Evaluation of paediatric osteosarcomas by classic cytogenetic and CGH analyses.

Classic cytogenetic and comparative genomic hybridisation (CGH) data on osteosarcomas have been reported extensively in the literature. However, the number of paediatric osteosarcoma cases studied below the age of 14 years remains relatively small. This study reports four new cases of paediatric osteosarcoma in patients aged 3 to 13 years, evaluated by classic cytogenetics and CGH analyses. Clonal chromosomal alterations were detected in all the cases and included structural rearrangements at 1p11-13, 1q11, 4q27-33, 6p23-25, 6q16-25, 7p13-22, 7q11-36, 11p10-15, 11q23, 17p11.2-13, 21p11, and 21q11-22. The CGH analysis revealed recurrent gains at 1p, 4q, 17p, and 21q and losses at 3q and 16p. Five amplification sites were observed at 1q11-23, 6p21, 8q13, 8q21.3-24.2, and 17p. The data are discussed and compared with other cytogenetic reports in the literature.

Infantile hemangiomas: speculation on placental trophoblastic origin.

BACKGROUND: The unique immunobiology of the placental trophoblast and the increased incidence of hemangiomas in infants born after chorionic villus sampling suggest that an immunologically regulated ectopic focus of trophoblasts could be the cell of origin for proliferative infantile hemangiomas. OBJECTIVE: To compare tissue from infantile hemangiomas with that of other vascular lesions for the presence of selected placental trophoblast-specific cellular markers. DESIGN AND PATIENTS: Twelve tissue specimens taken from infantile hemangiomas on patients aged 5 days to 2 years were retrospectively confirmed clinically and histologically. Negative controls were similarly confirmed, including 6 pyogenic granulomas and 4 vascular-lymphatic malformations. These tissues were used for immunohistochemical analysis of selected trophoblastic markers including human placental lactogen, placental alkaline phosphatase, and cytokeratins 7, 8, and 17. SETTING: Tissue submitted from patients seen at Saint Louis University Department of Dermatology and Cardinal Glennon Children's Hospital in St Louis, Mo, between January 1, 1997, and October 31, 1999. MAIN OUTCOME MEASURE: Differential staining for trophoblastic markers in infantile hemangiomas compared with control tissues. RESULTS: The 12 infantile hemangiomas were uniformly negative for all markers tested. Control tissues were also negative for these markers. Four of the 5 histochemical markers did recognize specific nonvascular, cutaneous elements: placental alkaline phosphatase stained smooth and striated muscle, cytokeratins 7 and 8 stained eccrine glands, and cytokeratin 17 stained pilosebaceous units. CONCLUSIONS: Our results do not support the placental trophoblast as the cell of origin for infantile hemangiomas, but we hope our observations and speculation will stimulate further study of this hypothesis.

Placental pathology for the surgical pathologist.

Pathologic examination of the placenta is of clinical importance in the evaluation of pregnancies with a less than perfect outcome. Morphologic alterations of the placenta can mirror disorders of the fetus and the mother and evaluation of the placenta can identify clinically significant lesions, allow understanding of a child's disability and may have a role in resolving medical-legal disputes. Pathologic findings in the placenta can provide information on the pathogenesis of cerebral palsy, mental retardation, or neurodevelopmental disorders. This review will cover a variety of frequently encountered, clinically important, and morphologically distinct disorders of the placenta. The current understanding of the clinical implications of lesions for the mother, infant, and for future pregnancies will also be considered.

The incidence of spermatic cord structures in inguinal hernia sacs from male children.

Inguinal herniorrhaphy is a common surgical procedure in children. Controversy exists regarding the usefulness of microscopic examination of hernia sacs, and changes in reimbursement schemes have heightened this controversy. We summarize our experience with histologic examination of these specimens to establish benchmarks for the number of spermatic cord structures in inguinal hernia sacs from male children. A 14 1/2 consecutive calendar year review of pathology reports and histologic sections of hernia sacs was conducted at a tertiary care children's hospital. Of 7,314 males (range newborn to 19 years old), 65% had bilateral and 29% had unilateral herniorrhaphy (6% unknown). Seventeen cases contained vas deferens (0.23%); 22 had epididymis (0.30%); and 30 had embryonal rests (0.41%). Either vas deferens or epididymis was found in 0.53% of patients. No cases contained bilateral vas deferens, bilateral epididymis, or vas deferens in one side with epididymis in the contralateral side. Three hernia sacs contained co-existing vas deferens and epididymis. Our study helps to provide surgeons with information for preoperative counseling regarding potential injury to the vas deferens or epididymis. This study provides baseline comparison data for quality improvement programs. We believe that each institution should weigh the costs, risks, and benefits of performing microscopic examinations on hernia sacs, depending on their own experience and data.

Fibrous hamartoma of infancy: current review.

This review examines 197 cases of fibrous hamartoma of infancy (FHI) described in the literature and provides a detailed clinicopathologic analysis of what is known to date of this peculiar lesion of the subcutis and lower dermis. The vast majority of these cases occurred within the first year of life (91%). Twenty-three percent were congenital. There was a predilection for boys with a male/female ratio of 2.4. Males and females had similar anatomic distribution with the most common locations being the axillary region, upper arm, upper trunk, inguinal region, and external genital area. Most cases presented as solitary masses, but four cases of multiple separate synchronous lesions have been reported. Most lesions presented as a painless nodule, sometimes with rapid growth. A few cases had overlying skin changes, including alteration in pigmentation, eccrine gland hyperplasia, and increased hair. No lesions were reported to have familial or syndromic association, or to occur in combination with other hamartomas. Spontaneous regression has not been reported. The treatment of choice is local excision. Even with incomplete excision, FHI has a low recurrence rate. Criteria for histologic diagnosis include the presence of well-defined bundles of dense, uniform, fibrous connective tissue projecting into fat, primitive mesenchyme arranged in nests, concentric whorls or bands, and mature adipose tissue intimately admixed with the other components. Flow-cytometric and conventional cytogenetic studies have not been reported; these may clarify any relationship to other fibroblastic/myofibroblastic proliferations in children, resulting in better classification and terminology of this unique lesion.

Nonmalignant renal disease in pediatric patients with Beckwith-Wiedemann syndrome.

OBJECTIVE: The objective of this retrospective review was to determine the incidence and spectrum of nonmalignant renal disease in patients with Beckwith-Wiedemann syndrome. MATERIALS AND METHODS: Patient records were obtained from the Beckwith-Wiedemann Registry of the National Cancer Institute. Imaging findings and medical records of 152 neonates, infants, children, and adults with Beckwith-Wiedemann syndrome (age range, 1 day to 30 years old; median age, 1 year 3 months old) were retrospectively reviewed by three radiologists. Available pathologic material also was reviewed. RESULTS: Thirty-eight (25%) of 152 patients with Beckwith-Wiedemann syndrome had 45 nonmalignant renal abnormalities, including medullary renal cysts (n = 19, 13%), caliceal diverticula (n = 2, 1%), hydronephrosis (n = 18, 12%), and nephrolithiasis (n = 6, 4%). Thirty-three (87%) of the 38 patients with nonmalignant renal disease were asymptomatic. Clinical manifestations of the remaining five patients included urinary tract infections (n = 4) and flank pain due to obstructive stone disease (n = 1). Nonmalignant renal disease was mistaken for Wilms' tumor in two patients, resulting in unnecessary nephrectomies. Seven children (18%) had Wilms' tumor and nonmalignant renal disease. CONCLUSION: Nonmalignant renal abnormalities occur in approximately 25% of patients with Beckwith-Wiedemann syndrome but are generally asymptomatic. Nonmalignant renal abnormalities should be considered in the differential diagnosis of a mass revealed during screening sonography of a patient with Beckwith-Wiedemann syndrome to avoid unnecessary surgery.

Rhabdoid tumor of the kidney in children: a comparative study of 21 cases.

OBJECTIVE: Rhabdoid tumor of the kidney (RTK) is unique among childhood renal neoplasms in its frequent association with primary or metastatic CNS lesions. Previous reports suggest that RTK has characteristic CT features. It has been proposed that if CT could accurately predict the correct diagnosis of RTK preoperatively, then imaging protocols might be modified during the examination to include imaging of the brain. We wished to determine if RTK could be reliably distinguished from other renal neoplasms of early childhood. MATERIALS AND METHODS: We retrospectively reviewed clinical, radiologic, and pathologic records of 21 patients with RTK. The study group included 13 males and eight females who were newborn to 36 months old (mean, 11 months). The study group was compared with 153 patients who were 3 years old or younger and who had solid renal masses. From the comparison group a subset of 54 patients 1 year old and younger was also selected for comparison with 13 (62%) of the 21 patients in the study group who were 1 year old or younger. Both comparison groups consisted of patients whose case material was consecutively added to the radiologic pathology archives at our institution. Diagnoses of the group of 153 patients were Wilms' tumor (n = 93), mesoblastic nephroma (n = 44), clear cell sarcoma of the kidney (n = 12), renal cell carcinoma (n = 3), and undifferentiated sarcoma (n = 1). RESULTS: A prominent eccentric crescent with the attenuation of fluid, representing sub-capsular renal hemorrhage or peripheral tumor necrosis adjacent to tumor lobules, was revealed on CT scans in 15 (71%) of the 21 patients with RTK and in seven (54%) of the 13 patients with RTK who were 1 year old or younger. Nineteen (12%) of 153 patients in the larger comparison group, representing patients with all tumor types, had CT features identical to those of the RTK group, including six (4%) patients with pathologic confirmation of sub-capsular renal hematomas. Six (11%) of the 54 comparison patients 1 year old and younger had CT features identical to those of the RTK group, and all proved to have mesoblastic nephroma. Associated CNS lesions were seen on CT or MR imaging in 11 (52%) of the 21 patients with RTK but none was seen in the comparison group of patients. CONCLUSION: On CT, a peripheral crescent with the attenuation of fluid is characteristic of RTK. However, 12% of renal neoplasms that occur more commonly than RTK in children had CT findings indistinguishable from those of RTK. Because the prevalence of RTK is relatively low, and because the CT findings are not pathognomonic, a renal mass seen on CT in a child is unlikely to represent RTK regardless of its CT features. We therefore conclude that the routine addition of CT of the brain for pediatric patients with renal masses that show a peripheral crescent of fluid attenuation is not justified. Supplemental imaging of the brain should be based on clinical findings or tissue diagnosis.

Ossifying renal tumor of infancy: a clinicopathologic study of nine cases.

We studied nine ossifying renal tumors of infancy (ORTI), including all five previously reported cases. There were eight boys and one girl ranging in age from 6 days to 14 months. Gross hematuria was the presenting sign in all nine patients. Eight tumors arose in the left kidney and six in the upper pole. All seven patients with follow-up information were free of recurrence. All lesions were attached to a renal papilla and presented mainly within the calyceal lumen. Two resembled staghorn calculi clinically. All tumors contained varying proportions of osteoid, osteoblastic cells, and spindle cells. The spindle cell component had features strongly suggesting that they represented hyperplastic intralobar nephrogenic rests (ILNR). The proportion of osteoid and degree of osseous maturation increased with increasing age of the patient. ORTI is a distinctive clinicopathologic entity, possibly representing a distinctive interaction between ILNR in the renal papilla with distal collecting duct or urothelial cells in the developing kidney.

Primary Ki-1 (anaplastic large cell) lymphoma of the brain and spinal cord.

The authors report a case of primary Ki-1 lymphoma of the brain. The patient was a 4 1/2-year-old black girl who presented with a 4- and 5-day history of headaches, nausea, vomiting, neck stiffness, and difficulty in walking. Computed tomography (CT) scan of the brain showed two discrete densities in the left occipital lobe and in the brain stem. Magnetic resonance imaging (MRI) showed multiple densities scattered over the brain surface and brain stem. Microscopically, the tumor was an anaplastic neoplasm that diffusely infiltrated brain parenchyma. The neoplastic cells were large with amphophilic cytoplasm, large nuclei with irregular nuclear contours and prominent nucleoli. A high mitotic rate including atypical mitotic figures was noted. Immunohistochemical stains showed diffuse strong positivity for CD30 and moderate focal staining for epithelial membrane antigen. Leukocyte common antigen, cytokeratin, neuron specific enolase, monocyte/macrophage and B- and T-marker stains were negative. The histology was characteristic for Ki-1 large cell lymphoma. Cytologic examination of cerebrospinal fluid (CSF) demonstrated similar neoplastic cells. This is one of the first reports of this variant in the pediatric population.

Assessment of argyrophilic nucleolar organizer region quantification in benign and malignant bone tumors.

Quantification of argyrophilic nucleolar organizer regions has been proposed as a technique that may aid in diagnosing and predicting the biologic behavior of a variety of neoplasms. A 1-step silver staining technique was used to identify and quantify argyrophilic nuclear organizer regions in a series of 96 bone tumor specimens. Malignant bone tumors had a higher mean argyrophilic nuclear organizer region count (3.05 +/- 0.82) than giant cell tumors (1.39 +/- 0.14, p < 0.001) and benign bone tumors (1.51 +/- 0.42, p < 0.001). Despite these differences in mean counts, an overlap of argyrophilic nuclear organizer region scores was observed in some benign and malignant cases. The argyrophilic nuclear organizer region counts of the osteosarcomas were analyzed to determine whether they correlated with tumor behavior. The mean argyrophilic nuclear organizer region count of specimens from patients in whom metastatic disease developed was not significantly different than that of patients who remained disease free.

Paroxysmal nocturnal hemoglobinuria associated with venous thrombosis and papillary endothelial hyperplasia presenting as ulcerated duodenal mass.

Paroxysmal nocturnal hemoglobinuria is an acquired clonal expansion of bone marrow stem cells that are deficient in the decay-accelerating factor, which is a complement regulatory glycoprotein (CD55), as well as in the membrane inhibitor of reactive lysis (CD59) and the C8-binding protein. These proteins are deficient on the membranes of red blood cells, granulocytes, monocytes, and platelets. The disorder is associated with intermittent hemolytic anemia, hemoglobinuria, infection, a tendency toward bone marrow aplasia, and venous thromboses. The thromboses, on resolution, may give rise to endothelial proliferation that may cause ischemia and ulceration, or, alternatively, the thromboses may cause ulceration leading to a granulation tissue response with exaggerated endothelial proliferation. We report a second case of paroxysmal nocturnal hemoglobinuria that presented roentgenographically as an ulcerated circumferential duodenal mass secondary to venous thrombosis accompanied by florid papillary endothelial hyperplasia. We also review the literature concerning this phenomenon.

Subdermal fibrous hamartoma of infancy: pathology of 40 cases and differential diagnosis.

Forty subdermal fibrous hamartomas of infancy occurred in 29 males and 11 females who were 7 months to 4 years of age at surgery. At least 4 were congenital. The lesions were situated in axilla, chest wall, and breast (17 cases); abdominal wall, inguinal region, and scrotum (8); buttock and lower limb (6); upper limb (4); neck and scalp (3); and low back (2). They were 0.7 to 10 cm, ill defined, and five underwent reexcision, which was curative in all. All had the characteristic mixture of fibrous and adipose tissue and nests of immature mesenchyme in different proportions, and nearly all showed lymphocytes and thick patent capillaries in the mesenchyme. However, the fibrous component varied considerably in amount, pattern, and cellularity, so that lesions that were typical in some areas, in others resembled collagenizing vascular granulation tissue, deep fibrous histiocytoma, or fibromatosis. Those in which adipose tissue predominated were distinguished from fibrolipoma by foci of immature mesenchyme and from lipoblastoma by their lack of a capsule and of a lobular pattern.

Cystic neuroblastoma in a newborn.

A neuroblastoma that presented as an adrenal cyst in a newborn infant is described. This is an extremely unusual presentation for neuroblastoma; it emphasizes the need for a high degree of suspicion when evaluating any abdominal mass in the newborn.

Congenital hemangiopericytoma: an unusual vascular neoplasm of infancy.

BACKGROUND: Hemangiopericytoma is an uncommon tumor of infants, which originates from the vascular pericytes. Although generally considered to benign, metastases can occur. METHODS: Five cases of congenital hemangiopericytoma were seen in infants; all were found in females. The mean age at diagnosis was 7 weeks (range, birth to 10 weeks). The lesions were located in the neck, the parotid, the axilla, and the retroperitoneum. One neck lesion was detected prenatally by ultrasonography. Each lesion was resected. The diagnosis of congenital hemangiopericytoma was established only after histologic examination. RESULTS: No evidence of recurrence has been found in four of the children. However, intrathoracic and intracranial metastases developed in one child with a neck lesion 28 months after the original resection, and the child was treated with chemotherapy, but she died of progressive disease. CONCLUSIONS: We advocate the consideration of congenital hemangiopericytoma in the newborn infant with a vascular mass. Because congenital hemangiopericytoma is unresponsive to steroid therapy, unlike other vascular malformations, resection is the treatment of choice. Long-term postoperative follow-up is essential for the early detection of metastases.

Growth-related gene expression in early cholestatic liver injury.

BACKGROUND: Extrahepatic biliary obstruction initiates cholestasis, bile duct proliferation, periportal fibrosis, and, eventually, lethal biliary cirrhosis. Little is known about the genetic regulation of the cellular proliferation and differentiation that begins with the onset of bile duct obstruction. To focus this and future gene expression studies, we sought to determine the time frame for growth-related gene expression and questioned whether the in vivo expression of the protooncogenes H-ras and c-myc was altered after bile duct obstruction. METHODS: Female Fisher rats underwent ligation and division of the common bile duct or sham laparotomy. RESULTS: After obstruction, serum bilirubin and gamma-glutamyl transpeptidase rose to 24% and 30%, respectively, of maximum levels by 10 days after ligation. Morphologic evidence of proliferation of bile duct epithelial cells was first evident after 3 days. After hybridization to c-DNA probes, densitometry for H-ras and beta-actin revealed an immediate and parallel increase in steady-state levels of expression after 24 hours of cholestasis. Levels of c-myc messenger RNA were elevated during the first 3 days of cholestasis; however, at 7 and 10 days c-myc expression was depressed 16% and 60%, respectively. CONCLUSIONS: These profiles of expression show an oncogene response induced by early cholestasis. These data showed that elevations in H-ras and c-myc steady-state expression accompany the proliferative response of bile duct epithelial cells. Decreased levels of c-myc after initial elevation infer that ductal proliferation may continue independently of its steady-state expression, a response usually seen in vitro rather than in in vivo proliferation.

The blood-brain barrier glucose transporter is conserved in preterm and term newborn infants.

Glucose, an essential substrate for brain oxidative metabolism, is transported across the adult blood-brain barrier by Glut 1, a facilitative glucose transporter. Employing postmortem human brain samples and Western blot analysis, we demonstrated the presence of a 47-55 kilodalton Glut 1 protein in preterm and term newborn. The level of Glut 1 in both the preterm (24-33 weeks; n = 12) and term (38-40 weeks; n = 4) neonates was comparable to that of the adult (n = 5). Using paraffin brain sections and immunohistochemical analysis, in the preterm (24-25 weeks) and term (40 weeks) infant, similar to the adult we demonstrated the presence of Glut 1 in microvascular endothelial cells which constitute blood-brain barrier forming cells. The ontogenic conservation of the blood-brain barrier Glut 1 make detecting defective glucose transport across the neonatal blood-brain barrier feasible. Genetic or acquired defects in Glut 1 can impede the transport of glucose across the blood-brain barrier, thereby, resulting in irreversible neurological compromise during infancy. Earlier detection during the neonatal period, and appropriate intervention, may set the stage for altering the outcome of affected infants.