Pediatric and Developmental Pathology最新文献

The etiologies of podocyte dysfunction that lead to pediatric nephrotic syndrome (NS) are vast and vary with age at presentation. The discovery of numerous novel genetic podocytopathies and the evolution of diagnostic technologies has transformed the investigation of steroid-resistant NS while simultaneously promoting the replacement of traditional morphology-based disease classifications with a mechanistic approach. Podocytopathies associated with primary and secondary steroid-resistant NS manifest as diffuse mesangial sclerosis, minimal change disease, focal segmental glomerulosclerosis, and collapsing glomerulopathy. Molecular testing, once an ancillary option, has become a vital component of the clinical investigation and when paired with kidney biopsy findings, provides data that can optimize treatment and prognosis. This review focuses on the causes including selected monogenic defects, clinical phenotypes, histopathologic findings, and age-appropriate differential diagnoses of nephrotic syndrome in the pediatric population with an emphasis on podocytopathies.

Introduction: Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility. While skeletal manifestations are well documented, few studies have explored the effect of OI on the fetal heart. This retrospective case series investigates cardiac pathology in OI type II fetuses, aiming to address this gap.

Methods: Medical records and autopsy reports of 6 genetically confirmed OI type II cases were examined. Fetuses had pathogenic variants in COL1A1 or PPIB, inducing structural defects in collagen type I. In addition to hematoxylin and eosin and Elastic van Gieson staining, the expression of collagen type I, COL1A1 and COL1A2 chains was examined by immunohistochemistry.

Results: Immunohistochemistry confirmed robust expression of collagen type I throughout the heart. Five fetuses had normal heart weight, while 1 had a low heart weight in the context of generalized growth retardation. None displayed structural heart anomalies.

Conclusion: This study reveals robust collagen type I expression in the hearts of OI type II fetuses without structural anomalies. We hypothesize that collagen type I abnormalities may not be causative factors for heart anomalies during early embryonic development. Instead, their impact may be conceivably related to an increased susceptibility to degenerative changes later in life.

Interfollicular Hodgkin lymphoma (IHL) has been rarely reported in the literature and is recognized by the WHO Classification as a morphologic pattern sometimes seen in mixed cellularity classic Hodgkin lymphoma (CHL). The changes may be subtle due to preservation of architecture. We report a case of a 9-year-old male with IHL showing preserved follicular architecture but with the presence of interfollicular infiltrates consisting of eosinophils, plasma cells, and Hodgkin-Reed-Sternberg (HRS) cells. Immunophenotyping confirmed the morphologic suspicion for IHL. A discussion and review of the literature are offered. We conclude that IHL is a variant that requires a high index of suspicion, as it may be easily missed due to the subtle morphologic features and preserved architecture seen in most cases. We further emphasize that unexplained interfollicular infiltrates of eosinophils may be clues that should prompt a search of HRS cells and consideration of immunohistochemical staining if needed.

We present 2 diagnostically challenging cases of pediatric/adolescent relapsed/refractory aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) within the spectrum of Burkitt lymphoma and diffuse large B-cell lymphoma and illustrate the different therapeutic regimens that are employed for pediatric and adult cancer centers. Both cases displayed varying-sized lymphoma cells with occasional single prominent nucleoli and heterogeneous BCL2 expression. Cytogenetics revealed complex karyotypes with t(8:14)(q24.2;q32) and IGH::MYC rearrangement by FISH. Next generation sequencing revealed deleterious TP53 and MYC mutations. We concluded that both could be diagnosed as "DLBCL-NOS with MYC rearrangement" using the current pathologic classifications, 2022 International Consensus Classification (ICC) and World Health Organization Classifications of Haematolymphoid Tumors (WHO-HAEM5). This report illustrates diagnostic challenges and treatment dilemmas that may be encountered, particularly for adolescent and young adults (AYA).

We report a case of a primary cardiac spindle cell neoplasm with concerning histological features and a rare PDGFRA::USP8 gene fusion in a 3 year old boy. The patient presented with a large cardiac mass predominantly in the right ventricle, originating from the ventricular septum. The mass was resected with grossly negative margins. Pathology revealed an unclassified spindle cell neoplasm with a PDGFRA::USP8 gene fusion. This gene fusion has only been previously reported twice in the medical literature, one in a pediatric cardiac sarcoma and the other in an abdominal soft tissue tumor in an adult woman. The patient is alive and well with no evidence of recurrence 11 months after excision.

Steroid resistant nephrotic syndrome (SRNS) accounts for 30% of all cases of nephrotic syndrome (NS) in children and frequently leads to end stage kidney disease (ESKD). About 30% of children with SRNS demonstrate causative mutations in podocyte- associated genes. Early identification of genetic forms of SRNS is critical to avoid potentially harmful immunosuppressive therapy. A 2-year-old male patient with NS and no family history of renal disease did not respond to 4-week steroid treatment. Kidney biopsy demonstrated mesangial proliferative glomerulopathy with basement membrane dysmorphism. Tacrolimus and Lisinopril were added to therapy pending results of genetic testing. Kidney Gene panel showed a NPHS2 c.413G>A (p.Arg138Gln) homozygous pathogenic variant. This missense variant is considered a common pathogenic founder mutation in European populations. A diagnosis of autosomal-recessive form of nonsyndromic SRNS due to NPHS2 causative variant was made. Immunosuppresive therapy was stopped, Lizinopril dose was increased and weekly infusions of Albumin/furosemide were initiated to manage edema. This case demonstrates that early genetic testing in children with SRNS avoids prolonged potentially harmful immunosuppressive therapy, allows for timely genetic family counseling, and allows earlier consideration for future living related donor kidney transplantation.

Brain death is a not uncommon phenomena in the adult and pediatric population. Most cases are removed from life support soon after brain death is declared. Less commonly, systemic perfusion is maintained by life support for some time after neurologic function stops. These cases present uncommon opportunities to explore the histology of necrosis and autolysis in the context of global hypoxic ischemic damage. Here, we describe the unusual case of an infant maintained on life support for 2 weeks after brain death was declared with an emphasis on the resulting gross and histologic findings including a discussion of their underlying physiology.