Hepatic tumors in children.

Although they account for only 1% to 4% of solid tumors in children, hepatic tumors and pseudotumors offer a diagnostic challenge to the clinician seeing only an occasional case. Metastatic lesions such as neuroblastoma, Wilms' tumor, and lymphoma are the most common neoplasm seen in the liver, but 10 distinct primary tumors and pseudotumors of the liver occur with some regularity, and a few others may be seen rarely, including leiomyosarcoma, rhabdoid tumor, and endodermal sinus tumor. Five of these neoplasms--hepatoblastoma, infantile hemangio-endothelioma, mesenchymal hamartoma, undifferentiated embryonal sarcoma, and embryonal rhabdomyosarcoma of the biliary tree--occur only in children and are the major focus of the article.

Extralobar sequestration with frequently associated congenital cystic adenomatoid malformation, type 2: report of 50 cases.

Extralobar pulmonary sequestration (ELS) represents a mass of pulmonary parenchyma separate from the normal lung. The coexistence of congenital cystic adenomatoid malformation (CCAM) in ELS has been reported. To define this association, the clinical, gross, and histologic features of 50 ELS cases were analyzed. The age at diagnosis varied from birth to 65 years with 24% of cases diagnosed prenatally and 61% (23/38) diagnosed within the first 3 months of life. Fifty-two percent of cases were in females and 48% in males. Forty-eight percent of ELS(s) were located in the left hemithorax, 20% in the right hemithorax, 8% in the anterior mediastinum, 6% in the posterior mediastinum, and 18% beneath the diaphragm. The blood supply to the sequestration in 77% of cases was directly from the aorta. Grossly, the lung, though hypoplastic in some cases, was otherwise unremarkable. Fifty percent (23/46) of ELS cases were associated with a coexistent CCAM. In contrast to the series as a whole, 92% (11/12) of the ELS/CCAM cases, excluding those prenatally diagnosed, were diagnosed within the first 3 months and 57% occurred in females. ELS/CCAM lesions, while randomly distributed, were more frequently seen on the left side. Gross features of the ELS/CCAM cases were similar to those cases with ELS alone. All CCAM cases had a type 2 pattern on histologic examination with 48% of those cases also displaying rhabdomyomatous dysgenesis. Our findings indicate that the occurrence of CCAM in ELS is more frequent than reported in the literature and differs in presentation from ELS cases not associated with CCAM.

Congenital disseminated malignant rhabdoid tumor: a distinct clinicopathologic entity demonstrating abnormalities of chromosome 22q11.

The clinical, pathologic, and immunohistochemical features of a widely disseminated tumor with rhabdoid phenotype are described in nine infants < or = 3 months of age. Five neonates had tumor evident at birth, two of which had placental metastases. The average survival following diagnosis was < 6 weeks. None of the infants had an apparent primary tumor in either the kidney or brain. In four cases, the dominant mass involved the head and neck region, and in two cases, the primary mass was paraspinal. The histologic features were those of a high-grade, round cell neoplasm with abundant cytoplasm and containing cells with cytoplasmic filamentous inclusions. Immunohistochemical studies revealed polyphenotypic antigen expression. Genetic information was available from eight of nine cases. Karyotype analysis revealed abnormalities of chromosome band 22q11-12 in three of six tumors. Fluorescence in situ hybridization studies or molecular studies demonstrated 22q11.2 deletions in all five cases with available frozen tissue, two of which had translocations involving 22q by karyotype analysis. The similar clinical and pathologic findings in these rapidly fatal tumors in infants and the demonstration of abnormalities of chromosome 22q11 in a majority of the cases supports their histogenetic and nosologic relationship to the family of malignant rhabdoid tumors that typically occur in young children in several anatomic sites, including kidney, soft tissues, liver, and brain. Like neuroblastoma and rhabdomyosarcoma, malignant rhabdoid tumor can appear as disseminated disease at birth or shortly thereafter.

Pathology of arrested acinar development in postsurfactant bronchopulmonary dysplasia.

To define the pathology of bronchopulmonary dysplasia (BPD) in surfactant-treated patients (S-BPD), we reviewed 22 BPD patients (14 S-BPD and eight non-surfactant-treated [NS-BPD]) and 15 age-matched controls, the lungs from which had been processed after formalin inflation. These were studied for surfactant therapy, postconceptional age, crown-rump length, weight at autopsy, radial alveolar count (RAC), mean linear intercept (MLI), RAC/MLI ratio, and amount and extent of fibrosis. On trichrome staining, there was no alveolar septal fibrosis in the control group, whereas there was mild to moderate alveolar septal fibrosis in 5 of 14 S-BPD patients, of which three had fibrosis in most or all of the acini. In contrast, seven of eight NS-BPD had moderate to severe alveolar septal fibrosis in scattered acini throughout the lung. The patients were divided into two groups, with the first group having a postconceptional age at the time of death of up to 40 weeks' gestation. In group 1, the RAC in S-BPD (nine patients) was significantly lower than that of the controls (seven patients); mean, 4.14 and 5.13, respectively (P = .016), whereas the RAC in the NS-BPD (four patients) and the MLI in both S-BPD and NS-BPD were not statistically significantly different. In group 2, those with adjusted age greater than term, the mean RAC, a measure of acinar complexity, was 3.89 in the S-BPD (five patients) and 3.90 in the NS-BPD (four patients), whereas in the control group (eight patients), it was 5.79 (P = .0007). The mean MLI, a measure of alveolar size, was 0.21 and 0.17 in the S-BPD and NS-BPD groups, respectively, each of which was significantly greater than the mean value of 0.12 in the control group (P = .0003). The comparison of RAC/MLI ratios showed similar statistically significant differences. Based on these results, we conclude that (1) the amount of alveolar septal fibrosis is substantially less and tends to be more diffuse in S-BPD than in NS-BPD; (2) during the period after birth, there is a partial to complete arrest in acinar development (alveolar saccular and alveolar) of similar severity for S-BPD and NS-BPD; and (3) even though on histological examination there are minimal changes, RAC, MLI, and their ratio may be used to support the diagnosis of BPD and help in assessing the amount of lung damage that occurs in S-BPD.

An approach to handling pediatric liver tumors.

Tumors and pseudotumors of the liver account for fewer than 2% of the tumors in children and vary considerably in incidence throughout the pediatric age range, with hepatoblastoma, infantile hemangioendothelioma, and mesenchymal hamartoma seen most frequently in the first 2 years of life and hepatocellular carcinoma, focal nodular hyperplasia, and undifferentiated "embryonal" sarcoma noted in older children. Despite the variety of malignant tumors seen in children and the number of patterns in individual tumors (eg, hepatoblastoma), the most important criterion for long-term prognosis is the stage of the tumor at the time of first resection. Accurate staging by the surgeon and pathologist is therefore the primary objective in examination of malignant hepatic tumors.

Pulmonary inflammatory pseudotumor: radiologic features.

PURPOSE: To define the radiologic features of pulmonary inflammatory pseudotumor. MATERIALS AND METHODS: Between 1966 and 1994, 61 cases of pulmonary inflammatory pseudotumor involved 36 male and 25 female patients (age range, 17 months to 61 years; mean, 28 years). Clinical presentation, pathologic features, and radiologic findings were noted. RESULTS: At radiography, 52 patients had solitary peripheral nodules or masses, and extraparenchymal involvement--including hilar, mediastinal, and airway invasion--was found in 11. At computed tomography, 12 lesions were of heterogeneous attenuation and five, homogeneous. At T1-weighted magnetic resonance imaging, five lesions had intermediate signal intensity; of two lesions studied with T2-weighted imaging, two had high signal intensity; and the one lesion studied with gadolinium-enhanced imaging had diffuse enhancement. CONCLUSION: Pulmonary inflammatory pseudotumor was typically a solitary, peripheral, sharply circumscribed mass with an anatomic bias for the lower lobes. Local invasion and primary involvement of the mediastinum and hilar structures were unusual manifestations.

Intralobar sequestration: radiologic-pathologic correlation.

Intralobar sequestration accounts for 75% of pulmonary sequestrations. The lesion consists of lung tissue that lacks normal communication to the tracheobronchial tree, has systemic arterial supply, and shares the pleura of the parent lobe. The majority of intralobar sequestrations are probably acquired lesions. Patients usually present before the age of 20 years with recurrent infection. At pathologic examination, intralobar sequestration is characterized by inflammation and fibrosis. At radiologic examination, intralobar sequestration typically appears as a consolidation or mass, with or without cavitation, within a lower lobe. In many cases, cystic change may be present within the affected lobe. Identification of a systemic arterial supply supports the diagnosis. Patients are treated with surgical excision, and prognosis is favorable.

Focal peliosis hepatis, a sequela of asphyxial death?

Focal peliosis hepatis seen incidentally in five children succumbing to an asphyxiating death is described. The patients include four females and one male, with age range from 10 months to 15 years. Autopsy liver findings include speckled yellow foci to large (multiple centimeters) yellow tumor-like tissue, which fade upon standing. Microscopically, the lesions are composed of multiple cystic lacunae, which appear to be dilated hepatic sinusoids, lined by reticulin fibers, Kupffer cells, and hepatocytes. Immunohistochemical stains for factor VIII-related antigen and Ulex europaeus are negative. The lesion may represent an early form of peliosis; the possibility of interstitial/sinusoidal air cannot be ruled out.

Infantile hemangioendothelioma of the liver.

Clinical and morphological findings in 91 patients with infantile hemangioendothelioma of the liver are reported. The study comprised 56 girls and 35 boys ranging in age from premature infant to 3 yr; one outlier patient was 18 yr old. Most patients with infantile hemangioendothelioma (87%) were first seen before the age of 6 mo. Congestive heart failure was evident in 15%. Skin hemangiomas were noted in 11%. Anemia, hyperbilirubinemia and increased AST level were present. Solitary lesions were more common than multiple ones (3:2). Immunohistochemical staining of tumor cells for factor VIII was positive in 20 of 21 cases tested; testing for blood group antigen was positive in 8 of 28 cases. Cytokeratin staining verified the presence of bile ducts, some of which appeared to be the result of transformation of injured liver. No pericytes were identified on electron microscopy. The 6-mo survival rate, based on 71 cases, was 70%. Average time of follow-up for the survivors was 7.7 yr. All deaths occurred during the initial presentation/hospitalization of infants, with the exception of two patients who died 3 mo and 7 mo after diagnosis. More recent analytic methods, including immunohistochemical stains and flow cytometric studies, do not contribute to the practical assessment of this tumor. Covariates with significant value in predicting death 6 mo after diagnosis included presence of congestive heart failure, jaundice, multiple tumor nodules and absence of cavernous differentiation.

Hepatoblastoma.

Hepatoblastoma is the most frequently occurring liver tumor in children, accounting for over 25% pediatric hepatic tumors and nearly 50% of those that are malignant. Histologically, the tumor can be divided into the following six patterns: (1) fetal epithelial; (2) embryonal and fetal epithelial; (3) macrotrabecular; (4) small cell undifferentiated; and (5) mixed epithelial and mesenchymal type with teratoid features or (6) without teratoid features. Immunohistochemical studies display a wide variety of immunostaining with monoclonal antibodies particularly those specific for epithelial-derived components. Tumor cytogenetics show a high incidence of trisomy 20 and trisomy of all or part of chromosome 2. The developing liver displays many features similar to those seen in hepatoblastoma, including uniform hepatocytes and cords two cells thick separated by sinusoids displaying hematopoiesis. Hepatoblastomas display only minimal ductular differentiation, similar to the fetal development of the liver that does not display significant ductular development until well into the second trimester.

Congenital cystic adenomatoid malformation within an extralobar pulmonary sequestration.

A type II congenital cystic adenomatoid malformation (CCAM II) occurring within an extralobar pulmonary sequestration (ELS) is described. This large malformation and accompanying pulmonary hypoplasia were diagnosed prenatally by ultrasound examination at 24-25 weeks gestational age. Based upon this diagnosis, the pregnancy was terminated. Autopsy revealed a 40.5 g supradiaphragmatic sequestration, severely hypoplastic lungs, and a hypoplastic heart. Morphologic and clinical features of both CCAM and ELS are compared. CCAM occurring within an ELS has been reported on at least twelve occasions. All the malformations in which the type was reported were of the less differentiated types II or III. We offer an explanation of this fact based on the timing of the embryologic maldevelopment.

Angiosarcoma of the liver in childhood: a clinicopathologic and follow-up study of 10 cases.

The clinical, morphologic, and follow-up findings in 10 cases of childhood hepatic angiosarcoma are reported. Six patients were female and four were male. The age range was 18 months to 7 years, with a mean of 3.7 years. The usual presenting feature was an abdominal mass, with or without associated symptoms. The histologic pattern of childhood hepatic angiosarcoma typically consists of large hypercellular whorls of spindled sarcoma cells intermingled with bile ducts, vessels, and collagen. Factor VIII staining of tumor cells is focal, cytoplasmic, and weak in character. Intracellular eosinophilic, PAS-positive globules are present in most cases and may be abundant. The prognosis is poor; follow-up available in seven cases showed only one to be alive 32 months after diagnosis. The remaining six patients had died 0-27 months (mean 10 months) after diagnosis.

Hepatoblastoma: the prognostic significance of histologic type.

The clinicopathologic features of 105 hepatoblastomas accessioned to the Armed Forces Institute of Pathology between 1967 and 1987 were reviewed. DNA content was analyzed by flow cytometry. A multivariate analysis using the Cox proportional hazards model was performed to evaluate the effect of stage, histologic type, and DNA content on the prognosis for survival. The relative risks of death for a given stage compared to the other stages combined were 0.1637, 0.5672, 2.8742, and 3.5148 for stages I-IV, respectively. The relative risk of death for a given histologic type adjusted for age, sex, and stage compared to the other types was 1.0739 (p = .8850) for the fetal pattern, 1.7409 (p = .1662) for the embryonal pattern, 0.5292 (p = .0754) for the mixed pattern, 1.1980 (p = .7729) for the macrotrabecular pattern, and 3.7096 (p = .1061) for the small-cell undifferentiated pattern. Of 19 hepatoblastomas analyzed for DNA content, 5 were DNA diploid and 11 were DNA aneuploid; 3 could not be classified. The stage of disease at presentation proved to be a significant prognostic factor, whereas histologic type and DNA content did not have a significant effect.

Congenital cystic adenomatoid malformation.

Congenital cystic adenomatoid malformation of the lung is a rare lesion that typically manifests as neonatal respiratory distress secondary to progressive expansion of the affected lung. Three distinct types have been described based on the size of the cysts and the microscopic appearance. Type I lesions are characterized by large cysts of varying sizes (measuring more than 2 cm in diameter), type II lesions typically contain cysts of a more uniform size (not exceeding 2 cm in diameter), and type III lesions contain microscopic cysts. Radiologic findings include single or multiple large cysts, multiple small cysts of uniform size, and solid-appearing masses. The treatment of choice is excision of the affected lobe. The prognosis is favorable in the absence of pulmonary hypoplasia, fetal hydrops, or associated congenital anomalies.

Placental teratoma: a case report.

A case of placental teratoma is presented. The world's literature of 7 previous cases is cited, and the criteria for making this diagnosis, with emphasis on differentiation from a fetus amorphous, are reviewed. Lack of a recognizable umbilical cord and no recognizable skeletal development are the criteria used for diagnosing a teratoma.

Pathologic features of long-standing "healed" bronchopulmonary dysplasia: a study of 28 3- to 40-month-old infants.

Alveolar septal fibrosis, the main residual feature in the "healed" stage of bronchopulmonary dysplasia (BPD), was the consistent finding in 28 infants who died at 3 to 40 months of age, all having had moderate to severe BPD in the neonatal period. The cause of death in 68 per cent of the cases was progressive respiratory failure related directly to the residual changes. An additional 18 pe cent of the infants died of pneumonia superimposed on the long-standing healed bronchopulmonary dysplasia. Cardiomegaly was present in 84 per cent of the cases; biventricular hypertrophy was present in 29 per cent of the cases, right ventricular hypertrophy alone in 21 per cent, and left ventricular hypertrophy alone in 21 per cent. Evidence of pulmonary hypertensive vascular disease was found in 68 per cent of the cases. The pulmonary changes of alveolar septal fibrosis are strikingly variable within individual infants, with moderate or severe fibrosis in one area and normally inflated or hyperinflated lung in the adjacent sublobule or lobe. It is postulated that this variability may be related to a protective effect of necrotizing bronchiolitis (a prominent feature of the acute stages of BPD), whereby the occlusion of the bronchioles shields the distal sublobule from the high oxygen tensions and ventilatory pressures used in treating BPD.