Pediatric and Developmental Pathology最新文献

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.

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.

Neuroblastoma (NB) is the most common extracranial solid neoplasm affecting the pediatric population. It shows a high prevalence of bone marrow infiltration (BMI), which substantially impacts the disease's staging and prognostic assessment. Conventional methodologies, including bone marrow biopsy (BMB) and aspirate (BMA), have been extensively employed; nevertheless, the advent of novel technologies presents a promising avenue for diagnostic accuracy. This systematic review is designed to critically analyze and compare the established techniques (BMB and BMA) versus novel diagnostic approaches-such as immunocytology, RT-qPCR, and multiparametric flow cytometry (FCM), along with functional imaging like MIBG scintigraphy and FDG-PET/CT-in assessing BMI in pediatric NB. An exhaustive search was performed across the PubMed and Embase databases, identifying 2694 scholarly articles. Following a meticulous screening process and the application of inclusion criteria centered on diagnostic accuracy, sensitivity, and specificity about BMI, a total of 140 articles were selected for qualitative analysis. While BMB remains the gold standard for diagnosing and staging BMI in NB, recent advances in molecular techniques and functional imaging have shown superior sensitivity and specificity. Immunocytology and RT-qPCR can detect minimal residual disease (MRD) with higher sensitivity compared to traditional methods. Functional imaging modalities, particularly FDG-PET/CT and MIBG scintigraphy, have demonstrated improved accuracy in assessing bone marrow involvement with the added advantage of evaluating the entire bone marrow, overcoming the limitations of focal sampling in BMB. The integration of advanced molecular diagnostics and functional imaging with traditional biopsy methods enhances the accuracy of BMI in NB.

The patients with Arthrogryposis-Renal dysfunction-Cholestasis (ARC) syndrome have genetic susceptibility to the opportunistic infections due to the involvement of VPS33B (vacuolar protein sorting 33 homolog B) in phagolysosome fusion in macrophages. Detailed pathologic studies in ARC patients are missing in literature due to the lack of autopsy. We described the first autopsy case of ARC syndrome in a 2-month-old male infant. His death was due to recurrent sepsis and multiorgan failure despite the appropriate poly-antibiotic therapy and supportive care. The autopsy showed invasive renal candidiasis including bilateral destructive pyelonephritis, pelvic obstructive fungal bezoars, and right large perinephric abscess. The main other findings included severe chronic liver changes and pneumonia. Liver exhibited intrahepatocyte cholestasis, large multinucleated hepatocytes, diffuse portal, bridging and perivenular fibrosis, and interlobular bile duct proliferation. The neuropathologic examination was unremarkable. This case report highlights 3 novel findings. The ARC syndrome-related immunodeficiency may predispose to renal fungal bezoars and perinephric abscess. Cholestatic stress may result in the proliferation of interlobular ducts as an adaptive response. Absence of spinal motor neuron degeneration suggests that the neurogenic amyotrophy is due to the lack of synaptic vesicle trafficking and membrane fusion rather than the defect in cell survival-related autophagosome-lysosome fusion.

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.

Dermatofibrosarcoma protuberans (DFSP) is an intermediate-grade fibroblastic neoplasm commonly seen in young and middle-aged patients and rarely in pediatric patients. Fibrosarcomatous transformation is common in adults but extremely uncommon in children. Here, we present a case of a 2-year-old child who presented with a progressively enlarging subcutaneous mass in the knee. Histopathological examination revealed a spindle cell tumor with a storiform and fascicular pattern. Immunohistochemistry showed variable cluster of differentiation 34 (CD34) expression, with positivity in storiform areas and negativity in fascicular regions. Next-generation sequencing confirmed the diagnosis by detecting a collagen type I alpha 1 (COL1A1)-platelet-derived growth factor subunit B (PDGFB) fusion, with the PDGFB breakpoint in exon 2 (chromosome 22) and COL1A1 in intron 47 (chromosome 17). This case represents only the fifth reported instance of fibrosarcomatous DFSP in a child under 10 years old. While wide local excision remains the standard treatment for DFSP, targeted therapy with imatinib may be considered for unresectable, recurrent, or metastatic cases, though guidelines for pediatric patients are not yet established. This case highlights the importance of molecular testing in confirming the diagnosis of rare pediatric soft tissue tumors and contributes to the limited literature on fibrosarcomatous DFSP in very young children.

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.

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.