Pediatric and Developmental Pathology最新文献

Acute respiratory distress in a neonate is a potentially critical condition with multiple possible causes. Developmental etiologies are particularly problematic by virtue of being refractory to routine modalities for enhancing ventilation and oxygen exchange. Some genetic causes of neonatal respiratory distress, such as surfactant protein deficiencies and alveolar capillary dysplasia with misalignment of pulmonary veins, are well known, and sequencing panels have been formulated to detect them. We present a case of fatal neonatal respiratory insufficiency in which the autopsy showed primary pulmonary hypoplasia and congenital alveolar dysplasia. A sequencing panel of genes associated with heritable pulmonary disorders gave a normal result; however, a chromosomal microarray identified a heterozygous deletion encompassing the TBX4 gene on chromosome 17. Haploinsufficiency for TBX4 is a known cause of disturbed pulmonary development. This case illustrates why work-up of pulmonary developmental disorders must look beyond standard sequencing panels in some instances, if rare causes of pulmonary maldevelopment such as deletions causing haploinsufficiency are not to be missed.

Background: Bile acids in the ileum act as a feedback regulator of their own synthesis by inducing the release of ileal fibroblast growth factor 19 (FGF19), which inhibits the cholesterol-7-alpha hydroxylase enzyme. In cholestasis, this feedback mechanism is dysregulated. FGF19 is not expressed in the healthy liver. We aimed to assess the hepatic expression of FGF19 in neonatal cholestasis (NC) and its relation to serum bile acids.

Methods: The study included 41 patients with NC. FGF19 immunohistochemical staining in liver tissue (hepatocytes, endothelial cells, bile ducts, and bile canaliculi) was evaluated as negative, weak, moderate, and strong staining. FGF19 staining in 6 liver samples from explants of children with Crigler-Najjar syndrome type-1 served as controls.

Results: Hepatocyte, endothelial, and canalicular FGF19 expression was significantly higher in cholestasis group compared to controls (P = .039, .006, and .028 respectively). Serum bile acids had significant correlation with hepatocyte FGF19, endothelial, and bile duct FGF19 expressions (P = .002, .003, and .01, respectively) but not with canalicular FGF19 expression. Hepatocyte FGF19 expression significantly associated with cholestasis severity in terms of serum total bilirubin, direct bilirubin, and aspartate transaminase levels (P = .01, .02, and .02, respectively).

Conclusion: Hepatic FGF19 expression significantly upregulated in NC and correlated with cholestasis severity.

Background: Sloughing esophagitis (esophagitis dissecans superficialis) is a benign, self-limited condition of uncertain etiology. It is most common in adults; pediatric literature is limited.

Methods: Ten years of records were queried for esophageal biopsies containing terms "sloughing" and/or "dissecans." Histologic inclusion criteria were "two-tone" appearance, sloughing/flaking of superficial epithelium, and parakeratosis. Degree of inflammation was documented and medical records were reviewed.

Results: Fourteen patients were identified ranging from 1 to 19 years (mean = 14 years) and included 3 males and 11 females. Two patients were excluded due to lack of histologic criteria/unavailability of slides for review. Of the 12 cases evaluated, 6 showed a classic inflammation pattern, 5 had minimal or no inflammation, and 1 displayed severe acute inflammation. Endoscopy did not correlate with histology. Sloughing esophagitis is traditionally associated with Selective serotonin reuptake inhibitors (SSRI) use; though 5/12 patients were taking medication for anxiety or depression, only 3 were taking SSRIs. Five patients had marijuana/cannabinoid exposure.

Conclusion: Sloughing esophagitis can present in the pediatric population across a wide age range. Similar to the adult population, etiology may be linked to medications. Additional associations such as marijuana/cannabinoid exposure need further clinical investigation. A subset of patients had a history of or subsequently developed eosinophilic esophagitis.

We report a teenage patient with a delayed diagnosis of compound heterozygous POLG pathogenic variants [(POLG c. 1943 C>G, p.P648R) and (POLG c. 679 C>T, p.R227W)] who presented with fatigue and neuropathy, as well as long standing malnutrition and cachexia, erroneously attributed to an eating disorder. She experienced multiple bowel perforations and pathologic examination revealed jejunal diverticula and features of visceral neuromyopathy. In addition to ganglion cell mega-mitochondrial inclusions, there were multiple foci of interrupted muscularis mucosae, an alteration not previously recognized in the intestines of patients with primary mitochondrial disorders. We provide a detailed account of the gastrointestinal pathologic findings in this patient and compare with prior cases of Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) phenotypes.

Acute necrotizing encephalopathy (ANE) is a rare immune-mediated disease in children that could progress rapidly, and lead to significant morbidity or mortality. ANE's diagnostic challenges render it difficult to recognize and treat in a timely and effective manner. Although infantile-onset cases have been reported, the presentation of ANE in preterm neonates has not been described. Herein, we report a case of a preterm newborn who had a relatively stable clinical course in the first week of life, after which the neonate exhibited sudden deterioration due to progressive encephalopathy with refractory status epilepticus. Despite aggressive management of seizures and sepsis, the patient succumbed. Whole-exome sequencing analyses of the patient and parents were negative. Viral and metabolic testing were non-contributory. An autopsy showed evidence of acute to subacute fulminant liquefactive necrosis with extensive hemorrhage diffusely in the cortex with relative sparing of the cerebellum and the brainstem. A major consideration highlighted by this case is that the adaptive immune response to the immune-mediated or cytokine storm-related proposed etiology of acute necrotizing encephalopathy may differ in preterm compared with full-term infants due to properties dictated by their innate immune responses. Clinical suspicion of ANE should be heightened whenever preterm neonates with early sepsis continue to deteriorate despite aggressive management.

Hypoplastic right heart syndrome (HRHS) is an uncommon congenital cardiac defect, characterized by variable underdevelopment of the right-sided heart structures. We report on a case of HRHS in a 25-week female fetus. Prenatal karyotype was normal. Autopsy performed following pregnancy termination demonstrated characteristic craniofacial dysmorphism and complex congenital heart disease encompassing severe hypoplasia of the right ventricle, main pulmonary artery and tricuspid valve, ostium secundum atrial septal defect, and ductus arteriosus agenesis. Macroscopic and histologic examinations of the brain and organs were unremarkable. Post-mortem array CGH didn't detect any unbalanced chromosomal abnormalities. Exome and Sanger sequencing revealed a novel de novo heterozygous missense variant in GATA6 (NM_005257.6:c.1385A>G) which is located in the hotspot exon 4 encoding the highly conserved C-terminal zinc finger domain. This report ascertains that GATA6 haploinsufficiency may cause a cardiocraniofacial syndrome consisting of distinctive craniofacial dysmorphism and HRHS.

Background: Digital pathology facilitates remote pathology consultations. Pediatric pathologists in Canada formed a nationwide digital pathology consultation network, mostly for second opinion review of pediatric cancer cases. Validation of such a large network for clinical use is challenging. Here we report our unique validation process of this digital pathology network.

Method: This study was designed in keeping with the College of American Pathologist (CAP) guidelines, and included 14 pathologists from 9 hospitals across Canada. All cases are pediatric pathology cases. Each pathologist reviewed multiple digital cases and the corresponding glass slide cases. For each review, intra-observer concordance (diagnosis on digital case versus diagnosis on glass slide case) was recorded, creating a data point.

Result: The study generated 269 valid diagnostic data points. Out of the 269 data points, 257 were concordant (95.5% concordance), exceeding the CAP recommendation of 95% concordance. Thus, the network was successfully validated.

Conclusion: This is a unique validation study for a large nationwide digital pediatric pathology network. The study involved all pathologists/hospitals in the network, closely emulating real world clinical process. The network was successfully validated.

We report a case of acute myeloid leukemia with megakaryoblastic differentiation (AMKL) that developed after an initial B-lymphoblastic leukemia (B-ALL) with low hypodiploidy. Although the AMKL was initially thought either to be a phenotypic change from the original B-ALL or to have arisen as a result of treatment (acute myeloid leukemia, post cytotoxic therapy, AML-pCT [WHO]; AML, therapy related [ICC]), genetic evaluation of both the AMKL and the B-ALL suggest that neither of these considerations was correct. Rather, the AMKL did not harbor the most common genetic hallmark of AML-pCT-rearrangement of KMT2- and was genetically distinct from the B-ALL. Both the B-ALL and the AMKL, however, showed an identical TP53 mutation by next generation sequencing (NGS), while germline testing was negative for this mutant allele. Hence, either the patient had a tissue restricted constitutional TP53 mutation or had a somatic mutation in a multipotent hematopoietic precursor. This case highlights the necessity for close monitoring of patients with TP53-mutant tumors, as they may develop multiple lesions despite negative germline testing.

In recent years, Bacillus cereus infection has emerged as a main concern in the field of children's public health. This bacterium, known to be a pollutant, can be found in various settings such as hospital wards, equipment, breast milk, nutrient solution, and so on. With its high pathogenicity and toxicity, Bacillus cereus infection can lead to severe and life-threatening symptoms, particularly in premature infants. This case report documents the death of a preterm infant due to Bacillus cereus sepsis, septic shock, meningitis, and pneumonia, all of which were linked to the use of a central venous catheter.