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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.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.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.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.

Background Necrotizing enterocolitis (NEC), while classically discussed in preterm and low birth weight neonates, also occurs in the term infant and accounts for 10% of all NEC cases. Despite there being fewer reported cases of NEC in term infants, these presentations demonstrate differences in the onset, severity and risk factors from the classic presentation observed in premature infants. We present a novel case of term NEC that contravenes the reported literature making departures from clinical presentation, risk factors and location of perforation in an otherwise healthy term two-day old infant born after an uncomplicated pregnancy who presented with hematochezia. Case presentation A healthy term baby born after an uneventful pregnancy presented with bloody stool at 2 days of life who was otherwise well. Investigations revealed pneumoperitoneum from a large proximal transverse colonic perforation secondary to NEC. No typical risk factors for NEC were found. Conclusion Given the life-threatening potential of an unrecognized perforation we recommend the inclusion of NEC on the differential for neonatal hematochezia.

This paper reviews the published literature regarding neurodevelopmental outcomes in neonates following in utero exposure to opioids. We have summarized available clinical and experimental data. Overall, clinical data is limited and equivocal with most studies showing no significant neurodevelopmental impairments in infants and children exposed to opioids in utero. Various outcome measures assessed language, communication, cognitive, psychomotor, and behavioural outcomes. The equivocality of the data may be a result of the complexity of the cohort and the inability to disentangle the effect of the opioids from the multiple comorbidities. Results from experimental data show that all opioids cross the placental barrier. Mouse studies show biochemical and neurophysiological changes, leading to long-term effects on learning and memory. Some data also suggests that epigenetic and imprinting changes in the central nervous system of mice may lead to multigenerational effects of opioid exposure. Ultimately, the benefits of opioid replacement therapy outweigh its risks, but it should be done in the context of a broader biopsychosocial risk reduction approach. Promoting mother-child bonding and care through skin-to-skin contact, rooming-in, and breastfeeding can reduce severity of neonatal abstinence syndrome and improve outcomes. This cohort of women and children requires advocacy for comprehensive multidisciplinary care. RésuméCet article passe en revue la littérature publiée concernant les résultats neurodéveloppementaux chez les nouveau-nés après exposition in utero aux opioïdes. Nous avons résumé les données cliniques et expérimentales disponibles. Dans l’ensemble, les don- nées cliniques sont limitées et équivoques, avec la plupart des études ne montrant aucune déficience neurodéveloppementale significative chez les nourrissons et les enfants exposés aux opioïdes in utero. Diverses mesures de résultats ont évalué les résultats linguistiques, de communication, cognitifs, psychomoteurs et comportementaux. L’équivocité des données peut être le résultat de la complexité de la cohorte et de l’incapacité à démêler l’effet des opioïdes des multiples comorbidités. Les résultats des données expérimentales montrent que tous les opioïdes traversent la barrière placentaire. Les études sur la souris montrent des changements biochimiques et neurophysiologiques, conduisant à des effets à long terme sur l’apprentissage et la mémoire. Certaines données suggèrent également que les changements épigénétiques et d’empreinte dans le système nerveux central des souris peuvent conduire à des effets multigénérationnels de l’exposition aux opioïdes. En fin de compte, les avantages de la thérapie de substitution aux opioïdes l’emportent sur ses risques, mais cela devrait être fait dans le contexte d’une approche plus large de réduction des risques biopsychosociaux. La promotion des liens et des soins entre la mère et l’enfant par le contact peau à peau, l’accoutumance et l’allaitement peut réduire la gravité du syndrome d’abstinence néonatale et améliorer les résultats. Cette cohorte de femmes et d’enfants a besoin de plaidoyer pour des soins multidisciplinaires complets.

The objective of this study is to determine whether rapidity of death in necrotizing enterocolitis (NEC) increased odds of discordance between clinical and pathological diagnosis.Retrospective case-series study including preterm infants admitted to the NICU.Twenty-two infants met the selection criteria. Gross pathologic evidence of NEC was present in 1/6 cases (17%) where demise occurred12 h after onset of symptoms, 3/5 cases (60%) within 12-24 h, and 8/11 cases (73%) in24 h. Histological evidence of necrosis was present in 4/6 (67%) cases when death occurred12 h, 4/5 (80%) in 12-24 h, and 9/11 (82%) in24 h. The percentage with gross pathologic evidence showed a monotonic trend (P = 0.031), while the trend was less clear for histologic findings (P = 0.496).Pathologic features of cell death may not have had sufficient time to develop. This study could reassure both healthcare providers and families when pathologic and clinical diagnoses are not consistent.

Inherited defects in the ubiquitous adenosine deaminase (ADA) enzyme disrupt the function of the immune system as well as many other organs and tissues. Some patients may also suffer from kidney damage. Here we report on an ADA-deficient patient who was treated with ADA replacement therapy from infancy and at 6 years of age developed acute kidney failure, thrombocytopenia, and severe anemia. A kidney biopsy demonstrated mesangiolysis and occlusion of kidney loops by erythrocytes and platelet aggregates, which is consistent with hemolytic-uremic syndrome (HUS). There was no evidence of exposure to Shiga toxins, nor were any complement abnormalities detected. The kidney function improved following hemodialysis. Our report demonstrates the increased susceptibility of ADA-deficient patients to develop HUS and expands the nonimmune abnormalities associated with ADA deficiency. This further emphasizes the vigilance required when caring for such patients. Statement of novelty: Here we provide the first detailed clinical and histological characterization of hemolytic-uremic syndrome developing in an ADA-deficient patient.

We describe a patient who presented with a congenital soft tissue lesion initially diagnosed as infantile fibromatosis at 15 days of age. Unusually, the mass demonstrated malignant progression leading to death at 20 months of age. Biological progression to malignancy is not known to occur in fibromatosis, and fibrosarcoma is not known to progress from a benign lesion. Whole-exome sequencing of the tumor identified a driver mutation in histone H3.1 at lysine (K)36. Our findings support the link between oncohistones and infantile soft tissue tumors and provide additional evidence for the oncogenic effects of p.K36M in H3 variants.

Alterations in interstitial cells of Cajal (ICC) distribution and density may seriously influence gut motility. We and others have documented a disturbance of ICC and neurons in Hirschsprung's disease (HD), intestinal ischemia, and inflammation. The ability to remove intestine with permanent dysmotility improves significantly the prognosis. This may be important in the developing intestine especially in HD. More complete pathological information increases the accuracy of surgical decisions. Therefore we sought to develop a rapid, intraoperative immunohistochemical protocol for ICC and neurons in surgical specimens for routine diagnostic and therapeutic assessment of pediatric patients. To date, cKit is the only reliable immunohistochemistry for ICC identification. There are multiple antibodies in use for neuronal identification. A comparison of fixation methods and immunostaining using cKit and multiple intestinal neuronal antibodies was done. Fresh segments of surgically resected intestine were sectioned and stained using antibodies for ICC cell identification (anti-cKit) and for neuronal characterization. By carefully changing tissue fixation methods, different neuronal antibodies were tested to determine an optimal rapid protocol. Each suggested protocol was tested on normal and pathological intestinal tissue and compared to the previous overnight immunostaining of the same tissue. A new rapid tissue fixation and immunostaining protocol using cKit for ICC identification and NF 68 was developed. By employing this protocol, we could obtain ICC and neuro-immunohistochemistry in unfixed frozen sections within 1 h with tissue vibration to diminish the time for immunostaining. Without vibration the protocol takes 3 h. ICC and enteric neuronal changes could be readily observed and the quality of staining was comparable to standard immunohistochemistry. Each gut pathology displayed characteristic changes in ICC and neuronal density/distribution in the affected bowel. The time-scale of the 1-h immunoprocessing is still longer than the standard clinical pathological "quick" sections using HE staining; however, the protocol duration is within the surgery timescale. Standard HE stain used in combination with our rapid neuronal and ICC immunohistochemistry protocol enables a fast, comprehensive, and accurate assessment of the pathophysiology of signaling networks controlling gut motility while the patient is still in the operating room. We propose that the addition of this simple and rapid immunohistochemical assessment in the pathologist evaluation of surgical specimens would result in a more complete characterization for diagnosis and prognosis of the pediatric patient. Specifically, we propose that this test will differentiate good versus poor prognosis HD patients based on their neuron/ICC ratio and present a rapid, standardized method for use in general pathology.

A 2-year-old girl who had a stage 2, favorable-histology Wilms tumor diagnosed when she was age 10 months presented with multiple brain metastases at second recurrence. She had been treated with combined radiotherapy, surgery, and chemotherapy; at 2 months after treatment, recurrent disease developed in the central nervous system and she died. Brain metastases are rare in the natural history of Wilms tumor. Although it does not appear that cerebral metastases are a barrier to tumor eradication and long-term survival if treated with combined modality therapy, treatment should be individualized.

Inflammatory cloacogenic polyp (ICP) is a rare lesion arising in the region of the anorectal transitional zone. It is likely caused by occult internal prolapse. Most cases reported in the literature are in the adult population. This is a report of ICP in four children. Awareness of this entity in children is important because of both the propensity for recurrence or persistence of the polyps if the underlying etiology is not corrected, as well as the long-term implications of internal intussusception: procidentia, descending perineum syndrome, and ultimately, incontinence.

Congenital midline cervical cleft is a relatively uncommon malformation of the anterior neck for which most of the current literature comprises case reports. There is a spectrum in clinical features, but the prototypical description is of a midline groove or cleft of atrophic skin with a skin tab at the cephalic end and an inferiorly oriented sinus tract at the caudal end. An underlying dense fibrous cord is usually described. The most widely postulated etiology is impaired midline fusion of the upper branchial arches. Some of the recent case reports advocate for removal of the defect and closure with Z-plasty. Here we report a case of a similar congenital lesion in a male patient. In our case, there was a conspicuous skin tab caudal to which there was a dense fibrous cord running vertically in the midline under the skin documented since the child was first examined at 5 months of age. The skin overlying the fibrous cord was mildly atrophic and only very subtly indented but was not desquamating or edematous. There was no open sinus tract at the caudal end, but within the skin tab, on histology, we did note an inclusion cyst lined by respiratory type mucosa with squamous metaplasia. The cord was composed of fibrous tissue and skeletal muscle, as has been described. In our case, we describe hamartomatous proliferations within the dermis of the skin tab, not previously described, which we feel provides further support to the embryologic closure defect hypothesis. Our case is distinct because the absence of an external cleft allowed for a more conservative surgical approach.

Diagnostic electron microscopic studies specific to the head and neck region are limited in both children and adults. Even information about the workload created by specimen acquisition from this region in the electron microscopy laboratory is lacking. To address these deficiencies, various specimens gathered from adults (N = 6607) and children (N = 1556), over a 5- and 10-year period, respectively, and blocked in plastic resin were surveyed. Head and neck samples accounted for 16.4% of these samples from adults and 13.5% from children, representing sizable contributions to workload from an anatomic region amounting to less than 10% of body mass. In adults, diagnostic problems posed by metastatic neoplasms account for a considerable proportion of the cases submitted for electron microscopy; in the pediatric age group, undifferentiated primary tumors of the head and neck region frequently require ultrastructural study. In both circumstances, spindle cell, look-alike, neuroendocrine, and small cell tumors can frequently be rapidly assessed and differentiated by ultrastructural details. Problem cases are inevitable given the complexity of this region and the number of different tissues and organs in close proximity. It is advantageous to anticipate the possibility of encountering difficult differential diagnostic problems by sampling lesions of the head and neck for glutaraldehyde fixation more frequently.

A 16-year-old girl presented with hematochezia and abdominal pain. The patient developed a small bowel obstruction that required a laparotomy, which showed a segment of grossly infarcted small bowel with 3 perforations, localized abscesses, and creeping fat. Resection and an end-to-end anastomosis were performed. Pathologic examination showed underlying mesenteric venous thrombosis with no evidence of Crohn's disease. Hematology workup showed no evidence of a congenitally inherent hypercoagulable state. The use of oral contraceptives was the only predisposing factor identified.

An infant who presented with a unilateral renal cystic process underwent nephrectomy due to hypertension. There was no evidence of any other disease process. Family history and investigation were negative for renal cystic disease or other genetic disease process. The pathology most resembled autosomal dominant polycystic kidney disease or a specific entity described as unilateral renal cystic disease.

A patient with fulminant hepatic failure who had a T8 malignant lymphona is described. A review of the literature yields 11 other cases with hematologic malignancies with similar presentation. To the authors’ knowledge this is the first case in which cell marker analysis was performed. Pitfalls in morpholog1c diagnosis are discussed.