BACKGROUND:Mitochondrial Contact Site and Cristae Organizing System (MICOS13)- related combined oxidative phosphorylation deficiency 37 is a rare autosomal recessive disorder caused by disruption of mitochondrial structure and function, leading to early-onset multisystem disease. Case report: A genetically confirmed case is described in a 5-month-old female infant born to consanguineous Iraqi parents, presenting with hypotonia, developmental delay, feeding difficulties, laryngomalacia, and recurrent cyanotic episodes. Clinical findings included diminished reflexes and a small atrial septal defect, while laboratory tests revealed hypoalbuminaemia and mild coagulopathy. Whole-exome sequencing identified a homozygous MICOS13 splice-site variant (c.260-2A >G). Despite supportive care, progressive respiratory failure developed, resulting in death at 5months. Review of 13 reported cases demonstrates consistent early onset, universal hepatic and neurological involvement, frequent respiratory compromise, and, among reported cases, uniformly fatal outcomes. Most identified variants are loss-of-function, predominantly frameshift, with no missense variants reported to date. CONCLUSION:The present report adds a genetically confirmed case and reinforces the value of considering MICOS13 deficiency in consanguineous infants with early encephalopathy and hepatic dysfunction.
Background: Hybrid benign peripheral nerve sheath tumors (BPNSTs) combine schwannomatous, neurofibromatous, and/or perineuriomatous components and are frequently associated with NF2-related schwannomatosis. Pediatric cases at retrovesical sites have not previously been reported. Case report: A 12-year-old boy presented with one-year voiding difficulty. Pelvic magnetic resonance imaging showed an indeterminate 27 × 33 mm retrovesical lesion in the seminal vesicle region. Laparoscopic excision yielded a solid mass composed of distinct schwannomatous and neurofibromatous components. The schwannomatous areas were strongly S-100 positive and CD34 negative, whereas the neurofibromatous areas showed patchy S-100 and diffuse CD34 positivity; factor XIIIa was more extensive in the neurofibromatous component. Ki-67 was 3%, without necrosis or mitoses. Multiplex ligation-dependent probe amplification identified a heterozygous germline NF2 deletion (upstream-exon 9). At 6 months, the patient was symptom-free without recurrence. Conclusion: Hybrid BPNST should be considered in pediatric indeterminate retrovesical masses; integrated histopathologic, immunohistochemical, and molecular analysis-including germline NF2-guides diagnosis and long-term surveillance.
BACKGROUND:Ectopic pregnancy is a major cause of first-trimester maternal morbidity and mortality, with diagnosis and management posing persistent clinical challenges. This review evaluates the emerging role of artificial intelligence, machine learning, and multi-omics technologies in enhancing diagnosis, treatment prediction, biomarker discovery, and surgical care. MATERIALS AND METHODS:A synthesis of 52 studies (1988-2026) was conducted, assessing machine learning algorithms, proteomic and metabolomic panels, multi-omics integrations, and robotic-assisted surgical outcomes using performance metrics including AUC, sensitivity, and specificity. RESULTS:Machine learning models achieved AUC values up to 0.929 for methotrexate failure prediction and surgical accuracies exceeding 98%. Biomarker panels combining sphingolipids and carnitines demonstrated 100% sensitivity and 95.9% specificity. Multi-omics uncovered GATA4-mediated ITGB3 dysregulation in cesarean scar pregnancy. Robotic-assisted techniques yielded cumulative pregnancy rates over 60% post-reanastomosis. CONCLUSION(S):AI and multi-omics integration offer significant promise for personalized ectopic pregnancy management. However, retrospective designs and small sample sizes limit generalizability, underscoring the need for prospective multicenter validation before routine clinical adoption.
Background: Acute myocardial infarction (MI) is an uncommon finding in the neonatal period, as well as in cases of hypoxic-ischemic encephalopathy (HIE). Case report: We report the case of a full-term newborn with HIE who developed extensive myocardial infarction secondary to perinatal asphyxia, accompanied by progressive neurological deterioration. Despite early initiation of therapeutic hypothermia (TH) and intensive supportive care, the infant developed refractory cardiogenic shock, rapid neurological decline, and died within the first hours of life. Postmortem examination revealed widespread subendocardial infarction affecting both ventricles, with structurally normal heart and coronary arteries. Conclusions: This case underscores the critical role of cardiovascular dysfunction in the pathogenesis of brain injury in neonates with HIE. Early interpretation of multimodal monitoring and timely detection and management of myocardial dysfunction may be essential to reduce secondary brain injury and improve outcomes in this high-risk population.
Background: Abdominal wall defects represent a significant spectrum of congenital anomalies, ranging from the more frequently encountered gastroschisis and omphalocele to the rare and intricate malformations such as limb-body wall complex, Pentalogy of Cantrell, and cloacal exstrophy. Understanding these conditions is crucial for improving patient outcomes. Materials and Methods: We conducted a comprehensive study presenting rare AWDs diagnosed at a tertiary referral center over two years. Our approach involved an in-depth correlation of prenatal ultrasound evaluations with findings from post-expulsion or postnatal external examinations to ensure accuracy. Results: Among the total eight cases of rare AWDs analyzed, we identified two cases of type IV body stalk anomaly, three cases of atypical gastroschisis, and one case each of Pentalogy of Cantrell, bladder exstrophy, and cloacal exstrophy. Each case illustrates the complexities inherent in these disorders. Conclusion: This series emphasizes the wide variety and diagnostic challenges of rare AWDs. A meticulous evaluation of defect location, umbilical cord insertion, and associated anomalies is vital for clear classification and enhanced prenatal counseling. By documenting these cases, we not only elevate our understanding of embryological development but also significantly improve our diagnostic capabilities, ultimately leading to better management strategies and outcomes for affected individuals.
OBJECTIVE:To explore the role of pathogenicity classification, genetic origin, and clinical decision-making in pregnancy outcomes for copy number variations (CNVs) detected by prenatal chromosome microarray analysis (CMA), and to assess the value of CNV reclassification in dynamic interpretation. METHODS:This retrospective study analyzed 43 fetuses with confirmed CNVs from 3,726 amniocenteses (2023-2025). CNVs were reclassified via literature and database review. RESULTS:Among 43 CNVs, 15 were pathogenic (P)/likely pathogenic (LP) (53.3% de novo) and 28 were variants of uncertain significance (VUS) (71.4% inherited). Reclassification updated 2 to P, 2 to VUS, and 23 to likely benign (LB). Incomplete penetrance and fetal sex influenced interpretation. CONCLUSION:CNV interpretation is dynamic; regular review incorporating updated data improves prenatal counseling accuracy.
Fetuses with trisomy 21 typically exhibit subtle but measurable deviations in early brain growth rather than frequent major malformations. This review synthesizes first-second trimester data from ultrasound, fetal MRI, and autopsy studies to characterize early neurodevelopmental alterations in Down syndrome. Especially, in second trimester, neurosonography reveals mild reductions in head and cerebellar biometry, a characteristic "seagull" cerebral hemisphere configuration, and thinned subplate, while fetal MRI demonstrates global but regionally accentuated brain and cerebellar hypoplasia with relatively preserved gross architecture. Autopsy and microscopic analyses confirm reduced cellularity and delayed lamination in cortex, basal ganglia, and cerebellum, supporting a primary disturbance of neurogenesis rather than migration. Severe structural malformations and obstructive hydrocephalus are rare but documented. Current evidence underscores the prognostic potential-and limitations-of early neuroimaging, highlighting the need for standardized, prospective studies linking prenatal brain metrics with long-term neurodevelopmental outcomes.
OBJECTIVE:To investigate the clinicopathological features and cytokeratin (CK) expression patterns of osteofibrous dysplasia (OFD) in children. METHODS:A total of 49 cases of OFD confirmed by the Department of Pathology, Anhui Provincial Children's Hospital from 2008 to 2025 were collected. Their clinicopathological data, CK expression, and follow-up information were analyzed. RESULTS:The male-to-female ratio is approximately 4:3. The age ranges from 9 months to 13 years. It is more commonly observed in the tibia and fibula. Imaging examinations mainly reveal irregular bone destruction and cortical thinning. Histologically, it manifests as fibrous-osseous lesions. CK immunohistochemical staining was positive in 29 cases (29/49, 59.1%) and negative in the remaining cases. Follow-up indicated no recurrence or malignant transformation. CONCLUSION:OFD is a fibro-osseous lesion that commonly occurs in children. Immunohistochemistry often reveals CK expression, typically in individual cells, and it must be distinguished from conditions like osteofibrous dysplasia-like adamantinoma.
Background: Epstein-Barr virus associated smooth muscle tumors (EBV-SMTs) have been established as a rare neoplasm closely associated with severe immunodeficiency. CARMIL2 deficiency, described in recent years, is a combined immunodeficiency disorder characterized by CD28-mediated T-cell costimulatory defect, altered cytoskeletal dynamics, susceptibility to recurrent infections, and EBV-SMTs. Case report: We report the first documented case of pediatric bronchial EBV-SMTs caused by CARMIL2 deficiency summarizing its clinical features, pathogenesis, key points for diagnosis and treatment. Conclusion: Children with recurrent infections, inflammatory bowel disease, and allergic phenotypes accompanied by NK cell depletion should undergo early genetic evaluation. Routine EBV encoded RNA in situ hybridization (EBER-ISH) is recommended for all smooth muscle tumors, and evidence of primary immunodeficiency (PID) should be investigated in patients without secondary immunodeficiency. Immunorestoration remains the fundamental therapeutic strategy, novel approaches such as exogenous IL-2 require further investigation.
BACKGROUND:Necrotizing enterocolitis (NEC), a life-threatening neonatal gastrointestinal disease, lacks reliable biomarkers. This study explores PANoptosis-a novel inflammatory cell death pathway-in NEC pathogenesis. MATERIALS AND METHODS:Ileal transcriptomic profiles from surgical NEC and non-inflammatory controls were retrieved from GSE64801 and GSE46619. Data were standardized via log-transformation and quantile normalization. After identifying differentially expressed genes, we intersected them with 902 PANoptosis-related genes. A diagnostic model was developed using LASSO regression and validated via ROC, calibration, and decision curve analyses. RESULTS:Fifty-five NEC-associated PANoptosis genes were identified, primarily enriched in inflammatory pathways. NFKBIA and PECAM1 emerged as pivotal biomarkers. The model achieved an AUC and C-index of 0.903, with calibration curves confirming reliability. DCA and clinical impact curves demonstrated significant clinical utility. CONCLUSION:NFKBIA and PECAM1 are promising biomarkers for surgical NEC linked to PANoptosis. This study establishes a diagnostic framework and proposes therapeutic targets for advanced NEC management.
Background: Pediatric clinical autopsy plays an important role; however, interpretation of autopsy findings is often challenging. Genome-wide postmortem testing has emerged as a promising approach, yet its utility in clinical autopsy remains uncertain. Methods: This retrospective, single-center study included systematic analysis of all pediatric clinical autopsies performed between 2020 and 2025, following institutional introduction of postmortem genomic testing using whole-exome sequencing. Results: Among 61 autopsies, postmortem genomic testing was performed in 27 cases, revealing primary findings in 8 (30%), including 6 (22%) identified by whole-exome sequencing. Among cases with primary findings, genomic findings confirmed the diagnosis in 5 cases and facilitated interpretation of autopsy findings in the remaining 3 cases. Conclusion: This study provides the first autopsy-based evaluation of postmortem genomic testing, demonstrating improved diagnostic precision and facilitating family counseling. These findings highlight the value of integrating postmortem genomic testing into pediatric autopsy practice.
PURPOSE:Inborn errors of immunity (IEIs) represent a heterogeneous group of genetic conditions that predispose individuals to severe infections, autoimmunity, and malignancy. This study aimed to characterize the clinical, radiological, and genetic profiles of pediatric patients with IEIs at a single tertiary-care hospital in southwestern Saudi Arabia. PATIENTS AND METHODS:This retrospective study was conducted at the Abha Maternity and Children Hospital from January 2015 to December 2024. The medical records of 56 pediatric patients with IEIs (aged 1 month to 15 years) were reviewed. Data on epidemiological, clinical, radiological (chest radiographs and computed tomography scans), laboratory (complete blood counts and immunoglobulin levels), genetic, and outcome parameters were also extracted. RESULTS:The cohort of 56 patients frequently presented with Severe Combined Immunodeficiency (SCID) (28.6%), Chronic Granulomatous Disease (CGD) (16.1%), and Predominantly Antibody Deficiencies (PAD) (14.3%), all demonstrating high consanguinity rates (94% in SCID and 100% in CGD). Pneumonia was the most prevalent clinical complication (85.7%). Genetic profiling of 40 patients revealed a predominantly autosomal recessive inheritance pattern (81%), with common gene mutations, including RAG1/2, DCLRE1C, IL2RG, and IL7R, in SCID and NCF1 in all CGD cases. Autosomal recessive SCID constituted 83% of SCID cases. Pulmonary complications were the leading cause of mortality, accounting for eight (44.4%) of the 18 deaths. CONCLUSIONS:This study highlights the distinct epidemiological, clinical, and genetic characteristics of pediatric IEIs in southwestern Saudi Arabia, which are characterized by a high prevalence of autosomal recessive disorders attributed to consanguinity. Complicated pneumonia emerged as a significant clinical challenge and the primary cause of mortality.
BACKGROUND:To guide prenatal recognition and management of this rare vascular ring formed by the left aortic arch and right ductus arteriosus. METHODS:A 23-week primigravida with an abnormal three-vessel tracheal (3VT) view underwent fetal ultrasound, chromosomal copy number variation (CNV) sequencing, and subsequent pregnancy termination. RESULTS:Ultrasound revealed a vascular ring formed by left aortic arch and right ductus arteriosus that encircled and compressed the trachea and esophagus, accompanied by thymic hypoplasia, enlarged posterior fossa, and single umbilical artery; CNV confirmed 22q11.2 deletion syndrome. Postmortem examination verified the structural abnormalities identified on prenatal ultrasound. CONCLUSION:This first reported case of a rare vascular ring with a left aortic arch and a right ductus arteriosus confirmed by postmortem examination validates the diagnostic efficacy and accuracy of prenatal ultrasound, with the 3VT view serving as the key diagnostic plane, and highlights the need for genetic assessment in perinatal management.
OBJECTIVE:The aim of this study is to characterize the clinicopathological and molecular features of pediatric breast fibroepithelial lesions (FELs) and evaluate the diagnostic and clinical relevance of distinguishing fibroadenomas (FAs) from phyllodes tumors (PTs). METHODS:We retrospectively analyzed 138 pediatric breast FELs. Pathologic evaluation, immunohistochemical staining, and Sanger sequencing of MED12 exon 2 and the TERT promoter were performed. RESULTS:Of the 138 cases, 133 were diagnosed as FAs (96.4%) and five as benign PTs (3.6%). CD34, Ki-67, and p16 expression were correlated with mitotic activity. CD34 also associated with atypia, and Ki-67 with stromal overgrowth. Larger sized tumors (≥4 cm) had mutant MED12 (30/45 cases). No TERT promoter mutations were detected. During follow-up (range 17-153 months), no true recurrences occurred; though, 13 patients developed new lesions in other quadrants or contralateral breast. CONCLUSIONS:Pediatric FELs likely represent a diagnostic continuum. In this cohort, the distinction between FA and benign PT did not impact clinical outcome, suggesting limited prognostic significance.
BACKGROUND:Spontaneous abortion affects up to 30% of conceptions, andfetal anomalies are frequently an underlying cause. This study aimed to characterize morphological anomalies in spontaneous abortions to clarify underlying etiologies and related factors. METHODS:A retrospective cohort of 180 spontaneous abortions (10-23 + 6 weeks) was analyzed at a tertiary hospital. All cases underwent fetal autopsy with clinical, pathological, and genetic review. Cases with and without anomalies were compared. RESULTS:Fetal anomalies were found in 39.4% of cases. Morphological anomalies were most frequent (57.7%), particularly fetal growth restriction, cardiac defects, and complications of monochorionic twin pregnancies. Trisomies 21, 13 and 18 accounted for 54.6% of chromosomal anomalies. No significant associations were found with maternal factors. Gestational age at fetal loss was significantly lower in chromosomal than in morphological anomalies (p = 0.004). CONCLUSION:This study highlights the value of autopsy and multidisciplinary assessment in identifying fetal anomalies and improving diagnostic accuracy and reproductive counseling.
BACKGROUND:Placenta previa (PP) is a major cause of preterm birth, yet the role of placental vascular pathology remains unclear. This study investigated maternal, fetal, and placental histopathological factors associated with preterm delivery in PP cases, emphasizing vascular malperfusion. METHODS:A retrospective case-control study included 88 singleton PP pregnancies without placental invasion: 56 preterm (<37 weeks) and 32 term (≥37 weeks) deliveries. Placental pathology was evaluated per the Amsterdam criteria. Multivariable logistic regression identified predictors of preterm birth. RESULTS:Maternal vascular malperfusion (MVM) was significantly more common in preterm cases (67.9% vs. 18.8%, p < 0.001) and was a strong independent predictor (OR = 11.08; p < 0.001). Fetal vascular malperfusion (FVM) was also more frequent (80.4% vs. 56.3%, p = 0.030), but not independently significant. CONCLUSION:Vascular lesions, especially MVM, are key drivers of preterm birth in PP. These findings highlight the importance of placental evaluation in clinical management.
Background: Pregnancies following in vitro fertilization (IVF) are associated with higher rates of intrahepatic cholestasis of pregnancy (ICP) compared to spontaneous conceptions. This study aimed to investigate oxidative stress biomarkers, endothelial nitric oxide synthase (eNOS) expression, and placental histopathology in ICP women undergoing intracytoplasmic sperm injection (ICSI). Methods: Placental samples from four groups-healthy spontaneous conception (non-ICP-SC, n = 7), ICP spontaneous conception (ICP-SC, n = 7), healthy ICSI (non-ICP-ICSI, n = 7), and ICP-ICSI (n = 7)-were analyzed. eNOS immunostaining, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and syncytial knots were evaluated. Results: The ICP ICSI group had the highest TAS and lowest eNOS levels (p < 0.05). Non-ICP-ICSI showed higher TOS and syncytial knots compared to non-ICP-SC (p = 0.026, p = 0.01). eNOS expression was lower in ICP-ICSI versus ICP-SC (p = 0.021). Conclusion: These findings suggest that ICP-ICSI placentas experience increased oxidative stress and decreased eNOS expression. ICSI may affect placental oxidative balance regardless of ICP status.
Background: Parvovirus B19 (B19V) is normally a self-limiting infection in immunocompetent individuals but can cause severe, persistent anemia in immunocompromised patients, particularly in solid organ transplant (SOT) recipients. Patient: Retrospective review of the patient's clinical, laboratory, and pathology findings to describe the disease progression and management. Results: The patient, a 3 y old girl, developed progressive anemia 15 months post-heart transplant. Bone marrow (BM) biopsy demonstrated B19V nuclear inclusions, and PCR confirmed viremia, consistent with erythroid aplastic crisis. Treatment with intravenous immunoglobulin (IVIG) led to hematologic improvement, but anemia and viral reactivation recurred after discontinuation. Her course was further complicated by Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD) and multi-organ dysfunction, resulting in death 34 months post-transplant. Conclusions: This case represents one of the youngest documented pediatric heart transplant recipients with B19V induced anemia, complicated by viral reactivation despite IVIG, leading to a fatal outcome. Continued viral surveillance and individualized management are needed to improve outcomes in this vulnerable population.
INTRODUCTION:Although exceedingly rare in children, malignant mesothelioma of the tunica vaginalis may be misinterpreted as more common pediatric testicular neoplasms due to overlapping histological features reported in isolated cases. Diagnostic errors can cause delayed treatment and legal consequences. CASE PRESENTATION:A 15-year-old male presented in Turkiye with abdominal distension, scrotal swelling, and suspected testicular malignancy. Pathology suggested a Leydig cell tumor, and chemotherapy was initiated. His condition deteriorated, leading to reevaluation abroad. Pathological reassessment from three international centers, including a German laboratory, confirmed malignant mesothelioma of the tunica vaginalis. The patient improved with appropriate treatment. Due to diagnostic discrepancies, a malpractice case was initiated in Turkiye. CONCLUSION:This case highlights the importance of accurate histopathological diagnosis in pediatric testicular tumors. Given the rarity of tunica vaginalis mesothelioma, multidisciplinary collaboration and second-opinion pathology reviews are essential for proper management and medicolegal accountability.
Introduction: Bladder exstrophy (BE) is a congenital anomaly within the exstrophy-epispadias complex (EEC), characterized by a defect in the closure of the lower abdominal wall and bladder. Case report: A female fetus at 20 weeks + 2 days showed at ultrasound (US) a homogeneous echogenic mass with a lobulated surface, protruding from the anterior lower abdominal wall. The bladder was not visualized. Doppler US displayed umbilical arteries laterally to the mass. The kidneys appeared normal. Amniotic fluid was regular. Legal termination of pregnancy occurred at 21 weeks + 4 days. Autopsy grossly and histologically confirmed BE. Microscopically, BE was layered by an urothelial-like epithelial layer and underneath, the muscularis propria was disarrayed with scarce nerve fibers, evidenced by immunohistochemistry for S-100. Conclusion: In case of prenatal diagnosis of BE, multidisciplinary counseling is mandatory for appropriate clinical management.
