Juvenile Xanthogranuloma of the Pancreas in a Pediatric Patient Mimicking Pancreatic Neoplasm With High CA 19-9: Case Report and Literature Review.

Juvenile xanthogranuloma (JXG) is a rare, non-Langerhans cell histiocytosis. It is usually a benign and self-limiting condition. The most common sites are skin and soft tissue. Pancreatic involvement is extremely rare. We present an unusual case of a 13-month-old female child with JXG of the pancreas and elevated cancer antigen 19-9. JXG should always be considered as a differential diagnosis for pediatric patients presenting with a pancreatic mass, solid and/or cystic in nature. Therefore, avoiding unnecessary invasive diagnostic procedures.

Giant Anal Fibroepithelial Polyp in a Healthy Teenage Boy: A Case Report and Literature Review.

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.

Histopathology of the Conduction System in Long QT Syndrome.

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.

Chronic Recurrent Multifocal Osteomyelitis (CRMO): A Study of 12 Cases from One Institution and Literature Review.

BACKGROUND: 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. MATERIALS AND METHODS: The medical records and histopathological slides of twelve patients were reviewed. RESULTS: 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. CONCLUSION: 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.

Revisiting the Newly Modified Criteria for Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (ARVC/D) and Reporting Newly Identified Genes.

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.

Five New Cases of Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome (MMIHS), with One Case Showing a Novel Mutation.

BACKGROUND: Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a lethal congenital disorder characterized by a large, non-obstructed bladder, microcolon, and lack of proper peristalsis. MATERIALS AND METHODS: Five cases of MMIHS were identified, confirmed histologically and were predominantly female (F:M, 4:1). DNA sequencing was also performed. RESULTS: Four cases showed mutations in the α3 and ß4 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. CONCLUSION: 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.

Calcineurin inhibitors and renal biopsy in children with idiopathic nephrotic syndrome.

Idiopathic nephrotic syndrome (NS) is common in children, and most patients respond to corticosteroid therapy. Patients who relapse may need additional immunosuppression with cyclophosphamide, mycophenolate mofetil, calcineurin inhibitors (CNI), or rituximab. Many such patients undergo protocol renal biopsies before and after the initiation of CNI therapy. The main objective of our study was to assess the role of protocol renal biopsies in the monitoring of CNI-induced nephrotoxicity in patients with steroid-dependent (SD)/frequent relapse (FR) NS. We did an Institutional Review Board (IRB)-approved retrospective chart review of patients who were diagnosed with NS at the Children's Hospital of Michigan from January 2000 to June 2019. Study inclusion criteria were a diagnosis of NS, age 1 - 21 years at initial diagnosis, SD/FR clinical course, patients with initial steroid resistance with renal biopsy showing minimal change disease, and renal biopsy before and after CNI initiation. The data is presented on 24 patients who met study inclusion criteria. Only 3 patients (12.5%) showed evidence of chronic CNI nephrotoxicity after a median treatment 66.5 months (range 12 - 153 months). Our study revealed that a baseline renal biopsy before starting CNI therapy for children with FR/SDNS is not necessary. A renal biopsy may be considered after 2 - 3 years of CNI administration in selected few cases in whom the diagnosis of CNI nephrotoxicity might help change the management.

Correlation Between E6 and E7 Oncogenes and Malignant Transformation of Laryngeal Papillomatosis (LP) with Human Papillomavirus (HPV) in Pediatric Population.

INTRODUCTION: Laryngeal papillomatosis (LP) is the most common benign neoplasm affecting the upper respiratory tract mucosa in children. The most common genotypes of HPV associated with LP are types 6 and 11. Methods: Among 187 patients identified in our institution with LP, four cases showed malignant transformation to invasive squamous carcinoma. Results: These patients had tumors with HPV viruses that showed high expression of oncogene E6 and E7 and low expression of E2. Conclusion: Malignant transformation of LP is associated with oncogenic expression of E6 and E7.

Pediatric Right Ventricular Cardiac Steatosis following Immunosuppressive Treatment.

Background Right ventricular myocardial fatty infiltration has been observed in pediatric cardiac allografts with an associated decrease in graft life expectancy. A possible explanation included an immunosuppressant drug effect which prompted us to examine common factors between non-cardiac transplanted immunosuppressed patients and postmortem hearts of pediatric patients who died of non-cardiac causes.Materials and Methods Sixty-one of 1,030 pediatric autopsies were from immunosuppressed children who were treated with corticosteroids for malignant tumors, non-cardiac transplantations, or other chronic clinical conditions. 62 children who died for non-medical reasons served as controls. Cardiac H&E autopsy slides were examined for right ventricular fatty infiltration.Results There was a significant increase in right ventricular fatty infiltration in patients that were non-cardiac transplanted and immunosuppressed compared to controls. None of the index patients had other features of arrhythmogenic right ventricular dysplasia.Conclusions Immunosuppression may lead to right ventricular fatty infiltration in childhood.

Cardiac Magnetic Resonance Imaging Macroscopic Fibro-Fatty Infiltration of the Myocardium in Pediatric Patients with Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia.

Background: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited, progressive form of cardiomyopathy, which is characterized by fibrofatty replacement of the myocardium. While the gold standard for diagnosis remains pathologic evaluation of biopsy, advances in noninvasive imaging, including cardiac magnetic resonance imaging (CMRI), have led to improved clinical diagnosis.Case report: We report three additional cases of pediatric patients that have pathologically confirmed ARVC/D with CMRI images, demonstrating extensive macroscopic fatty infiltration of the right and left ventricular myocardium. The identification using CMRI allowed timely transplantation and patient survival.Conclusion: Our study is designed to highlight how fibrofatty changes are minimal using CMRI in the pediatric population and how this can be a valuable tool to provide an additional method of diagnosis.

Monozygotic twins with neuroblastoma MS have a similar molecular profile: a case of twin-to-twin metastasis.

Fetoplacental neuroblastoma metastasis has been postulated as a mechanism accounting for concordant cases where one twin develops a primary tumour and the second twin manifests the disease without an identifiable primary site. These tumours may originate and spread concomitantly due to the same genetic background shared by monozygotic twins. This study investigated the molecular profile of stage MS neuroblastoma presenting concomitantly in monozygotic twins. Comparative genomic hybridisation (aCGH) was done for each of the twin liver tumour and peripheral blood samples at diagnosis. Comparison of copy-number variation (CNV) regions revealed a set of CNVs that were common to both tumour specimens and not apparent in the blood. The CNV signature in both twins' tumours was highly similar, suggesting a common clonal origin. Additional findings included large deletion of chromosome 10 and amplification of chromosome 17. Notably, both liver samples had amplification of a short region involving DEIN (chromosome 4q34.1). Similar CNVs strongly support a common clonal origin and metastatic spread from one twin to the other. DEIN is a long-coding RNA (IncRNA) that has been found highly expressed in stage MS neuroblastoma and is likely involved in biological processes such as cell migration and metastasis.

Syncytial Variant Nodular Sclerosis Classical Hodgkin Lymphoma in an Adolescent and Review of the Literature: A Unique Entity.

Syncytial variant of nodular sclerosis (SV-NS) classical Hodgkin lymphoma (cHL) with its histologic features and clinical presentation is uncommon in adults and extremely rare in children. Here, we report a female teenager presenting with long-standing B symptoms, prominent soft tissue and bone involvement mimicking sarcoma and significant nodal disease who is diagnosed with advanced SV-NS cHL. Rare Reed-Sternberg-like cells displaying neutrophil and erythrocyte emperipolesis were seen on bone marrow aspiration slides. Despite initial complete response to chemotherapy and radiotherapy, the patient experienced early relapse suggestive of high-risk biology. This variant may constitute a unique entity.

Intravascular Papillary Endothelial Hyperplasia in the Coronary Artery: An Unusual Cause of Massive Myocardial Infarction in Hypoplastic Left Heart Syndrome.

Background: Intravascular papillary endothelial hyperplasia (IPEH) is a benign vascular lesion that usually involves the head and neck or extremities. Involvement of the coronary arterial system is unreported. Case: A 1-month-old patient born with hypoplastic left heart syndrome died from a massive myocardial infarction shortly after first stage palliation with Norwood/Sano. Autopsy demonstrated a massive univentricular hemorrhagic infarction with complete occlusion of the left main coronary artery and its intramural branches by intraluminal papillary endothelial hyperplasia (IPEH). Immunostaining with CD34 and CD31 confirmed the diagnosis. The inferior and superior mesenteric artery branches also had IPEH. Conclusion: IPEH can involve the coronary vasculature, can be multifocal and can occur in the newborn.

The Protean Neuropsychiatric and Vestibuloauditory Manifestations of Neurosarcoidosis.

BACKGROUND: A rare subset of sarcoidosis, neurosarcoidosis, is reported to occur in 5-7% of sarcoid patients and can manifest in a variety of ways. The most common are facial paralysis and optic neuritis, less commonly causing cochleovestibulopathy, blindness, anosmia, and other cranial nerve (CN) palsies. The sensory deficit may be severe and psychiatric symptoms may result from the effects of the disease or steroid treatment. Although MRI-compatible cochlear implants are now available, concerns about the feasibility of recoverable hearing with cochlear implantation in these patients as well as the practical difficulty of disease monitoring due to implant artifact must be considered. RESULTS: We present 3 recent cases from different institutions. The first is a 39-year-old man with a history of progressively worsening hearing loss, followed by visual loss, delusions, agitation, ataxia, and musical auditory hallucinations, diffuse leptomeningeal enhancement on MRI with a normal serum angiotensin-converting enzyme (ACE) level but elevated cerebrospinal fluid (CSF) ACE levels, suggesting neurosarcoidosis, was treated with corticosteroids, and underwent successful cochlear implantation. The second is a 36-year-old woman with rapid-onset horizontal diplopia, left mixed severe sensorineural hearing loss (SNHL) and tinnitus, diffuse leptomeningeal enhancement on MRI, and progressive palsy of the left CNs IV, VI, VII, IX, X and XI, with altered mental status requiring admission following high-dose intravenous corticosteroids. The third is a 15-year-old boy who presented with sudden, bilateral, profound SNHL, recurrent headaches, and left facial weakness refractory to antivirals, ultimately diagnosed with neurosarcoidosis following an aborted cochlear implantation where diffuse inflammation was found, and histopathology revealed Schaumann bodies; he was treated with methotrexate and later underwent successful cochlear implantation. CONCLUSIONS: Neurosarcoidosis is an elusive diagnosis and can cause hearing loss and psychiatric symptoms. Cochlear implantation for patients with severe hearing loss should be considered once the diagnosis is confirmed, as it is possible to achieve a successful level of hearing. Psychiatric symptoms can manifest with the onset of neurosarcoidosis, result from CN deficits, or develop as a side effect from long-term, high-dose corticosteroids, and should be monitored carefully in patients with neurosarcoidosis.

Concomitant Use of Panobinostat and Reirradiation in Progressive DIPG: Report of 2 Cases.

Diffuse intrinsic pontine glioma (DIPG) remains a devastating disease. Panobinostat has been shown to have therapeutic efficacy both in vitro and in DIPG orthotopic xenograft models; however, clinical data in patients with DIPG are lacking. We present 2 cases of DIPG, who were treated with panobinostat at 22 to 25 mg/m/dose, 3 times weekly for 2 weeks in 3-week cycles and concomitant reirradiation after disease progression. Two episodes of asymptomatic thrombocytopenia were observed in 1 patient. Hyperacetylation of histone H4 of peripheral blood mononuclear cells was evident following treatment. In our experience, panobinostat administered with reirradiation was well tolerated at a relatively higher dose than that used in adult studies.

Diffuse intrinsic pontine glioma biopsy: a single institution experience.

Tumor biopsy is rarely performed in diffuse intrinsic pontine glioma (DIPG) due to the presumed risk of surgical complications, although data on the surgery related morbidity of DIPG biopsy is sparse. We performed a retrospective review on 22 consecutive cases of DIPG diagnosed from 2002 to 2012 at Children's Hospital of Michigan, 15 of which underwent biopsy. Transient new or worsening neurological deficits were observed in three of 15 cases following surgery. No surgery related mortality or permanent deficit was observed, and the mean overall survival was 10.4 ± 3.8 months. Undergoing biopsy did not adversely affect the outcome.

Passage of decidual cast following poor compliance with oral contraceptive pill.

BACKGROUND: Decidual cast describes the spontaneous sloughing of endometrium as an entire piece while retaining the shape of the endometrial cavity. It may be associated with increased serum progesterone levels and must be considered as a differential diagnosis in a patient who passes tissue per vagina while on progesterone containing hormonal contraception. CASE: A 13-year-old adolescent with a history of menorrhagia since menarche, presented to the pediatric emergency room with worsening abdominal pain and heavy vaginal bleeding stopping her oral contraceptive pill 10 days prior to presentation. Her symptoms resolved spontaneously following passage of tissue per vagina which was later by histopathology to be a decidual cast. CONCLUSION: Decidual cast is a rare pathological entity that may be a side effect of progesterone-containing hormonal contraceptives, requiring patient education before use.