Pediatric and Developmental Pathology最新文献

Background: Lymphocytic colitis (LC) in the pediatric population has been associated with immune dysregulation.

Methods: Single-center retrospective study of pediatric LC.

Results: 50 patients (35 female, 70%) with a median age of 12 years at diagnosis (interquartile range: 5.7-15.8) of LC were identified. At presentation, 11 patients (22%) had malnutrition, 16 (32%) had a known underlying immune dysregulation, 4 (8%) had celiac disease (CD), and none had a diagnosis of inflammatory bowel disease. The most common medications prior to diagnosis were non-steroidal anti-inflammatory drugs, proton pump inhibitor, and selective serotonin reuptake inhibitors (10% each). Colonic biopsies showed a median number of intraepithelial lymphocytes (IELs)/100 epithelial cells of 48 (range: 25-85), and only 10% of cases had neutrophilic cryptitis. Upper gastrointestinal tract findings included lymphocytic esophagitis (4%), and duodenal IELs without and with villous blunting (9% each) (n: 47). Ten patients (23%) had increased IELs in the terminal ileum (n: 43). Treatments including 5-ASA, budesonide, prednisone, and gluten-free diet improved symptoms in <50% of patients (n: 42), and all follow-up colonoscopies showed persistent LC (n: 13).

Conclusion: Our study supports the association of LC with immune-mediated conditions, most commonly celiac disease. Symptomatic improvement was seen in <50% of patients with none of the patients with repeat colonoscopy showing histologic improvement.

Hepatoblastomas (HB) are embryonal tumors with quiet genomes diagnosed mostly in children under 3 years of age and often cured by surgical resection and chemotherapy. However, a subset of HBs behave aggressively, displaying characteristic histologic features and higher genomic instability. Hepatocellular neoplasm-not otherwise specified (HCN-NOS) is a provisional diagnostic category for tumors exhibiting either intermediate or a combination of both HB and hepatocellular carcinoma (HCC) histological features. In this study, we characterized an HCN-NOS diagnosed in a 3-year-old patient presenting with a liver mass, in which both HB and HCC histological components were amendable to macro-dissection and molecular profiling. The spectrum of mutations, copy number changes, mRNA, and protein expression profiles within these 2 histologically distinct tumor areas demonstrate molecular heterogeneity and suggest intratumoral clonal evolution of this hepatocellular CTNNB1-mutant lesion.

The differential diagnosis for neonatal primary lung masses includes developmental anomalies and congenital lung tumors. Fetal lung interstitial tumor (FLIT) is a rare benign mesenchymal lesion which presents either antenatally or within the first 3 months of age. FLIT is a circumscribed solid-cystic mass which histologically resembles the fetal lung during the canalicular stage at 20-24 weeks of gestation. It is composed of immature mesenchymal cells expanding the interstitium and irregular airspace-like structures. Of all published cases, only 1 identified an α2-macroglobulin (A2M)::anaplastic lymphoma kinase (ALK) fusion and all cases underwent surgical resection in the neonatal or infancy period. We present the second case of FLIT with an A2M::ALK fusion diagnosed postnatally in a neonate which partially regressed spontaneously during conservative management with interim resection at 39 months of age, and provide a review of the literature.

While conventional autopsy is the gold-standard for determining cause of demise in the fetal and neonatal population, molecular analysis is increasingly used as an ancillary tool. Testing methods and tissue selection should be optimized to provide informative genetic results. This institutional review compares testing modalities and postmortem tissue type in 53 demises occurring between 20 weeks of gestation and 28 days of life. Testing success, defined as completion of analysis, varies by technique and may require viable cells for culture or extractable nucleic acid. Success was achieved by microarray in 29/30 tests (96.7%), karyotype in 40/54 tests (74.1%), fluorescent in situ hybridization in 5/9 tests (55.6%), and focused gene panels in 2/2 tests (100%). With respect to tissue type, postmortem prepartum amniotic fluid was analyzed to completion in 100% of tests performed; compared to 84.0%, 54.5%, and 80.8% of tests using placenta, fetal only, and mixed fetal-placental tissue collection, respectively. Sampling skin (83.3%, in cases with minimal maceration) and kidney (75.0%) were often successful, compared to lower efficacy of umbilical cord (57.1%) and liver (25.0%). Addition of genetic testing into cases with anomalous clinical and gross findings can increase the utility of the final report for family counseling and future pregnancy planning.

B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is a precursor B-cell neoplasm that often harbors specific cytogenetic/molecular abnormalities with distinctive clinical, phenotypic, and prognostic characteristics. Subcategorization of B-ALL/LBL therefore requires extensive cytogenetic and/or molecular testing to determine the appropriate classification and therapeutic interventions for these patients. Herein, we present a case of a 17-year-old young woman diagnosed with B-LBL harboring not only an IGH::MYC rearrangement but also BCL2 and BCL6 rearrangements (so-called "triple-hit") and somatic biallelic TP53 inactivation. MYC rearrangements are relatively rare in B-ALL/LBL, and the identification of a "triple-hit" elicited an initial diagnostic dilemma. However, a multimodal approach allowed for the classification of this complex case and helped guide selection of an appropriate therapeutic regimen.

Coffin-Siris syndrome is an autosomal dominant disorder with neurological, cardiovascular, and gastrointestinal symptoms. Patients with Coffin-Siris syndrome typically have variable degree of developmental delay or intellectual disability, muscular hypotonia, dysmorphic facial features, sparse scalp hair, but otherwise hirsutism and fifth digit nail or distal phalanx hypoplasia or aplasia. Coffin-Siris syndrome is caused by pathogenic variants in 12 different genes including SMARCB1 and ARID1A. Pathogenic SMARCB1 gene variants cause Coffin-Siris syndrome 3 whereas pathogenic ARID1A gene variants cause Coffin-Siris syndrome 2. Here, we present two prenatal Coffin-Siris syndrome cases with autosomal dominant pathogenic variants: SMARCB1 gene c.1066_1067del, p.(Leu356AspfsTer4) variant, and a novel ARID1A gene c.1920+3_1920+6del variant. The prenatal phenotype in Coffin-Siris syndrome has been rarely described. This article widens the phenotypic spectrum of prenatal Coffin-Siris syndrome with severely hypoplastic right ventricle with VSD and truncus arteriosus type III, persisting left superior and inferior caval vein, bilateral olfactory nerve aplasia, and hypoplastic thymus. A detailed clinical description of the patients with ultrasound, MRI, and post mortem pictures of the affected fetuses showing the wide phenotypic spectrum of the disease is presented.

Introduction: In osteosarcoma, the most significant indicator of prognosis is the histologic changes related to tumor response to preoperative chemotherapy, such as necrosis. We have developed a method to measure the osteosarcoma treatment effect using whole slide image (WSI) with an open-source digital image analytical software Qupath.

Materials and methods: In Qupath, each osteosarcoma case was treated as a project. All H&E slides from the entire representative slice of osteosarcoma were scanned into WSIs and imported into a project in Qupath. The regions of tumor and tumor necrosis were annotated, and their areas were measured in Qupath. In order to measure the osteosarcoma treatment effect, we needed to calculate the percentage of total necrosis area over total tumor area. We developed a tool that can automatically extract all values of tumor and necrosis areas from a Qupath project into an Excel file, sum these values for necrosis and whole tumor respectively, and calculate necrosis/tumor percentage.

Conclusion: Our method that combines WSI with Qupath can provide an objective measurement to facilitate pathologist's assessment of osteosarcoma response to treatment. The proposed approach can also be used for other types of tumors that have clinical need for post-treatment response assessment.

Background: Next generation sequencing (NGS) has increased the detection of fusion genes in cancer. NGS has found multiple fusions in single tumor samples; however, the incidence of this in pediatric soft tissue and bone tumors (PSTBTs) is not well documented. The aim of this study is to catalogue the incidence of multiple fusions in a series of PSTBTs, and apply a modified gene fusion classification system to determine clinical relevance.

Methodology: RNA from 78 bone and soft tissue tumors and 7 external quality assessment samples were sequenced and analyzed using recently-described Metafusion (MF) software and classified using a modification of previously-published schema for fusion classification into 3 tiers: 1, strong clinical significance; 2, potential clinical significance; and 3, unknown clinical significance.

Results: One-hundred forty-five fusions were detected in 85 samples. Fifty-five samples (65%) had a single fusion and 30 (35%) had more than 1 fusion. No samples contained more than 1 tier 1 fusion. There were 40 tier 1 (28%), 36 tier 2 (24%), and 69 (48%) tier 3 fusions.

Conclusions: A significant percentage of PSTBTs harbor more than 1 fusion, and by applying a modified fusion classification scheme, the potential clinical relevance of such fusions can be determined.

Introduction: This study aimed to evaluate the potential value of placental anatomic features and various types of normal and abnormal cord insertion types in predicting adverse maternal-fetal outcomes in singleton pregnancies. We also tried to assess the association between these outcomes and various types of placental cord insertion.

Method: This prospective observational study was performed on singleton pregnancies. For each patient placental features including diameter, thickness, type of cord insertion, and the shortest distance between the cord insertion point and placental edge were recorded. The relationship between these factors and the development of multiple adverse pregnancy outcomes including preterm labor, intrauterine fetal death (IUFD), and the rate of neonatal intensive care unit (NICU) admissions were evaluated and reported.

Results: Overall 308 patients were enrolled in the study. Smoker mothers had significantly smaller placentas (P-value = .008), and those with lower diameter placentas were more likely to suffer from IUFD (P-value = .0001). Shorter placental cord insertion distances led to more episodes of preterm labor (P-value = .057). Eccentric-type placental cord insertion was significantly associated with the development of preeclampsia (P-value = .006).

Discussion: Abnormalities in placental diameter and cord insertion can lead to significant maternal-fetal complications including preterm labor, IUFD, and preeclampsia.