.1%; LMS 53.3%). No statistically significant difference in median progression-free survival and overall survival was detected between patients with LPS and LMS (p = 0.807 and p = 0.519, respectively). Patients with LMS (n = 2) had received fewer previous therapy lines than patients with LPS (n = 14) (≤ previous treatment lines, p < 0.001). Toxicity was generally manageable, and grade 3 + 4 events were rare. Conclusion: The activity and tolerability of eribulin in LPS as in well in LMS patients in the routine clinical setting is comparable to outcomes reported in published phase 3 trials.

Fetal congenital heart disease (CHD) is often associated with chromosomal abnormalities. Our primary aim was to assess stillbirth and neonatal mortality rates for pregnancies complicated by trisomies 13, 18, and 21 in the presence of CHD, from a single tertiary referral center during 2000–2020 in a retrospective cohort study. The secondary aims were to investigate maternal morbidity in these pregnancies, and to study the gestational or neonatal age when mortality occurred. Inclusion criteria were the prenatal diagnosis of at least one structural CHD, together with prenatally diagnosed fetal trisomy 13, 18, or 21. One-hundred and sixty patients with fetal trisomy 13 (14.4%), fetal trisomy 18 (28.8%), and fetal trisomy 21 (56.9%) were evaluated. In total, 98 (61.3%) families opted for the termination of pregnancy (TOP). Of the remaining 62 (38.8%) pregnancies, 16 (25.8%) resulted in intrauterine fetal death/death during delivery. Ten out of twenty-one (47.6%) infants with trisomy 13 or 18 were born alive. The livebirth rate was 87.8% (36/41) for infants with trisomy 21. Early neonatal death was observed in nine (19.6%) infants. Thirty-one (86.1%) infants with trisomy 21 survived the first year of life. These data may be helpful for counseling affected parents when the decision to terminate or continue the pregnancy should be considered.

The adult human skin contains a vast number of T cells that are essential for skin homeostasis and pathogen defense. T cells are first observed in the skin at the early stages of gestation; however, our understanding of their contribution to early immunity has been limited by their low abundance and lack of comprehensive methodologies for their assessment. Here, we describe a new workflow for isolating and expanding significant amounts of T cells from fetal human skin. Using multiparametric flow cytometry and in situ immunofluorescence, we found a large population with a naive phenotype and small populations with a memory and regulatory phenotype. Their molecular state was characterized using single-cell transcriptomics and TCR repertoire profiling. Importantly, culture of total fetal skin biopsies facilitated T cell expansion without a substantial impact on their phenotype, a major prerequisite for subsequent functional assays. Collectively, our experimental approaches and data advance the understanding of fetal skin immunity and potential use in future therapeutic interventions.

The hyperintense bronchus sign is a frequently detectable fetal MRI feature of airway obstruction. Background Fetal MRI–based differential diagnosis of congenital lung malformations is difficult because of the paucity of well-described imaging markers. Purpose To characterize the hyperintense br...

T cells in human skin play an important role in the immune defense against pathogens and tumors. T cells are present already in fetal skin, where little is known about their cellular phenotype and biological function. Using single-cell analyses, we identified a naive T cell population expressing αβ and γδ T cell receptors (TCRs) that was enriched in fetal skin and intestine but not detected in other fetal organs and peripheral blood. TCR sequencing data revealed that double-positive (DP) αβγδ T cells displayed little overlap of CDR3 sequences with single-positive αβ T cells. Gene signatures, cytokine profiles and in silico receptor–ligand interaction studies indicate their contribution to early skin development. DP αβγδ T cells were phosphoantigen responsive, suggesting their participation in the protection of the fetus against pathogens in intrauterine infections. Together, our analyses unveil a unique cutaneous T cell type within the native skin microenvironment and point to fundamental differences in the immune surveillance between fetal and adult human skin.

Mini-commentary on BJOG-20-1156.R2: Post-mortem confirmation of fetal brain abnormalities: challenges highlighted by the MERIDIAN cohort study