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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.

Hirschsprung disease (HD) is characterized by circumferential aganglionosis of the rectum with variable proximal bowel involvement. The underlying pathogenesis is due to failure of caudal migration of neural crest cells during pre-natal development, causing functional bowel obstruction. Definitive therapy is surgical resection; however, a subset of patients will require reoperation. An important cause of reoperation is the rare but distinct entity described as the ganglion cell "vanishing" phenomenon. In this phenomenon, affected patients have normal circumferential ganglion cells present at the proximal margin during primary resection. They undergo a variable asymptomatic period post-primary resection but ultimately develop recurrent symptoms. Upon reoperation, ganglion cells seemingly vanish and are no longer present in the previously functioning and ganglionated bowel proximal to the initial anastomotic site. To further characterize and investigate this poorly understood pathology, here we present 2 cases of HD patients who required reoperation. Our small series implicates that an immune component may contribute as patient 2 had a brisk neurotrophic eosinophilic infiltrate only present in the reoperation specimen. However, this was not observed in patient 1. Other possible etiologies include post-operative ischemia/hypoxia, visceral neuropathy, or signaling abnormalities within the residual ganglion cells themselves. [ABSTRACT FROM AUTHOR]

Background: While much is known about the channelopathy disorder Long QT Syndrome (LQTS), the histopathological findings and their implications on the disease have remained largely unexplored to date. In this review, we discuss the background of LQTS and highlight the importance of histological findings in the absence of genetic markers or when genetic testing is unavailable.Materials and methods: Three pediatric cases of LQTS were identified, evaluated histologically, and compared to two adult cases.Results: Histological examination of three pediatric LQTS patients demonstrated fibrotic alterations to the cardiac conduction system with markedly decreased conductive tissue density and volume. Both adult cases revealed fibrosis with similar reductions in tissue volume.Conclusion: When diagnostic methods such as genetic testing are unavailable, histopathology offers clinicians an alternative tool for postmortem diagnosis of LQTS when considered alongside clinical presentation. Confirmation of diagnosis in a proband can prevent the death of relatives in hereditary LQTS. [ABSTRACT FROM AUTHOR]

Background: Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia is an inherited cardiomyopathy, characterized by replacement of the RV muscle wall with fibrofatty tissue. The diagnosis is challenging, due to the absence of a unique presentation and a lack of specific reproducible diagnostic criteria. Materials and methods: Slides and additional clinical information including follow up from 16 cases were reviewed. Pediatric criteria of >30% of muscle replacement was used, instead of >40% as used in adults. Results: All 16 cases were confirmed by genetic testing and show ARVC/D. Applying the adult criteria, 7 cases would not have been categorized as ARVC/D. Conclusion: The modified pediatric criteria for ARVC/D should be used for pediatric patients. Better detection will aid in genetic counseling in order to identify those additional family members susceptible to sudden cardiac deaths so they can be followed optimally. [ABSTRACT FROM AUTHOR]

Background: Urothelial rests, also known as Walthard rests, are benign nests of epithelial cells that most often are found in the female gynecologic tract. Only four of these urothelial rests have been described in the appendix. Case report: A 10-year-old female underwent an appendectomy for appendicitis. Histologically, there was acute appendicitis, and an incidental urothelial rest was identified, confirmed by immunostains positive for p63, CK7, and negative for synaptophysin. CD34 highlighted a rim of endothelial cells. Conclusion: Urothelial rests, which often appear in the female gynecologic tract, can occur in other sites such as the appendix. These benign lesions require differentiation from neuroendocrine lesions. The rim of endothelial cells in our report supports a vascular migrational origin. [ABSTRACT FROM AUTHOR]

CRMO is a sterile auto inflammatory bone disease that affects the pediatric population. Recently, single gene mutations in LPIN2, DIRA, and IL1RN have been reported in murine models of CRMO. The medical records and histopathological slides of twelve patients were reviewed. The diagnosis was determined by multiple lesions, imaging, negative cultures, bone biopsy, and lack of antibiotic response. Biopsy showed early neutrophilic infiltrates, and older lesions showed lymphoplasmacytic infiltrates and fibrosis. Patients were treated with anti-inflammatory medication with some lesions completely resolving. Bone biopsy aids the diagnosis of CRMO in correlation with clinical presentation, imaging, and culture findings. Our findings indicate the kinetics of CRMO is not well defined and the fibrosis may be reached after months, in contrast to the previously reported several years. We hope that these genetic mutations can be further studied in human models to describe the genetics behind CRMO. [ABSTRACT FROM AUTHOR]

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a lethal congenital disorder characterized by a large, non-obstructed bladder, microcolon, and lack of proper peristalsis. Five cases of MMIHS were identified, confirmed histologically and were predominantly female (F:M, 4:1). DNA sequencing was also performed. Four cases showed mutations in the α3 and β4 nicotinic acetylcholine receptor (ηAChR) subunits (CHRNA3 and CHRNB4, respectively) on chromosome 15q24. The 5th case had a delayed clinical presentation of intussusception at 11 months and showed a novel missense mutation in ATP2B4 on Chromosome 1q32. The first four patients showed a previously identified mutation. The 5th patient shows a novel mutation in ATP2B4. This novel gene was associated with a less severe presentation and increases success of multiorgan transplant than the other four patients. This highlights how identifying various mutations may impact prognosis and clinical treatment plans for MMIHS patients. [ABSTRACT FROM AUTHOR]

Background: Fibroepithelial polyps of the anus have been described as mucosal hypertrophy in response to chronic irritation or tissue damage. Lesions usually remain small and mostly present in elderly adults with local disease. Case Report: An otherwise healthy 15-year-old male presented with a giant pedunculated mass projecting out of the anal verge that enlarged over 2 years, causing discomfort. Results: Upon surgical excision and histologic examination, the mass resembled a fibroepithelial polyp with numerous dilated lymphatics. Conclusions: While literature describes the spectrum of pathology possible in such lesions, often consisting of a mixture of stromal and epithelial components, dilated lymphatics are less common. This giant anal fibroepithelial polyp characterized by edematous stroma and numerous dilated lymphatics is consistent with lymphangioma. To our knowledge, this presentation is novel in this age group with no underlying risk factors. [ABSTRACT FROM AUTHOR]