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The article reports that mutation of galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) genes results in inflammatory diseases such as chronic recurrent multifocal osteomyelitis (CRMO) and hyperphosphatemic familial tumoral calcinosis (HFTC). Bilateral elbow swelling, hyperphosphataemia, and normal serum were observed in an 8-year old boy diagnosed with HFTC. The need for further research on HFTC and CRMO is discussed.

Abstract Primary neoplasms of the mesentery are very rare. They are usually of mesenchymal origin and include desmoid tumor, lipoma, liposarcoma, and fibrosarcoma. Metastatic carcinomas and lymphoma are more common. We report a rare case of localized mesenteric Castleman's disease, presenting as intestinal obstruction. Clinical and radiological findings were suspicious for lymphoma. Localized mesenteric Castleman's disease, though rare, has to be considered in the differential diagnosis of mesenteric tumors, particularly in the young and in the absence of history for other tumor, an abnormal blood picture, or splenomegaly.

Abstract Papillary carcinoma of the thyroid (PTC) is the commonest thyroid cancer. In the recent decades an obvious increase in the incidence of PTC has occurred. The pathological diagnosis of PTC is usually an easy diagnosis in the majority of cases. However since the introduction of follicular variant of PTC and the wide threshold range in interpretation of the clearly set pathological criteria for diagnosis of PTC, between pathologists including experts, the diagnosis in some cases became quite difficult. Unfortunately some cases are unjustifiably over-called as follicular variant of PTC as a result of the wide inter observable variability between pathologists, including thyroid pathologists. Ancillary studies such as immmunohistochemistry may be helpful, but till now there is no 100% consistent marker(s), that distinct between PTC and other follicular thyroid lesions and tumors. We assessed expression of antibodies against CD56, CK19, P63 and E-Cadherin in PTC and other follicular thyroid lesions and neoplasms. A total of 175 cases were studied. The neoplastic cases included 75 carcinomas (72 papillary, 2 follicular, 1 Hurthle cell) and 35 adenomas (32 follicular and 3 Hurthle cell). The non-neoplastic thyroids included 65 cases, (25 nodular hyperplasia, 5 thyrotoxic hyperplasia (Grave's disease), 19 lymphocytic thyroiditis and 6 Hashimoto's thyroiditis). All cases were evaluated by immunohistochemistry for the expression of the above mentioned markers. The markers' patterns and intensities of staining were scored. Positive expression of the markers equal or >10% of the follicular epithelium within the tumor or lesional cells was considered positive. An expression of Our results showed CD56 positive in all the lesions and tumors except for PTC in all cases (100%). CD56 was negative in all PTC cases (100%). CK 19 showed positive expression in PTC accounting for 85% of cases and in 26% of non PTC lesions/tumors. P63 showed selective focal positivity in PTC cases, in contrast to other non PTC lesions/tumors. P63 expression was in 70% of cases of PTC and was consistently absent in all the non PTC cases. E-Cadherin showed consistent non discriminatory expression in all cases included in the study. We concluded that a panel consisted of CD56, CK19 and P63 is of value in distinction of PTC from other thyroid follicular lesion. P63 is a specific but less sensitive marker for PTC than CK19. CD56 is more specific and sensitive marker than CK19, however it is a negative rather than a positive marker for PTC. E-Cadherin is of no value in the diagnosis of thyroid follicular lesions/tumors. We recommend application of a panel composed of CK19, P63 and CD56 by a group of expert thyroid pathologists on a large series of follicular malignant thyroid neoplasms of uncertain malignant.

Abstract Colorectal small cell carcinoma (SmCC) is a rare tumor with an aggressive course. The aim of this study is to summarize our experience with this tumor and to highlight its immunohistochemical profile. Ten cases of colorectal SmCC were identified in our files and a panel of immunostains was performed. Follow up was available for the average of 3 years, during which 7 patients died and 3 were alive with disease. All cases were positive for LMWK, CK 19 and pancytokeratin but were negative for TTF-1 and CA 125. EGFR was positive in 7 cases. TTF-1 negative staining may be valuable in differentiating it from its pulmonary counterpart. CDX2, mCEA, CD56, synaptophysin, NSE and chromogranin can help differentiate it from non-endocrine poorly differentiated adenocarcinoma. The expression of EGFR in a subset of patients has not been reported earlier and has to be evaluated in larger series to assess its role in the planning of targeted biologic therapy.

Abstract Synchronous composite tumors have been described but are uncommon. Moreover, simultaneous occurrence of synchronous tumors in the same tissue or organ is even less common. We report a case of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma and malignant melanoma (MM) occurring synchronously in the same lymph node. Several cases of an association between cutaneous malignancies and lymphoproliferative disorders have been reported. Some of which included CLL and MM, occurring in the same patient often CLL after MM. The risk of having CLL after MM has been reported to be increased. Various genetic and environmental etiologies have been postulated, but have as yet not been proven. To our knowledge this is the first time that synchronous occurrence of these two malignant processes in the same tissue is described. In this case it is important that the melanoma was recognized in the excised lymph node, as this finding had much more critical treatment and long term survival consequences.

Abstract Synchronous composite tumors though described are uncommon. Moreover, simultaneous occurrence of synchronous tumors involving the same tissue or organ at multiple sites is even less common. We report a case of acute lymphoblastic leukemia (ALL) and basal cell carcinoma (BCC) occurring simultaneously in multiple skin sites. Several cases showing an association between cutaneous malignancies and lymphoproliferative disorders have been reported. Some of these cases included ALL and BCC and occurred often in the pediatric population with the BCC arising as a post-ALL therapy sequela. Other rare genetic causes may be considered. To our knowledge this is the first time that the synchronous occurrence of these two malignant processes in the same tissue involving multiple sites in an elderly patient is described.

Introduction: Villitis of unknown etiology (VUE) is a histopathological lesion associated with adverse neonatal outcomes. We seek to define the obscure relationship between the severity and distribution of VUE and adverse neonatal outcomes., Methods: A retrospective chart review was conducted of pathologic findings from singleton placentas diagnosed with VUE between 2013 and 2019. Control placentas were matched 1:1 for gestational age and presence/absence of fetal IUGR. Neonatal outcomes of interest included: newborn resuscitation, NICU admission, Apgar scores and cord blood acidosis. Odds ratio and 95 % confidence intervals were calculated with controls as the reference., Results: 452 placentas were included. 35 % of pregnancies were complicated by IUGR. When analyzed by severity (low-grade: OR = 4.75 [2.86-8.14]; high-grade: OR = 4.76 [2.71-8.79]) and distribution (focal: OR = 5.24 [2.87-10.17]; multifocal: OR = 4.90 [2.90-8.59]), VUE was significantly associated with need for newborn resuscitation. No other neonatal outcomes of interest were significantly associated with VUE diagnosis., Discussion: We determined a statistically significant association between VUE severity and distribution and the need for newborn resuscitation. VUE lesions were not associated with any additional neonatal outcomes of interest. Further studies with larger sample sizes are required to confirm these associations for obstetric and neonatal case management., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Placental pathology is key for investigating adverse pregnancy outcomes, however, lack of standardization in reporting has limited clinical utility. We evaluated a novel placental pathology synoptic report, comparing its robustness to narrative reports, and assessed interobserver agreement., Methods: 100 singleton placentas were included. Histology slides were examined by 2 senior perinatal pathologists and 2 pathology residents using a synoptic report (32 lesions). Historical narrative reports were compared to synoptic reports. Kappa scores were calculated for interobserver agreement between senior, resident, and senior vs resident pathologists., Results: Synoptic reporting detected 169 (51.4%) lesion instances initially not included in historical reports. Amongst senior pathologists, 64% of all lesions examined demonstrated fair-to-excellent agreement (Kappa ≥0.41), with only 26% of Kappas ≥0.41 amongst those examined by resident pathologists. Well-characterized lesions (e.g., chorioamnionitis) demonstrated higher agreement, with lower agreement for uncommon lesions and those previously shown to have poor consensus., Discussion: Synoptic reporting is one proposed method to address issues in placenta pathology reporting. The synoptic report generally identifies more lesions compared to the narrative report, however clinical significance remains unclear. Interobserver agreement is likely related to differential in experience. Further efforts to improve overall standardization of placenta pathology reporting are needed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Placental histopathology provides insights, or "snapshots", into relevant antenatal factors that could elevate the risk of perinatal brain injury. We present a systematic review and meta-analysis comparing frequencies of adverse neurological outcomes in infants born to women with placental abruption versus without abruption. Records were sourced from MEDLINE, Embase, and the CENTRAL Trials Registry from 1946 to December 2019. Studies followed the PRISMA guidelines and compared frequencies of neurodevelopmental morbidities in infants born to pregnant women with placental abruption (exposure) versus women without placental abruption (comparator). The primary endpoint was cerebral palsy. Periventricular and intraventricular (both severe and any grades of IVH) and any histopathological neuronal damage were the secondary endpoints. Study methodologic quality was assessed by the Ottawa-Newcastle scale. Estimated odds ratios (OR) and hazards ratio (HR) were derived according to study design. Data were meta-analyzed using a random effects model expressed as pooled effect sizes and 95% confidence intervals. We included eight observational studies in the review, including 1245 infants born to women with placental abruption. Results of the random effects meta-analysis show that the odds of infants born to pregnant women with placental abruption who experience cerebral palsy is higher than in infants born to pregnant women without placental abruption (OR 5.71 95% CI (1.17, 27.91); I 2 = 84.0%). There is no statistical difference in the odds of infants born to pregnant women with placental abruption who experience severe IVH (grade 3+) (OR 1.20 95% CI (0.46, 3.11); I 2 = 35.8%) and any grade of IVH (OR 1.20 95% CI (0.62, 2.32); I 2 = 32.3%) vs. women without placental abruption. There is no statistically significant difference in the odds of infants born to pregnant women with placental abruption who experience PVL vs. pregnant women without placental abruption (OR 6.51 95% CI (0.94, 45.16); I 2 = 0.0%). Despite our meta-analysis suggesting increased odds of cerebral palsy in infants born to pregnant women with placental abruption versus without abruption, this finding should be interpreted cautiously, given high heterogeneity and overall poor quality of the included studies.

Patients with early-onset lysosomal storage diseases are ideal candidates for prenatal therapy because organ damage starts in utero. We report the safety and efficacy results of in utero enzyme-replacement therapy (ERT) in a fetus with CRIM (cross-reactive immunologic material)-negative infantile-onset Pompe's disease. The family history was positive for infantile-onset Pompe's disease with cardiomyopathy in two previously affected deceased siblings. After receiving in utero ERT and standard postnatal therapy, the current patient had normal cardiac and age-appropriate motor function postnatally, was meeting developmental milestones, had normal biomarker levels, and was feeding and growing well at 13 months of age., (Copyright © 2022 Massachusetts Medical Society.)

We examined neonatal outcomes in pregnancies complicated by placental abruption (PA) and acute chorioamnionitis (CA). Exposure was acute CA; primary outcome - fetal death; secondary outcomes - adverse Apgar score, neonatal intensive care unit (NICU) admission, and cardiac depression. 267 placentas - 18.4% exhibited acute CA. PA pregnancies with CA - 29% experienced fetal death. Funisitis, acute CA and adverse neonatal outcomes are dependent. Without accounting for funisitis, aforementioned findings hold, though effect sizes are smaller. PA, acute CA with funisitis could affect fetal death and NICU admission. Acute CA and PA alone could impact fetal death and adverse Apgar scores., Competing Interests: Declaration of interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Workload measurement is important to help determine optimal staffing and workload distribution for pathology laboratories. The Level 4 Equivalent (L4E) System is the most widely used Anatomical Pathology (AP) workload measurement tool in Canada. However, it was initially not developed with subspecialties in mind., Methods: In 2016, a Pan-Canadian Pediatric-Perinatal Pathology Workload Committee (PCPPPWC) was organized to adapt the L4E System to assess Pediatric-Perinatal Pathology workload. Four working groups were formed. The Placental Pathology Working Group was tasked to develop a scheme for fair valuation of placental specimens signed out by subspecialists in the context of the L4E System. Previous experience, informal time and motion studies, a survey of Canadian Pediatric-Perinatal Pathologists, and interviews of Pathologists' Assistants (PA) informed the development of such scheme., Results: A workload measurement scheme with average L4E workload values for examination and reporting of singleton and multiple gestation placentas was proposed. The proposal was approved by the Canadian Association of Pathologist - Association canadienne des pathologistes Workload and Human Resources Committee for adoption into the L4E System., Conclusion: The development of a workload measurement model for placental specimens provides an average and fair valuation of these specimen types, enabling its use for resource planning and workload distribution.

Introduction: Villitis of unknown etiology (VUE) is associated with fetal growth restriction (FGR) and adverse short-term neonatal outcomes. No investigation to date has found which VUE features are driving the association with FGR diagnosis., Methods: A retrospective cohort study of placenta pathology specimens (2013-2017) was conducted. Independent variables of interest were: VUE distribution (focal vs diffuse), location (basal vs non-basal), and grade (high vs low). The primary outcome was FGR, and secondary outcomes were neonatal intensive care unit (NICU) admission, NICU length of stay, Apgar scores <7 at 1, 5, and 10-min, and recurrence rate of villitis in subsequent pregnancies. Association between VUE characteristics and our primary outcome were investigated using logistic regression. Secondary outcomes were explored with regression analyses and recurrence rate of VUE for members of the cohort with a recorded subsequent pregnancy was calculated., Results: One hundred and twenty seven placentas were included. Adjusted models showed no difference in the odds of FGR between high-grade versus low-grade VUE [aOR 1.25 95% CI (0.50, 3.26), p = 0.6], focal/multi-focal vs diffuse cases [aOR 1.03 95% CI (0.28, 4.34), p = >0.9], and basal vs non-basal VUE [aOR 0.06 95% CI (0.00, 1.10), p = 0.058]. After adjusting for prematurity <37 weeks, there were lower odds of NICU admission in basal vs non-basal cases [aOR 0.25, 95% CI (0.06, 0.90), p = 0.048). There was no difference in the odds of neonates presenting with Apgar <7 for the distinct VUE histopathology features. Three cases had recurrent VUE, resulting in a 6.8% [95% CI (3.02%, 10.61%)] recurrence rate. All recurrent cases were high-grade and identified with basal localization., Discussion: There are no statistical associations between distinct VUE features and FGR diagnosis, however location of villitis may be associated with worse neonatal outcomes. Villitis of any type (severity, degree, location) could potentially drive insufficient placental function and poor fetal growth., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

No systematic review to date has examined histopathological parameters in relation to native liver survival in children who undergo the Kasai operation for biliary atresia (BA). A systematic review and meta-analysis is presented, comparing the frequency of native liver survival in peri-operative severe vs. non-severe liver fibrosis cases, in addition to other reported histopathology parameters. Records were sourced from MEDLINE, Embase, and CENTRAL databases. Studies followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and compared native liver survival frequencies in pediatric patients with evidence of severe vs. non-severe liver fibrosis, bile duct proliferation, cholestasis, lobular inflammation, portal inflammation, and giant cell transformation on peri-operative biopsies. The primary outcome was the frequency of native liver survival. A random effects meta-analysis was used. Twenty-eight observational studies were included, 1,171 pediatric patients with BA of whom 631 survived with their native liver. Lower odds of native liver survival in the severe liver fibrosis vs. non-severe liver fibrosis groups were reported (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.08-0.33; I 2 =46%). No difference in the odds of native liver survival in the severe bile duct destruction vs. non-severe bile duct destruction groups were reported (OR, 0.17; 95% CI, 0.00-63.63; I 2 =96%). Lower odds of native liver survival were documented in the severe cholestasis vs. non-severe cholestasis (OR, 0.10; 95% CI, 0.01-0.73; I 2 =80%) and severe lobular inflammation vs. non-severe lobular inflammation groups (OR, 0.02; 95% CI, 0.00-0.62; I 2 =69%). There was no difference in the odds of native liver survival in the severe portal inflammation vs. non-severe portal inflammation groups (OR, 0.03; 95% CI, 0.00-3.22; I 2 =86%) or between the severe giant cell transformation vs. non-severe giant cell transformation groups (OR, 0.15; 95% CI, 0.00-175.21; I 2 =94%). The meta-analysis loosely suggests that the presence of severe liver fibrosis, cholestasis, and lobular inflammation are associated with lower odds of native liver survival in pediatric patients after Kasai., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2022 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.)

A 10-month-old girl presented with a 4-month history of a rapidly growing lesion on the lower lip. Initial assessment and Doppler ultrasound supported a diagnosis of pyogenic granuloma. However, emergent biopsy revealed an embryonal rhabdomyosarcoma, a highly malignant tumor commonly associated with cancer-susceptible syndromes including neurofibromatosis type 1 (NF1). Despite having no apparent clinical features of NF1 at initial presentation, she was later found to have multiple café-au-lait spots and a subsequent diagnosis of NF1 was made., (© 2022 Wiley Periodicals LLC.)

Objective: To establish reference intervals (RIs) for fetal and neonatal small and large intestinal lengths., Methods: Linear measurements on small and large intestines were made upon postmortem examination of 131 preterm and term infants with gestational ages between 13 and 41 weeks. All cases were referred from the Eastern Ontario and Western Québec regions to a tertiary care hospital. Age and sex partitions were considered and RI limits were estimated., Results: Data consisted of 72 male (54.96%) and 59 female (45.04%) fetuses and neonates with mean gestational age of 25.6 weeks. Results showed that small and large intestinal lengths increased linearly with gestational age. RIs for small intestinal length (cm) of fetuses and neonates aged 13-20 weeks were (21.1, 122.4); of those aged 21-28 weeks were (57.7, 203.8); of those aged 29-36 weeks were (83.6, 337.1); and of those aged 37-41 weeks were (132.8, 406.4). RIs for large intestinal length (cm) of fetuses and neonates from the same four age groups were (5.1, 21.4), (12.7, 39.7), (32.4, 62.4), and (29.1, 82.2)., Conclusions: Establishing accurate RIs for premature and term infants has clinical relevance for pathologists performing postmortem analysis and for surgeons planning postoperative management of patients. The results of this study reaffirm that fetal small and large intestinal lengths increase linearly with gestational age irrespective of sex. Future studies should aim to further investigate the role of possible confounders on growth of fetal intestinal length, including maternal factors such as age and substance use during pregnancy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Collins et al developed a histology scoring system (EoE HSS) to assess multiple pathologic features. The aim of this study is to identify if the EoE HSS can better detect endoscopic and symptom improvement vs the Peak Eosinophilic Count (PEC)., Methods: A retrospective chart review was performed for patients during 2014-2016. All patients ≤18 years old with a diagnosis of EoE and whose records included initial and follow-up upper gastrointestinal endoscopies were included. Severity and extent of endoscopic features were scored using 8 parameters, from normal to maximum change for each location of the esophageal biopsy., Results: Forty patients with EoE were included in the study, of which 35 (87.5%) patients demonstrated symptom and 25 (62.5%) endoscopic improvement at the time of follow-up. In the proximal esophagus, the EoE HSS outperformed the change in eosinophil count of the Children's Hospital of Eastern Ontario (CHEO) practice in predicting endoscopic improvement by 16.8% when examining the change in grade and 17.1% when examining the change in stage scores., Conclusions: At our institution, adoption of the EoE HSS in assessing biopsies of EoE patients might be warranted, compared to the traditional practice. However, a bigger sample size may give a more robust difference in all locations.

ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity., (© 2022 by The American Society of Hematology.)

Placental abruption (PA) is a concern for maternal and neonatal morbidity. Adverse neonatal outcomes in the setting of PA include higher risk of prematurity. Placental pathologies include maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM), acute chorioamnionitis, and villitis of unknown etiology (VUE). We aimed to investigate how placental pathology contributes to acute neonatal outcome in PA. A retrospective cohort study of all placentas with PA were identified. Exposures were MVM, FVM, acute chorioamnionitis and VUE. The primary outcome was NICU admission and the secondary outcomes included adverse base deficit and Apgar scores, need for resuscitation, and small-for-gestational age. A total of 287 placentas were identified. There were 160 (59.9%) of placentas with PA alone vs 107 (40.1%) with PA and additional placental pathologies. Odds of NICU admission were more than two times higher in pregnancies with placental pathologies (OR = 2.37, 95% CI 1.28-4.52). These estimates were in large part mediated by prematurity and birthweight, indirect effect acting through prematurity was OR 1.79 (95% CI 1.12-2.75) and through birthweight OR 2.12 (95% CI 1.40-3.18). Odds of Apgar score ≤ 5 was more than four times higher among pregnancies with placental pathologies (OR = 4.56, 95% CI 1.28-21.26). Coexisting placental pathology may impact Apgar scores in pregnancies complicated by PA. This knowledge could be used by neonatal teams to mobilize resources in anticipation of the need for neonatal resuscitation.

Introduction: The reported effects of SARS-CoV-2 on pregnancy outcomes are conflicting; studies frequently overlook the placenta, which is critical for the health of the mother and infant(s). This study aimed to determine the effect of pandemic stress ± SARS CoV-2 infection on placental histopathology., Methods: Women were recruited in Canada (n = 69); France (n = 21) or in the UK (n = 25), between March and October 2020. Historic controls (N = 20) were also included. Placenta and fetal membrane samples were collected rapidly after delivery and were fixed and stained for histopathological analysis. Maternal demographical data and obstetric outcomes were recorded., Results: Over 80% of the placentas from SARS-CoV-2+ pregnancies had histopathological abnormalities: predominantly structural (71-86%) or inflammatory (9-22%), depending on geographical location. Excessive fibrin was seen in all sites, whereas deciduitis (Canada), calcifications (UK), agglutinations and chorangiosis (France) predominated in different locations. The frequency of abnormalities was significantly higher than in SARS-CoV-2 negative women (50%, p < 0.05). Demographic and obstetric data were similar in the SARS-CoV-2+ women across all sites - characterised by predominantly Black/Middle Eastern women, and women with elevated body mass index., Discussion: Overall, the frequency of placental abnormalities is increased in SARS-CoV-2+ women, but the incidence of placental abnormalities is also higher in SARS-CoV-2- women that gave birth during the pandemic, which highlights the importance of appropriate control groups to ascertain the roles of pandemic stress and SARS-CoV-2 infection on the placenta and pregnancy outcomes., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Gastroschisis is a congenital malformation characterized by intestinal herniation through an abdominal wall defect. Despite its unknown pathogenesis, known risk factors include maternal smoking, alcohol use, and young maternal age. Previous work has shown that gastroschisis is associated with placental delayed villous maturation, and the goal of this study was to assess for additional associated placental pathologies that may help clarify the pathogenesis of gastroschisis., Methods: We conducted a retrospective slide review of 29 placentas of neonates with gastroschisis. Additionally, we reviewed pathology reports from one control group of 30 placentas with other congenital malformations. Gross and histological data were collected based on a standardized rubric., Results: Gastroschisis was associated with increased placental fetal vascular malperfusion (FVM) in 62% of cases (versus 0% of controls, p < 0.0001). It was also associated with increased placental villous maldevelopment in 76% of cases (versus 3% of controls, p < 0.0001)., Conclusion: Our study demonstrates an association between gastroschisis and FVM. While FVM could be the consequence of vascular disruption due to the ventral location of gastroschisis, it could also reflect estrogen-induced thrombosis in early pregnancy. Further research is needed to separate these possibilities and determine the cause of the placental FVM observed in gastroschisis.

Introduction: Assisted reproductive technology including in vitro fertilization (IVF) and oocyte donation (OD) may increase risk for placenta-mediated diseases. Comprehensive analysis of histopathological placental lesions according to source of oocytes used in the IVF procedure - recipient derived (RD-IVF) vs oocyte donation (OD-IVF), has not been conducted in a population with a hypertensive disorder of pregnancy (HDP) and/or intrauterine growth restriction (IUGR)., Methods: A retrospective cohort study of archived placenta specimens from RD-IVF and OD-IVF pregnancies affected by HDP and/or IUGR was conducted with blinded histopathological placental examination. Three categories of lesions were differentiated and defined as main outcomes: maternal vascular malperfusion (MVM), chronic inflammation, and fetal vascular malperfusion (FVM). To determine the relationship between conception method and placental lesions, multivariable regressions were performed with maternal age, gestational age, HDP, birth and placental weight percentiles as model covariates., Results: 115 placentas were included 83 (72.2%) RD-IVF, 32 (27.8%) OD-IVF. Adjusted OR (aOR) for conception method was 5.05 (95%CI 0.58-43.90, p=0.142) for MVM, 1.87 (95%CI 0.68-5.15, p=0.228) for chronic inflammatory and 0.61 (95%CI 0.15-2.37, p=0.471) for FVM lesions. Multiple gestation demonstrated borderline association with MVM (aOR=0.24, 95%CI 0.04-1.51, p=0.129) and total pathology score (aRR=0.79, 95%CI 0.62-1.01, p=0.058). Subgroup analysis suggested greater odds of villitis of unknown etiology (VUE) for OD-IVF (aOR=2.98, 95%CI 1.12-7.93, p=0.029)., Discussion: Source of oocyte derivation demonstrated no evidence of association with main outcomes in cases of HDP and/or IUGR. Subgroup analysis demonstrated increased rates of inflammatory lesions for OD-IVF. Multiple gestation may be associated with decreased MVM and total lesions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Pregnant women are susceptible to viral infections due to physiological changes such as cell-mediated immunity. No severe adverse pregnancy or neonatal outcomes have been consistently reported in 2019 novel coronavirus disease (COVID-19) positive pregnancy cases. There are controversies around the role of COVID-19 in pregnancy. A systematic review was conducted to examine clinical maternal and neonatal clinical outcomes. Studies were included if they reported SARS-CoV-2 infection among pregnant women and/or COVID-19 positive neonates as validated by positive antibody testing or viral testing using polymerase chain reaction. Case series, case reports, case-control studies, and comparative studies were included. Eight hundred and thirty-seven records were identified, resulting in 525 records for level I screening. Forty-one were included after full-text review. Results suggest elevated rates of intensive care unit (ICU) admission, gestational diabetes, preeclampsia, C-sections, pre-term birth, and C-reactive protein (CRP) in comparison to pregnant women without SARS-CoV-2. Careful monitoring of pregnancies with SARS-CoV-2 is recommended., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

We sought to assess chronic inflammatory responses in patients who achieved pregnancy by oocyte donation and non-oocyte donation-assisted reproductive technology and delivered at The Ottawa Hospital. Data describing maternal health, obstetrical outcomes, neonatal outcomes, and placental pathology were collected and analyzed from electronic medical records. An increased frequency of adverse obstetrical outcomes was observed. In the oocyte donation-assisted reproductive technology group, placental pathology data demonstrated increased frequency of fetal vascular malperfusion (p = 0.02) and placenta accreta (p < 0.001), representing a chronic inflammatory response. Placental pathology reflecting dysregulated immune processes and vasculopathy is associated with oocyte donation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Oocyte donation (OD) is associated with an increased risk of pregnancy-induced hypertension, but the evidence of an association between OD and infant outcomes, including birth weight and gestational age, is conflicting. This study sought to determine the associations between oocyte donation and birth weight or gestational age compared with other forms of autologous oocyte assisted reproductive technology (ART)., Methods: Medline, Embase, and the CENTRAL Trials Registry of the Cochrane Collaboration were searched using a comprehensive search strategy. Studies of women over 24 weeks gestation compared infant outcomes among OD pregnancies versus other ART. Study quality was assessed, and a meta-analysis of mean birth weight and gestational age was conducted using a random effects model., Results: Nineteen studies were included. Four studies showed a significant association between OD and lower birth weights, and five studies found significant differences in gestational age between OD and autologous oocyte ART. The pooled difference in birth weight means between OD and autologous ART was -42 (-88, 4) . The pooled difference in gestational age was -0.4 weeks (-0.8, 0.0 weeks)., Conclusion: A high degree of interstudy heterogeneity exists, and the association between OD and infant outcomes remains unclear., (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

We report a rare case of sclerosing pneumocytoma occurring in a child with PTEN mutation. A 13-year-old female presented to the emergency department of an adult hospital following 2 to 3 days of upper respiratory tract infection symptoms. A primary lung lesion was discovered during her initial chest X-ray to rule out pneumonia. The patient underwent an uneventful thoracoscopic right upper lobe segmentectomy. The pathology demonstrated a sclerosing pneumocytoma of the lung. She tested positive for PTEN hamartoma tumor syndrome with a pathogenic variant at c.388 C > T. The PTEN mutation was also identified in the sclerosing pneumocytoma. Further study of PTEN mutation in sclerosing pneumocytoma is warranted.

Residual tumor after curative intent therapy in patients with Ewing's sarcoma is of great clinical significance. Surgeons use the resection margin to indicate the completeness of a surgical excision. However, this margin may be either nonviable/necrotic or viable. This systematic review examines the 5-year event-free survival rate and local recurrence as a function of positive resection margins that are nonviable/necrotic versus those that are viable. Multiple databases were searched using the Ovid interface. After full text screening, 45 articles that reported either margin or postchemotherapy histology and one or more outcomes of interest were identified, and two articles reported on margin and histology simultaneously. An attempt was made to contact the remaining authors and one author was able to provide additional data. The data from the three studies suggest that prognosis in ES depends on both margin involvement and the postchemotherapy histological response simultaneously. However, radiation therapy likely improves local control in patients with inadequate surgical margins, regardless of histological response. This is an area where there is a paucity of evidence that needs to be rectified to ensure that ES patients are provided the highest quality of evidence-based care., (© 2019 John Wiley & Sons Australia, Ltd.)

Objective: To report the clinical and variations in the histopathological features of pilomatrixoma of the ocular adnexa in 3 young individuals., Design: A retrospective case series was performed with clinical, histological, and immunohistochemical analysis., Participants: Case 1 is an 18-year-old male who presented with a reddish-blue swelling under the left eyebrow. The lesion measured 2 × 1 cm. Case 2 is a 2-year-old female who presented with a reddish-blue nodule inferior to the right eyebrow with telangiectatic vessels. The lesion measured 6 × 4 × 4 mm. Case 3 is a 14-year-old female who presented with a subcutaneous lesion under the right upper eyebrow with fluctuating inflammation. The lesion measured 12 × 3 × 2 mm. Histopathological examination of case 1 disclosed peripheral basaloid cells and central shadow cells containing calcific foci, separated by a transition zone. In case 2, histopathological analysis revealed central calcific foci in islands of shadow cells with more peripheral basaloid cells. In case 3, we observed numerous clusters of shadow cells with focal calcifications, as well as basaloid cells in a disorganized configuration., Conclusion: Pilomatrixoma is an uncommon benign skin neoplasm originating from the matrix of the hair root. We describe a spectrum of histopathological findings in pilomatrixoma of the ocular adnexal in 3 young individuals., (Copyright © 2018. Published by Elsevier Inc.)

Background: Central giant cell granulomas are benign tumours of the mandible, presenting in children and young adults. Divided into non- and aggressive subtypes, the aggressive subtype is relatively rare and can occasionally progress rapidly, resulting in significant morbidity., Case Presentation: We present a case of an aggressive central giant cell granuloma (CGCG) in a six year-old female. The lesion originated in the right mandibular ramus and progressed rapidly to involve the condyle. Diagnosis was made using a combination of imaging and pathology. A timely en bloc resection of the hemi-mandible was performed with placement of a reconstructive titanium plate and condylar prosthesis., Conclusion: Our case demonstrates the importance of considering CGCG in the differential diagnosis of rapidly progressive mandibular lesions in the pediatric population. Prompt diagnosis and management can greatly improve long-term outcomes.

Hepatic mesenchymal hamartoma is a rare benign neoplasm principally encountered in young children. Its origin is unknown. We report an unusual hepatic mesenchymal hamartoma in a 7-month-old girl, including histopathologic findings, immunophenotype, and karyotype. Chromosomal microarray analysis of tumoral tissue and circulating lymphocytes found 4 copies of a segment at 1q44 and fluorescence in situ hybridization indicated tandem triplication, ascribed to expansion of a paternal tandem duplication. This genetic abnormality may have played a role in pathogenesis.

Background: Twin anemia-polycythemia sequence (TAPS) is a complication of monochorionic, multiple gestation pregnancies in which blood shunting through placental anastomoses results in chronic anemia in one fetus and chronic polycythemia in another. The outcomes of different treatment modalities for TAPS are not well known., Objective: To determine the outcomes of the intrauterine interventions used to treat TAPS., Study Design: A systematic literature search of MEDLINE, EMBASE, and CENTRAL was performed in June 2016. Primary outcomes were mortality, morbidity, and adverse perinatal outcomes. Data were summarized in the form of weighted means, and statistical difference was determined., Results: Twenty-one articles were identified for inclusion in this review and were composed of 105 cases of TAPS. In the cases presented in the literature, there was no statistically significant difference in mortality, morbidity, or emergent Caesarean section rates between expectant management, intrauterine transfusion (IUT), and laser ablation therapy. Laser ablation therapy and IUT were found to have a significantly lower rate of adverse perinatal outcomes when compared to expectantly managed cases., Conclusions: The literature looking into the treatment of TAPS is very limited, with no randomized controlled trials and only one includable comparative study. Based on the data in the case report and case study literature, there is no mortality difference between any of the treatment modalities. Expectant management may be associated with an increase in adverse perinatal outcomes when compared to laser therapy and IUT. More comparative studies are needed to assist clinicians in adopting an evidence-based approach to the treatment of TAPS., (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Cow's milk protein allergy/intolerance (CMPA/CMPI) is a common entity in the pediatric population with a nonspecific presentation ranging from gastrointestinal symptoms to systemic manifestations. Most infants with CMPI are term, and symptoms often appear in the week following the introduction of cow's milk-based formula. There is typically a significant delay in the onset of milk allergy in premature infants compared to full term. We report a rare case of a premature neonate who presented with symptoms of CMPA within the first 2 days of life.

Metabolic bone disease (MBD) is a broad term that describes a clinically heterogeneous group of diseases that are only united by a common denominator of an aberrant bone chemical milieu leading to a defective skeleton and bone abnormalities. From a forensic pathologist's perspective, MBDs create a challenging diagnostic dilemma in differentiating them from child abuse, particularly when the victim is an infant. Through this brief narrative review on MBD, bone pathophysiology and two relatively challenging pediatric MBDs will be discussed., Competing Interests: Disclosures & Declaration of Conflicts of Interest: The authors, reviewers, editors, and publication staff do not report any relevant conflicts of interest

Dermal non-neural granular cell tumors, also known as primitive polypoid granular cell tumors, are a rare group of distinct cutaneous non-neural granular cell tumors. Pediatric cases are rare, and to the best of our knowledge, we report the youngest patient with dermal non-neural granular cell tumors., (© 2018 Wiley Periodicals, Inc.)

The Native American Pima population has the highest incidence of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) of any reported population, but the pathophysiologic mechanism is unknown. Genetic studies in Pima Indians have linked acyl-CoA dehydrogenase 10 (ACAD10) gene polymorphisms, among others, to this predisposition. The gene codes for a protein with a C-terminus region that is structurally similar to members of a family of flavoenzymes-the acyl-CoA dehydrogenases (ACADs)-that catalyze α,β-dehydrogenation reactions, including the first step in mitochondrial FAO (FAO), and intermediary reactions in amino acids catabolism. Dysregulation of FAO and an increase in plasma acylcarnitines are recognized as important in the pathophysiology of IR and T2DM. To investigate the deficiency of ACAD10 as a monogenic risk factor for T2DM in human, an Acad-deficient mouse was generated and characterized. The deficient mice exhibit an abnormal glucose tolerance test and elevated insulin levels. Blood acylcarnitine analysis shows an increase in long-chain species in the older mice. Nonspecific variable pattern of elevated short-terminal branch-chain acylcarnitines in a variety of tissues was also observed. Acad10 mice accumulate excess abdominal adipose tissue, develop an early inflammatory liver process, exhibit fasting rhabdomyolysis, and have abnormal skeletal muscle mitochondria. Our results identify Acad10 as a genetic determinant of T2DM in mice and provide a model to further investigate genetic determinants for insulin resistance in humans.

Lipoma is a benign tumor, typically of adulthood, with characteristic cytogenetic findings, including rearrangement of 12q13-15; these rearrangements often lead to the fusion of the HMGA2 gene at this locus to the transcriptional regulatory domain of its fusion partner, resulting in neomorphic activity that presumably facilitates the neoplastic process. Herein, we report a rare case of pediatric lipoma with t(9;12)(p22;q14) and evidence of HMGA2-NFIB gene fusion in a 9 year-old boy. This case provides further evidence of the link between NFIB rearrangement and early-onset, deep-seated lipomatous tumors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive hematologic malignancy characterized by frequent skin involvement that most commonly affects older patients. BPDCN is known to have a poor prognosis. Our objective was to assess if outcome and disease prognosis were independently influenced by age when evaluated with clinical presentation, sex, and treatment regimens. We conducted a systematic review to identify BPDCN cases, to compare pediatric BPDCN cases with adult cases. A total of 125 publications were identified detailing 356 cases. Including 1 pediatric case from our institution, 74 were children, and 283 were adults aged 19 or over. Age was shown to be an independent prognostic factor predictive of more favorable outcomes across measures including initial response to therapy, likelihood of relapse, and overall survival at follow-up. The distribution of affected organs at diagnosis was similar across children and adults and type of clinical presentation did not disproportionately influence 1 age group's prognosis over the other. Acute lymphoblastic leukemia-type chemotherapy regimens were shown to be superior to other chemotherapy regimens (acute myeloid leukemia, lymphoma, acute lymphoblastic leukemia/lymphoma, other, or none) in inducing complete remission. Allogeneic stem cell transplantation was shown to increase mean survival time. Future research may be directed toward elucidating the further morphologic, cytogenetic, and cytochemical differences between younger and older BPDCN patients.

Refractory ulcerative colitis (UC) occurs in patients who experience a severe disease manifestation that is unresponsive to medical therapy. The assessment of upper endoscopic microscopic findings and its correlation with refractory UC has not been fully studied in pediatric patients and is the focus of this study. Medical records of UC patients treated at a tertiary pediatric center between 2000 and 2014 were reviewed. Endoscopic biopsies of the upper gastrointestinal (GI) tract of patients meeting a priori inclusion criteria were compared between refractory UC patients and nonrefractory UC patients for active inflammation. Statistically significant differences were determined between groups, and tissues shown to have significant differences were further evaluated for their diagnostic performance. A total of 52 patients were included, 26 in each group. Significant differences were observed in intraepithelial neutrophil infiltration and percentage involvement of crypts/glands for the antrum, body, and duodenal bulb (P ≤ .001, .005, and .01 [intraepithelial neutrophil infiltration] and P = .001, .009, and .015 [% involvement], respectively). Microabscesses of mucosal glands/crypts were also experienced in a greater number of refractory UC patients in the stomach (ie, antrum and/or body of stomach; P = .005) and duodenum (ie, duodenum and/or duodenal bulb; P = .023). The sensitivity and specificity of upper GI tissues to predict refractory UC were moderate, with sensitivities ranging from 38% to 67% and specificities ranging from 81% to 100%. Our results suggest that children with refractory UC are more likely to have active inflammation in the upper GI tract, and thus, this may represent a predictor of responsiveness to current medical therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Rickets was a common metabolic disease of bone a century ago in Europe, North America, and East Asia (mainly due to vitamin D deficiency) but was largely eradicated in growing children by use of cod liver oil and the introduction of vitamin D fortification of milk in the 1930s in the United States. Vitamin D deficiency (VDD) remains the most common form of metabolic bone disease that is entirely preventable and treatable. Historically, rickets has appeared in sporadic epidemics and, despite the introduction of numerous preventive strategies, VDD has remained a global health problem amongst children. Moreover, developed countries such as Canada, Australia, the United Kingdom, and the United States have not been exempt from this. The radiological and histological features of rickets are both distinctive and characteristic and they reflect the underlying pathophysiological issue of decreased mineralization of bone as a result of VDD. The radiological features include 1) metaphyseal cupping and fraying, 2) poor mineralization of epiphyseal centers, 3) irregular and widened epiphyseal plates, 4) increased distance between the end of shaft and epiphyseal center, 5) cortical spurs at right angles to the metaphysis, 6) coarse trabeculation, and 7) periosteal reactions. Fractures may also be evident. The histological features of rickets reflect the failure of cartilage to mineralize and undergo resorption. This results in 1) disordered proliferation of chondrocytes in the hypertrophic zone secondary to a lack of apoptosis, 2) loss of the columnar arrangement of chondrocytes that results in thickening and disorganization of the hypertrophic zone, 3) tongue-like projections of cartilage that extend into the spongiosa, 4) irregularity of the limit between the proliferative and hypertrophic zones, and 5) penetration of blood vessels into the hypertrophic zone. The case of a premature 3-month-old female infant, born in the winter months in the arctic region of Canada who died from a lobar pneumonia with an incidental finding of radiological and pathological evidence of rickets, is presented. The case is used to review the entity of rickets from historical, pathophysiological, radiological, and histological perspectives., Competing Interests: DISCLOSURES & DECLARATION OF CONFLICTS OF INTEREST The authors, reviewers, editors, and publication staff do not report any relevant conflicts of interest