Pediatric and Developmental Pathology

Lewis and Huff briefly described the presence of “microcystic cryptitis” in some of fetal vermiform appendices (VA) at autopsy. We further characterized these crypt changes (CC), their timing of occurrence, and tested their association with infection/inflammatory conditions.

Hematoxylin and eosin-stained slides of 345 VA were evaluated for the presence or absence of CC and their different morphologies. Autopsy reports were reviewed for evidence of amniotic fluid or fetal systemic infection and placental inflammatory conditions.

Crypt dilatation with or without irregularity of the lumen, crypt dilatation with semiattenuated epithelium, intraluminal apoptotic debris and inflammatory cells, especially eosinophils, and foci of swirled spindled cells with calcifications or multinucleated giant cells were observed, either alone or in combination, in at least 58.5% (202/345) of the VA. CC began to appear at 17 weeks, peaked at 20 to 25 weeks (with up to 82% of VA exhibiting CC during this time), and followed by a steady decline beyond 28 weeks gestation. χ² test of independence showed no significant association (P = .435; >0.05) between the presence and absence of CC and infection status of the fetus or placenta.

The underrecognized CC of the developing fetal vermiform appendix (VA) showed distinct temporal pattern of occurrence and did not seem to be affected by the presence or absence of infection, which so far favored their being a part of the normal gut developmental process.

Placental pathology in fetal congenital anomalies in second half of pregnancy is largely unknown.

Twenty-six clinical and 45 independent placental phenotypes from pregnancies ≥20 weeks of gestation with congenital anomalies divided into 4 groups were retrospectively compared with analysis of variance or χ ² with 3 degrees of freedom and with Bonferroni correction for multiple comparisons: group 1 : 112 cases with heart malformations (with or without chromosomal anomalies), group 2 : 41 cases with abnormal karyotypes and anomalies other than heart malformations, group 3 : 87 cases with intrathoracic or intraabdominal mass-forming anomalies (mostly congenital diaphragmatic hernias and adenomatoid airway malformation), and group 4 : 291 miscellaneous cases with mostly skeletal, renal, and central nervous system anomalies not fulfilling the criteria of inclusion into groups 1 to 3.

Eight of 26 clinical (30.8%) and 16 of 45 (35.5%) placental phenotypes varied statistically significantly among the 4 groups (P <  .05), of those, 7 (26.9%) and 4 (8.9%), respectively, remained statistically significant after Bonferroni correction (P Bonferroni ≤  .002). Those placental phenotypes were placental weight, chorionic disc chorionic microcysts, fetal vascular ectasia, and luminal vascular abnormalities of chorionic villi.

Fetal anomalies in second half of pregnancy feature abnormal clinical phenotypes much more frequently than abnormal placental phenotypes. Chromosomal abnormalities with or without heart malformations tend to feature villous edema, and erythroblastosis of fetal blood, likely due to fetal heart failure. Mass-forming fetal anomalies feature placental histological lesions of shallow placental implantation, diffuse chronic hypoxic patterns of placental injury, and lesions of fetal vascular malperfusion, likely stasis-induced.

The risk of neonatal early-onset sepsis (EOS) is traditionally assessed on maternal signs of clinical chorioamnionitis. Recently, an online EOS risk calculator was developed by Kaiser Permanente using maternal and neonatal clinical parameters. We were interested in whether an increased Kaiser sepsis risk score correlates with histologic acute chorioamnionitis or acute funisitis.

Included in this retrospective review are 119 chorioamnionitis-exposed term neonates from January 1, 2015 and December 31, 2016. Clinical charts from mother–baby pairs were reviewed. An EOS risk score was obtained using the online Kaiser Sepsis Calculator. The presence and severity of acute chorioamnionitis and acute funisitis were recorded. A SPSS software was used for statistical analysis (IBM, New Jersey, USA).

The Kaiser Sepsis Calculator could identify 97 of 119 (81.5%) neonates without increased risk for sepsis. Histologic acute chorioamnionitis was present in 100 of 119 cases (84%), in which 44 cases (44%) show severe acute chorioamnionitis. Acute funisitis was recognized in 87 of 119 (73.1%) cases, all of which had concurrent acute chorioamnionitis. Severe funisitis was seen in 38 of the 87 cases (43.7%). The Kaiser Sepsis risk score correlates with the presence and severity of acute funisitis (P = .037 and P = .044, respectively) but not with the presence or the severity of acute chorioamnionitis (P = .105 and P = .672, respectively).

Our study provides histological evidence to support that the Kaiser Sepsis Calculator may help to effectively reduce unwarranted blood culture, antibiotics exposure, and neonatal intensive care unit admission in term neonates.

Hippocampal sclerosis (HS) is one of the major causes of intractable epilepsy. Astrogliosis in epileptic brain is a peculiar condition showing epileptogenesis and is thought to be different from the other pathological conditions. The aim of this study is to investigate the altered expression of astrocytic receptors, which contribute to neurotransmission in the synapse, and channels in HS lesions.

We performed immunohistochemical and immunoblotting analyses of the P2RY1, P2RY2, P2RY4, Kir4.1, Kv4.2, mGluR1, and mGluR5 receptors and channels with the brain samples of 20 HS patients and 4 controls and evaluated the ratio of immunopositive cells and those expression levels.

The ratio of each immunopositive cell per glial fibrillary acidic protein-positive astrocytes and the expression levels of all 7 astrocytic receptors and channels in HS lesions were significantly increased. We previously described unique astrogliosis in epileptic lesions similar to what was observed in this study.

This phenomenon is considered to trigger activation of the related signaling pathways and then contribute to epileptogenesis. Thus, astrocytes in epileptic lesion may show self-hyperexcitability and contribute to epileptogenesis through the endogenous astrocytic receptors and channels. These findings may suggest novel astrocytic receptor-related targets for the pharmacological treatment of epilepsy.

Central nervous system (CNS) anomalies are the second most frequent category of congenital anomalies after congenital heart defects (CHDs). In this study, the aim was to investigate the distribution of different CNS anomalies with associated anomalies and karyotype in a fetal autopsy population of terminated pregnancies over a 30-year period and to correlate the ultrasonographic diagnoses of CNS anomalies with autopsy findings.

This study includes 420 intact fetuses with CNS anomalies terminated at gestational ages 11^+ 0 to 33^+ 6 over a 30-year period from 1985 to 2014. An ultrasound (US) examination was performed at the National Centre for Fetal Medicine, St. Olavs Hospital, Trondheim. The autopsies were performed at the Department of Pathology at the same hospital or a collaborating hospital. The anomalies were subcategorized according to the classification by the World Health Organization.

Neural tube defects such as anencephaly (22.4%, 107/477) and spina bifida (22.2%, 106/477) constituted the most common CNS anomalies, followed by congenital hydrocephalus (17.8%, 85/477). In total, the karyotype was abnormal in 21.0% of all termination of pregnancies (TOPs), with trisomy 18 as the most frequent abnormal karyotype. CHDs, skeletal anomalies, and urinary anomalies were the most common associated organ anomalies. Throughout the study period, there was full agreement between US and postmortem findings of CNS anomalies in 96.9% (407/420) of TOPs.

In this study of autopsy findings of CNS anomalies in intact fetuses terminated after prenatal US diagnosis, neural tube defects were most common. About half of the fetuses had isolated serious CNS anomalies, while the other half were CNS anomalies associated with structural and/or chromosomal anomalies. The prenatal US diagnoses were in good concordance with autopsy findings. In particular, due to challenges of diagnoses made early in pregnancy, it is necessary to continue the validation practice.

The exact etiology of ureteropelvic junction obstruction (UPJO) is unknown, and inadequate excision of the narrow segment has been proposed as a cause of failure in 5% to 7% of cases of pyeloplasty.

To study whether frozen section can be useful to detect normal ureter distal to UPJO during pyeloplasty.

Histological sections from 31 patients with UPJO were analyzed for collagen to muscle ratio (CMR) on conventional (formalin) and rapid (frozen section) Masson’s trichrome staining. Pathological findings were correlated with postoperative outcomes analyzed at 1-year follow-up and expressed as excellent, moderate, or mild improvement, static and deterioration based on ultrasound grade, differential renal function, and renogram drainage pattern.

There was a very strong positive correlation (r = .94; P = .001) between CMR by conventional and rapid frozen Masson’s trichrome staining. There was a very strong negative correlation between pyeloplasty outcomes and CMR on conventional staining (r = −.94; P = .001) or rapid frozen Masson’s trichrome staining (r = −.91; P = .001). Regression analysis revealed that a CMR of 1.2 or less (95% confidence interval: 1.9–0.7) was associated with a successful outcome.

It is feasible to intraoperatively identify normal ureter distal to UPJO using CMR analysis on the novel rapid frozen section technique reported.