Fetal and Pediatric Pathology最新文献

Background: β-thalassemia is a common monogenic disorder in India, yet early neonatal detection remains challenging due to high fetal hemoglobin levels.

Objective: To determine the prevalence of β-globin gene mutations in term neonates with HbA ≤15% and to identify an optimal HbA cutoff for screening.

Methods: In this cross-sectional study conducted from January 2020 to October 2021 at two tertiary hospitals in Delhi, 2,600 newborns were screened using capillary electrophoresis. Neonates with HbA ≤15% underwent parental screening by HPLC, and genetic confirmation was performed using ARMS-PCR and sequencing.

Results: Among 91 neonates with parental consent, 14 (15.4%) harbored β-globin gene mutations, predominantly IVS 1-5(G→C). ROC analysis revealed an optimal HbA cutoff of ≤12.4%, with 93% sensitivity and 56% specificity.

Conclusion: HbA ≤12.4% at birth is a useful threshold for early identification of β-thalassemia, enabling timely counseling and prevention strategies through neonatal screening.

Background: Megacystitis-megacolon-intestinal hypoperistalsis syndrome is a phenotypic variant of visceral neuromuscular dysfunction. Megacystitis-microcolon-intestinal hypoperistalsis syndrome is a recognized entity. However, presentation with megacolon is rarely reported, with only one case documented in association with intestinal neuronal dysplasia (IND) and malrotation.

Case report: We report such a case of Megacystitis-megacolon-intestinal hypoperistalsis coexisting with IND type B and atypical malrotation in a 2-year-old male, presented with intestinal obstruction. Despite multiple surgical interventions, the patient remained TPN-dependent and eventually succumbed to sepsis. Histopathology evaluation revealed hyperganglionosis, including the presence of immature and giant ganglion cells, which supported the diagnosis of IND type B, alongside the features of visceral myopathy.

Conclusion: This case highlights the diagnostic and therapeutic complexity posed by overlapping features of megacolon and MMIHS, especially when hyperganglionosis was present. Our case highlights the need for clinico-pathological correlation and genetic analysis in diagnosing complex pediatric motility disorders.

Introduction: Large language models (LLMs) such as ChatGPT are emerging tools in pathology. This study evaluated their diagnostic utility in pediatric neoplastic pathology.

Materials and methods: Thirty-three pediatric tumor cases were retrospectively analyzed. Clinical data and histology images were input to ChatGPT-4o (03-06/2025) and GPT-5 (10/2025) for diagnostic suggestions, immunohistochemical (IHC) panels, and report generation. GPT outputs were graded for diagnostic concordance (2 = concordant, 1 = partial, 0 = discordant).

Results: ChatGPT-4o achieved at least partial concordance in 27/35 (77.1%) cases (toal and mean score 42, 1.2), with highest accuracy in small round blue cell tumors (SRBCT, 100%) and IHC interpretation accuracy 74.4%. GPT-5 showed 19/33 (57.6%) concordance (total and mean 25, 0.76), highest in SRBCT (87.5%) and IHC accuracy 60.7%. (p < 0.05 between 4o and 5, Mann-Whitney U).

Conclusions: ChatGPT demonstrates promise as a diagnostic and educational adjunct in pediatric pathology, though expert oversight and further validation remain essential.

Periodontal Ehlers-Danlos Syndrome (pEDS) is a rare autosomal dominant connective tissue disorder with fewer than 200 cases reported. In addition to typical Ehlers-Danlos Syndrome (EDS) features of joint hypermobility, skin fragility and tissue friability, it is characterized by periodontal abnormalities, leading to periodontal bone and teeth loss. The article presents a case of a 10-year-old boy diagnosed with pEDS, exhibiting typical symptoms of violaceous pretibial plaques, hypermobile joints, and periodontal disease with mobile teeth. Additionally, the patient displayed atypical features observed in other types of connective tissue diseases such as mitral valve prolapse, severe myopia, esotropia, tortuous optic nerves and partial empty turcica, suggesting that the phenotypic spectrum of this syndrome may be broader than previously understood. Interestingly, neither of the parents met the diagnostic criteria for pEDS. The article highlights the importance of timely diagnosis of pEDS, as early intervention is crucial in preventing premature tooth loss, and potential systemic complications associated with the syndrome.

Background: BCOR mutations occur in about 5% in pediatric rhabdomyosarcoma (RMS), their clinical significance and mechanistic roles remain undefined. This study characterizes BCOR-mutant RMS as a molecularly distinct, high-risk subgroup. Methods: Multimodal analysis of four pediatric embryonal RMS cases with BCOR mutations, integrating histopathology, immunohistochemistry, genomic profiling, and clinical outcomes. Results: All patients (ages 1.9-11 years) presented with stage IV fusion-negative ERMS. Histology ranged from conventional (Cases 1,2,4) to undifferentiated (Case 3). IHC revealed: Universal MyoD1 nuclear positivity (70-95%), variable myogenin (5-50%). BCOR protein status potentially related to mutation VAF (15.1-96.16%): aberrant cytoplasmic staining with loss of nuclear expression in frameshift mutants (Case 3) vs. partial retention or completely loss in missense mutants (Cases 1,2,4). Molecular profiling identified recurrent co-alterations (TP53, MDM2/MYC). Despite multimodal therapy, all patients progressed (median EFS 16.5 months), with poorest outcomes in older children (Cases 1,3,4). Conclusions: BCOR mutations may define an aggressive RMS subtype in pediatric group.

Background: NTRK-rearranged spindle cell neoplasms (NTRK-RSCNs) are an emerging entity, molecularly characterized by NTRK rearrangements. Advances in molecular testing have revealed that NTRK fusions are prevalent in various tumor types, particularly in soft tissue tumors.

Case report: A 5-year-old boy presented with frequent urination and a low fever. Imaging studies showed a large mass in the right kidney. Laboratory tests revealed hypophosphatemia and hypercalcemia. The patient received chemotherapy and radiation followed by nephrectomy. The tumor exhibited diverse high-grade sarcomatous morphological features distinct from common NTRK-RSCNs and was initially diagnosed as a malignant phosphaturic mesenchymal tumor (PMT) without molecular alteration evidence. Subsequent upgraded next-generation sequencing identified a TPM4::NTRK1 fusion, CDKN2A/B deletion, SDHD and NOTCH3 variants. Based on these molecular findings, the diagnosis was confirmed as an NTRK-rearranged high-grade sarcoma with an unusual histomorphological phenotype.

Conclusion: This case highlights novel molecular characteristics of NTRK-rearranged high-grade sarcoma and underscores the critical role of comprehensive molecular profiling in diagnosing challenging cases.

In Algeria, the misuse of pregabalin in the context of drug addiction, particularly among pregnant women, poses a significant risk to the fetus. Our objective was to confirm prenatal exposure to this substance through the analysis of maternal and neonatal samples. In utero exposure to pregabalin can lead to early neonatal symptoms and chronic effects on child development. This case study details the toxicological analysis performed on samples from a newborn whose mother, a drug user, consumed pregabalin during pregnancy. Immunochromatographic screening revealed the presence of pregabalin in maternal urine, while the initial meconium test was negative. However, further analysis by GC-MS successfully detected pregabalin in the meconium, thereby confirming prenatal exposure. This case underscores that meconium is a key matrix in prenatal toxicology, capable of accumulating xenobiotics and enabling their detection long after they have been cleared from blood or urine.

Introduction: Placental teratomas are benign germ cell tumors composed of mature tissues from multiple germ layers. They may mimic a cardiac fetus but lack organized fetal structures and an umbilical cord.

Case presentation: A 25-year-old G5P1224 woman delivered at 34 weeks of gestation following PPROM. Examination of the placenta revealed a 3.5 cm intraplacental, mixed solid and cystic lesion without a pedicle. Histology showed mature tissues including cartilage, ganglion cells, choroid plexus, and ciliated epithelium, consistent with a mature cystic teratoma.

Discussion: The absence of an umbilical cord and embryonic organization distinguishes a mature cystic teratoma from an acardiac twin. Unlike the TRAP sequence, placental teratomas occur in singleton pregnancies, carry no recurrence risk, and pose no threat to fetal or maternal health. Accurate diagnosis is crucial to avoid misclassification and unnecessary intervention.

Preeclampsia (PE) remains a leading cause of maternal and neonatal morbidity and mortality globally. Among several experimental models developed to interrogate the pathogenesis of PE, the mouse model employing systemic infusion or transgenic overexpression of soluble fms-like tyrosine kinase-1 (sFlt1) has gained widespread use due to its capacity to induce cardinal features of the human disease. These include maternal hypertension, renal injury, endothelial dysfunction, placental abnormalities, fetal growth restriction, and adverse long-term outcomes. This review critically evaluates the sFlt1-based mouse model of PE, highlighting its utility for understanding the pathogenesis of angiogenic imbalance and its sequelae. We contrast findings from this model with clinical observations in human PE and discuss applications for studying early-onset versus late-onset forms. Finally, we address limitations and propose strategies to enhance its translational relevance. Placing the model in the context of human disease helps guide its use in future preclinical and translational research.

Background/objectives: To report the complete neuropathologic description of an infant with terminal deletion q31-q35 of chromosome 4 (4q- syndrome), because much published work has been devoted to the genetics of 4q- syndrome and almost nothing to its neuropathology. Most patients with 4q31-4q35 deletion have suggestive phenotypic features and moderate to severe developmental and language delay; rare patients with autistic behavior and facioscapulohumeral muscular dystrophy have been associated with small deletions limited to 4q31 and 4q35, respectively. Materials and methods: Clinically, the patient reported here had severe hypotonia, poor respiratory and feeding autonomy, and undescribed drug-resistant seizures from the first days of life until death at one year of age. A comprehensive neuropathologic examination of the brain was completed with a late muscle biopsy. Results and conclusions: The callosal dysgenesis, paucity of cortical neurons and subependymal germ cells, cerebral and cerebellar neuronal heterotopies, and suggestive muscular findings in this new patient may broaden the understanding of the clinical features.