James Barrish

Lipoblastoma and lipoblastomatosis in infancy and childhood: histopathologic, ultrastructural, and cytogenetic features.

Lipoblastoma is a relatively rare tumor that occurs in infancy and early childhood and arises from embryonic white fat. Although a benign tumor, lipoblastomas tend to recur and may resemble myxoid liposarcoma. The authors report 26 cases over a 15-year period at Texas Childrens Hospital. There was a slight female predilection (14F:12M). The most common symptom was a painless mass with or without increasing size. The trunk, extremities, head and neck, retroperitoneum, inguinal canal, peritoneal cavity, and lung were the tumor sites. Most tumors were circumscribed lipoblastomas and the minority were diffuse infiltrative lipoblastomatosis. Reexcision for residual or recurrent tumor was necessary more frequently in patients with lipoblastomatosis. Histopathologic examination and ultrastructural examination revealed cellular neoplasms composed of immature adipocytes with relatively well-defined septa, frequent lipoblasts, a fine vascular network, and often a myxoid appearance resembling myxoid liposarcoma. Cytogenetics was performed in 4 cases with chromosome 8q abnormality being most common. The major concern with lipoblastoma in children is to completely excise the tumor to avoid leaving residual tumor and to prevent recurrences. Confusion with myxoid liposarcoma, well-differentiated liposarcoma, and typical lipomas may occur. Although asymptomatic, lipoblastomas may cause dysfunction of other organ systems due to mass effect. Complete surgical excision with at least 2 years of follow-up is the preferred therapy.

Neonatal Syncytial Giant Cell Hepatitis with Paramyxoviral-like Inclusions

Syncytial giant cell hepatitis in the neonatal period has been associated with many different etiologic agents and may present initially as cholestasis. Infectious causes are most common and include: (1 ) generalized bacterial sepsis, (2) viral agents, (3) toxoplasmosis, (4) syphilis, (5) listeriosis, and (6) tuberculosis. Viral hepatitis may be due to cytomegalovirus, rubella virus, herpes simplex, HHV-6, varicella, coxsackievirus, echovirus, reovirus 3, parvovirus B19, HIV, enteroviruses, paramyxovirus, and hepatitis A, B, or C (rare). Giant cell hepatitis may result in fulminant liver failure with massive hepatocyte necrosis and severe liver dysfunction leading to death, resolution with severely compromised liver function, or liver transplantation. The authors report a 6-week-old male who had an unremarkable perinatal period, became jaundiced after developing diarrhea, and subsequently developed liver dysfunction with massively increased liver enzymes and a coagulopathy. Open wedge and core liver biopsies were performed to determine if the patient should be listed for liver transplantation. Giant cell hepatitis with a significant mixed lymphocytic and neutrophilic infiltrate was present on both the wedge and core biopsies. The residual 60% of hepatocytes had ballooning degeneration and many possessed pyknotic nuclei. The hepatocytes were arranged in a pseudoacinar pattern. Electron microscopy showed paramyxoviral-like inclusions in the giant cells, characterized as large inclusions with fine filamentous, beaded substructures (18-20 nm). Paramyxoviridae are nonsegmented, negative-sense, single-stranded RNA viruses. This family is divided into the Paramyxovirinae subfamily containing respirovirus (Sendai virus, parainfluenza virus type 3), rubulavirus (mumps, parainfluenza virus type 2), and morbillivirus genera (measles); and Pneumovirinae subfamily (pneumovirus genus [respiratory syncytial virus]). Supportive care to determine if hepatic function resolves following the viral episode, liver transplantation with fulminant liver failure, and ongoing evaluation in those who recover to assess chronic liver disease are necessary. Ultrastructural evaluation may unmask the etiologic agent for hepatitis and direct therapy.Syncytial giant cell hepatitis in the neonatal period has been associated with many different etiologic agents and may present initially as cholestasis. Infectious causes are most common and include: (1) generalized bacterial sepsis, (2) viral agents, (3) toxoplasmosis, (4) syphilis, (5) listeriosis, and (6) tuberculosis. Viral hepatitis may be due to cytomegalovirus, rubella virus, herpes simplex, HHV-6, varicella, coxsackievirus, echovirus, reovirus 3, parvovirus B19, HIV, enteroviruses, paramyxovirus, and hepatitis A, B, or C (rare). Giant cell hepatitis may result in fulminant liver failure with massive hepatocyte necrosis and severe liver dysfunction leading to death, resolution with severely compromised liver function, or liver transplantation. The authors report a 6-week-old male who had an unremarkable perinatal period, became jaundiced after developing diarrhea, and subsequently developed liver dysfunction with massively increased liver enzymes and a coagulopathy. Open wedge and core liver biopsies were performed to determine if the patient should be listed for liver transplantation. Giant cell hepatitis with a significant mixed lymphocytic and neutrophilic infiltrate was present on both the wedge and core biopsies. The residual 60% of hepatocytes had ballooning degeneration and many possessed pyknotic nuclei. The hepatocytes were arranged in a pseudoacinar pattern. Electron microscopy showed paramyxoviral-like inclusions in the giant cells, characterized as large inclusions with fine filamentous, beaded substructures (18-20 nm). Paramyxoviridae are nonsegmented, negative-sense, single-stranded RNA viruses. This family is divided into the Paramyxovirinae subfamily containing respirovirus (Sendai virus, parainfluenza virus type 3), rubula virus (mumps, parainfluenza virus type 2), and morbillivirus genera (measles); and Pneumovirinae subfamily (pneumovirus genus [respiratory syncytial virus]). Supportive care to determine if hepatic function resolves following the viral episode, liver transplantation with fulminant liver failure, and ongoing evaluation in those who recover to assess chronic liver disease are necessary. Ultrastructural evaluation may unmask the etiologic agent for hepatitis and direct therapy.

Tracheomalacia in a neonate with kniest dysplasia: histopathologic and ultrastructural features.

Kniest dysplasia is an autosomal-dominant chondrodysplastic condition characterized by disproportionate dwarfism, short trunk, small pelvis, kyphoscoliosis, short limbs, prominent joints, premature osteoarthritis, and craniofacial manifestations. The craniofacial abnormalities include tracheomalacia, midface hypoplasia, cleft palate, early onset myopia, retinal detachment, prominent eyes, and sensorineural hearing loss. Radiologic features include dumbbell-shaped femora, platyspondylia with anterior wedging of vertebral bodies, coronal clefts of thoracolumbar vertebral bodies, low broad ilia, and short tubular bones with broad metaphyses and deformed large epiphyses. This form of chondrodysplasia is associated with mutations in type II collagen splicing sequences. Mutations have been identified in the COL2A1 (type II collagen) gene between exons 12 and 24. Type II collagen is the predominant structural protein in cartilage, and mutations in this collagen account for the Kniest dysplasia phenotype. Histopathologic and ultrastructural features of epiphyseal plate cartilage have been described, but tracheal cartilage in an affected neonate has not been examined. The authors report the histopathologic and ultrastructural findings of anterior tracheal cartilage from a 35-day-old female with suspected chondrodysplasia who had tracheomalacia with airway obstruction. The tracheal cartilage was moderately cellular, but lacked cystic and myxoid changes in its matrix. The chondrocytes had abundant cytoplasmic PAS-positive inclusions. Some of these inclusions were diastase-resistant and were also highlighted on Alcian blue staining. Ultrastructural examination revealed chondrocytes with greatly dilated rough endoplasmic reticulum containing granular proteinaceous material. There were also frequent aggregates of typical glycogen. The defect in the COL2A1 gene is secondary to mutations, especially at splice junctions, and this markedly disrupts triple helix formation. The mutated type II procollagen results in intracellular retention within the chondrocytes, as abundant granular proteinaceous material within the dilated RER. A relationship is known to exist between the proportion of mutated to normal type II collagen in the matrix and the severity of the phenotype. With low levels of normal type II collagen, the phenotypic manifestations become more severe, such as in achondrogenesis type II. Both the quantity and quality of type II collagen modulates the phenotypic expression of type II collagenopathies.Kniest dysplasia is an autosomal-dominant chondrodysplastic condition characterized by disproportionate dwarfism, short trunk, small pelvis, kyphoscoliosis, short limbs, prominent joints, premature osteoarthritis, and craniofacial manifestations. The craniofacial abnormalities include tracheomalacia, midface hypoplasia, cleft palate, early onset myopia, retinal detachment, prominent eyes, and sensorineural hearing loss. Radiologic features include dumbbell-shaped femora, platyspondylia with anterior wedging of vertebral bodies, coronal clefts of thoracolumbar vertebral bodies, low broad ilia, and short tubular bones with broad metaphyses and deformed large epiphyses. This form of chondrodysplasia is associated with mutations in type II collagen splicing sequences. Mutations have been identified in the COL2A1 (type II collagen) gene between exons 12 and 24. Type II collagen is the predominant structural protein in cartilage, and mutations in this collagen account for the Kniest dysplasia phenotype. Histopathologic and ultrastructural features of epiphyseal plate cartilage have been described, but tracheal cartilage in an affected neonate has not been examined. The authors report the histopathologic and ultrastructural findings of anterior tracheal cartilage from a 35-day-old female with suspected chondrodysplasia who had tracheomalacia with airway obstruction. The tracheal cartilage was moderately cellular, but lacked cystic and myxoid changes in its matrix. The chondrocytes had abundant cytoplasmic PAS-positive inclusions. Some of these inclusions were diastase-resistant and were also highlighted on Alcian blue staining. Ultrastructural examination revealed chondrocytes with greatly dilated rough endoplasmic reticulum containing granular proteinaceous material. There were also frequent aggregates of typical glycogen. The defect in the COL2A1 gene is secondary to mutations, especially at splice junctions, and this markedly disrupts triple helix formation. The mutated type II procollagen results in intracellular retention within the chondrocytes, as abundant granular proteinaceous material within the dilated RER. A relationship is known to exist between the proportion of mutated to normal type II collagen in the matrix and the severity of the phenotype. With low levels of normal type II collagen, the phenotypic manifestations become more severe, such as in achondrogenesis type II. Both the quantity and quality of type II collagen modulates the phenotypic expression of type II collagenopathies.

Recurrent Intrapulmonary Malignant Small Cell Tumor of the Thoracopulmonary Region with Metastasis to the Oral Cavity: Review of Literature and Case Report

Malignant small cell tumor of the thoracopulmonary region (MSCT) was first described in 1979 and has been referred to as the Askin tumor. This malignant neoplasm is a member of the peripheral primitive neuroectodermal tumor (PPNET) family and typically involves the periosteum, soft tissue, and extrapulmonary tissue of the thoracic wall. MSCT may also involve the lung parenchyma by local extension or may arise de novo in peripheral lung tissue. Local recurrence, abdominal involvement by tumor extravasation across the diaphragm, and skeletal metastatic disease are relatively common. However, metastasis to the head and neck region and in particular to the oral cavity is extremely rare. We present a recurrent intrapulmonary MSCT with metastasis to the oral cavity in an adolescent Hispanic boy, and review the literature regarding this member of the PPNET family. Differentiation from neuroblastoma may be made based on immunoreactivity for beta 2 microglobulin and HBA71 and lack of immunoreactivity for chromogranin in PPNET and MSCT. Ultrastructural features commonly seen in MSCT and PPNET are round to ovoid tumor cells with occasional cytoplasmic processes with relatively few pleomorphic dense core granules. These tumors lack the gangliocytic and Schwann cell differentiation that is characteristic of neuroblastoma. MSCT and PPNET have a common reciprocal cytogenetic translocation [t(11;22)q(24;q12)], which is shared with Ewings sarcoma. Prognosis in MSCT is quite dismal, with a 2-year survival of 38% and a 6-year survival of only 14%.

Adherence kinetics of Haemophilus influenzae type b to eucaryotic cells.

ABSTRACT: Haemophilus influenzae type b (Hib) adhere in vitro to buccal epithelial cells (BEC) via pili (fimbriae). In vivo studies have conflicting lines of evidence concerning the role of pili in adherence. This study characterizes the kinetics of Hib binding to BEC and compares pilus versus nonpilus adherence. Adherence was assessed using radioactive, immunofluorescence, and electron microscopic techniques. Paired Hib strains were obtained from three children with Hib meningitis; piliated Hib were isolated from the nasopharynx and nonpiliated isolates from the cerebrospinal fluid. Piliated strains adhered avidly to BEC after a 1-h incubation, whereas nonpiliated strains adhered poorly p = 0.002). Kinetic analysis revealed increased adherence to BEC by piliated and nonpiliated strains with time, with maximum adherence occurring between 24-36 h. Immunofluorescence and electron microscopic assays visually confirmed the radioactive adherence findings. These results characterize the kinetics of Hib adherence to BEC. BEC incubated with nonpiliated Hib for 30 h were found to be coated with piliated strains, suggesting the induction of pilus production or the selection of a piliated subpopulation.

Does the Use of Hydrochloric Acid Damage Silicone Rubber Central Venous Catheters

BACKGROUND Hydrochloric acid (HCl) is commonly used to clear obstructions in central venous catheters (CVC). METHODS To determine if HCl adversely affects the integrity of a CVC we infused 0.1 N HCl daily into CVC in vitro. At weekly intervals sections of the CVC were removed and examined using scanning electron microscopy. RESULTS Over 8 weeks, no damage to the CVC was visible. CONCLUSIONS HCl administration poses no threat to the structural integrity of a CVC.

α1-Antitrypsin Deficiency in Liver Disease in Infancy and Childhood: Complementary Role of Immunocytochemical and Ultrastructural Evaluation

1-Antitrypsin deficiency is the most common metabolic disease of the liver in childhood and is the second leading cause of liver transplantation in children. Typically, the neonate or infant presents with cholestatic jaundice with mildly elevated transaminases and a conjugated hyperbilirubinemia that may be persistent. In the neonate and young infant, ultrasound and bile excretory studies may be inconclusive in establishing whether extrahepatic biliary atresia exists or not. Percutaneous or open liver biopsy in the neonate or young infant may have features that mimic extrahepatic biliary atresia, neonatal hepatitis with giant cell transformation, and bile duct paucity characteristically associated with Alagille’s syndrome. Although PAS-positive, diastase-resistant cytoplasmic inclusions in hepatocytes are commonly associated with 1-antitrypsin retention, bile pigment in the cholestatic neonate and infant may stain similarly. In the neonate and young infant under 12 weeks of age, 1-antitrypsin accumulation is typically inadequate for detection with PAS-diastase and 1-antitrypsin antibody immunocytochemical stains. Electron microscopic study is important in the neonate and young infant in order to provide a definitive diagnosis of 1-antitrypsin deficiency. Ultrastructural evaluation allows for the detection of the finely granular homogenous material distending the rough endoplasmic reticulum that is characteristic for retained 1-antitrypsin glycoprotein. Further characterization of the 1-antitrypsin phenotype can be performed by isoelectric focusing studies on serum proteins. A certain proportion of children with 1antitrypsin deficiency have progressive disease and develop juvenile cirrhosis, necessitating liver transplantation. In all children with 1-antitrypsin deficiency, long-term follow-up is necessary to determine whether their liver disease will progress, stabilize or undergo resolution.