Glutaredoxin 5 (GLRX5) is a mitochondrial protein encoded by the GLRX5 gene, which is essential for cellular redox homoeostasis, lipoic acid synthesis, and iron-sulfur cluster transfer. Rare cases of pathogenic GLRX5 mutations have been associated with sideroblastic anemia and non-ketotic hyperglycinemia with progressive spasticity and cavitating leukoencephalopathy. We report an 11-month-old child, who died following aspiration, with severe cardiomyocyte mitochondrial abnormalities and cerebral white matter degeneration in the context of a homozygous GLRX5 variant (c.208A>G, p.S70G).

Pediatric granular cell tumors (GCT) involving the gastrointestinal tract (GIT) are rare with limited case report/series reported to date. Multicenter retrospective study of pediatric GIT GCT. A total of 10 cases were included in the study with a median age of 13.5 years (range: 7-18 years) and were predominantly female patients (60%). In half of the patients no significant medical history was present with the remaining 5 having Crohn disease (10%), eosinophilic esophagitis (EoE) (10%), Crohn disease and EoE (10%), growth hormone deficiency (10%), and aplasia cutis congenita (10%). The GCT median size was 1.3 cm (range: 1-1.6 cm) and were more commonly located in the esophagus (70%) followed by the stomach (20%) and rectum (10%). Most of the cases showed round/polygonal tumor cells with abundant granular cytoplasm, and none of the cases had nuclear atypia, increased mitotic activity, or tumor cell necrosis. None of our cases received specific therapy for GCT other than clinical follow-up, and none of the patients had evidence of local recurrence or metastatic disease. We present our multicenter experience with GIT GCT, all cases had a benign course. Interestingly, 4 of the esophageal GCT cases (including 2 patients with EoE) showed an eosinophil-rich esophagitis in the underlying mucosa.

Caseinolytic peptidase B homolog (CLPB) is a mitochondrial protein which is highly expressed in brain. Its deficiency may be associated with severe neonatal encephalopathy. This report describes a case of fatal neonatal encephalopathy associated with biallelic stop-gain mutation in CLPB (NM_001258392.3:c.1159C>T/p.Arg387*). Neurologic disorder encompasses pre- and post-natal features including polyhydramnios, intrauterine growth restriction, respiratory insufficiency, lethargy, excessive startle reflex, generalized hypertonia, and epileptic seizures. Brain macroscopic examination demonstrates frontal severe periventricular cystic leukoencephalopathy, along with mild ex-vacuo tri-ventricular dilatation. The most striking immunohistopathologic features are striato-thalamic neurodegeneration and deep white matter loss associated with strong reactive astrogliosis. This report supports that CLPB deficiency should be considered among the neurometabolic disorders associated with severe prenatal-onset neurologic impairment that may result from cystic leukoencephalopathy.

To elucidate particular placental pathology findings that are associated with hypoxic ischemic encephalopathy (HIE) and determine which patterns are associated with adverse fetal/neonatal outcomes. Multi-institutional retrospective case-control study of newborns with HIE (2002-2022) and controls. Four perinatal pathologists performed gross and histologic evaluation of placentas of cases and controls. A total of 265 placentas of neonates with HIE and 122 controls were examined. Infants with HIE were more likely to have anatomic umbilical cord abnormalities (19.7% vs 7.4%, P = .003), fetal inflammatory response in the setting of amniotic fluid infection (27.7% vs 13.9%, P = .004), and fetal vascular malperfusion (30.6% vs 9.0%, P = <.001) versus controls. Fetal vascular malperfusion with maternal vascular malperfusion was more common in those who died of disease (P = .01). Placental pathology examination of neonates with HIE may improve our understanding of this disorder and its adverse outcomes.

Restricted accessAbstractFirst published online November 27, 2023Abstracts from the 69th Annual Meeting of the Paediatric Pathology Society, Madrid, Sept 14th-16thVolume 26, Issue 5https://doi.org/10.1177/10935266231211427

Uterine involution has 2 major components-(1) involution of vessels; and (2) involution of myometrium. Involution of vessels was addressed by Rutherford and Hertig in 1945; however, involution of myometrium has received little attention in the modern literature. We suggest that the pathophysiology of myometrial involution may lead to uterine atony and postpartum hemorrhage. The myometrium dramatically enlarges due to gestational hyperplasia and hypertrophy of myocytes, caused by hormonal influences of the fetal adrenal cortex and the placenta. After delivery, uterine weight drops rapidly, with physiologic involution of myometrium associated with massive destruction of myometrial tissue. The resulting histopathology, supported by scientific evidence, may be termed "postpartum metropathy," and may explain the delay of postpartum menstrual periods until the completion of involution. When uterine atony causes uncontrolled hemorrhage, postpartum hysterectomy examination may be the responsibility of the perinatal pathologist.Postpartum metropathy may be initiated when delivery of the baby terminates exposure to the hormonal influence of the fetal adrenal cortex, and may be accelerated when placental delivery terminates exposure to human chorionic gonadotrophin (HCG). This hypothesis may explain why a prolonged third stage of labor, and delays in management, are risk factors for severe hemorrhage due to uterine atony.

The pathology of second trimester fetal loss is not well-characterized due to lack of comprehensive autopsy studies. The purpose of this study is to compare autopsy pathology of second trimester and third trimester stillbirth. In this retrospective cohort study, fetal autopsies performed in-house with complete placental examination were included. From autopsy reports, maternal demographics, gestational age, sex, body and placental weight, congenital anomalies, and cause of death (COD) were obtained. Immediate COD was coded "probable" or "possible" according to Initial Causes of Fetal Death (INCODE). Among 68 second trimester and 54 third trimester fetal autopsies, at least 1 probable COD was identified in 59/68 (87%) second trimester and 44/54 (81%) third trimester cases. 42/68 (62%) second trimester and 28/54 (52%) third trimester fetuses had probable COD secondary to placental pathology. Among placental causes, 29/42 (69%) second trimester and 14/28 (50%) third trimester stillbirths were related to compromised fetal microcirculation with umbilical cord abnormality. Among stillborn first and second trimester fetuses who undergo autopsy, the most prevalent COD is pathologic placental conditions, particularly those associated with umbilical cord obstruction. This study stresses the importance of placenta examination for establishing COD in both second and third trimester fetuses.

A paraduodenal hernia is a rare type of hernia, however it is the most common type of internal hernias. It can develop after surgery, trauma, or be congenital. Paraduodenal hernias are rare in children. Clinical presentation is nonspecific. Patients range from being asymptomatic to presenting with clinical symptoms associated with small bowel obstructions. Diagnostic tools such as X-ray, plain abdominal radiography, and computed tomography may be used to diagnose paraduodenal hernias. Described is the case of a 5-year-old female who died suddenly of a bowel obstruction due to a paraduodenal hernia found at postmortem examination. In the hours prior to death, she reported stomach pain, vomiting, and later developed a fever. Postmortem CT study showed free fluid in the abdomen and bowel distention. Internal examination showed an obstructed bowel with ischemic sections extending from the distal portions of the small bowel up to the proximal portions of the transverse colon. The ischemic portions were entrapped within a clear membranous sac within the abdominal cavity. The sac was concluded to be a paraduodenal hernia. Paraduodenal hernias are rare and difficult to diagnose but they must be considered in the diagnostic process, as without surgical intervention the mortality rate can be high.

Glypican-3 is often used to discriminate between neoplastic and nonneoplastic liver. In focal lesions, positivity may be considered suggestive of a malignancy such as hepatoblastoma. However, glypican-3 is also normally expressed in the immature liver. We present a series of 5 cases of focal nodular hyperplasia (FNH)-like lesions arising in very young patients with glypican-3 expression and highlight the challenges these lesions present in the differential diagnosis of hepatoblastoma. Cases were obtained from the files of 3 tertiary pediatric hospitals. Clinical data were obtained from the electronic medical record and histopathologic material including immunohistochemical stains were reviewed. Patients were aged 2 weeks to 6 months with peak AFP levels ranging from 88.6 to 204,696 ng/mL. Microscopically, all were variably demarcated hepatocellular lesions with cords of hepatocytes, marked sinusoidal dilatation, and occasional fibrous bands and areas reminiscent of central scar with bile ducts. No significant cytologic atypia or increased mitotic activity were present. All showed glypican-3 expression and were negative for nuclear beta-catenin with intact reticulin framework. Our study highlights the pitfalls of evaluating focal liver lesions in infants when high AFP levels and glypican-3 expression may reflect immaturity rather than neoplasia.