James E. Dimmick

Rhabdomyosarcoma arising within congenital pulmonary cysts : report of three cases

Over the past 9 months, three cases of primary pulmonary rhabdomyosarcoma have been treated at British Columbia Childrens Hospital. Two patients (aged 24 and 37 months) presented with spontaneous pneumothoraces and had cystic changes in the affected lung on chest radiograph. The third patient (aged 42 months) was evaluated for chronic cough, fever, and failure to thrive. Chest x-ray showed a large mass in the left lower lobe as well as mediastinal adenopathy. All three of these lesions originated within congenital lung cysts, one a peripheral bronchogenic cyst and the others cystic adenomatoid malformations. This report suggests that there is a significant risk for the development of rhabdomyosarcoma within malformed pulmonary tissue.

Inflammatory pseudotumors in children

Inflammatory pseudotumors are so named because they mimic malignant tumors clinically and radiologically. Most often seen in the lungs of young adults, they consist of localized proliferations of mononuclear inflammatory cells and myofibroblasts. There are scattered reports of these tumors occurring in various sites in children. We report five cases of these rare lesions in children; four arising intraabdominally and one in the lung. In contrast to the usual presentation in adulthood, these children were all previously healthy. One child, with the tumor arising from the urinary bladder, was originally diagnosed as having a malignant sarcoma and underwent pelvic exenteration and chemotherapy for this subsequently-proven benign lesion. Local recurrence occurred in one case. Total excision is indicated and is usually possible without unacceptable morbidity. Our cases and a review of the literature point out the importance of pathologic differentiation of these lesions from malignancy with early appropriate surgery.

Biliary atresia and cytomegalovirus infection: a DNA study.

ABSTRACT The cause of extrahepatic biliary atresia (EHBA) is undetermined in most instances, but an infectious agent is widely suspected. Cytomegalovirus (CMV) infection has been associated with intrahepatic bile duct destruction and paucity, raising the question of its role in EHBA. We identified 12 children in the past 5 years with biliary atresia and examined the bile duct biopsy. These showed acute/chronic inflammation and epithelial degeneration. CMV inclusions were not identified. We used in situ hybridization and the polymerase chain reaction (PCR) for CMV-DNA on formalin-fixed, paraffin-embedded tissue. All samples showed the presence of amplifiable DNA using β-globin primers. No biopsy tissue showed CMV DNA using specific probes and primers. The absence of demonstrable CMV DNA by in situ hybridization and PCR in EHBA biopsies implies that it is unlikely that this virus has any major role in the pathogenesis of this condition.

Oropharyngeal and upper respiratory tract mucosal-gland siderosis in neonatal hemochromatosis: An approach to biopsy diagnosis

ll. Tubergen DG, Krooth RS, Heyn RM. Hereditary orotic aciduria with normal growth and development. Am J Dis Child 1969;118:864. 12. McClard RW, Black M J, Jones ME, et al. Neonatal diagnosis of orotic aciduria: an experience with one family. J PEDIATR 1983;102:85. 13. Harris ML, Orbeholzear VG. Conditions affecting the colorimetry of orotic acid and orotidine in urine. Clin Chem 1980;26:473. 14. Prabhakararao K, Jones ME. Radioassay of orotic acid phosphoribosyltransferase and orotidylate decarboxylase utilizing a high-voltage paper electrophoresis technique or an improved 14CO;-release method. Anal Biochem 1975;69:451. 15. Worthy TE, Grobner W, Kelley WN. Hereditary orotic aciduria: evidence for a structural gene mutation. Proc Natl Acad Sci USA 1974;71:3031.

Histopathologic approach to metabolic liver disease: Part 1.

INTRODUCTION Traditional approaches to the diagnosis of genetic metabolic diseases are often based on descriptions of metabolic pathways, for example, urea cycle disorders, or by moiety classes, such as carbohydrates, amino acids, lipids, or structural proteins. The address might be by clinical presentation, a method of value to the pediatrician and of assistance to the pathologist. Some disorders are expressed acutely and severely in the fetus and neonate, others in a more chronic manner in older infants and children. Ultrastructural morphologists, using an organelle-based approach, discuss peroxisomopathies, mitochondrial and lysosomal disorders. These viewpoints broaden the approach to differential diagnoses, but the analysis of diagnostic possibilities often begins with the histologic picture seen by the pathologist examining a liver biopsy. Inherited disorders of metabolism may have no morphologic impact on the liver, or the manifestation may be minimal, as, for example, in most urea cycle disorders where trivial steatosis, congestion, or very occasional hepatocellular necrosis occurs. Under these circumstances, the pathologist has no opportunity to offer a diagnosis, except an exclusionary one. Many metabolic diseases affecting the liver do create typical histopathologic patterns that assist the pathologist in the diagnostic workup (Table 1). Others show a limited number of patterns, while some evolve from one pattern to another. The interpretation, therefore, requires knowledge of the histologic mosaic and is improved by understanding the pathogenesis, pace, and course of metabolic diseases. The presentation here highlights lightand electron-microscope manifestations in the liver at the time of biopsy, with emphasis on the value of morphology in guiding the investigation of metabolic diseases.

Wilms Tumorlet, Nodular Renal Blastema and Multicystic Renal Dysplasia

We reviewed 60 cases of multicystic renal dysplasia collected during a 10-year period. Differentiated nonproliferative nodular renal blastema occurred in 6.7 per cent of the cases, which is similar to the incidence of nodular renal blastema in kidneys of other infants with congenital obstructive uropathy. A unique case of cystic dysplasia containing nodular renal blastema and Wilms tumorlet indicates the possibility that a persistently proliferative nephroblastomatous lesion may rarely occur.

Multiple infiltrating glomus tumors in children.

Two children with multiple infiltrating glomus tumors of the lower extremities presented in infancy with clinical and, in one, radiological, signs of varicose veins. Surgical therapy was followed by multiple recurrences, a phenomenon attributable to the infiltrative properties of the tumor. This variant of multiple glomus tumor may be congenital and is probably hamartomatous in nature.

Cytomegalovirus infection of the bowel in infancy : pathogenetic and diagnostic significance

Three infants had cytomegalovirus (CMV) infection of the bowel. Infected enteric ganglion cells were found in two, one of whom had hypoganglionosis and colonic dysmotility. The third infant had classic short segment Hirschsprungs disease and colitis with CMV inclusions in vascular endothelium, a situation wherein viral transformed cells may have led to misinterpretation of the diagnostic biopsy.

Biochemical and Histologic Pathology in an Infant with Cross-Reacting Material (Negative) Pyruvate Carboxylase Deficiency

ABSTRACT: An infant with the acute neonatal form of pyruvate carboxylase deficiency (cross-reacting material negative) presented with severe intractable lactic acidosis within 4 h after birth. He also had hyperammonemia, hypercitrullinemia, and hyperlysinemia. Plasma glutamine was not elevated. He had a rapidly deteriorating clinical course with severe liver dysfunction, repeated septicemia and seizures; he was comatose and was on a ventilator throughout; death occurred at 8 wk of age. Skin fibroblast study confirmed the enzyme deficiency. Detailed biochemical parameters and histopathology of the brain and liver are presented. The evidence from this infant suggests that disturbances of intracellular oxaloacetate levels as a result of the primary enzyme defect might also contribute to deficiency in ATP generation which may explain the various other biochemical changes and liver pathology.

Congenital rubella syndrome associated with calcific epiphyseal stippling and peroxisomal dysfunction

An infant girl had the clinical and immunologic findings of congenital rubella syndrome but also had arthrogryposis multiplex and calcific epiphyseal stippling. Spastic quadriparesis developed, and both physical and behavioral development were slow. Increased spasticity of the legs at 5 1/2 years was related not to progressive rubella encephalomyelopathy but to spinal cord compression by abnormal cartilaginous tissue. The presence of a peroxisomal disorder was demonstrated by a greatly increased level of phytanic acid and slightly increased levels of hexacosanoate in serum and by reduced activity of peroxisomal dihydroxyacetone phosphate acyltransferase and a slightly increased ratio of cytosolic to peroxisomal catalase activity in cultured fibroblasts. A reduction in the number and size of peroxisomes was demonstrated in cultured fibroblasts, and a needle biopsy specimen of the liver also showed the peroxisomes to have a smaller diameter than usual. We recommend that any child with epiphyseal stippling be assessed for peroxisomal disease and that the potential for spinal cord compression by dysplastic bone or cartilage be recognized. The association of peroxisomal dysfunction with congenital rubella has not been described previously. The interaction between rubella virus infection and peroxisomal function may need further investigation.