Meconium periorchitis (MPO) is an unusual entity that presents as a scrotal mass in the early neonatal period and is seen in 1 in 30,000 live births. MPO is associated with meconium peritonitis, that leads to leakage of...Meconium periorchitis (MPO) is an unusual entity that presents as a scrotal mass in the early neonatal period and is seen in 1 in 30,000 live births. MPO is associated with meconium peritonitis, that leads to leakage of sterile meconium through patent processus vaginalis into the developing scrotum. Clinically, this entity presents as a para-testicular mass which shows scattered calcifications on imaging, thus warranting diagnostic work up and histopathological confirmation. Our case is an 8 month-old male baby with a firm to hard scrotal cyst. Intraoperatively, a diagnosis of teratoma was considered due to the complex solid cystic nature of the lesion and it was excised. Histology confirmed the diagnosis of MPO. Although some cases of MPO show spontaneous regression, about 65% warrant a surgical intervention. However, lack of awareness of this entity can lead to unnecessary orchiectomy.
Spondylocostal dysostosis type 1 is caused by mutations in the DLL3 gene, which encodes a Notch1 ligand. These mutations lead to defective somitogenesis, resulting in a consistent pattern of abnormal vertebral segmentati...Spondylocostal dysostosis type 1 is caused by mutations in the DLL3 gene, which encodes a Notch1 ligand. These mutations lead to defective somitogenesis, resulting in a consistent pattern of abnormal vertebral segmentation. Disruptions in the Notch1 signaling pathways can potentially lead to extraskeletal anomalies, although specific associations with mutations are less well-documented. We report a 23-week female fetus presenting with characteristic "pebble beach" sign and rib anomalies. Autopsy revealed pulmonary hypoplasia and a 4 mm fundic nodule bulging on both inner and outer gastric surfaces. Histological examination of the stomach walls revealed multifocal pancreatic heterotopia in the fundus and pylorus, invading the submucosa and/or the muscularis propria. Genetic analysis confirmed a novel homozygous likely pathogenic frameshift variant in (NM_000435.3:c.183_184del, p.Arg61Serfs*39). This case report expands the mutational spectrum in spondylocostal dysostosis type 1 and highlights associated pancreatic heterotopia.
A woman in her mid-20s with repaired congenital heart disease (CHD) delivered a 33-week neonate in 2024 following preterm labor and a 24-week neonate in 2025 for non-reassuring fetal heart tones. Placental examination in...A woman in her mid-20s with repaired congenital heart disease (CHD) delivered a 33-week neonate in 2024 following preterm labor and a 24-week neonate in 2025 for non-reassuring fetal heart tones. Placental examination in both cases revealed grossly abnormal, red-brown discolored membranes with a circumvallate insertion. Histologic evaluation demonstrated diffuse chorioamniotic hemosiderosis (DCH) in both cases. This report describes a novel case of recurrent DCH in a mother with CHD and proposes that Fontan physiology may contribute to impaired uteroplacental perfusion, increasing the risk for marginal hemorrhage.
BACKGROUND: Upper GI involvement is common in pediatric IBD, but the relative frequencies of specific endoscopic and histologic abnormalities at diagnosis remain poorly defined. OBJECTIVE: To determine whether specific u...BACKGROUND: Upper GI involvement is common in pediatric IBD, but the relative frequencies of specific endoscopic and histologic abnormalities at diagnosis remain poorly defined. OBJECTIVE: To determine whether specific upper GI endoscopic and histologic features differ among pediatric Crohn disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC) at diagnosis. METHODS: We retrospectively analyzed 243 pediatric patients (<18 years) with newly diagnosed IBD (CD 64.6%, UC 31.2%, IC 4.1%). Clinical parameters, upper GI endoscopic findings, and histologic features were compared using Fisher's exact and non-parametric tests. RESULTS: Age at diagnosis, gender, BMI, and fecal calprotectin did not differ among CD, UC, and IC. Primary sclerosing cholangitis was more prevalent in UC (5.3%, = .04), and eosinophilic esophagitis was more frequent in IC (20%, = .03). CD showed more esophageal erosions/aphthae (12%, < .01), gastric erosions/ulcers (24% vs UC 17%, < .01), and duodenal erosions/ulcers (35%, < .01). Histologically, lymphocytic esophagitis (29%, < .001), epithelioid granulomas (14%, < .001), and active duodenitis (28%, = .007) were significantly more common in CD. CONCLUSIONS: Upper GI abnormalities are not limited to CD. Specific upper GI features-particularly lymphocytic esophagitis, epithelioid granulomas, and active duodenitis-are more strongly associated with CD at diagnosis and may assist subclassification in challenging pediatric IBD cases.
Primary hepatic angiosarcoma (HAS) is an exceedingly rare tumor that is often idiopathic and usually fatal. It typically occurs in a bimodal age distribution, in older adults or very young children. We describe a unique...Primary hepatic angiosarcoma (HAS) is an exceedingly rare tumor that is often idiopathic and usually fatal. It typically occurs in a bimodal age distribution, in older adults or very young children. We describe a unique case of HAS arising at an unusual age, in an adolescent who was one of a pair of identical twins affected by cryptogenic cirrhosis and who were found to have germline loss-of-function variant in , a gene that has recently been shown through animal models to be crucial in the specification of liver sinusoidal endothelial cells (LSECs). The case is the first known report of liver disease in the setting of germline variants. It implicates LSEC dysfunction in both non-neoplastic and neoplastic liver disease and lends insight into the importance of LSECs in liver health and homeostasis.
Chronic histiocytic intervillositis with recurrence risk and perinatal adverse outcome is defined by the detection of maternal CD68-positive macrophages. Intervillous accumulation of B lymphocytes is a rare finding in mi...Chronic histiocytic intervillositis with recurrence risk and perinatal adverse outcome is defined by the detection of maternal CD68-positive macrophages. Intervillous accumulation of B lymphocytes is a rare finding in miscarriage specimens and preterm and term placentas. However, there are case reports with manifestation of maternal B cell lymphoma. We present a case with focal brisk intervillous accumulation of CD20-positive lymphocytes in a placenta of a stillbirth from the 21st gestational week with additional maternal floor infarction and umbilical hypercoiling. Immunohistochemically, staining for CD3, CD5, CD10, and CD23 was negative in the intervillous lymphocytic population. Furthermore, neither clonal B cell-proliferation nor lymphoma were found in molecular pathological investigations. Clinical and/or histological signs of an infectious etiology were also not present. Accumulation of intervillous lymphocytes without clinical signs of infectious or neoplastic disease is probably a rare form of intervillositis due to a pathological immune reaction. The uncommon lesion may have contributed to the adverse outcome in this case.
OBJECTIVES: We describe the clinical characteristics of patients with Stage 2 Basal plate myometrial fibers (BPMF), a histologic lesion resembling Placenta accreta spectrum (PAS). STUDY DESIGN: This is a retrospective an...OBJECTIVES: We describe the clinical characteristics of patients with Stage 2 Basal plate myometrial fibers (BPMF), a histologic lesion resembling Placenta accreta spectrum (PAS). STUDY DESIGN: This is a retrospective analysis of patients sequentially diagnosed with BPMF. Clinical variables: indication for placenta examination, intrapartum hemorrhage, retained placenta, manual extraction, and surgical intervention. Histologic variables followed Amsterdam Placental Classification with additional description of local inflammation, excess fibrin deposition, and smooth muscle injury. RESULTS: Of 121 patients with BPMF, only 5 (4.1%) had clinical suspicion for PAS. Surgical intervention consistent with FIGO definition of PAS was required in 24 (19.8%). Intrapartum use of blood products was seen in only 8 (6.6%), with estimated blood loss greater than 2 L in 6 (5 %). Among the most common indication for pathology examination were "Retained/adherent placenta" and "Manual extraction" in 52 (43.0%) and 20 (16.5%). Manual extraction was performed in 47 (39%). We found no clinical association with histologic findings other than BPMF. CONCLUSIONS: While BPMF often coincides with partial placental retention at delivery, only 1 in 5 cases met FIGO criteria for PAS and serious hemorrhage was rare.
In this report, we describe the case of a child with iron deficiency anemia associated with markedly elevated platelet count. We provide detailed sequential data showing platelet count correction towards normal levels as...In this report, we describe the case of a child with iron deficiency anemia associated with markedly elevated platelet count. We provide detailed sequential data showing platelet count correction towards normal levels as anemia improved with treatment. We discuss the association between iron deficiency and thrombocytosis, the role of IL-6, the potential interaction with other variables such as infections and possible serious complications such as thrombosis.
Bullous pemphigoid (BP) is a rare autoimmune blistering disorder in pediatric patients. Although various medications have been implicated as potential triggers, hypersensitivity reactions associated with Rivaroxaban, a d...Bullous pemphigoid (BP) is a rare autoimmune blistering disorder in pediatric patients. Although various medications have been implicated as potential triggers, hypersensitivity reactions associated with Rivaroxaban, a direct Factor Xa inhibitor, are rarely documented. We present a case of an 8-year-old male who developed widespread BP after 3 months of Rivaroxaban therapy. Histopathological and immunofluorescence findings confirmed the diagnosis. Discontinuation of Rivaroxaban and administration of systemic corticosteroids led to rapid clinical improvement. This case highlights Rivaroxaban-induced BP as a potential adverse reaction in children and underscores the need for awareness and prompt management of this rare but treatable condition.
We report an infrequent case of a full-term male neonate presenting with a large congenital hernia of the umbilical cord (6 cm × 6 cm) containing only the entire left lobe of the liver. Prenatal ultrasonography suggested...We report an infrequent case of a full-term male neonate presenting with a large congenital hernia of the umbilical cord (6 cm × 6 cm) containing only the entire left lobe of the liver. Prenatal ultrasonography suggested an omphalocele; however, the definitive postnatal diagnosis was established based on the presence of a narrow rim of normal skin encircling the umbilical ring and the proximal umbilical cord. Primary closure of the fascial defect was achieved successfully, with no intraoperative or postoperative complications observed. The patient recovered well postoperatively and was discharged in stable condition. Accurate differentiation from an omphalocele is crucial for appropriate management. Unlike omphaloceles, congenital hernias of the umbilical cord (CHUC) typically do not require extensive genetic or cardiac evaluation, and their surgical repair is generally less complex. However, awareness of atypical presentations of CHUC can aid in timely diagnosis, guide surgical planning, and improve clinical outcomes.
Pediatr Dev Pathol
· 2026 · PMID 41355708
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Full text
We report a fetus at 20 + 5 weeks' gestation with an exceptionally rare constellation of congenital anomalies. Prenatal imaging revealed left congenital diaphragmatic hernia, rightward cardiac displacement, possible trac...We report a fetus at 20 + 5 weeks' gestation with an exceptionally rare constellation of congenital anomalies. Prenatal imaging revealed left congenital diaphragmatic hernia, rightward cardiac displacement, possible tracheoesophageal fistula (TEF), transposition of the great vessels, and a large ventricular septal defect. Autopsy confirmed complete absence of tracheoesophageal separation from the larynx to the carina, consistent with Kluth type Xc2, incorporating extralobar pulmonary sequestration with esophageal communication. The findings met criteria for a communicating bronchopulmonary foregut malformation (CBPFM), Srikanth Group III. Additional anomalies included bilateral pulmonary hypoplasia, bilateral unilobar lungs with eparterial bronchi, mirror-image dextrocardia, L-looped ventricles with concordant atrioventricular and ventriculoarterial alignments, right-sided aortic arch, bilateral superior vena cava, cardiac-type total anomalous pulmonary venous connection with drainage into the morphologic right atrium, and anomalous coronary origin from the pulmonary artery. Cytogenetic studies and whole-exome sequencing were normal. To our knowledge, this is the first report of Kluth type Xc2 TEF with Srikanth Group III CBPFM since Stolte's original description in 1952, and the first to combine this unique constellation. This case broadens the recognized spectrum of foregut and cardiopulmonary maldevelopment and underscores the importance of comprehensive evaluation in fetuses with multiple anomalies.
In forensic pathology, estimating the timing of intrauterine death in stillbirths is still challenging. The current gold standard methods involve the macroscopic assessment of fetal maceration integrated with the histolo...In forensic pathology, estimating the timing of intrauterine death in stillbirths is still challenging. The current gold standard methods involve the macroscopic assessment of fetal maceration integrated with the histological examination of the fetus and placenta. This study proposes a maceration scoring system and its predictive value in estimating the postmortem interval (PMI) in stillbirths. A retrospective analysis was conducted on stillbirths delivered between 2017 and 2024. Circumstantial, clinical, postmortem data, and color photographs taken at delivery and/or autopsy, were collected. A total macroscopic maceration score (TMMS), ranging from 4 to 20, was developed and applied to photographs of 52 stillbirth cases. The association between TMMS and PMI, calculated at delivery (dPMI) and at post-mortem examination (pPMI) was evaluated, and a cross-validation was performed. TMMS values ranged from 4 to 20 and showed high interobserver agreements (from 88% to 93%). The correlation between TMMS and pPMI was stronger than that with dPMI, and was best described by a second order polynomial regression, with an value of .958 and a mean absolute error of 0.39 days. The TMMS showed promising results and, when integrated with current gold-standard methods, it may be an additional tool to assess the PMI in stillbirths.
BACKGROUND: Intervillous thrombi (IVT) is one of the most common pathology findings during placental examination. The etiology and clinical significance of IVT are controversial. MATERIALS AND METHODS: We previously coll...BACKGROUND: Intervillous thrombi (IVT) is one of the most common pathology findings during placental examination. The etiology and clinical significance of IVT are controversial. MATERIALS AND METHODS: We previously collected placental data with fetal birth data and maternal pregnancy characteristics, and we examined IVT in the context of maternal, fetal, and placental pathology. RESULTS: A total of 3119 placentas with fetal birth and maternal pregnancy characteristics were examined, and IVT was found in 644 placentas (20.6%). IVT was statistically associated with advanced maternal age ( = .01) and clinical preeclampsia ( = .02). IVT was significantly associated with placental infarcts ( < .01), mural arterial hypertrophy ( = .02) as well as placental abruption ( < .01). In addition, IVT was significantly associated with velamentous cord insertion ( < .01). Regression analysis demonstrated the persistence of association between IVT placental infarct, in addition to 2 vessel cord (SUA) and fetal inflammatory response (FIR, acute funisitis/fetal vasculitis). CONCLUSION: Our data showed that IVT was independently associated with placental infarct, single umbilical artery, and fetal inflammatory response after regression analysis. The association of IVT with single umbilical artery and fetal inflammatory response points to fetal blood flow as potential pathogenic basis, providing new insight into pathogenic mechanisms and clinical significance.
BACKGROUND: We sought to investigate gene expression in placentas impacted by major patterns of injury: acute inflammation (AI), chronic inflammation (CI), and maternal vascular malperfusion (MVM). METHODS: We utilized p...BACKGROUND: We sought to investigate gene expression in placentas impacted by major patterns of injury: acute inflammation (AI), chronic inflammation (CI), and maternal vascular malperfusion (MVM). METHODS: We utilized placental tissue prospectively collected between 2017 and 2020. Chorionic villous biopsies were collected following delivery and samples were also submitted for histologic examination. Placentas with ≥2 types of placental injury after histology examination were excluded. Linear models, adjusted for covariates, were used to compare each pathology group to histologically normal control placentas. Transcripts with fold-change of >2 or <0.5 served as input for higher-order bioinformatic analyses, focused on identifying transcription control pathways and the cellular populations involved. RESULTS: One hundred and sixty-four placentas were included: 60 AI, 25 CI, 39 MVM, and 40 controls. In bioinformatic analyses each pathology group displayed a unique signature, with distinct transcription binding factor activity involved including pathways involved in cell signaling, cell proliferation, and cell differentiation. CONCLUSION: We show unique patterns of transcriptional control for each pathology-defined type of placental injury. MVM, CI, and AI represent not only unique histologic patterns, but also express unique molecular signatures.
BACKGROUND: Congenital hyperinsulinism (HI) is a severe form of hypoglycemia presenting in newborns and infants. Some affected patients develop conjugated hyperbilirubinemia potentially raising concern for biliary atresi...BACKGROUND: Congenital hyperinsulinism (HI) is a severe form of hypoglycemia presenting in newborns and infants. Some affected patients develop conjugated hyperbilirubinemia potentially raising concern for biliary atresia. METHODS: Retrospective study characterizing the liver biopsies of patients with congenital HI presenting with cholestasis. RESULTS: Seven patients were identified with a median age of 2 months (range: 1-8) and a median gestational age of 36 weeks at birth (range: 28-38). Three patients had an underlying variant, and 2 patients had Beckwith-Wiedemann/11p Overgrowth syndrome. The median total bilirubin, conjugated bilirubin, and gamma-glutamyl transferase levels were 6.5 mg/dL (range: 1.1-18.1), 2.0 mg/dL (range: 0.0-10.7), and 176 Units/L (range: 60-395), respectively. Four patients were on total parental nutrition at the time of biopsy. All cases demonstrated hepatocyte giant cell transformation with cholestasis. Half of the cases showed periportal fibrosis and all had some degree of bile duct proliferation; however, ductular reaction was absent in most cases. None of the cases demonstrated portal stromal edema, bile plugs, or a generalized ductular reaction. All patients received ursodiol and at most recent follow up 5 patients had improvement in, or resolution of, the cholestasis. CONCLUSIONS: Liver biopsies from patients with HI and cholestasis show a giant cell hepatitis pattern without features of a biliary obstructive process.
Spleno-gonadal fusion (SGF) is an infrequent developmental disorder that can mimic a gonadal tumor due to mass formation in a peri-gonadal location. Continuous and discontinuous forms were documented in the literature. A...Spleno-gonadal fusion (SGF) is an infrequent developmental disorder that can mimic a gonadal tumor due to mass formation in a peri-gonadal location. Continuous and discontinuous forms were documented in the literature. An accurate pre-operative diagnosis is often difficult due to the rarity of this entity. We describe a case of ten 10-year-old child presenting with an empty left scrotum. Diagnostic laparoscopy confirmed left cryptorchidism but showed 2 discrete masses in the left inguinal region in the vicinity of the testicle and spermatic cord, which falsely alarmed the surgeon for a para-testicular tumor. However, histopathological examination confirms the mass to be splenic tissue. Hence, better knowledge of this disease can prevent a misdiagnosis of this anomaly and obviate the unnecessary surgical intervention.
We report a rare case of gestational alloimmune liver disease (GALD) and congenital athymia in a 3-week-old premature male neonate, born via in vitro fertilization (IVF) surrogacy. The neonate initially presented with di...We report a rare case of gestational alloimmune liver disease (GALD) and congenital athymia in a 3-week-old premature male neonate, born via in vitro fertilization (IVF) surrogacy. The neonate initially presented with disseminated intravascular coagulation and septic shock, and subsequently developed liver failure. Despite aggressive treatment, he succumbed. Autopsy confirmed GALD, congenital athymia, splenomegaly, and extensive hemorrhage in the gastrointestinal mucosa and brain. Congenital athymia, characterized by a lack of functional T cells, might impair immune regulation or tolerance mechanisms and reduce the neonate's capacity to recover from GALD-induced liver injury. The additional context of an IVF surrogate pregnancy further complicates the immunologic landscape. This case highlights the need for further investigation into potential causal or synergistic relationships among these conditions to optimize management strategies for affected neonates.
Ebstein anomaly (EA) is a rare congenital heart defect characterized by an abnormal development of the tricuspid valve (TV) and ventricular myocardium. The TV is displaced downward into the right ventricle (RV), leading...Ebstein anomaly (EA) is a rare congenital heart defect characterized by an abnormal development of the tricuspid valve (TV) and ventricular myocardium. The TV is displaced downward into the right ventricle (RV), leading to an atrialized basal portion of the RV above the closure plane of the TV and an often hypoplastic functional RV. Common consequences include cyanosis, TV regurgitation, arrhythmias, and heart failure. Although primarily a valve defect, EA can be regarded as a cardiomyopathy as well. Coexistence of EA with other cardiomyopathies, including left ventricular non-compaction (LVNC), suggests a shared genetic or developmental basis. Diagnostic advancements such as echocardiography, cardiac magnetic resonance, and electrophysiological studies have greatly improved early identification, risk stratification, and management of EA. However, challenges persist, particularly in prenatal detection and differentiation of EA from other congenital TV malformations. Autopsy is fundamental in fatal EA cases to ascertain the diagnosis, understand the cause of death, and guide family counseling. Significant knowledge gaps remain concerning the exact etiology of EA. Future research should focus on unveiling the genetic/epigenetic pathways and environmental factors involved in the pathogenesis of this heart malformation. Filling these gaps will be essential for developing targeted and effective treatments and improving patient outcomes.
Germ cell tumours are heterogeneous tumours arising in the gonads, though they also affect extragonadal sites, including midline structures of the central nervous system (CNS). While intracranial germ cell tumours (iGCTs...Germ cell tumours are heterogeneous tumours arising in the gonads, though they also affect extragonadal sites, including midline structures of the central nervous system (CNS). While intracranial germ cell tumours (iGCTs) are extensively characterised, their developmental origin remains speculative. The most frequently cited hypothesis posits that primordial germ cells (PGCs) from the embryonic yolk sac aberrantly migrate to the brain in-utero and form tumours after neoplastic transformation. However, there is currently no direct evidence for PGCs in the human brain. We report for the first time the presence of apparently non-tumour forming PGCs in 2 fetal brains, incidentally discovered on post-mortem examination for non-CNS indications. One case demonstrated PGCs in the ventrolateral thalamus, while the other demonstrated PGCs in the anterior germinal matrix, septal area, and anterior thalamus. These cases demonstrate for the first time the presence of PGC's in the human fetal brain, and that the foundation for iGCTs may be present in the CNS during early development. The distribution seems to favour the hypothesis that PGCs may be derived from germinal matrix neural stem cells rather than necessarily from extracranial midline migration to the brain.