Subcortical band heterotopia (SBH), also known as “double cortex syndrome,” is a rare neuronal migration disorder most commonly arising from mutations in the DCX gene. The DCX gene encodes doublecortin, a protein essential for normal neuronal migration during fetal brain development. Due to its X-linked inheritance, pathogenic variants in DCX typically lead to clinically distinct neurologic disorders between males and females. We present a case of a 19-year-old male with a history of epilepsy and sudden death. Autopsy examination revealed diffuse gray matter heterotopia, leading to a diagnosis of subcortical band heterotopia. Postmortem genetic analysis identified a single amino acid deletion mutation in the DCX gene classified as a “variant of uncertain significance.” Based on the clinical presentation, autopsy findings, and genetic results, we propose that this specific variant be reclassified as likely pathogenic.
Stillbirth remains a major challenge in perinatal and forensic pathology, particularly when the timing of fetal death and the mechanisms of hypoxic injury are difficult to establish using conventional morphological criteria alone. Nuclear factor erythroid 2–related factor 2 (Nrf2) is a key regulator of cellular responses to oxidative stress and may represent an early marker of fetal cellular stress. We conducted a retrospective forensic study of stillbirth cases that underwent complete autopsy between 2017 and 2024. Clinical, pathological, and placental data were examined to estimate the timing of fetal distress and the death–delivery interval. Immunohistochemical analysis of Nrf2 expression was performed on fetal cardiac tissue sections, and cases were classified as Nrf2-positive or Nrf2-negative based on unequivocal nuclear immunoreactivity. Nrf2 nuclear expression was identified in 10/44 cases (22.7%) and was observed more frequently in cases with shorter death–delivery intervals and clinicopathological patterns compatible with acute or subacute fetal hypoxic stress, particularly placental abruption and selected acute umbilical cord–related events. These findings suggest that Nrf2 nuclear immunoreactivity may represent a potential ancillary marker of early fetal cellular stress in well-preserved stillbirth tissues. However, tissue preservation may represent an important confounding factor. Further prospective studies with controlled temporal parameters are needed to clarify its diagnostic and forensic value.
Metanephric tumors (MTs) are rare benign pediatric renal neoplasms. Metanephric adenoma has occasionally been reported in association with epithelial-type Wilms tumor (nephroblastoma), suggesting either malignant transformation of the benign component or hyperdifferentiation of the malignant counterpart. We present an unusual malignant mesenchymal neoplasm arising within a metanephric stromal tumor. This unique case expands the spectrum of entities associated with MTs and supports their potential of malignant transformation as the underlying pathogenic mechanism in these rare composite lesions.
BACKGROUND Minute pulmonary meningothelial-like nodules (MPMN) are benign lung lesions-called "incidental" but of unknown etiology and significance. Usually identified during histologic examination for other diseases, they have to date been identified virtually only in adults, where they are more common in females and overweight/obese individuals. We aimed to confirm MPMN's existence in pediatric patients and gain insight into their early stages. METHODS Archival reports were examined for patients <20 with MPMN. Record review and histologic examination were conducted. RESULTS We identified 7 MPMN in 6 patients, age 11 to 19; 4 were male. Five underwent biopsy and 1 underwent autopsy. One was obese, 2 underweight, and 3 within normal weight range. Underlying diseases included immune-mediated interstitial disease, chronic airway disease, metastatic osteosarcoma, and fatal cerebrovascular accident. Thoracic CT showed diverse findings including small nodules in 3 patients. Lesional cells showed round-to-ovoid nuclei and moderate amounts of pink cytoplasm; they were disposed in vaguely whorled clusters surrounding/abutting small blood vessels. Size ranged from 165 to 343 µm. CONCLUSION Our findings confirm MPMN are not exclusive to adults; within pediatrics, susceptibility occurs in the second decade. Given diverse identified underlying medical and histopathologic conditions, it remains difficult to pinpoint pathogenic mechanisms driving MPMN.
Limb Body Wall Complex (LBWC) is a rare, severe congenital malformation syndrome characterized by thoracoabdominal wall defects, craniofacial anomalies, and limb and spinal malformations. Its incidence ranges from 0.04 to 3.3 per 10,000 births. We present a case of LBWC diagnosed in a monochorionic diamniotic twin pregnancy at 17 weeks of gestation. The mother was 28-year-old, primigravida, and had no notable medical history. Ultrasound identified abnormal positioning of 1 embryo, suggestive of adherence to the amnion. First-trimester scans revealed increased nuchal translucency and foot malposition in fetus A, while fetus B showed a cystic hygroma along with significant abdominal wall and spinal anomalies. Selective termination of fetus B was performed at 17 weeks but was complicated by the intrauterine demise of both fetuses. Postmortem examination of fetus B confirmed classical LBWC features: abdominopelvic wall defect with evisceration adherent to the placenta, lower limb amyotrophy, severe kyphoscoliosis, and craniofacial abnormalities. The pathogenesis of LBWC remains unclear, with hypotheses including early amnion rupture, vascular disruptions, and embryonic developmental errors. Diagnosis is typically made by prenatal ultrasound in the first trimester. LBWC is generally lethal, warranting pregnancy termination. While multiple pregnancies may increase the risk, discordant presentation in monochorionic twins remains exceptionally rare.
