SARS-CoV-2 infection as cause of in-utero fetal death: regional multicenter cohort study.

OBJECTIVE: Placental infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to placental insufficiency and in-utero fetal death (IUFD). The objective of this study was to confirm and quantify the extent to which fetoplacental infection with SARS-CoV-2 is a cause of fetal death. METHODS: This was a multicenter retrospective cohort study of fetal deaths that underwent postmortem examination between January 2020 and January 2022 in three fetal pathology units in Paris, France. All cases of IUFD and termination of pregnancy (TOP) occurring in 31 maternity hospitals in the Paris region undergo detailed placental pathological examination in these units. Databases were searched for cases of IUFD and TOP. Cases with fetal malformation or cytogenetic abnormality were excluded to avoid bias. We included cases of IUFD with a placental or undetermined cause and cases of TOP in the context of severe intrauterine growth restriction (IUGR). Placentas were sent to a single virology unit for reverse-transcription polymerase chain reaction (RT-PCR) testing by a single laboratory technician blinded to the initial postmortem examination report. Our primary endpoint was the proportion of positive placental SARS-CoV-2 RT-PCR tests in the cohort. RESULTS: Among 147 722 deliveries occurring over 2 years, 788 postmortem examinations for IUFD and TOP for severe IUGR were recorded, of which 462 (58.6%) were included. A total of 13/462 (2.8%) placentas tested positive for SARS-CoV-2 by RT-PCR. Wild-type virus and alpha and delta variants were identified. All positive cases had histological lesions consistent with placental dysfunction. There was a strong correlation between SARS-CoV-2 placentitis and the presence of chronic intervillositis and/or massive fibrin deposits in the placenta. When both lesion types were present, the specificity and negative predictive value for the diagnosis of placental SARS-CoV-2 infection were 0.99 (95% CI, 0.98-1.00) and 0.96 (95% CI, 0.94-0.98), respectively. CONCLUSIONS: At the height of the SARS-CoV-2 pandemic, the cause of more than half of fetal deaths in the Paris area was determined by postmortem analysis to be of placental or undetermined origin. Of these cases, 2.8% were due to placental SARS-CoV-2 infection with a specific pattern of histological involvement. This study highlights the need for SARS-CoV-2 screening in stillbirth assessment. The impact of vaccination coverage remains to be established. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Characterization of children with FLT3-ITD acute myeloid leukemia: a report from the AIEOP AML-2002 study group.

Recurrent molecular markers have been routinely used in acute myeloid leukemia (AML) for risk assessment at diagnosis, whereas their post-induction monitoring still represents a debated issue. We evaluated the prognostic value and biological impact of minimal residual disease (MRD) and of the allelic ratio (AR) of FLT3-internal-tandem duplication (ITD) in childhood AML. We retrospectively screened 494 children with de novo AML for FLT3-ITD mutation, identifying 54 harboring the mutation; 51% of them presented high ITD-AR at diagnosis and had worse event-free survival (EFS, 19.2 versus 63.5% for low ITD-AR, <0.05). Forty-one percent of children with high levels of MRD after the 1st induction course, measured by a patient-specific real-time-PCR, had worse EFS (22.2 versus 59.4% in low-MRD patients, P<0.05). Next, we correlated these parameters with gene expression, showing that patients with high ITD-AR or persistent MRD had characteristic expression profiles with deregulated genes involved in methylation and acetylation. Moreover, patients with high CyclinA1 expression presented an unfavorable EFS (20.3 versus 51.2% in low CyclinA1 group, P<0.01). Our results suggest that ITD-AR levels and molecular MRD should be considered in planning clinical management of FLT3-ITD patients. Different transcriptional activation of epigenetic and oncogenic profiles may explain variability in outcome among these patients, for whom novel therapeutic approaches are desirable.

[Tumor-to-tumor metastasis in a renal carcinoma: A rare and surprising event]. / Métastase d'une tumeur primitive dans un carcinome rénal : un évènement rare et surprenant.

Tumor-to-tumor metastasis is a very rare event. We report three cases of tumor metastasizing in a clear cell renal cell carcinoma: two breast carcinomas and a sigmoid carcinoma. So we objectified a prevalence of 1.5% of renal tumors in our series. It's a rare situation but to be considered in daily practice because it changes oncological management offered to the patient. According to the literature, clear cell renal cell carcinoma is the most common tumor recipient of metastasis. Several physiopathological mechanisms can explain this phenomenon, but many of them are still unknown. A better understanding of this phenomenon makes it possible to improve the diagnosis and thus the management of patients with several cancers.

Prenatal ultrasonographic diagnosis of polymicrogyria.

We report a rare case of polymicrogyria diagnosed at 27 weeks' gestation on ultrasound examination and associated with cytomegalovirus (CMV) infection. The ultrasound finding suggesting this diagnosis was the direct visibility of the overfolded cortical ribbon. The cerebral surface was clearly visible because of a markedly enlarged pericerebral space associated with micrencephaly secondary to CMV infection. Bilateral opercular dysplasia was also present. Very few sonographic markers of infectious fetopathy were observed other than periventricular cysts located behind both ventricular horns. Magnetic resonance imaging (MRI) of the fetal brain confirmed the ultrasound findings and also showed the presence of marked micrencephaly, whereas cephalic measurements acquired on ultrasound examination (biparietal diameter and head circumference) were within the normal range. This case emphasizes the complementary roles of sonography and MRI in the prenatal diagnosis of cerebral abnormalities. Moreover, it illustrates the fact that polymicrogyria is easier to diagnose on ultrasound examination during the second trimester, before the development of secondary sulci.

Papillary thyroid carcinoma: 6 cases from 2 families with associated lymphocytic thyroiditis harbouring RET/PTC rearrangements.

Familial papillary thyroid carcinoma (PTC) is a well recognized disease. However, genetic predisposition to familial PTC is rare and the molecular alterations at the origin of the pathology are unknown. The association between PTC and lymphocytic thyroiditis (LT) has been reported recently. We communicate here 6 cases of PTC associated with LT in 2 unrelated families. PTC was diagnosed on classical nuclear and architectural criteria. It was bilateral in 5 cases. Architecture was equally distributed between typical PTC and its follicular variant. LT was present in variable degrees, including in 4 cases, oncocytic metaplasia. Using the RT-PCR technique, we observed a RET/PTC rearrangement in the carcinomatous areas of patients of both families: PTC1 in family 1 and PTC3 in family 2 and a RET/PTC rearrangement in non-malignant thyroid tissue with LT in family 2. The RET/PTC band was weaker or absent in pure LT areas. Furthermore, using a polyclonal ret antibody, an apical or a diffuse cytoplasmic ret onc protein immunolabelling was observed in the three patients with RET/PTC1 rearrangement and in the three patients with RET/PTC3 rearrangement. In conclusion our data: (1) show the presence of a RET/PTC 1 or 3 rearrangement (depending on the family) together with a variable expression of ret protein in all the PTCs; (2) suggest that the molecular event at the origin of the PTCs seems to be particular to each one of the studied families; and (3) confirm that the ret proto-oncogene activating rearrangement(s) is an early event in the thyroid tumorigenic process and that it can be observed in association with LT.