Evaluating the Prognostic Implication of the Collins Histology Scoring System in a Pediatric Eastern Ontario Population With Eosinophilic Esophagitis.

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.

Diagnostic Value of Mid-esophageal Biopsies in Pediatric Patients With Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic esophagitis (EoE) is histologically defined as the presence of 15 or more intraepithelial eosinophils per high-power fields. Limited consensus exists on where to sample the esophagus in pediatrics. This study aimed to identify whether endoscopic and histologic examination of the mid esophagus offers diagnostic value compared to proximal/distal esophageal biopsies. METHODS: A retrospective chart review of pediatric patients with EoE was performed. Endoscopic and histologic parameters were assessed at the initial and follow-up visits, and concordance between proximal/distal biopsy and mid biopsy was determined. RESULTS: A total of 100 patients with a mean age of 9.6 ± 4.07 years were included. Endoscopic parameters between proximal/distal and mid esophagus were concordant in 84% to 97% of patients (initial assessment) and in 80% to 97% of patients (at follow-up). Mid esophagus showed endoscopic abnormalities, which were absent at the proximal/distal esophagus in 1% to 5% of patients, as well as histologic abnormalities in 2% to 8% of patients overall at initial and follow-up examinations. CONCLUSIONS: We recommend continued endoscopic and histologic assessment of the proximal/distal biopsy; however, examination of the mid esophagus does offer small diagnostic value in our subset of patients. Future studies need to be conducted before conclusive recommendations supporting the use of mid-esophageal biopsies can be made.

Combination of MCM2 With Ki67 and p16 Immunohistochemistry Can Distinguish Uterine Leiomyosarcomas.

Our objective was to evaluate the diagnostic utility of 2 new proliferation markers, cyclin D1 and minichromosome maintenance complex component 2 (MCM2), in comparison with p16, p53, and Ki67 in differentiating the spectrum of smooth muscle tumors. An institutional database search from 2009 to 2017 identified 10 cases of uterine leiomyoma with bizarre nuclei (LBN), 12 smooth muscle tumors of uncertain malignant potential, and 13 leiomyosarcomas (LMS). Ten resected leiomyomas (LM) were included as controls. Immunohistochemistry was performed on the befitting representative block from each case. Ki67 was <10% in all LMs and LBNs, whereas >10% in all LMSs. Although wild-type in majority of cases, p53 was overexpressed in 38% of LMSs. Cyclin D1 nuclear positivity in LMs, LBNs, and smooth muscle tumors of uncertain malignant potentials ranged from 0% to 65% of neoplastic cells with mostly weak to moderate staining intensity. Instead, cyclin D1 expression was <5% in all LMSs. The ratio of MCM2 positivity exhibited a similar wide range (<1%-80%) in LMs, LBNs, and smooth muscle tumors of uncertain malignant potentials but interestingly, 92% (12/13) of LMSs were diffusely and strongly positive for MCM2 (>80% cell positivity). Overall, for diagnosis of LMS, the sensitivity for diffuse intense MCM2 staining was higher (92%) compared with diffuse staining for p16 (77%); however, specificity of MCM2 and p16 was comparable (94% and 97%, respectively). Herein, we describe the immunohistochemical profile of 2 new proliferation markers, cyclin D1 and MCM2 in uterine smooth muscle tumors. A combination of diffuse strong MCM2 and p16 reactivity with increased Ki67 index can reliably distinguish LMSs from benign histologic mimics.

Update on molecular findings in rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumour in children and adolescents. Histologically RMS resembles developing fetal striated skeletal muscle. RMS is stratified into different histological subtypes which appear to influence management plans and patient outcome. Importantly, molecular classification of RMS seems to more accurately capture the true biology and clinical course and prognosis of RMS to guide therapeutic decisions. The identification of PAX-FOXO1 fusion status in RMS is one of the most important updates in the risk stratification of RMS. There are several genes close to PAX that are frequently altered including the RAS family, FGFR4, PIK3CA, CTNNB1, FBXW7, and BCOR. As with most paediatric blue round cell tumours and sarcomas, chemotherapy is the key regimen for RMS therapy. Currently there are no direct inhibitors against PAX-FOXO1 fusion oncoproteins and targeting epigenetic cofactors is limited to clinical trials. Failure of therapy in RMS is usually related to drug resistance and metastatic disease. Through this review we have highlighted most of the molecular aspects in RMS and have attempted to correlate with RMS classification, treatment and prognosis.

Histologic analysis of eosinophils and mast cells of the gastrointestinal tract in healthy Canadian children.

Many gastrointestinal (GI) disorders, including GI eosinophilia and inflammatory bowel disease, can be characterized by increased mucosal eosinophils (EOs) or mast cells (MCs). Normal mucosal cellular counts along the GI tract in healthy children have not been established for a Canadian pediatric population. To establish a benchmark reference, we quantified EO and MC from 356 mucosal biopsies of the GI tract obtained during upper and lower endoscopic biopsies of 38 pediatric patients in eastern Ontario. Mean total counts of EO varied for the 11 tissues we examined, from a low of 7.6±6.5/high-power field (HPF) (×40 [×400, 0.55mm(2)]) in the body of the stomach to a high of 50.3±17.4/HPF in the cecum. The lower GI tract (ileum, cecum, colon, sigmoid, and rectum) generally had higher total EO counts than the upper GI tract (antrum and body of stomach, duodenum, and duodenal cap) (combined average of 32.1±20.6 versus 19.3±15.8, respectively). Similarly, the number of mucosal MC was different in the various regions of the GI tract ranging from 0.04±0.2/HPF in the duodenal cap to 0.9±2.6/HPF in the ileum. Total counts for EO and MC in the lamina propria were not significantly different between sexes when adjusted for multiple testing. EO polarity was absent in many cases, irrespective of the GI region. These numeration and localization of EO and MC will provide normative data for upper and lower endoscopic GI biopsies in the pediatric population of Eastern Ontario.

Langerhans cell histiocytosis: a comprehensive review.

Langerhans cell histiocytosis (LCH) is currently regarded as a myeloid neoplasm, with remarkably broad clinical spectrum, ranging from isolated skin or bone lesions to a disseminated disease that can involve nearly any organ. LCH is generally regarded as a sporadic disease that occurs predominantly in the paediatric population. The diagnosis of LCH is confirmed by immunohistochemistry (IHC) by demonstrating the presence of dendritic cell markers such as S100 protein, in addition to CD1a and langerin. Contrary to previous beliefs, recent literature reveals that the pathogenesis of LCH might involve a clonal process implicating BRAF c.1799T>A (p.Val600Glu) and other mutations [(600DLAT) B-RAF and (T599A) B-RAF, somatic MAP2K1 mutations].Through this review article, we have summarised the latest understanding of the biological and salient histological characteristics of LCH and its potential morphological mimics.