Pediatric and Developmental Pathology最新文献

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.

Introduction: Inflammatory and immunologic homeostasis in the basal plate of the placenta is essential for the fetal development and growth, since the fetus immunologically constitutes a semi-allograft. Bone marrow derived eosinophilic granulocytes are usually not found in the basal plate.

Materials and methods: We retrospectively analyzed the occurrence of eosinophilic granulocytes in the basal plate of singleton placentas and investigated clinical and pathologic-anatomic associations.

Results: In 5 singleton placentas (0.3% of all investigated cases from the archive) eosinophilic granulocytes were detectable. All these cases also displayed chronic deciduitis. Two cases had a clinical history of substitution therapy with methadone, in 2 instances the mothers had a history of atopic diseases, and 1 mother had a SARS-CoV-2-infection during pregnancy.

Conclusions: The infiltration of eosinophilic granulocytes in the decidua is a rare feature of placentas with perinatal clinical findings. Strikingly, all 5 affected cases also presented with chronic deciduitis. This may hint at a contribution of the eosinophilic infiltrate to a non-infectious pathologic inflammatory process with an increased risk for perinatal complications.

Chronic intervillositis of unknown etiology (CIUE) is an aberrant maternal inflammatory infiltrate comprised primarily of macrophages that collect in the intervillus space and is associated with poor outcomes including recurrent pregnancy loss. An abnormal maternal Th1-type response to pregnancy may be the basis for pathogenesis of CIUE but macrophage in the maternal infiltrate of CIUE have been reported to have an anti-inflammatory M2 phenotype characterized by increased expression of CD163. This study assesses expression of CD163 in CIUE and SARS-CoV-2 placentitis, which has a similar histopathological presentation, using an automated approach to minimize observer-related variability. The data show that the maternal inflammatory infiltrate of CIUE contains a blended population of high and low CD163 expressing macrophage with a prominent bias towards an anti-inflammatory M2 phenotype when compared to normal control tissue. A similar pattern is seen in SARS-CoV-2 placentitis, suggesting pathophysiologic similarity with CIUE, although SARS-CoV-2 also appears to promote decreased CD163 expression in Hofbauer cells, which is not seen in CIUE.

The pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) is multifactorial and includes aberrations in the composition of gastrointestinal mucosal inflammatory cells. Accurate identification of CD and UC is important as treatment and prognosis differs; however, CD and UC may be difficult to differentiate. Interferon γ (IFNγ) expression appears to be increased in ileal mucosa from CD patients, implying that IFNγ could be a diagnostically useful marker to differentiate CD from UC. This study uses automated assessment of IFNγ immunohistochemical expression in archival GI mucosal biopsies from stomach, duodenum, terminal ileum, and colon in a pediatric population to address this possibility. IFNγ positive mucosal cells are increased in the colon in both CD and UC compared to normal colon and in the ileum of CD compared to normal and UC. The abundance of IFNγ positive cells is not correlated with the presence of active inflammation, indicating that active inflammation is not responsible for the variance in abundance of IFNγ positive cells between cohorts and sites. Overlap between CD, UC, and normal suggests that IFNγ immunohistochemistry may only be clinically useful in select situations such as undetermined inflammatory bowel disease and additional study in these areas is warranted.

Sarcomas characterized by BCOR gene alterations, are a distinct clinico-pathological group of high-grade tumors, that represent 5% of small round cell tumors without EWSR or FUS fusion. Diverse genetic alterations characterize this group, including BCOR-CCNB3 gene fusion being the most common alteration and less frequently internal tandem duplications (ITDs). We present a compelling case of a 3-year-old girl diagnosed with a high-grade nasoethmoidal sarcoma exhibiting BCOR-ITD. The diagnostic process illustrates the histological and immunophenotypic spectrum, requiring an extensive immunohistochemical panel and diverse molecular tests for accurate classification. Additionally, this case highlights the challenges in detecting BCOR-ITDs using different NGS panels, advocating for alternative molecular approaches. Our patient after 10 months since diagnosis is alive with progressive disease. This emphasizes the urgency for ongoing research to refine diagnostic methods and develop effective therapeutic strategies for these rare and aggressive tumors.

Lymphoblastic lymphoma (LBL) with an early T-cell precursor phenotype has only been rarely reported. Nijmegen breakage syndrome (NBS) is an inherited chromosomal instability disorder with known predisposition to malignancies that is very rare as well. We report a case of early T-precursor LBL (ETP-LBL) in a patient with NBS, a rare combination that has not been reported. We raise the question of whether a chromosomal instability disorder such as NBS increases the propensity for early T-precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL), given that ETP-ALL has been shown to have increased genomic instability compared to T-ALL.

Maude Abbott was a pioneering female Canadian physician who became a world authority on medical museums and congenital heart disease. Abbott spent almost all her career in highly sexist, discriminatory work environments. This paper reviews Abbott's life and accomplishments, but, more importantly, analyzes her pathway to success in the masculine world of early 20th-century academic pathology. Abbott, though well-trained as a pathologist, never provided clinical service, but instead worked as museum curator at McGill University. She established the International Association of Medical Museums (predecessor to the International Academy of Pathology), edited its journal, and essentially ran the organization. Abbott, surrounded by influential males, dealt differently with each. In general, she recognized that male doctors believed women lacked the gravitas to lead major initiatives but that she could circumnavigate this supposed impediment by co-leading projects with male counterparts, preferably ones too busy to get in her way. She repeatedly used this approach, and by doing most of the work but sharing credit, succeeded in gaining reputation, accomplishment, and advancement. Abbott's pioneering work on congenital heart disease established her as one of the founders of pediatric pathology, and, overall, her career promoted the entry of women physicians into the pathology profession.

The proper evaluation of abortion specimens and placentas from stillbirth and post-partum cases is important for adequate clinical care of post-abortion and post-partum patients. The following topics will be reviewed: (1) the importance of evaluation of both fetal and placental tissue in first trimester abortions to confirm an intrauterine pregnancy versus an ectopic pregnancy; (2) the clinical history associated with an abortion specimen or retained products of conception (POC) influences how the pathologist should triage the specimen; (3) the criteria for diagnosis of a molar pregnancy, which is critical for clinicians to know which patients need follow-up; (4) the utility of genetic studies for both diagnosis and appropriate follow-up of the patient; and (5) the pathologic evaluation of specimens from patients with post-partum hemorrhage for placenta accreta spectrum and subinvolution of maternal vessels.

Aim: Acute appendicitis (AA) is treated primarily surgically with histopathology being the gold standard for confirmation of appendicitis and reported rates of negative appendicectomies (NA) ranging between 3.2% and 19% worldwide and 15.9-20.6% in the UK. NA rates are frequently used to identify poor performing centers as part of a Model Health System and form an integral part of appendicitis scoring systems. This study aims to evaluate the prevalence of negative appendicectomies within our institution and critically analyze the appropriateness of its use as a quality metric and its impact on clinical practice and research.

Patients and methods: Data analysis from a prospective dataset of pediatric appendicitis patients between 2015 and 2021 in a tertiary center in the UK was performed. Detailed analysis of negative appendicectomies was performed and further stratified by two distinct age and gender groups looking at the incidence of NA and the classification of non-histologically normal appendix specimens.

Results: In our series, 819 patients met inclusion criteria, 736 (89.9%) had acute appendicitis. Our overall institutional negative appendicectomy rate was 10.1% (83 patients) with the breakdown as follows: 65 histologically normal appendix (7.9%), 10 Enterobius vermicularis, 3 eosinophilic appendicitis, 2 neoplasms, 1 isolated faecolith, 1 fibrous obliteration of the lumen, and 1 peri-appendiceal inflammation.

Conclusion: Our negative appendicectomy rate is below established UK pediatric NA rates. This rate ranges from 7.9% to 10.1% depending on the definition of NA utilized. A single standard pathological definition for histological acute appendicitis is required when being used as a comparative quality metric. Centers engaged in clinical research should be aware of variations in NA definitions both in scoring systems and individual centers to avoid skewing derived results.