In-utero Diagnosis of Prostatic Embryonal Rhabdomyosarcoma.

Though rhabdomyosarcoma is the most common soft-tissue tumor diagnosed in children there are no reported cases of prenatally detected prostatic embryonal rhabdomyosarcoma. This report demonstrates the first reported case of this phenomenon and its subsequent workup, diagnosis, and treatment.

Giant mediastinal teratoma in a young infant: a case report.

Background: Giant mediastinal tumors in the pediatric population can pose unique challenges for resection such as cardiovascular collapse on induction of anesthesia and injury to surrounding structures that may be compressed, displaced, or invaded by the mass. Principles that must be borne in mind during removal of giant mediastinal masses include: appropriate cross-sectional imaging to define extent of mass; airway control during induction of anesthesia; a multidisciplinary collaborative approach including cardiothoracic surgery; preparation for urgent sternotomy; plan for peripheral cannulation to institute cardiopulmonary bypass if needed; preservation of neurovasculature structures during dissection; complete resection whenever possible. While complete resection is desirable and results in an excellent prognosis, it may not be achievable especially if the tumor encases coronary arteries, and it is acceptable to leave small amounts of tumor behind. Case Description: Here we present a case describing surgical management of a giant mediastinal teratoma in a two-month-old female. The patient was found to have a large mediastinal mass during workup for cough and noisy breathing. She underwent preoperative echocardiogram demonstrating normal cardiac function followed by uncomplicated, open resection of the mass. Conclusions: Giant mediastinal tumors give rise to unique challenges for resection in small infants. The principles of airway control, preparation for urgent sternotomy, preparation for peripheral cardiopulmonary bypass cannulation, and preservation of neurovasculature during dissection must be borne in mind.

Case of the Season: Asymmetric Chronic Recurrent Multifocal Osteomyelitis.

Chronic recurrent multifocal osteomyelitis is a rare noninfectious inflammatory bone disease diagnosed based on the synthesis of clinical, radiological, and pathological findings. The differential diagnostic considerations are led by multifocal infectious osteomyelitis and multifocal neoplasms. We report a case of a 9-year-old girl who emergently presented with worsening back pain, inability to walk, and normal vital signs. C-reactive protein and erythrocyte sedimentation rate were elevated, whereas the white blood cell count was normal. Initial radiographs and MRI of the spine showed multiple edematous vertebral body lesions. Subsequent whole-body MRI demonstrated multiple additional edematous bone lesions in the right half of the body, including the scapula, femur, and tibia. The lack of symmetrical bone lesion distribution indicated image-guided percutaneous core biopsy to exclude neoplastic disease. Pathological examination of an osseous core biopsy specimen showed a noninfectious osteomyelitis pattern with no findings of Langerhans cell histiocytosis, malignancy, or infectious osteomyelitis. The synthesis of clinical, radiological, and pathological findings was diagnostic of asymmetric right-sided chronic recurrent multifocal osteomyelitis, representing an atypical presentation that deviates from the typically symmetrical bilateral chronic recurrent multifocal osteomyelitis pattern.

Assessment Question Characteristics Predict Medical Student Performance in General Pathology.

CONTEXT.­: Evaluation of medical curricula includes appraisal of student assessments in order to encourage deeper learning approaches. General pathology is our institution's 4-week, first-year course covering universal disease concepts (inflammation, neoplasia, etc). OBJECTIVE.­: To compare types of assessment questions and determine which characteristics may predict student scores, degree of difficulty, and item discrimination. DESIGN.­: Item-level analysis was employed to categorize questions along the following variables: type (multiple choice question or matching answer), presence of clinical vignette (if so, whether simple or complex), presence of specimen image, information depth (simple recall or interpretation), knowledge density (first or second order), Bloom taxonomy level (1-3), and, for the final, subject familiarity (repeated concept and, if so, whether verbatim). RESULTS.­: Assessments comprised 3 quizzes and 1 final exam (total 125 questions), scored during a 3-year period, (total 417 students) for a total 52 125 graded attempts. Overall, 44 890 attempts (86.1%) were correct. In multivariate analysis, question type emerged as the most significant predictor of student performance, degree of difficulty, and item discrimination, with multiple choice questions being significantly associated with lower mean scores (P = .004) and higher degree of difficulty (P = .02), but also, paradoxically, poorer discrimination (P = .002). The presence of a specimen image was significantly associated with better discrimination (P = .04), and questions requiring data interpretation (versus simple recall) were significantly associated with lower mean scores (P = .003) and a higher degree of difficulty (P = .046). CONCLUSIONS.­: Assessments in medical education should comprise combinations of questions with various characteristics in order to encourage better student performance, but also obtain optimal degrees of difficulty and levels of item discrimination.

Inflammation, Active Fibroplasia, and End-stage Fibrosis in 172 Biliary Atresia Remnants Correlate Poorly With Age at Kasai Portoenterostomy, Visceral Heterotaxy, and Outcome.

Published histologic studies of the hilar plate or entire biliary remnant at the time of Kasai portoenterostomy (KHPE) have not provided deep insight into the pathogenesis of biliary atresia, relation to age at surgery, prognosis or the basis for successful drainage. We report detailed histologic findings in 172 centrally reviewed biliary remnants with an average of 6 sections per subject. Active lesions were classified as either necroinflammatory (rare/clustered in a few subjects) or active concentric fibroplasia with or without inflammation (common). Inactive lesions showed bland replacement by collagen and fibrous cords with little or no inflammation. Heterogeneity was common within a given remnant; however, relatively homogenous histologic patterns, defined as 3 or more inactive or active levels in the hepatic ducts levels, characterized most remnants. Homogeneity did not correlate with age at KHPE, presence/absence of congenital anomalies at laparotomy indicative of heterotaxy and outcome. Remnants from youngest subjects were more likely than older subjects to be homogenously inactive suggesting significantly earlier onset in the youngest subset. Conversely remnants from the oldest subjects were often homogenously active suggesting later onset or slower progression. More data are needed in remnants from subjects <30 days old at KHPE and in those with visceral anomalies. Prevalence of partially preserved epithelium in active fibroplastic biliary atresia lesions at all ages suggests that epithelial regression or injury may not be a primary event or that reepithelialization is already underway at the time of KHPE. We hypothesize that outcome after KHPE results from competition between active fibroplasia and reepithelialization of retained, collapsed but not obliterated lumens. The driver of active fibroplasia is unknown.

Educational Case: A Uterine Neoplasm: Leiomyoma-A Benign Neoplasm.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.

Key Histopathologic Features of Liver Biopsies That Distinguish Biliary Atresia From Other Causes of Infantile Cholestasis and Their Correlation With Outcome: A Multicenter Study.

The liver biopsy guides diagnostic investigation and therapy in infants with undiagnosed cholestasis. Histologic features in the liver may also have prognostic value in the patient with biliary atresia (BA). We assessed the relative value of histologic features in 227 liver needle biopsies in discriminating between BA and other cholestatic disorders in infants enrolled in a prospective Childhood Liver Disease Research Network (ChiLDReN) cohort study by correlating histology with clinical findings in infants with and without BA. In addition, we reviewed 316 liver biopsies from clinically proven BA cases and correlated histologic features with total serum bilirubin 6 months after hepatoportoenterostomy (the Kasai procedure, HPE) and transplant-free survival up to 6 years. Review pathologists were blinded to clinical information except age. Semiquantitative scoring of 26 discrete histologic features was based on consensus. Bile plugs in portal bile ducts/ductules, moderate to marked ductular reaction, and portal stromal edema had the largest odds ratio for predicting BA versus non-BA by logistic regression analysis. The diagnostic accuracy of the needle biopsy was estimated to be 90.1% (95% confidence interval [CI]: 85.2%, 94.9%), whereas sensitivity and specificity for a diagnosis of BA are 88.4% (95% CI: 81.4, 93.5) and 92.7% (95% CI: 84.8, 97.3), respectively. No histologic features were associated with an elevated serum bilirubin 6 months after HPE, although it (an elevated serum bilirubin) was associated with an older age at HPE. Higher stages of fibrosis, a ductal plate configuration, moderate to marked bile duct injury, an older age at HPE, and an elevated international normalized ratio were independently associated with a higher risk of transplantation.

Swallowed Fluticasone Propionate Is an Effective Long-Term Maintenance Therapy for Children With Eosinophilic Esophagitis.

OBJECTIVES: Although effective in the treatment of eosinophilic esophagitis (EoE) in children, limited data exist on long-term safety and efficacy of swallowed topical corticosteroids. We investigated whether long-term use of swallowed fluticasone in children with EoE leads to sustained reduction in esophageal eosinophils, and endoscopic and clinical improvement. METHODS: In an open-label, prospective, single-center study, we offered pediatric patients with active EoE fluticasone 2 puffs to swallow twice a day (strengths in µg/puff: 2-4 years: 44, 5-11 years: 110, ≥12 years: 220). Clinical, endoscopic, and histological assessments were performed at baseline and shortly after therapy. If histological remission was seen, fluticasone was continued with clinical follow-ups every 4 months and endoscopic and histological follow-ups yearly. Clinical scores were derived from eight symptoms (abdominal pain, nausea, vomiting, regurgitation, chest pain, dysphagia, food impaction, and early satiety). Endoscopic scores were derived from six features (rings, exudates, furrows, edema, stricture, and shearing). Scores were expressed as ratio (features present/total). In addition to peak eosinophils/high power field (HPF) (primary outcome), histological features (eosinophilic microabscesses, degranulation, superficial layering, basal zone hyperplasia, dilated intercellular spaces, and lamina propria fibrosis) were assessed. Median clinical and endoscopic scores and individual histologic features were compared over 4 time intervals: <4 months, 4-12 months, 13-24 months, and >24 months. Growth and adverse effects were monitored. RESULTS: We enrolled 54 patients, 80% male, median age 6.5 years (range 2-17 years), 85% atopic (57% asthma, 68% allergic rhinitis, and 31% atopic dermatitis), and 74% with food allergy. Mean follow-up was 20.4 months, the longest being 68 months (5.7 years). Esophageal eosinophil counts significantly decreased (median peak eosinophils/HPF at baseline 72, <4 months: 0.5, 4-12 months: 1.75, 13-24 months: 10, and >24 months: 12, all P<0.01). All histological features significantly decreased from baseline to all follow-up time points (all P<0.01). Lamina propria fibrosis significantly decreased (% patients with fibrosis at baseline 92, <4 months: 41, 4-12 months: 50, 13-24 months: 45, and >24 months: 39, all P<0.01). Endoscopic features improved (score at baseline 0.37, <4 months: 0.17, 4-12 months: 0.17, 13-24 months: 0, and >24 months: 0.1, all P<0.01, except at >24 months: P<0.05). Symptoms improved (score at baseline 0.22, <4 months: 0, 4-12 months: 0.11, 13-24 months: 0.11, and >24 months: 0.11, all P<0.05 except at >24 months: P=0.05). In a mixed linear regression model that accounts for correlation of repeated observations in the patient in a per-patient analysis, we found that treatment with swallowed fluticasone led to a statistically significant and sustained decrease in peak esophageal eosinophil counts. Asymptomatic esophageal candidiasis was seen in three children but resolved with anti-fungal therapy. Height and weight z-scores followed expected growth curves. CONCLUSIONS: We demonstrate that swallowed fluticasone is effective as a long-term maintenance therapy for children with EoE, without growth impediment or serious side effects.

Tissue reaction to porcine intestinal Submucosa (CorMatrix) implants in pediatric cardiac patients: a single-center experience.

BACKGROUND: Decellularized porcine small intestine submucosa (CorMatrix, Atlanta, GA) patches have been used in the repair of congenital heart malformations. Tissue reaction to the material may create hemodynamic dysfunction and necessitate explantation. We reviewed our series of congenital cardiac patients who had a reoperation after the implantation of CorMatrix patches. METHODS: Medical records of pediatric cardiac patient who received CorMatrix patches and those of patients who underwent reoperation were reviewed. Routine histologic sections of explanted CorMatrix specimens were examined. RESULTS: Of 25 patients who had received CorMatrix patches during cardiac operations at our institution, 6 patients had undergone reoperations. All patients had hemodynamically significant lesions at the site of the CorMatrix implantation. Explanted specimens were associated with an intense inflammatory reaction consisting of numerous eosinophils, histiocytes, and plasma cells, with accompanying granulation tissue and fibrosis. CONCLUSIONS: Reaction to implanted CorMatrix patches may cause hemodynamic dysfunction and produce an intense, predominantly eosinophilic inflammatory response with developing fibrosis. Although our report is limited to a small sample of congenital cardiac patients, one should take precautions in its use in pediatric cardiac patients, and long-term follow-up is warranted.

Consensus Guidelines for Practical Competencies in Anatomic Pathology and Laboratory Medicine for the Undifferentiated Graduating Medical Student.

The practice of pathology is not generally addressed in the undergraduate medical school curriculum. It is desirable to develop practical pathology competencies in the fields of anatomic pathology and laboratory medicine for every graduating medical student to facilitate (1) instruction in effective utilization of these services for optimal patient care, (2) recognition of the role of pathologists and laboratory scientists as consultants, and (3) exposure to the field of pathology as a possible career choice. A national committee was formed, including experts in anatomic pathology and/or laboratory medicine and in medical education. Suggested practical pathology competencies were developed in 9 subspecialty domains based on literature review and committee deliberations. The competencies were distributed in the form of a survey in late 2012 through the first half of 2013 to the medical education community for feedback, which was subjected to quantitative and qualitative analysis. An approval rate of ≥80% constituted consensus for adoption of a competency, with additional inclusions/modifications considered following committee review of comments. The survey included 79 proposed competencies. There were 265 respondents, the majority being pathologists. Seventy-two percent (57 of 79) of the competencies were approved by ≥80% of respondents. Numerous comments (N = 503) provided a robust resource for qualitative analysis. Following committee review, 71 competencies (including 27 modified and 3 new competencies) were considered to be essential for undifferentiated graduating medical students. Guidelines for practical pathology competencies have been developed, with the hope that they will be implemented in undergraduate medical school curricula.

Small-bowel allograft biopsies in the management of small-intestinal and multivisceral transplant recipients: histopathologic review and clinical correlations.

CONTEXT: Intestinal transplant has become a standard treatment option in the management of patients with irreversible intestinal failure. The histologic evaluation of small-bowel allograft biopsy specimens plays a central role in assessing the integrity of the graft. It is essential for the management of acute cellular and chronic rejection; detection of infections, particularly with respect to specific viruses (cytomegalovirus, adenovirus, Epstein-Barr virus); and immunosuppression-related lymphoproliferative disease. OBJECTIVE: To provide a comprehensive review of the literature and illustrate key histologic findings in small-bowel biopsy specimen evaluation of patients with small-bowel or multivisceral transplants. DATA SOURCES: Literature review using PubMed (US National Library of Medicine) and data obtained from national and international transplant registries in addition to case material at Columbia University, Presbyterian Hospital, and Mount Sinai Medical Center, New York, New York. CONCLUSIONS: Key to the success of small-bowel transplantation and multivisceral transplantation are the close monitoring and appropriate clinical management of patients in the posttransplant period, requiring coordinated input from all members of the transplant team with the integration of clinical, laboratory, and histopathologic parameters.

The integration of pathology into the clinical years of undergraduate medical education: a survey and review of the literature.

Pathology as a basic science discipline traditionally is a component of the preclinical medical school curriculum. While there have been regional and nationwide surveys reporting on the curricular organization and instructional formats of preclinical pathology instruction, the extent of required pathology integration into the clinical medical school curriculum, particularly as it relates to practical issues of patient management, has not been studied. A survey soliciting information about required pathology programs in the clinical years was distributed to the members of the Undergraduate Medical Educators Section of the Association of Pathology Chairs (APC). A literature search of such programs was also performed. Thirty-seven respondents representing 30 medical schools (21% of the 140 Liaison Committee on Medical Education-accredited medical schools in the APC) described a total of 16 required pathology programs in the clinical years. An additional 10 programs were identified in the literature. Advantages of required pathology activities in the clinical years include educating medical students in effective utilization of anatomic and clinical pathology for patient care and exposing them to the practice of pathology. Reported challenges have been competition for curricular time in the clinical years, attitudinal resistance by clerkship directors, failure to recognize pathology as a clinical discipline, and insufficient number of faculty in pathology departments. By survey sample and literature review, there has been relatively little progress in the integration of required pathology exposure into the clinical years. Development of practice-related pathology competencies may facilitate introduction of such curricular programs in the future.

Cholangiolocellular carcinoma in a pediatric patient with small duct sclerosing cholangitis: a case report.

Although guidelines exist for routine screening for malignancy in adults with primary sclerosing cholangitis, no imaging guidelines exist for the pediatric population. Cholangiolocellular carcinoma is a rare malignant liver tumor that has been found in adults with chronic liver disease. We present a case of cholangiolocarcinoma found in an adolescent boy with small duct sclerosing cholangitis. The diagnosis of small duct sclerosing cholangitis was made at the age of 6 at which time he also had advanced fibrosis histologically, but no evidence of decompensation either clinically or biochemically. Several years after this diagnosis, a small liver lesion was found incidentally on computed tomography scan following a motorcycle accident. This lesion was shown to be stable by magnetic resonance imaging over the course of 2 years. At 15 years of age, magnetic resonance imaging findings changed with features suggestive of malignancy. This led to resection of the lesion. Pathologic examination confirmed the presence of cholangiolocarcinoma, a tumor found primarily in adults with a history of viral hepatitis. To our knowledge, this is the first such report in a pediatric patient.

Atypical presentation of Wilson disease.

A 15-year-old Caucasian female on human chorionic gonadotropin (HCG) diet presented with fever, cholestasis, coagulopathy, hemolytic anemia, and acute renal dysfunction. Imaging of the biliary system and liver were normal. She responded to intravenous antibiotics, vitamin K and blood transfusions but experienced relapse upon discontinuation of antibiotics. She had remission with reinstitution of antibiotics. Liver biopsy revealed pronounced bile ductular reaction, bridging fibrosis, and hepatocytic anisocytosis and anisonucleosis with degenerative enlarged eosinophilic hepatocytes, suggestive of Wilson disease. Diagnosis of Wilson disease was further established based on the low serum ceruloplasmin, increased urinary and hepatic copper and presence of Kayser-Fleischer rings. The multisystem involvement of the liver, kidney, blood, and brain are consistent with Wilson disease; however, the clinical presentation of cholangitis and reversible coagulopathy is uncommon, and may result from concurrent acute cholangitis and/or the HCG diet regimen the patient was on.

Progressive familial intrahepatic cholestasis (PFIC) type 1, 2, and 3: a review of the liver pathology findings.

Progressive familial intrahepatic cholestatic diseases encompass a group of autosomal recessive hereditary diseases, which usually present in infancy or childhood, with cholestasis of hepatocellular origin. The currently preferred nomenclature for the three PFIC disorders that have been characterized to date is FIC1 deficiency, BSEP deficiency, and MDR3 deficiency, relating to mutations in the specific genes involved in bile acid formation and transport. Since the first description of these diseases, extensive clinical, biochemical, and molecular studies have increased our understanding of the features specific to each one of them. This review focuses mainly on the liver histology, summarizing their characteristic pathologic features, the correlation to specific genotypes, and complications arising with disease progression.

Chronic rejection preceded by central perivenulitis, rapidly ensuing after liver transplantation in a pediatric patient.

A 15-year-old boy who underwent liver transplantation for fulminant Wilson's disease, presented with elevated transaminases 2 months post-transplant. He had recently seroconverted from previous Epstein-Barr virus (EBV) naive status and by polymerase chain reaction (PCR) had increasing viral load copies of EBV in blood. A liver biopsy was obtained 6 weeks post-transplant, which showed isolated central perivenulitis (CP). His immunosuppresion was reduced and antiviral therapy was added with subsequent increase in liver transaminases. A second liver biopsy 6 weeks later again showed isolated CP. Subsequent further reduction in immunosuppression was followed by the appearance of portal-based moderate acute cellular rejection that was resistant to immunosuppressive treatment and rapidly evolved into ductopenic chronic rejection. This case report underlines the difficulties in interpreting isolated perivenulitis, especially in the setting of EBV seroconversion, and suggests that it may not only represent a form of acute rejection but also a predictor of rapidly progressing chronic rejection.

Successful split liver-kidney transplant for factor H associated hemolytic uremic syndrome.

BACKGROUND AND OBJECTIVES: A male infant with a family history of thrombotic microangiopathy developed atypical hemolytic uremic syndrome (aHUS). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Case report. RESULTS: Genetic analysis demonstrated a heterozygous mutation (S1191L) of CFH, the gene coding complement factor H (CFH). The child suffered many episodes of HUS, each treated with plasma exchange. In time, despite initiation of a prophylactic regimen of plasma exchange, his renal function declined significantly. At the age of 4 yr he received a (split liver) combined liver-kidney transplant (LKT) with preoperative plasma exchange and enoxaparin anticoagulation. Initial function of both grafts was excellent and is maintained for nearly 2 yr. CONCLUSIONS: This report adds to the small but growing number of individuals in whom LKT has provided a favorable outcome for aHUS associated with CFH mutation, expands the technique of using a split liver graft, and describes the unique histologic features of subclinical liver disease in HUS.

Esophageal subepithelial fibrosis in children with eosinophilic esophagitis.

OBJECTIVES: Esophageal subepithelial fibrosis has been reported in adults with eosinophilic esophagitis (EE). Our goal was to determine the prevalence of esophageal fibrosis in children with EE, to determine whether it is specific for EE, and to correlate it with clinical and pathological features. PATIENTS AND METHODS: Twenty-one children with EE, 7 with eosinophilic gastroenteritis, 6 with gastroesophageal reflux disease, and 17 control children were studied. Distal esophageal biopsy specimens containing lamina propria were evaluated for extent of subepithelial collagen deposition by use of trichrome staining. Fibrosis was defined as abnormally increased collagen deposition, determined after the establishment of normal patterns on sections of esophagus from pediatric autopsies. Maximum numbers of intraepithelial and lamina propria eosinophils per high-power field by hematoxylin and eosin staining and mast cells per high-power field by immunohistochemical staining for tryptase were determined. Eosinophil and mast cell degranulation in epithelium and lamina propria was determined by use of immunohistochemical staining for major basic protein and tryptase, respectively. The patients' records were reviewed. RESULTS: Esophageal subepithelial fibrosis was present in 12 (57%) patients with EE, 1 with eosinophilic gastroenteritis, 0 with gastroesophageal reflux disease, and 1 control patient. Forty-two percent of those with fibrosis had dysphagia, 80% of whom had food impactions; these symptoms were present only in patients with fibrosis. Within the EE group, fibrosis was not associated with duration of symptoms or with increasing numbers of infiltrating eosinophils/mast cells, but it was associated with eosinophil degranulation. CONCLUSIONS: Esophageal subepithelial fibrosis is prevalent in EE and is specific for the disease in children. It is associated with dysphagia, and it may explain and predict future esophageal dysmotility. Fibrosis is related to the extent of esophageal eosinophil activation, as evidenced by eosinophil degranulation.