Congenital mesoblastic nephroma: a study of 19 cases using immunohistochemistry and ETV6-NTRK3 fusion gene rearrangement.

Mesoblastic nephroma (MN) is the most common renal tumour in the first 3 months of life and accounts for 3-5% of all paediatric renal neoplasms. To further understand the morphological variants of MN, we identified 19 cases of MN (five classic, eight cellular and six mixed) and examined each case for markers known to be important in urogenital embryological development (PAX8, WT1 and RCC), stem cell associated markers (Oct 4, CD34 and c-kit), muscle/myofibroblastic markers (muscle specific actin, calponin and h-caldesmon), aberrant transcription factors, cell cycle regulation and other oncogenic proteins (p16, cyclin D1 and beta-catenin). Fluorescence in situ hybridisation (FISH) testing for ETV6-NTRK3 gene fusion/rearrangement revealed further differentiation between the subtypes with ETV6-NTRK3 gene fusion detected in 0/5 of the classic MN, 8/8 of the cellular MN and 5/6 of the mixed MN cohorts, respectively. Our results conclude that cyclin D1 and beta-catenin may be useful markers for differentiating between cellular MN and classic MN when the histology is not conclusive. The absence of expression of stem cell markers and markers involved in urogenital development suggests that MN is not a nephroma and most likely represents a soft tissue tumour, with congenital infantile fibrosarcoma representing cellular MN with a predilection to arise in the kidney. In addition, the immunophenotype and genetic fingerprint of mixed MN most likely represents a heterogenous group of tumours that are mostly cellular type, with areas that are phenotypically less cellular.

Does MAP2 have a role in predicting the development of anti-NMDAR encephalitis associated with benign ovarian teratoma? A report of six new pediatric cases.

Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a potentially fatal neurologic syndrome in which patients present with a spectrum of central nervous system deficits. Sixty percent of the cases can be attributed to the presence of tumors, most often ovarian teratomas. This report examines 6 pediatric patients who presented with neurologic deficits associated with the presence of such tumors. These cases illustrate a perplexing phenomenon, where benign teratomas could have a possible association with anti-NMDAR encephalitis. The purpose of this study was to compare the histology and immunohistochemistry of tumors associated with this syndrome to ovarian teratomas found in patients presenting with no neurologic symptoms. After obtaining institutional review board approval, 57 cases of ovarian teratomas were identified at our institution over 12 years. Six patients were identified with anti-NMDAR encephalitis. A panel of immunostains, including S100, GFAP, MAP2, and NeuN was applied to patients' tumor sections as well as the 6 controls from age-matched patients. No qualitative histologic or immunohistochemical differences were seen between the study cases and control group. Because no qualitative differences were identified between the study cases and the control group, testing of paired serum and cerebrospinal fluid remains the best method for diagnosis of anti-NMDAR encephalitis. Tumor banking with molecular analysis of ovarian teratomas, including whole-genome sequencing and comparative genomic hybridization between ovarian tissue saved from patients with and without anti-NMDAR encephalitis, is necessary to fully understand the etiopathogenesis of anti-NMDAR encephalitis.

Xeroderma pigmentosa: three new cases with an in depth review of the genetic and clinical characteristics of the disease.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by hypersensitivity of the skin and eyes to UV-radiation as a result of a defect in one of eight genes. Seven genes (XPA-XPG) have a defect in Nucletoide Excision Repair (NER), while the eighth gene XPV has a defect in polymerase η, which is responsible for replication of UV-damaged DNA to produce corrected daughter strands. We present the varied clinical courses of three African-American female patients with XP. Additionally, we present a review of the literature that focuses on the various clinical manifestations as well as the genetic and molecular mechanisms underlying this disease.

Noniatrogenic neonatal gastric perforation: the role of interstitial cells of Cajal.

Noniatrogenic neonatal gastric perforation is a rare and life-threatening condition whose etiology is often unclear. Interstitial cells of Cajal act as gastrointestinal pacemaker cells and express the proto-oncogene c-Kit. Six new cases were identified at our institution which presented with no mechanical, pharmacologic, or otherwise medical-related intervention prior to rupture. The number of interstitial cells of Cajal in nonnecrotic muscularis propria from five random high-power fields per specimen was compared using immunohistochemical stains for c-Kit. The authors show that a lack of interstitial cells of Cajal in the stomach musculature may be implicated in the development of noniatrogenic gastric perforation (p = 0.008). Further large-scale studies, including molecular and genetic analysis, may help to better understand this phenomenon.

Epstein-Barr virus associated smooth muscle tumors in post transplant pediatric patients two cases of rare locations, and review of the literature.

Epstein-Barr virus (EBV) may present few or no symptoms in immunocompetent individuals; however, in immunocompromised patients as in the case of AIDS and post-transplant patients, the virus occasionally stimulates neoplastic transformations. Epstein-Barr virus may play a role in the development of smooth muscle tumors (SMT). In the case of Epstein-Barr associated smooth muscle tumors (EBV+SMT), the virus is thought to be the leading factor to the tumorigenic pathway. We report two pediatric patients (6 and 13 years old) who underwent liver transplantation and developed EBV+SMT in the colon and orbit. These two cases represent rare locations for this kind of lesion.

The spectrum of pulmonary malformation in trisomy-21 patient. A review with emphasis on the molecular-genetic basis.

Gene overexpression has been identified as a primary determining factor for the distinct Down syndrome (DS) phenotypes. Previous genetic research has identified a spectrum of gene expressions responsible for many of the observed traits in DS patients including cardiovascular, brain, and GI anomalies. However, the molecular/genetic basis underlying pulmonary anomalies are yet to be identified, even though respiratory complications represent the leading cause of morbidity and mortality in DS patients. In this article, we will discuss the Etiopathogenesis and spectrum of pulmonary anomalies in DS patients.

Unusual presentation of extracardiac fetal rhabdomyoma of the larynx in a pediatric patient with tuberous sclerosis.

Tuberous sclerosis (TSC) is an autosomal-dominant genetic disease characterized by a spectrum of pathologic manifestations involving skin, brain, kidney, and heart. These manifestations include neuroectodermal, mesodermal, and skin lesions as well as a variety of associated tumors and hamartomas. We report an 11-year-old male with previously diagnosed TSC who presented with a laryngeal mass shown on histology to be fetal cellular rhabdomyoma. Cardiac rhabdomyomas are common in TSC patients, but to our knowledge, the association between TSC and extracardiac rhabdomyomas has not been previously reported.

Usefulness of OCT4/3 immunostain in pediatric malignant germ cell tumors.

Octamer4/3 is a POU transcription factor that regulates pluripotentiality in embryonic stem and germ cells and primordial germ cells. When expressed in post-embryonic life, Octamer4/3 may lead to malignant germ cell tumors (GCT). Thirty samples were selected for this study (26 GCT samples and 4 cryptorchid testes samples) and 16 non-GCT were used as controls. Samples were stained with an anti-Octamer4/3 antibody. All cases of GCT were positive for Octamer4/3, and the non-GCT were negative. This article focuses on pediatric populations where we found that Octamer4/3 immunostaining is a useful diagnostic tool in undifferentiated pediatric tumors.

Nephrogenic rest within a lipomyelomeningocele in a patient with unilateral renal agenesis.

Nephrogenic rests (NR) are foci of embryonal renal tissue that persist beyond the normal period of renal morphogenesis. They are commonly found in kidneys bearing Wilms tumor but may also rarely occur in different locations. Nephrogenic rests have been reported in the lumbosacral area in a total of nine cases, including our case. Of the nine cases, only one case prior to ours showed agenesis of one kidney in association with the NR. We report a 2-year-old female with a lipomyelomeningocele containing NRs and agenesis of the right kidney and discuss the molecular genetic basis of lumbosacral NR.