Acquired Esophageal Strictures in Children: Morphometric and Immunohistochemical Analyses.

BACKGROUND: Esophageal strictures (ES) in children are not well characterized pathologically. We report unique histopathologic analyses of resected acquired ES and control esophagi (CE). METHODS: Muscle layer thicknesses were measured in intact well-oriented areas; inflammatory cells were counted in the most inflamed high power field (hpf). Sections were stained with relevant antibodies. Results were expressed as median, lower and upper quartiles. Wilcoxon Rank Sums non-parametric test was used to compare groups; P ≤ 0.05 was considered significant. RESULTS: All ES (N = 10) showed focal replacement of lamina propria, muscularis mucosa and submucosa by actin+ fibers emanating from muscularis propria. Compared to CE (N = 8), ES displayed significantly thickened muscularis mucosa and propria, and increased mast cells (tryptase- and chymase-positive), and eosinophils in muscle layers (all P ≤ 0.01). Matrix proteins periostin and fibronectin were identified in the muscle layers of CE, and in the extracellular matrix in areas of disrupted architecture in ES. CONCLUSIONS: Compared to CE, acquired ES in children show significant structural alterations, including obliterative muscularization, inflammatory cell mural infiltrates, and extracellular matrix protein deposits. Therapies targeting connective tissue expansion, mast cells, eosinophils and inflammation may be beneficial to treat ES.

Gardner Fibroma: Clinical and Histopathologic Implications of Germline APC Mutation Association.

The proportion and clinical characteristics of Gardner fibromas (GAFs) that are sporadic versus familial adenomatous polyposis (FAP)-associated have not been clearly established. We report on 7 patients diagnosed with GAF who underwent APC sequencing and duplication/deletion testing. Three (43%) were found to have underlying APC germline perturbations consistent with FAP; these patients had multifocal (1) or large; unresectable (2) GAFs. The 4 patients with negative APC testing each had a single resectable GAF. ß-catenin reactivity was noted in all FAP-associated GAFs and in 1/4 APC wild-type cases. FAP-associated GAFs may be less common than sporadic GAFs and can demonstrate clinically distinct features.

DICER1 Mutations and Differentiated Thyroid Carcinoma: Evidence of a Direct Association.

CONTEXT: DICER1 germline mutation carriers have an increased predisposition to cancer, such as pleuropulmonary blastoma (PPB) and Sertoli-Leydig cell tumor (SLCT), and a high prevalence of multinodular goiter (MNG). Although differentiated thyroid carcinoma (DTC) has been reported in some DICER1 mutation carriers with PPB treated with chemotherapy, the association of DTC with DICER1 mutations is not well established. CASE DESCRIPTION: We report a family with DICER1 mutation and familial DTC without a history of chemotherapy. A 12-year-old female (patient A) and her 14-year-old sister (patient B) presented with MNG. Family history was notable for a maternal history of DTC and bilateral ovarian SLCT. Both sisters underwent total thyroidectomy. Pathological examination showed nodular hyperplasia and focal papillary thyroid carcinoma within hyperplastic nodules. Subsequently, patient A developed virilization secondary to a unilateral ovarian SLCT. During her evaluation, an incidental cystic nephroma was also found. Three other siblings had MNG on surveillance ultrasound examination; two had thyroidectomies, and one had two microscopic foci of papillary carcinoma. Patient A, her mother, and four affected siblings had a germline heterozygous pathogenic DICER1 mutation c.5441C>T in exon 25, resulting in an amino acid change from p.Ser1814Leu of DICER1. Somatic DICER1 RNase IIIb missense mutations were identified in thyroid nodules from three of the four siblings. CONCLUSIONS: This family provides novel insight into an emerging phenotype for DICER1 syndrome, with evidence that germline DICER1 mutations are associated with an increased risk of developing familial DTC, even in the absence of prior treatment with chemotherapy.

Idiopathic Facial Aseptic Granuloma: Review of an Evolving Clinical Entity.

Idiopathic facial aseptic granuloma (IFAG), originally termed pyodermite froide du visage, describes a generally asymptomatic facial nodule presenting in childhood with clinical resemblance to pyoderma or cystic, granulomatous, or vascular lesions. Clinical understanding is constantly evolving, with recent observations indicating that IFAG may represent a subtype of childhood rosacea. We present a case of IFAG associated with eyelid chalazions in a 19-month-old boy. Although his clinical course paralleled previously reported IFAG cases, we observed a unique ultrasound variation during initial diagnostic examination. Further delineation of clinical, imaging, and histologic properties of IFAG may reveal insights into etiologic associations and ideal management.

Pharmacokinetics, antitumor and cardioprotective effects of liposome-encapsulated phenylaminoethyl selenide in human prostate cancer rodent models.

PURPOSE: Cardiotoxicity associated with the use of doxorubicin (DOX), and other chemotherapeutics, limits their clinical potential. This study determined the pharmacokinetics and antitumor and cardioprotective activity of free and liposome encapsulated phenyl-2-aminoethyl-selenide (PAESe). METHODS: The pharmacokinetics of free PAESe and PAESe encapsulated in liposomes (SSL-PAESe) were determined in rats using liquid chromatography tandem mass-spectrometry. The antitumor and cardioprotective effects were determined in a mouse xenograft model of human prostate (PC-3) cancer and cardiomyocytes (H9C2). RESULTS: The encapsulation of PAESe in liposomes increased the circulation half-life and area under the drug concentration time profile, and decreased total systemic clearance significantly compared to free PAESe. Free- and SSL-PAESe improved survival, decreased weight-loss and prevented cardiac hypertrophy significantly in tumor bearing and healthy mice following treatment with DOX at 5 and 12.5 mg/kg. In vitro studies revealed PAESe treatment altered formation of reactive oxygen species (ROS), cardiac hypertrophy and gene expression, i.e., atrial natriuretic peptide and myosin heavy chain complex beta, in H9C2 cells. CONCLUSIONS: Treatment with free and SSL-PAESe exhibited antitumor activity in a prostate xenograft model and mitigated DOX-mediated cardiotoxicity.

Myocardial infarction due to a retained epicardial pacing wire.

A 20-year-old man with a temporary epicardial pacing wire retained after infant repair of an atrioventricular septal defect presented with cardiopulmonary arrest. After resuscitation with extracorporeal membranous oxygenation, a coronary angiogram demonstrated a retained epicardial pacing wire compressing the left anterior descending artery and obtuse marginals. Owing to poor prognostic findings on a computed tomography scan of his head, he was terminally withdrawn from mechanical support. This case demonstrates a potential devastating complication of a retained temporary epicardial pacing wire.

Fatal neurotoxic response to neuroleptic medications: case report and review of the literature.

Neuroleptic malignant syndrome (NMS) is a diagnosis of exclusion difficult to make due to a lack of pathognomonic features. Diagnosing NMS by postmortem examination becomes increasingly challenging when possible underlying brain pathology is obscured. The diagnosis is based on clinical history and laboratory findings. Autopsy and histologic findings, if any, usually are reflective of hyperthermia or complications (eg, aspiration pneumonia) of NMS. The authors describe a case of a 36-year-old Hispanic woman with a presumptive diagnosis of pseudoseizures, treated with various combinations of neuroleptic medications over a 6-week period prior to her sudden, unexpected, in-hospital death. Neuroleptic malignant syndrome is likely to have contributed to this patient's death. Confounding factors and medicolegal issues of a postmortem diagnosis of NMS are discussed.

Fatal birth trauma due to an undiagnosed abdominal teratoma: case report and review of the literature.

The fetus is subjected to mechanical forces during labor and delivery, which may result in traumatic injuries. Such injuries include intracranial hemorrhage, spinal cord lesions, cephalhematoma, cranial or peripheral nerve palsies, intraabdominal organ rupture, or bony fractures. Risk for perinatal trauma and mortality is increased in primigravidas, multiple gestations, abnormal presentations, maternal-fetal disproportion, oligohydramnios, forceps or vacuum extractions, and internal version maneuvers. Very-low-birth-weight neonates (<1500 g) are at high risk due to ease of deformity of the cranium. Infants with certain congenital anomalies or pathologic processes that distort normal anatomy are also at increased risk, especially when a prenatal diagnosis is lacking. The authors present a case of a term gestation neonate who sustained a cervical spine dislocation fracture of C5-7, with subtotal transection of the spinal cord and resultant paralysis. The fetus was in vertex presentation, and a manual vaginal delivery was attempted. When the infant lodged in the birth canal following a difficult delivery of the head and arms, its enlarged abdomen was palpated, and the delivery was converted to an emergent cesarean section. The infant lived for 3 days and then expired due to neurologic complications of trauma sustained during the attempted vaginal delivery. Autopsy revealed a previously undiagnosed intraabdominal immature teratoma. The pathology of teratomas, the most common neonatal tumor and occasionally implicated in cases of birth trauma, will be addressed, followed by a review of the literature concerning birth trauma.

A rare case of clear cell adenocarcinoma of the bladder with unique pathological features.

Clear cell adenocarcinomas of the urinary bladder are rare tumors with an unknown histogenesis. Since these tumors appear histologically similar to clear cell tumors of the female genital tract, a mullerian histogenesis has been proposed. Several publications have examined the immunohistochemical properties of clear cell adenocarcinomas to improve understanding of the cause and pathogenesis of this tumor. While specific criteria for a diagnosis of clear cell adenocarcinoma have not been defined, there are consistent staining patterns suggested for characterization. We present an important case of clear cell adenocarcinoma of the bladder with a unique staining pattern. We review the literature and discuss the differential diagnosis and various theories concerning the origin of this rare tumor.