Pediatric and Developmental Pathology最新文献

The COVID-19 pandemic presents several challenges during pregnancy including thromboembolic complications, direct placental infection, transplacental transmission, and systemic hyperinflammatory state. The liver is the second most commonly affected organ in SARS-CoV-2 infection after the lungs. Mechanisms of liver injury in COVID-19 patients can include: direct viral cytopathic effect, worsening of underlying liver disease, cytokine storm, hypoxic ischemic injury, and cholangiopathy leading to persistent marked cholestasis. Here we describe 3 infants at Texas Children's Hospital with perinatal SARS-CoV-2 exposure with persistent cholestasis and histologic evidence of extrahepatic biliary obstruction suggesting underlying biliary atresia (BA) with some atypical features possibly exacerbated by SARS-CoV-2 infection. All 3 patients described in this case series developed liver failure in the setting of low GGT cholestasis, and all 3 required liver transplantation within the first year of life. Though post-COVID cholangiopathy is described in adults in the literature, none of the infants in our series had moderate or severe COVID infection but still progressed to advanced liver disease. Instead it is very likely that the patients in our series had underlying BA with some atypical features, with the commonality of having been exposed perinatally to SARS-CoV-2 Though further studies are needed to determine causality, our case series raises the question of if the timing of exposure/infection plays a role in prognosis.

The oral mucosal calcified nodule (OMCN) is a rare soft tissue lesion with only 7 cases reported in the English literature. It typically presents in the pediatric population as an asymptomatic submucosal nodule of less than 2 cm size affecting the maxillary ridge or palate, though other sites are reported. The histopathology displays stratified squamous epithelium overlying fibrous connective tissue with embedded calcified aggregates bordered by variable numbers of multinucleated giant cells. Surgical excision is curative. In this report, we present a new case of OMCN, outline the characteristic histopathologic features and review the cases reported in the English literature.

In this report, we describe a case of classic Hodgkin lymphoma presenting with lytic bone lesions and pancytopenia, but with no significant lymphadenopathy or mediastinal mass. We report detailed clinical, radiologic, and pathologic findings. We discuss the scant medical literature of similar cases. We conclude that such cases often represent diagnostic challenges at the clinical and microscopic levels. We emphasize that awareness of this rare presentation of Hodgkin lymphoma is key to avoid diagnostic delay or interpretation pitfalls.

An 11-year-old girl presented with a soft tissue lesion on the dorsal aspect of the left middle finger. Ultrasound imaging demonstrated a 2.8 cm × 0.8 cm × 0.8 cm lesion overlying the dorsal aspect of the base of the digit near the metacarpophalangeal joint. The patient's past medical history is remarkable for neuroblastoma, diagnosed at 9 months of age, with no MYCN amplification or 1p loss. We report a pediatric schwannoma harbouring a SH3PXD2A::HTRA1 gene fusion with a distinctive serpentine histology. The lesion consisted of well-circumscribed nodules surrounded by thin EMA-positive perineural capsules. Each nodule was composed of lesional cells arranged in short fascicles with occasional clefting and a distinct "serpentine" palisading pattern. The lesion demonstrated Antoni A regions with Verocay body formation. No significant Antoni B areas were seen. The lesional Schwannian cells were bland with elongated and tapered nuclei, showing strong and diffuse positivity for S100. This pre-pubescent girl (Tanner Stage 2) is currently the youngest reported case of fusion-positive schwannoma. In addition, she has a significant prior history of a malignant neoplasm, and the lesion arose in an appendicular location.

A 15q11.2 (BP1-BP2) deletion was detected in a 4-day-old boy who had hypoplastic left heart syndrome (HLHS) diagnosed prenatally by echocardiography. Postmortem examination revealed an anomalous origin of the right coronary artery from the pulmonary trunk (ARCAPT). This genetic defect is known to cause syndromic presentations and believed to participate in cardiovascular defects but to the best of our knowledge no HLHS with ARCAPT was reported to have this genetic defect before. This case presents a novel association and suggests involvement of the 15q11.2 deletion in a syndromic presentation. Further studies are necessary to explore this genetic link and its clinical implications.

Cystic partially differentiated nephroblastoma (CPDN) is a rare pediatric renal tumor composed of multiple cystic spaces divided by septa containing immature nephrogenic elements. The presence of expansile solid areas in the septa of such a lesion indicates an alternative diagnosis of Wilms tumor (WT). We present a unique case of CPDN associated with grossly visible polypoid proliferations, which histologically correspond to botryoid growth of intralobar nephrogenic rests. Correct pathological diagnosis of CPDN and its differentiation from cystic WT can be challenging, but is critical, because of the distinct treatment approaches and prognoses of these entities, since CPDN is a low-risk tumor not requiring further postoperative therapy.

The integration of artificial intelligence (AI) into healthcare is becoming increasingly mainstream. Leveraging digital technologies, such as AI and deep learning, impacts researchers, clinicians, and industry due to promising performance and clinical potential. Digital pathology is now a proven technology, enabling generation of high-resolution digital images from glass slides (whole slide images; WSI). WSIs facilitates AI-based image analysis to aid pathologists in diagnostic tasks, improve workflow efficiency, and address workforce shortages. Example applications include tumor segmentation, disease classification, detection, quantitation and grading, rare object identification, and outcome prediction. While advancements have occurred, integration of WSI-AI into clinical laboratories faces challenges, including concerns regarding evidence quality, regulatory adaptations, clinical evaluation, and safety considerations. In pediatric and developmental histopathology, adoption of AI could improve diagnostic efficiency, automate routine tasks, and address specific diagnostic challenges unique to the specialty, such as standardizing placental pathology and developmental autopsy findings, as well as mitigating staffing shortages in the subspeciality. Additionally, AI-based tools have potential to mitigate medicolegal implications by enhancing reproducibility and objectivity in diagnostic evaluations. An overview of recent developments and challenges in applying AI to pediatric and developmental pathology, focusing on machine learning methods applied to WSIs of pediatric pathology specimens is presented.

An infant with intrauterine growth restriction, suspected of having MIRAGE syndrome based on prenatal ultrasound, presented with genital ambiguity, adrenal insufficiency, intractable diarrhea from birth, and a pathogenic SAMD9 mutation (c.1376G>A, p.R459Q). Endoscopic biopsies of the duodenum revealed complex light and electron microscopic abnormalities. Hypoplastic villi without signs of enteritis suggests a disorder of mucosal growth with reduced absorptive surface area contributes to intractable diarrhea. Ultrastructural study showed prominent dilated endoplasmic reticulum, abnormalities of Golgi morphology, specialized granule, and mucin processing. We hypothesize that the SAMD9 mutation alters mucosal growth, and the processing of mucin, Paneth and neurosecretory granules, with premature degradation of specific granules in enterocyte lysosomes. These distinctive morphological findings support the idea that multisystem manifestations of MIRAGE syndrome are due to a primary disorder of microsomal trafficking.

Translocations within the TFE gene resulting in oncogenic fusion proteins have been associated with multiple neoplasms. De novo mutations in the X-linked gene TFE3 in exons 3 and 4 are considered to contribute to lysosomal storage disorder-like features. However, the histologic findings within the livers of patients with TFE3 mutations are not well characterized. The authors report a case of a 12 day old term male who was admitted to the pediatric intensive care unit and went on to develop worsening direct hyperbilirubinemia and hepatomegaly. Due to the constellation of clinical findings, whole genome sequencing was performed and a rare de novo hemizygous mutation was identified in the TFE3 gene (c.560C > T; p.Thr187Met) which was thought to be likely pathogenic. The patient subsequently had 2 liver biopsies performed, both with similar histologic findings. The liver was found to have a giant cell hepatitis pattern of injury with severe cholestasis and extensive pseudorosette formation. Additional studies are needed to understand the histologic changes which could be associated with mutations in the TFE3 gene. The impact of a TFE3 mutation on the liver represents an area where further study is necessary to provide prognostic and therapeutic guidance for future patients.

Tumors are increasingly defined by molecular alterations but approach to cases with discordant histologic and molecular features is unclear. Myxoid glioneuronal tumor (MGNT), histologically similar to dysembryoplastic neuroepithelial tumor (DNET), is characterized by dinucleotide mutations in PDGFRA gene (K385L or K385I). Here, we report PDGFRA K385L mutation in a neonatal high-grade glioma. A male neonate presented at birth with hydrocephalus. Subsequent imaging showed a large, lobulated cerebral mass. He died at day 37 of life from intracranial hemorrhage. A brain-only autopsy was performed, which showed a diffusely infiltrative hemorrhagic glial tumor with variable histology. Regions with distinct mucin pools and monomorphic oligodendroglioma-like cells were present. Elsewhere, there was little mucin and markedly atypical nuclei. Increased mitotic rate and foci of microvascular proliferation were widely present. Targeted panel sequencing found PDGFRA K385L mutation. DNA methylation studies showed a match with diffuse pediatric-type high-grade glioma, H3-wildtype, and IDH-wildtype, RTK1 subtype with a high calibrated score. In summary, we report the occurrence of PDGFRA hotspot mutation in a neonatal high-grade glioma without distinct features of MGNT, demonstrating that this genetic alteration is not specific to MGNT. We recommend caution in classifying a tumor as MGNT solely by the presence of PDGFRA alteration.