Workload Measurement in Subspecialty Placental Pathology in Canada.

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.

Cranial fasciitis: a rare pediatric non-neoplastic lesion with 14-year follow up.

Cranial fasciitis is a fibroblastic lesion found in the cranium of children three weeks to six years of age. It most commonly manifests as a solitary, rapid growing mass on the scalp with frequent involvement of underlying bone and occasional intracranial expansion. Patients with cranial fasciitis may present with a wide range of associated symptoms. Otologic symptoms such as otalgia, otorrhea, hearing loss and middle ear effusion are not frequently encountered. We present a case of cranial fasciitis with intracranial involvement and associated otologic symptoms in a four year old boy with subsequent follow up 14 years later.

Novel splice-site mutation in ATP8B1 results in atypical progressive familial intrahepatic cholestasis type 1.

BACKGROUND AND AIM: Our objective was to identify the molecular genetic basis of an Alagille-like condition not linked to JAG1 or NOTCH2 in two related sibships. METHODS: Because of common ancestry, and an autosomal recessive mode of inheritance, it was hypothesized that all affected and no unaffected individuals would be homozygous for the same haplotype in the region of the causative gene. Single nucleotide polymorphism arrays were therefore used to genotype 3 affected individuals from two sibships, their mothers and four unaffected siblings, to identify regions of homozygosity. Genes within the largest regions were prioritized and sequenced for mutations. Mutant RNA transcripts were also sequenced. RESULTS: A novel splice acceptor site mutation in the ATP8B1 gene was identified (a G-C preceding exon 16 resulting in a 4 bp deletion and frameshift from the 5' end of exon 16). This result was unexpected because ATP8B1 mutations are associated with progressive familial intrahepatic cholestasis type 1 (PFIC1). Intrahepatic bile duct paucity, cardiac anomalies, renal tubular acidosis and hypothyroidism led to an initial diagnosis of Alagille syndrome. However, in retrospect, abnormal sweat chloride, normal gamma-glutamyl transferase, normal to low cholesterol, and an autosomal recessive mode of inheritance were consistent with PFIC1. Renal tubular acidosis, hypothyroidism and cardiac anomalies have not previously been associated with PFIC1. CONCLUSION: This work expands the phenotypic spectrum of PFIC1, and highlights the overlap in clinical phenotype between Alagille syndrome and PFIC1. Knowledge of the causative mutation allows for carrier testing and prenatal diagnosis in this community.

Placental pathology and clinical outcomes in a cohort of infants admitted to a neonatal intensive care unit.

BACKGROUND: Placental pathology predicts persistent neurological impairment, even in normally grown infants. However, few studies have linked placental pathology with neonatal outcomes in a large population. METHODS: We matched the clinical outcomes of a cohort of neonates admitted to a neonatal intensive care unit (NICU) with placental pathology, where available, and examined (by multivariable logistic regression) the relationship between placental pathologies and these outcomes. The outcomes included neonatal death, necrotizing enterocolitis, and intraventricular hemorrhage > or = grade 3. A forward selection model (10% significance level for entry) was used after adjusting for onfounding factors. RESULTS: A detailed gross and microscopic pathological report was available for 1296 eligible infants (64%). Specific placental features were associated with specific neonatal outcomes. The Canadian Neonatal Network has previously determined that specific changes in the pattern of neonatal care can alter the incidence and severity of these outcomes. In the placentas from pregnancies delivering small for gestational age infants who were subsequently admitted to NICU, two different patterns of placental pathologies were found, one ischemic and the other inflammatory. CONCLUSION: Frozen section examination of placentas may facilitate more timely delivery of tailored neonatal therapy.

Chorioamnionitis with a fetal inflammatory response is associated with higher neonatal mortality, morbidity, and resource use than chorioamnionitis displaying a maternal inflammatory response only.

OBJECTIVE: This study was undertaken to evaluate whether the proximity of infection of the chorion/amnion and fetal vessels affects neonatal outcomes. STUDY DESIGN: We examined all (n=2012) infants admitted to the British Columbia's Children's Hospital Neonatal Intensive Care Unit, from January 1996 to October 1997. We included infants with a placental examination (n=1296), and stratified those with histologic chorioamnionitis into cases displaying a maternal inflammatory response only and cases also displaying a fetal inflammatory response (funisitis and/or fetal surface vessel angiitis). RESULTS: Histologic evidence of chorioamnionitis was present in 31% of placentas. Of those, 38% exhibited maternal inflammation only, whereas 62% also exhibited fetal inflammation. Neonatal mortality (9.2% vs 7.2%), morbidity, and resource use were significantly (P < .05) higher when fetal inflammation was present compared with when only maternal inflammation was present. CONCLUSION: Chorioamnionitis with a fetal inflammatory response is associated with higher neonatal mortality, morbidity, and resource use than when only a maternal inflammatory response is present.

Ultrasound features of a paratesticular arteriovenous malformation: a case report of an 11-year-old boy.

A paratesticular arteriovenous malformation (AVM) in an 11-year-old boy with a solitary testicle led to a testicle-sparing excision. The radiological features of this rare lesion are reviewed.

The crucial role of tumour specimen handling in childhood cancer outcomes.

The significant advances achieved in the care of children with cancer have been the result of carefully conducted clinical trials in international cooperative group settings. Specialized biological testing of tumour specimens is now an essential component of risk and treatment assignment for many childhood cancers. Thus, the appropriate collection and handling of tumour specimens is crucial to maintaining and further advancing the excellent outcomes that we have achieved. We recommend that all children with a strongly suspected malignancy, or cases in which the situation is unclear, be discussed with a paediatric oncologist before obtaining a tumour specimen. When a tumour is discovered incidentally at surgery, we recommend that the tumour be placed in a saline-soaked gauze and a paediatric pathologist or oncologist contacted immediately. Further progress in understanding and treating childhood cancer is intimately linked to basic studies of biology, translational research and determining the role of biological markers in risk stratification. Early and careful collaboration between front-line physicians and tertiary care oncology specialists is essential to the continuing success of treatment of children with cancer.

The association of placental abnormalities with maternal and neonatal clinical findings: a retrospective cohort study.

OBJECTIVES: (1) To determine the nature and extent of placental pathologic findings; (2) to associate placental pathologic findings with clinical indicators of infection; (3) to evaluate placental pathology in the context of the guidelines outlined by the College of American Pathologists (CAP). METHODS: A retrospective cohort study, through review of maternal and neonatal charts and placental pathology, of 100 sequential pregnancies in which placentas were submitted to pathology. Data were examined using descriptive statistics, and proportional differences were compared using the chi-square test and Fisher's exact test. RESULTS: Overall, 75% of placentas submitted for pathology review had pathologic abnormalities. Fifty percent had findings consistent with inflammation, 38% had findings consistent with vascular abnormalities, and 18% had findings consistent with meconium. Fetal clinical indicators of infection were associated with placental findings of chorioamnionitis (p < or = 0.01), while maternal clinical indicators were not. Similarly, fetal clinical indicators were associated with placental findings of fetal inflammation (p < or = 0.025), whereas maternal indicators were not associated with placental findings of maternal inflammation. A diagnosis of chorioamnionitis in labour by the attending physician was associated with pathologic findings (p < or = 0.05). A CAP indication was found in 75% of the placentas. There was no difference in incidence of placental pathology between those placentas submitted with and without a CAP indication. CONCLUSION: Placental findings of inflammation or infection were associated with fetal clinical indicators of infection, but not with maternal indicators. Placental pathology is very useful in identifying undiagnosed maternal infection or inflammation.