In recent years, 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...In recent years, 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, 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 sepsis, septic shock, meningitis, and pneumonia, all of which were linked to the use of a central venous catheter.
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 phagol...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.
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...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.
Indian childhood cirrhosis is a chronic liver disease in infants and children. Indian childhood cirrhosis is unique to the Indian subcontinent and occurs from 6 months to 5 years of age. We report 2 cases in a period of...Indian childhood cirrhosis is a chronic liver disease in infants and children. Indian childhood cirrhosis is unique to the Indian subcontinent and occurs from 6 months to 5 years of age. We report 2 cases in a period of 5 years, including 1 male and 1 female. Both children were less than 3 years of age. Presenting complaints were jaundice and hepatosplenomegaly. The clinical diagnosis was metabolic liver disease. Histological findings included diffuse hepatocellular ballooning degeneration, prominent Mallory Denk bodies, diffuse pericellular fibrosis, and marked copper/copper-associated protein deposits, along with the absence of steatosis and glycogenated nuclei. Mettalothionein immunohistochemistry was performed in 1 case and showed strong positivity. The first child developed liver failure and died. The second child was started on oral penicillamine therapy and is alive on the most recent follow-up. Whole-exome studies of both patients showed no significant findings. None of the children had exposure to excess dietary copper. Sporadic cases of Indian childhood cirrhosis continue to occur. There should be greater awareness among pediatricians and pathologists of the disease to enable earlier diagnosis. Awareness of metallothionein expression in biopsies of patients with Indian childhood cirrhosis is important to prevent misdiagnosis of Wilson disease.
A desmoplastic small round cell tumor (DSRCT) presented in a 13-year-old female with an acute abdomen due to torsion of a fallopian tube cyst. She was found to have an incidental 2 cm pedunculated, solid, and multicystic...A desmoplastic small round cell tumor (DSRCT) presented in a 13-year-old female with an acute abdomen due to torsion of a fallopian tube cyst. She was found to have an incidental 2 cm pedunculated, solid, and multicystic mass attached to the pelvic floor on laparoscopy. The neoplasm had a variably myxoid and spindle cell pattern with nests and cords of small cells, forming pseudocysts, and true cysts lined by ciliated epithelium which were PAX-8+ and ER+/PR+. The tumor had the EWSR1::WT1 fusion. Numerous peritoneal nodules less than 1 cm were noted on repeat laparoscopy 3 months later. These had similar features including the ciliated epithelial cysts. Our case illustrates yet another potential variant pattern of DSRCT with Mullerian-like ciliated epithelial cysts.
Glembocki A, Siddaway R, Arnoldo A
… +2 more, Jakeman M, Lafreniere A
Pediatr Dev Pathol
· 2025 · PMID 39717921
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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 dig...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 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.
Neuronal ceroid lipofuscinosis type 2 (CLN2) results from biallelic pathogenic variants in the gene, leading to deficient activity of the lysosomal enzyme tripeptidyl peptidase 1. We report an autopsy case of CLN2 chara...Neuronal ceroid lipofuscinosis type 2 (CLN2) results from biallelic pathogenic variants in the gene, leading to deficient activity of the lysosomal enzyme tripeptidyl peptidase 1. We report an autopsy case of CLN2 characterized at molecular level. The patient exhibited a spectrum of neurologic symptoms including epilepsy, behavioral alterations, cognitive regression, motor impairment, and visual loss. In fundus exam, a cherry-red spot was observed. She died at 7 years old, autopsy demonstrated severe atrophy of the brain and cerebellum with neuronal loss and gliosis. Neurons were distended by autofluorescent ceroid lipofuscin of 2 types: fine granular deposits and coarse round bodies. In addition, electron microscopy study revealed characteristic curvilinear profiles. After autopsy, a germline molecular test was performed that found the c.1226 G>T variant in a homozygous state. This variant has been referenced in a single undetailed report and is classified as of uncertain significance. Our findings support that cherry-red spot can be present in CLN2 and confirm the pathogenicity of the c.1226 G>T variant. Current management of CLN2 includes enzyme replacement that requires early diagnosis, which can be facilitated by clinical delineation of the disease and appropriate classification and public reporting of variants.
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 coron...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.
Syphilis is a preventable and treatable disease, which continues to strike low-income countries and vulnerable populations in high-income countries. It is caused by , a spirochete capable of traversing the placental barr...Syphilis is a preventable and treatable disease, which continues to strike low-income countries and vulnerable populations in high-income countries. It is caused by , a spirochete capable of traversing the placental barrier, with a high rate of fetal and placental infection. Congenital syphilis (CoS) has poor prognosis if left untreated. Autopsy and placental evaluation are important tools to diagnose this disease in the obstetric scenario, to reveal the correct cause of demise and prevent complications in future pregnancies. We describe the histologic findings of eleven feto-placental examinations of non-treated CoS with fetal hydrops and stillbirth. Fetal findings are variable, with hydrops, X-ray long bone metaphyseal bands and hepatic lesions as the most consistent autopsy findings. The combination of chronic and acute villitis/intervillitis is a common placental feature in CoS, and the presence of mixed inflammatory populations is a key to suspect treponemal infection. Mothers from vulnerable populations and with poor obstetric care also deserve increased efforts to rule out CoS as cause of death. This constellation of findings must lead to further testing with direct methods (PCR or tissue immunohistochemistry for ).
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 ne...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 gene (K385L or K385I). Here, we report 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 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 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 alteration.
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...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 mutation (). 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 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.
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...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.
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 lysosom...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.
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 pro...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 deriv...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 r...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.
Hereditary multiple intestinal atresia (HMIA) with mutation is caused by homozygous or compound heterozygous gene mutation. It is characterized by multiple small and large intestinal atresias and/or stenoses. mutation...Hereditary multiple intestinal atresia (HMIA) with mutation is caused by homozygous or compound heterozygous gene mutation. It is characterized by multiple small and large intestinal atresias and/or stenoses. mutation is described in some patients with inflammatory bowel disease and mild-severe forms of severe combined immunodeficiency without intestinal atresia or stenosis. We present 2 cases of intestinal atresia and documented mutation with a novel variant. Both cases had different clinical and pathological manifestations. The first case is a male infant born at 35 weeks of gestation with failure to pass meconium. Intestinal biopsy reveals apoptotic enteropathy with villous atrophy and increased mucosal eosinophils. The second case is referred at birth for antenatally detected umbilical hernia, polyhydramnios and possible upper intestinal obstruction. The resected specimen reveals ileal atresia with partial villous atrophy, decreased number of lamina propria inflammatory cells and absence of plasma cells. In conclusion, these cases reflect an emerging pathogenic variant with different histological manifestations and leads to characterization as immune dysregulation disorder. There is a need to differentiate mutation associated ones from cases labeled as very early onset IBD and rule out other hereditary immunodeficiencies.
Suhren JT, Hussein K, Kreipe H
… +1 more, Schaumann N
Pediatr Dev Pathol
· 2025 · PMID 39394687
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BACKGROUND: In a non-forensic hospital setting, neonatal death within the first week of life is often related to premature birth and/or lung diseases. Without post-mortem examination, the identification of the cause of d...BACKGROUND: In a non-forensic hospital setting, neonatal death within the first week of life is often related to premature birth and/or lung diseases. Without post-mortem examination, the identification of the cause of death may be challenging. Autopsy can confirm the clinical diagnosis, uncover additional information or change the diagnosis. Our study aimed to assess the correlation between the clinical diagnosis and post-mortem findings in early neonatal deaths. METHODS: The retrospective study included autopsy cases with neonatal deaths within the first 7 days of life (arbitrary time interval 2006-2021). Discrepancies between clinical and histopathological findings were classified into 3 groups: (i) full agreement, (ii) additional findings discovered by autopsy, or (iii) autopsy changed the diagnosis. RESULTS: A cohort of 27 cases could be identified and lung pathologies were the most common finding (56%). Additional findings could be discovered in 48% of cases. Major discrepancies which changed the clinical diagnosis could be found in 11% (n = 3/27) of cases. CONCLUSION: Frequently, post-mortem examinations validate the clinical diagnosis while revealing crucial information in a few cases. In these discrepant cases, autopsy findings can provide information for genetic counselling and quality control of clinical management.
Pediatr Dev Pathol
· 2024 · PMID 39351994
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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....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.