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Byline: Lei Shao (1), D. Ashley Hill (2), Elizabeth J. Perlman (3) Keywords: Bcl-2; CD34; clear cell sarcoma of the kidney; mesoblastic nephroma,WT-1; Wilms tumor Abstract: The confident diagnosis of renal spindle cell tumors in children is often difficult. An immunohistochemical study of WT-1, Bcl-2, and CD34 was performed to determine their expression profiles and to assess the potential utility of these immunohistochemical markers in the differential diagnosis of 36 cases of renal spindle cell tumors of childhood. The cases included 11 stromal predominant Wilms tumors, 12 cellular mesoblastic nephromas, 9 clear cell sarcomas of the kidney (CCSK), and 4 monophasic synovial sarcomas. WT-1 was uniformly positive in primitive undifferentiated stromal Wilms tumors (6 of 6) and negative in the differentiating and differentiated stromal elements of Wilms tumors (0 of 5). WT-1 was also negative in cellular mesoblastic nephromas (0 of 12), CCSKs (0 of 12), and synovial sarcomas (0 of 4). Bcl-2 was expressed in all stromal Wilms tumors (11 of 11), all synovial sarcomas (4 of 4), some CCSKs (4 of 9), and none of the cellular mesoblastic nephromas (0 of 12). Although CD34 was absent in the tumor cells of all the tumors studied (0 of 36), CD34 immunohistochemistry nicely demonstrated the evenly distributed septal capillaries characteristic of CCSK in all 9 cases of this tumor. We conclude that a combination of WT-1 and Bcl-2 immunohistochemistry may aid in the distinction of stromal Wilms tumor, monophasic synovial sarcoma, cellular mesoblastic nephroma, and CCSK. Author Affiliation: (1) Department of Pathology and Laboratory Medicine, Children's Mercy Hospital, 2401 Gillham Road, Suite 2567, Kansas City, MO, 64108, USA (2) Department of Pathology and Immunology, Washington University Medical Center, 660 S. Euclid Avenue, St. Louis, MO, 63110, USA (3) Department of Pathology and Laboratory Medicine, Children's Memorial Medical Center, 2300 Children's Plaza, Box 17, Chicago, IL, 60614, USA Article History: Registration Date: 01/01/2004 Received Date: 12/04/2004 Accepted Date: 13/07/2004 Online Date: 08/11/2004

Byline: Haytham H. Dimashkieh (1), Jun Q. Mo (2), Josephine Wyatt-Ashmead (3), Margaret H. Collins (2) Keywords: angiosarcoma; hepatic; infantile hemagioendothelioma; liver; pediatric; transplant Abstract: Pediatric hepatic angiosarcoma (PHAS) is a rare tumor, which usually presents as a rapid enlargement of the liver. To date, surgery, chemotherapy, and radiotherapy have not improved the poor prognosis of PHAS with only three survivors reported. The histology of PHAS is distinct from adult angiosarcoma, because PHAS displays hypercellular whorls of sarcomatous cells, or 'kaposiform' spindle cells, in addition to the general features of angiosarcoma. We report a case of PHAS that was treated with vascular ablation, chemotherapy, and liver transplantation. Lung metastases occurred 14 months posttransplant. Author Affiliation: (1) Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA (2) Division of Pathology, MLC 1010, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45229-3039, USA (3) Department of Pathology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA Article History: Registration Date: 01/01/2004 Received Date: 12/04/2003 Accepted Date: 21/04/2004 Online Date: 30/07/2004

Byline: Gino R. Somers (1), Mary Shago (2), Maria Zielenska (2), Helen S.L. Chan (3), Bo Y. Ngan (1) Keywords: subcutaneous primitive neuroectodermal tumor; electron microscopy; immunohistochemistry; karyotype; metastases; reverse transcriptase polymerase chain reaction Abstract: Primitive neuroectodermal tumor/Ewing sarcoma (PNET/ES) rarely occurs in the skin and subcutaneous tissues. We present a case of a 16-year-old girl with primary cutaneous and subcutaneous PNET/ES of the abdominal wall. Despite wide local excision and chemotherapy, she rapidly developed cranial bone and brain metastases, followed by lung and skeletal metastases, and died shortly thereafter. The recurrent tumor exhibited light microscopic features of a small, round, blue cell tumor with intracytoplasmic glycogen. Immunohistochemical analysis showed positivity for CD99, CD56, S100, and glial fibrillary acid protein, and ultrastructural features included cytoplasmic glycogen and focal complex interdigitating synaptic junction-like cytoplasmic folds. Cytogenetic analysis of the relapsed tumor showed a complex karyotype: 47,XX,i(1)(q10), der(4)t(4 19) (q33[proportional to]q35 q13.1), + 8,t(15 17)(q24 p11.2[proportional to]p12),der(19)t (19 20)(q13.1 p11.2),der(22)t(20 22)(q13 q13). Cytogenetic, interphase fluorescence in situ hybridization, and molecular genetic analyses failed to show t(11:22) (q24 q12) or abnormalities of chromosome region 22q12. The clinical behavior and atypical and complex cytogenetic abnormalities exhibited by the tumor in this patient are unusual and represent the most aggressive end of the clinical spectrum of cutaneous and subcutaneous PNET/ES. Author Affiliation: (1) Division of Pathology, Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada (2) Division of Molecular Genetics, Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada (3) Division of Haematology/Oncology, Department of Paediatrics, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada Article History: Registration Date: 01/01/2004 Received Date: 18/02/2004 Accepted Date: 17/05/2004 Online Date: 06/10/2004

Byline: H. Isaacs (1) Keywords: Fetal cardiac tumors; Neonatal cardiac tumors; Tuberous sclerosis Abstract: Primary tumors of the heart are uncommon in the fetus and neonate. Nevertheless, the widespread use of new imaging techniques has contributed significantly to earlier diagnosis, treatment, and thus improved survival. The clinical findings, imaging studies, pathology, and outcome of 224 fetuses and neonates with cardiac tumors collected from the literature are evaluated and discussed. Most tumors are benign, and of these rhabdomyoma is the most common, followed by teratoma, fibroma, oncocytic cardiomyopathy, vascular tumors, and myxoma. Malignant and metastatic tumors are described but are rare. Murmurs, arrhythmias, cyanosis, respiratory distress, and cardiac failure are the main presenting signs of cardiac tumors in the perinatal period. Disturbances in hemodynamic function are correlated with the size and location of the tumor. Cardiac vascular tumors have the best outcome, whereas malignant tumors have the worst. The purpose of this review is to concentrate on the fetus and neonate in an attempt to determine the various ways cardiac tumors differ clinically and morphologically in this age group from those occurring in older children and adults and to show that certain types of tumors have a better prognosis than others. Author Affiliation: (1) Department of Pathology, Children's Hospital San Diego, 3020 Children's Way, MC 5007, San Diego, CA 92123 and University of California San Diego School of Medicine, La Jolla, CA 92093-0612, USA Article History: Registration Date: 01/01/2003 Online Date: 19/04/2004

Byline: Tadashi Iwanaka (1), Mari Arai (1), Hiroshi Kawashima (1), Sumi Kudou (1), Jun Fujishiro (1), Satohiko Imaizumi (1), Keiko Yamamoto (1), Ryouji Hanada (1), Akira Kikuchi (1), Toshinori Aihara (1), Hiroshi Kishimoto (1) Keywords: Neuroblastoma; Ovarian tumor; Laparoscopy; Thoracoscopy; Children Abstract: The aim of this study was to evaluate the advantages and complications of endosurgical procedures for benign and malignant pediatric solid tumors. Endosurgical techniques of biopsy and excision were used for diagnosis and treatment of solid tumors, respectively. Since July 1997, a total of 24 biopsies and 24 excisions have been performed laparoscopically for neuroblastoma (n=24), ovarian solid tumors (n=10) and other tumors. Seventeen biopsies and six excisions were performed for abdominal neuroblastoma, while ten excisions were performed for ovarian tumor. In these patients, the length of the operation, blood loss, time to start postoperative feeding, time to start postoperative chemotherapy and length of hospital stay were evaluated and compared to the those of the open surgery group. Furthermore, intra- and postoperative complications were analyzed in all patients of both groups. The length of the hospital stay and time to start postoperative feeding were significantly shorter in the group of patients who underwent endosurgical procedures for either abdominal neuroblastoma or ovarian tumor when compared to the open procedure group. The time to start postoperative chemotherapy was shorter only in the abdominal neuroblastoma group. The procedure for two patients undergoing endosurgical tumor excision had to be converted to open surgery due to large tumor size. Two weeks after thoracoscopic excision of a dumb bell-type neurofibroma, one patient underwent open repair of the dura mater because of leakage of cerebrospinal fluid. There were no port-site recurrences in any tumor types. Endosurgical procedures for solid tumors are effective and minimally invasive. However, better indicators are needed for their implementation in order to prevent complications and subsequent conversions to open procedures. Author Affiliation: (1) Saitama Children's Medical Center, 2100 Magome, Iwatsuki, 339-8551, Saitama, Japan Article History: Registration Date: 01/01/2003 Online Date: 20/12/2003

Byline: S. W. Moore (1), D. Satge (2), A. J. Sasco (3), A. Zimmermann (4), J. Plaschkes (5) Keywords: Neonatal tumours; Congenital tumours; Neonate; Children Abstract: Neonatal tumours occur every 12,500--27,500 live births and comprise 2% of childhood malignancies, but there is little clarity as to their real prevalence, sites of origin and pathological nature as reported series vary. As an entity, neonatal tumours provide a unique window of opportunity to study tumours in which minimal environmental interference has occurred. The majority of tumours present with a mass at birth (e.g., teratomas, neuroblastomas, mesoblastic nephroma, fibromatosis), which are not infrequently identified on antenatal ultrasound. Histologically, teratoma and neuroblastoma remain the two main tumour types encountered with soft tissue sarcoma, renal tumours, CNS tumours and leukaemia being the next most common tumour types identified. Malignant tumours are uncommon in the neonatal period per se and benign tumours may have malignant potential. A particular problem exists in clinical classification, as histological features of malignancy do not always correlate with clinical behaviour. Benign tumours may also be life threatening because of their size and location. Other tumours may demonstrate local invasiveness, but no metastatic potential, and tumours that are clearly malignant may demonstrate unpredictable or uncertain behaviour. Screening programmes have brought more tumours to light, but do not appear to affect the overall prognosis. They may provide clues to the stage at which tumours develop in foetu. The aetiology of cancer in children is multifactorial and includes both genetic and environmental factors. The association between congenital abnormalities and tumours is well established (15% of neonatal tumours). Genetic defects are highly likely in neonatal tumours and include those with a high risk of malignancy (e.g., retinoblastoma), but also genetically determined syndromes with an increased risk of malignancy and complex genetic rearrangements. Tumours are mostly genetically related at a cellular level and factors influencing cellular maturation or apoptosis within the developing foetus may continue to operate in the neonatal period. Cytogenetics of neonatal neoplasms appear to differ from neoplasms in older children, thus possibly explaining some of the observed differences in clinical behaviour. Certain constitutional chromosome anomalies, however, specifically favour tumuors occurring in the foetal and neonatal period. In support of this hypothesis, certain cytogenetic anomalies appear to be specific to neonates, and a number of examples are explored. Other environmental associations include ionizing radiation, drugs taken during pregnancy, infections, tumours in the mother and environmental exposure. Author Affiliation: (1) Department of Paediatric Surgery, University of Stellenbosch, P.O. Box 19063, Tygerberg, 7505, Cape Town, South Africa (2) Laboratoire d'Anatomie Pathologique Centre Hospitalier, Tulle, France (3) Epidemiologie Analytique Centre International de Recherche sur le Cancer, Lyon, France (4) Department of Pathology, University Children's Hospital, Berne, Switzerland (5) Department of Paediatric Surgery, University Children's Hospital, Berne, Switzerland Article History: Online Date: 11/09/2003

Byline: Pimlak Charoenkwan (), Christof Senger (), Sheila Weitzman (), Elizabeth Sexsmith (), Christopher G. Sherman (), David Malkin (), Paul S. Thorner () Abstract: Twenty-nine pediatric immature teratomas were reviewed to determine the frequency and clinical significance of p53 expression. Tumors were stained for p53 expression by immunohistochemistry and results were correlated with the presence of other germ cell tumor elements and with outcome. Sequencing of p53 for mutations was performed on positive cases. Eighteen cases showed widespread positive p53 staining of the immature teratoma elements, 9 showed staining only in very occasional cells, and 2 cases showed no staining. Of the 18 positive cases, 5 recurred. All five were pure immature teratomas at diagnosis. Four recurred as immature or mature teratoma and one as a sarcoma all except one showed frequent cells positive for p53 in the recurrent tumor. Another 5 of the 18 diffusely positive cases contained immature teratoma as well as other malignant germ cell elements at diagnosis none of these recurred. None of the remaining eight cases with frequent positive cells, the nine cases with occasionally positive p53 staining, or the two cases with no staining recurred or demonstrated other germ cell tumor elements. We conclude that p53 expression is not unusual in immature teratoma and diffuse p53 immunopositivity is associated with recurrence or the presence of malignant elements in ~50% of cases. In only 1 of 29 cases tested was p53 immunopositivity associated with mutations in the p53 gene hence, overexpression in the majority of cases is presumed to reflect increased half-life of the protein from undetermined stabilizing factors. Expression of p21, a p53 target gene, was only focal, suggesting impaired transcriptional activation by p53. The finding of frequent p53-positive cells in immature teratoma should prompt a search for malignant elements within the tumor and affected patients should be followed closely for evidence of recurrence. Author Affiliation: () Division of Hematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada, M5G 1X8, CA () Division of Pathology, The Hospital for Sick Children, Toronto, Canada, CA () Department of Pediatrics, University of Toronto, Toronto, Canada, CA () Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada, CA () Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, TH Article History: Received Date: 08/12/2001 Accepted Date: 21/05/2002

Byline: David S. Dickens (), Rafal Kozielski (), Javed Khan (), Anne Forus (), Timothy P. Cripe () Abstract: Therapies for metastatic pediatric sarcomas have reached maximum tolerated doses, but continue to provide suboptimal cure rates. Additionally, these treatments are associated with numerous short- and long-term side effects. Therefore, the search for newer, less toxic therapeutic agents is warranted. Overexpression of the inducible enzyme, cyclooxygenase-2 (COX-2), has been discovered in a variety of adult solid tumors and numerous studies have shown COX-2 inhibitors to have significant antiproliferative effects. Therefore, we sought to determine the expression of COX-2 in pediatric sarcomas. We evaluated rhabdomyosarcoma (RMS), osteosarcoma (OS), and Ewing sarcoma (EWS) samples for COX-2 expression by immunohistochemical analysis as well as by cDNA microarray analysis. COX-2 expression was detected in 48/58 (82.8%) tumors by immunohistochemistry and in an additional 52/59 (88.1%) tumors tested by microarray gene analysis. There was a trend toward increased COX-2 expression in metastatic rhabdomyosarcoma and osteosarcoma, though it did not reach clinical significance. The degree of COX-2 immunoreactivity did not vary significantly with other clinicopathologic features such as age, gender, or histologic classification. We conclude that the majority of these pediatric sarcoma samples express COX-2 to varying degrees. Therefore, studies testing the efficacy of COX-2 inhibitors in the treatment of pediatric sarcomas are warranted. Author Affiliation: () Department of Pediatrics, Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA, US () Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA, US () Pediatric Oncology Branch, National Cancer Institute, Gaithersburg, MD 20877, USA, US () Department of Tumor Biology, Norwegian Radium Hospital, Montebello, N0310 Oslo, Norway, NO Article History: Received Date: 19/06/2001 Accepted Date: 10/03/2002

Byline: Hwei-Yee Lee (), Chui-Shuen Yoon (), Nicolas Sevenet (), Vasanthi Rajalingam (), Olivier Delattre (), Norman Q. Walford () Abstract: The rhabdoid predisposition syndrome (RPS) is characterized by pedigrees in which two or more individuals carry germline mutations of the hSNF5/INI1 tumor suppressor gene. The tumors associated with the syndrome include atypical teratoid/rhabdoid tumor (AT/RT), choroid plexus carcinoma, medulloblastoma, and extrarenal rhabdoid tumor. Rhabdoid tumor of the kidney (RTK) has not been described as part of the RPS. We report a case of a 7-month-old boy with RTK whose sister had a malignant cerebellar tumor followed by a malignant lung and pleural tumor of childhood with typical rhabdoid histology. Molecular genetic analysis of the RTK and tissue from the pleural tumor revealed in both cases identical nonsense mutations of the hSNF5/INI1 gene on chromosome 22q11.2, where thymidine was substituted for cytosine in base 472. The proband had an identical germline mutation. This is the fifth genetically analyzed RPS pedigree and the first to include an RTK. Author Affiliation: () Department of Pathology, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore, SG () Laboratoire de Pathologie Moleculaire des Cancers, INSERM U 509, Institut Curie, 26, Rue d'Ulm, 75248 Paris Cedex 05, France, FR () Department of Paediatric Medicine, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore, SG Article History: Received Date: 14/11/2001 Accepted Date: 15/03/2002

Byline: Michael A. Liew (1), Cheryl M. Coffin (2), Jonathan A. Fletcher (3), Minh-Thu N. Hang (1), Katsumi Tanito (1), Michihito Niimura (4), David Viskochil (1) Keywords: Key words: neurofibromatosis type 1, polymerase chain reaction, synovial sarcoma Abstract: Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder that is caused by a mutation in the NF1 gene. Hallmark characteristics include dermal neurofibromas, cafe-au-lait spots, and learning disabilities. In approximately 25% of NF1 cases, plexiform neurofibromas, or peripheral nerve sheath tumors (PNSTs) that involve large segments of nerve sheath and nerve root, can form, of which a small percentage become malignant (MPNST). Most MPNSTs are composed of spindled neoplastic cells, and they can resemble other spindle-cell sarcomas, including leiomyosarcoma and monophasic synovial sarcoma. Histological diagnosis of MPNST is not always straightforward, and various immunohistochemical and molecular adjuncts can be critical in establishing a correct diagnosis. One example of genetic testing is the assay for the t(X 18) chromosomal translocation, which has been found to be common in synovial sarcomas. The aim of this study was to determine whether MPNSTs contain the t(X 18) chromosomal translocation. To detect the t(X 18) translocation product, SYT-SSX, total RNA was extracted from frozen archival tumors (15 dermal neurofibromas, 4 plexiform neurofibromas, and 7 MPNSTs) using Trizol. The RNA was then subjected to reverse-transcriptase polymerase chain reaction (RT-PCR) to specifically amplify SYT-SSX. None of the dermal neurofibromas, plexiform neurofibromas, or MPNSTs analyzed were positive for SYT-SSX mRNA. The results indicate that the t(X 18) translocation is absent in neurofibromas and is not a marker for MPNST in patients with NF1. Author Affiliation: (1) Department of Pediatrics, Division of Medical Genetics, University of Utah, 50 North Medical Drive, Salt Lake City, UT 84132, USA, US (2) Department of Pathology, Primary Children's Medical Center and University of Utah, 100 North Medical Drive, Salt Lake City, UT 84132, USA, US (3) Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA, US (4) Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan, JP Article note: Received July 29, 2001 accepted October 15, 2001.

Byline: Francesca Diomedi Camassei (1), Paola Francalanci (1), Fabio Ferro (2), Nicola Capozza (3), Renata Boldrini (1) Keywords: Key words: cystic dysplasia of rete testis, testicular tumor, renal malformations Abstract: Cystic dysplasia of the rete testis (CDT) is a rare congenital defect, characterized by multiple irregular cystic spaces in the mediastinum of the testis that may involve the whole gonad. A review of the literature has shown 32 reported cases, the majority of which were associated with ipsilateral renal malformations (agenesis/cystic dysplasia). Pathogenesis may be attributed to an early insult involving mesonephric duct development. Although treatment is surgical, when feasible, a conservative or nonoperative approach is suggested. Here we report two cases, one in a 3-year-old boy and one in a 10-day-old newborn. Concomitant cystic dysplasia of ipsilateral kidney was present in the former patient, while CDT was the solitary finding in the latter patient. Orchiectomy was performed in both patients, for extensive gonad involvement in the older boy and for suspected gonad torsion in the newborn patient. Author Affiliation: (1) Department of Pathology, 'Bambino Gesu' Children's Hospital (Research Institute), Piazza S. Onofrio 4, 00165 Rome, Italy, IT (2) Department of Pathology, Andrologic Surgery Unit, 'Bambino Gesu' Children's Hospital (Research Institute), Rome, Italy, IT (3) Department of Pathology, Urologic Surgery Unit, 'Bambino Gesu' Children's Hospital (Research Institute), Rome, Italy, IT Article note: Received May 19, 2001 accepted July 16, 2001.

Byline: Douglas K. Graham (1), Linda C. Stork (1), Qi Wei (2), J. David Ingram (3), Frederick M. Karrer (4), Gary W. Mierau (2), Mark A. Lovell (2) Keywords: Key words: peripheral primitive neuroectodermal tumor, pPNET, Ewing's sarcoma, EWS-FLI1, pediatric oncology, small bowel tumor Abstract: We present a pediatric peripheral primitive neuroectodermal tumor (pPNET) localized exclusively to the small bowel. The tumor presented in an adolescent male and the diagnosis was confirmed by electron microscopy, CD99 immunopositivity, and molecular genetic analysis that demonstrated an EWS-FLI1 type 2 fusion transcript. This case report and a review of the literature underscore the considerable phenotypic overlap in EWS-related tumors in this site and the necessity for molecular genetic analysis to permit accurate classification. Author Affiliation: (1) Department of Hematology, Oncology, and Bone Marrow Transplant, The Children's Hospital, University of Colorado Health Sciences Center, 1056 East 19th Avenue, Denver, CO 80218, USA, US (2) Department of Pathology, The Children's Hospital, University of Colorado Health Sciences Center, 1056 East 19th Avenue, Denver, CO 80218, USA, US (3) Department of Radiology, The Children's Hospital, University of Colorado Health Sciences Center, 1056 East 19th Avenue, Denver, CO 80218, USA, US (4) Department of Surgery, The Children's Hospital, University of Colorado Health Sciences Center, 1056 East 19th Avenue, Denver, CO 80218, USA, US Article note: Received September 13, 2001 accepted September 28, 2001.

Byline: Sandy S. Wu (1), Margaret H. Collins (2), Jean-Pierre de Chadarevian (1) Keywords: Key words: cardiac rhabdomyoma, spider cells, ubiquitin, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling, tuberous sclerosis Abstract: Rhabdomyomas are the most common primary cardiac tumors in children, and have been shown to undergo spontaneous regression. The aim of our study was to investigate morphologically and immunohistochemically some mechanisms that may explain this clinical phenomenon. Eleven tumors from three term newborn girls who had physical and radiographic features pathognomonic of tuberous sclerosis were evaluated. Control specimens were left and right heart sections from five autopsies of age- and sex-matched patients who died of causes unrelated to the cardiovascular system. The tumors had been surgically excised from various regions in the heart, and all had similar 'typical' histology. Histomorphologic evaluation with von Kossa and alizarin-red stains and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method were performed to evaluate cell calcifications, necrosis, and apoptosis. Ubiquitin immunohistochemical study was also conducted to evaluate intracytoplasmic protein degradation. In cardiac rhabdomyomas (CR), all myocytes with acidophilic cytoplasmic myofibrils showed strong intracytoplasmic ubiquitin immunoreactivity, compared with the occasional weak cytoplasmic and focal nuclear positivity in control heart sections. Calcified myocyte nuclei were commonly seen in CR tumoral and nontumoral rhabdomyocytes, whereas control nontumoral cardiac myocytes did not show any calcification. The incidence of TUNEL reactivity seen in CR (4.8 nuclei per 100 cardiac rhabdomyocyte nuclei) was higher than that seen in control heart sections (1.7 nuclei per 10.sup.6 cardiac myocytes, P &lt 0.005). The data led us to conclude that the cytoplasmic contents in CR were degraded via the ubiquitin pathway, and from our observation of increased TUNEL positivity, the rate of cell death in CR appeared increased. These findings may explain, to some extent, the mechanism of tumor regression. Author Affiliation: (1) Department of Pathology and Laboratory Medicine, MCP Hannemann University School of Medicine and St. Christopher's Hospital for Children, Front Street at Erie Avenue, Philadelphia, PA 19134, USA, US (2) Department of Pathology, Children's Hospital Medical Center, 333 Burnet Avenue, Cincinnati, OH 45229, USA, US Article note: Received February 18, 2000 accepted October 25, 2000.

Byline: Hong Zhou (1), Wei Cheng (1), K. Y. Lam (2), Godfrey C. F. Chan (3), P. L. Khong (4), Paul K. H. Tam (5) Keywords: Keywords Solid-cystic papillary tumor of the pancreas; Children; Asian Abstract: Solid-cystic papillary tumor (SCPT) of the pancreas is a rare neoplasm in children. The current study attempted to estimate the incidence and possible pathological origin of the tumor. Clinicopathologic features of the children under the age of 16 years with pancreatic tumors managed in a single institution between January 1993 and November 1999 were reviewed. Representative blocks of SCPT specimens were immunostained for neuron-specific enolase (NSE) chromogrannin, synaptophysin, insulin, glucagon, somatostatin, and gastrin. There were three SCPTs, two pancreatic endocrine tumors, and one acinar cell carcinoma during the study period. The estimated yearly incidence in the referral area of 2 million population is about 0.01 pediatric SCPT per year per 100,000 population. The children underwent surgical removal of the tumors. Postoperatively, they were followed up for 6 months to 4 years and were well. Immunostaining for NSE, chromogranin, synaptophysin, insulin, somatostatin, and gastrin was negative in all cases. SCPT may thus be the most common pancreatic tumor in the Asian pediatric population. The pathological origin of the tumor remains unclear and requires further investigations. Author Affiliation: (1) Division of Pediatric Surgery, Department of Surgery, Queen Mary Hospital, The University of Hong Kong Medical Centre, Hong Kong, China, CN (2) Department of Pathology, Queen Mary Hospital, The University of Hong Kong Medical Centre, Hong Kong, China, CN (3) Department of Pediatrics, Queen Mary Hospital, The University of Hong Kong Medical Centre, Hong Kong, China, CN (4) Department of Radiology, Queen Mary Hospital, The University of Hong Kong Medical Centre, Hong Kong, China, CN (5) Division of Pediatric Surgery, Department of Surgery, The University of Hong Kong Medical Centre, Queen Mary Hospital, Pok Fu Lam Road, Hong Kong, China, CN Article note: Accepted: 30 October 2000

Byline: Adam C. Smith (1), Jeremy A. Squire (3), Paul Thorner (5), Maria Zielenska (5), Cheryl Shuman (7), Ronald Grant (9), David Chitayat (7), Joy L. Nishikawa (7), Rosanna Weksberg (1) Keywords: Key words: 11p15, alveolar rhabdomyosarcoma, Beckwith-Wiedemann syndrome, cancer Abstract: Rhabdomyosarcoma (RMS) is a soft tissue tumor of childhood frequently diagnosed between the first and fifth year of life. Children with the Beckwith-Wiedemann syndrome (BWS), a congenital overgrowth syndrome characterized by exomphalos, macroglossia, and macrosomia, have an increased risk of developing childhood tumors including Wilms tumor, hepatoblastoma, neuroblastoma, and RMS. Although an association between RMS and the BWS is well accepted, only four cases have been reported to date, and of these, three were reported as embryonal RMS. Based on these data, an association between BWS and embryonal RMS has been proposed. We report three additional cases of BWS with RMS and review the clinical data for each patient as well as the pathology of their tumors. All three cases of BWS had histology consistent with alveolar RMS and were diagnosed at 6 weeks and 5 and 13 years of age. In two of these BWS cases, constitutional defects of 11p15 imprinting were demonstrated. Furthermore, cytogenetic analysis of the tumors did not detect the t(2 13) or t(1 13) translocations that generate the PAX3- or PAX7-FKHR fusion proteins common to alveolar RMS. These observations suggest that the development of alveolar RMS tumors in BWS may occur without the chromosomal rearrangement producing the PAX-FKHR fusion protein. In summary, we present three new cases of RMS demonstrating a new association between BWS and an uncommon subtype of alveolar RMS. The absence of the translocations commonly associated with alveolar rhabdomyosarcoma suggests a common 11p15 pathway for alveolar RMS and BWS. Author Affiliation: (1) Institute of Medical Sciences, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada, CA (2) Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada, CA (3) Departments of Laboratory Medicine and Pathobiology and Medical Biophysics, University of Toronto, 100 College Street, Toronto, Ontario M5G 1L5, Canada, CA (4) Department of Pathology, Princess Margaret Hospital and Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada, CA (5) Department of Pediatric Laboratory Medicine, Division of Pathology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada, CA (6) Department of Laboratory Medicine and Pathobiology, University of Toronto, 100 College Street, Toronto, Ontario M5G 1L5, Canada, CA (7) Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada, CA (8) Department of Pediatrics and Medical and Molecular Genetics, The University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada, CA (9) Department of Pediatrics, Division of Hematology Oncology, Hospital for Sick Children and University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada, CA Article note: Received May 25, 2001 accepted July 11, 2001.

Byline: Amilcar Antonio Castellano-Sanchez (1), Erwin Schemankewitz (2), Claire Mazewski (3), Daniel J. Brat (1) Keywords: Key words: brain neoplasm, glioma, chordoid, metaplasia, cartilage Abstract: Chordoid gliomas are uncommon primary brain tumors that arise in the region of the third ventricle. Reports of this entity to date have been limited to adults. We present a case of a chordoid glioma arising in the hypothalamic/third ventricle region of a 12-year-old male who presented with visual symptoms. The neoplasm consisted of cords and clusters of well-differentiated, spindled-to-rounded cells containing abundant eosinophilic cytoplasm within a prominent mucinous matrix. Unlike other chordoid gliomas, this lesion contained islands and sheets showing cartilaginous differentiation intermixed with the glial component. A graded transition between neoplastic glial and chondroid regions was evident, and cells in both regions were strongly immunoreactive for GFAP and S-100. Cartilaginous metaplasia is infrequent in gliomas, but occurs most often in pediatric neoplasms of the midline such as this chordoid glioma. Thus, chondroid metaplasia represents an unusual histopathologic feature of chordoid glioma--in this case, presenting in a child. Author Affiliation: (1) Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 1364 Clifton Road NE, Atlanta, GA 30322, USA, US (2) Department of Pathology, Children's Healthcare of Atlanta at Scottish Rite, 1001 Johnson Ferry Road, Atlanta, GA 30342, USA, US (3) Department of Hematology and Oncology, Children's Healthcare of Atlanta at Scottish Rite, 1001 Johnson Ferry Road, Atlanta, GA 30342, USA, US Article note: Received March 30, 2001 accepted May 31, 2001.

Byline: Josephine Wyatt-Ashmead (1), Bette Kleinschmidt-DeMasters (2), Gary W. Mierau (1), David Malkin (3), Edmund Orsini (1), Loris McGavran (4), Nicholas K. Foreman (5) Keywords: Key words: choroid plexus carcinoma, rhabdoid tumor, deletion of chromosome 22, monosomy 22, p53 Abstract: Five of six poorly differentiated choroid plexus carcinomas identified at our institution contained cells displaying a rhabdoid phenotype. Immunoperoxidase stains showed focal positivity for cytokeratin, epithelial membrane antigen, glial fibrillary acidic protein, S100, and vimentin. The MIB-1 proliferative index ranged from 7.0% to 27.1%. All six tumors were p53 positive. Only the one child with Li-Fraumeni syndrome had a p53 germline mutation. Electron microscopy verified choroid plexus differentiation and the co-existence of rhabdoid cells. Of the five studied, four had deletions of chromosome 22 [three with monosomy 22 and one with del(22)(q12)]. Thus, there was a phenotypic and genotypic overlap between choroid plexus carcinomas and rhabdoid tumors. Author Affiliation: (1) Pathology Department, The Children's Hospital, 1056 East 19th Avenue B120, Denver, CO 80218, USA, US (2) Neuropathology Department, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA, US (3) Department of Pediatrics, Division of Oncology, The Hospital for Sick Children and University of Toronto, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8 (4) Colorado Genetics Laboratory, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA, US (5) Neuro-Oncology Department, The Children's Hospital, 1056 East 19th Avenue B120, Denver, CO 80218, USA, US Article note: Received December 5, 2000 accepted May 20, 2001.

Byline: Sara O. Vargas (1), Vania Nose (1), Jonathan A. Fletcher (1), Antonio R. Perez-Atayde (1) Keywords: Key words: chromosomes, human, pair 8, pair 17, cytogenetics, fluorescence in situ hybridization, lung neoplasms, pulmonary blastoma, pleuropulmonary blastoma, rhabdomyosarcoma Abstract: Pleuropulmonary blastoma, an aggressive tumor that is emerging as a distinct entity of childhood, is characterized by mesenchymal elements (including undifferentiated blastema and often cartilaginous, rhabdomyoblastic, or fibroblastic differentiation) and epithelium-lined spaces. We investigated two patients with pleuropulmonary blastoma, a 3-year-old boy and an 11-year-old girl, both with large cystic masses replacing one lung. In both children, the post-chemotherapy resection specimens showed more maturation of rhabdomyoblasts and more nuclear pleomorphism in all mesenchymal cell lines, compared with biopsies sampled before treatment. Karyotypic analysis demonstrated gains in chromosome 8 in both cases and 17p deletion in one case. Fluorescent in situ hybridization analysis demonstrated that the chromosome 8 gains were present in all mesenchymal elements, including undifferentiated blastematous, rhabdomyoblastic, fibroblastic, and chondroblastic areas. Epithelial cells showed no chromosome 8 gains. The chromosome 8 aberrations were not appreciably different in pre- versus post-chemotherapy tissue. Our findings substantiate previous reports that polysomy of chromosome 8 is a consistent feature of pleuropulmonary blastoma. Further, they indicate that clonal proliferation in pleuropulmonary blastoma is restricted to the malignant mesenchymal elements, supporting the notion that the epithelial components of this tumor are non-neoplastic. Author Affiliation: (1) Department of Pathology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA, US (2) Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA, US Article note: Received December 5, 2000 accepted April 25, 2001.

Byline: Alyson M. Booth (1), Robin D. LeGallo (1), Mark H. Stoler (1), Peter E. Waldron (2), Lisa A. Cerilli (1) Keywords: Key words: heart, angiosarcoma, malignant hemangioendothelioma, metastatic, pediatric, ovary, vascular tumor, sarcoma, cardiac Abstract: We report the seventh case of angiosarcoma of the heart in a child. The patient was a 23-month-old female who presented for lower extremity limping and underwent open surgical biopsy of the femur. Immediately postoperatively, she developed pericardial tamponade, and a bulky intracardiac mass was discovered as the underlying cause. The mass was composed of highly pleomorphic tumor cells reactive for the endothelial markers CD31, CD34, and factor VIII--related antigen (FVIII-RA). Staging evaluation revealed widespread metastases involving the brain, ovaries, and bone marrow. She died of complications of metastatic disease 8 months following initial presentation. Unusual features of this case include the young age of the patient, left-sided nature of the cardiac tumor, presentation secondary to metastatic disease, and the pattern of metastases. The literature on cardiac angiosarcoma, which is limited to six case reports in the pediatric population, is also reviewed. Author Affiliation: (1) Department of Pathology, University of Virginia Health System, Box 800214, Charlottesville, VA 22908, USA, US (2) Department of Pediatrics, University of Virginia Health System, Box 800386, Charlottesville, VA 22908, USA, US Article note: Received September 15, 2000 accepted February 9, 2001.

Byline: Cheppail Ramachandran (1), Steven J. Melnick (1), Enrique Escalon (3), Ziad Khatib (3), Perseus Jhabvala (1), Hugo B. Fonseca (2), Stanley Smith (1), Arturo Alamo (2), Santiago Medina (4) Keywords: Key words: congenital mesoblastic nephroma, infantile fibromatosis, gene expression, reverse transcriptase-polymerase chain reaction assay, apoptosis, cell proliferation, drug resistance Abstract: A newborn baby boy was diagnosed with the mixed form of congenital mesoblastic nephroma (CMN) representing both classic and cellular histology features in the renal tumor. Additionally, the patient had skin and bone lesions consistent with multifocal involvement of a generalized infantile fibromatosis (IFS). Both skin and bone lesions were distinctly different from CMN and did not represent metastasis. The primary tumor cell line (MCH-MN-1), established from the resected right kidney tumor, had a diploid DNA content. Cytogenetic studies revealed deletion on the long arm of chromosome 3 (q21q24) and duplication on the short arm of chromosome 11 (p15). MCH-MN-1 cells expressed ETV6-NTRK3 gene fusion transcripts, characteristic of cellular and mixed forms of CMNs. The cells had high p21 and low Bax mRNA expression in the reverse transcriptase-polymerase chain reaction (RT-PCR) assay. The high level of proliferative marker (Ki67) mRNA expression correlated well with the pluripotent nature of MCH-MN-1 in tissue culture (cell doubling time = 12.4 h). Our results showed that MCH-MN-1 might be a good model cell line for investigations on mesoblastic nephroma. Author Affiliation: (1) Department of Pathology, Miami Children's Hospital, 3100 SW 62nd Avenue, Miami, FL 33155, USA, US (2) Research Institute, Miami Children's Hospital, 3100 SW 62nd Avenue, Miami, FL 33155, USA, US (3) Department of Hematology and Oncology, Miami Children's Hospital, 3100 SW 62nd Avenue, Miami, FL 33155, USA, US (4) Department of Radiology, Miami Children's Hospital, 3100 SW 62nd Avenue, Miami, FL 33155, USA, US Article note: Received July 31, 2000 accepted January 29, 2001.

Byline: John E. Fisher (1), Peter C. Burger (2), Elizabeth J. Perlman (2), Paul S. Dickman (3), David M. Parham (4), Van H. Savell, Jr. (4), Robert E. Hutchison (5), Charles N. Paidas (2), Elaine Rappaport Lev (6) Keywords: Key words: frozen section, pediatric neoplasms, history of medicine Abstract: This article is the offshoot of a Pediatric Oncology Group (POG) seminar presented at the Adams Mark Hotel, Denver, Colorado, Friday, May 21, 1999, titled 'The Frozen Section in Pediatric Solid Tumors--Crucial Issues.' There were eight presenters who spoke on a wide range of topics that included historical perspectives of the frozen section and discussion of the following systems: brain, renal, germ cell, bone, soft tissue, and lymph nodes. To complement these presentations, a pediatric surgeon explained his concern and philosophy regarding the use of frozen sections, and a lawyer tackled the issues and risks in rendering a frozen section diagnosis. We think that this review covers all the important aspects of the frozen section in our current practice of pediatric pathology. Author Affiliation: (1) Department of Pathology, Children's Hospital of Buffalo--Kaleida Health and State University of New York at Buffalo, 219 Bryant Street, Buffalo, NY 14222, USA, US (2) Department of Pathology, John Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21205, USA, US (3) Department of Pathology, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213-2583, USA, US (4) Department of Pediatric Pathology, Arkansas Children's Hospital, University of Arkansas-Medical School, 800 Marshall Street, Little Rock, AR 72202, USA, US (5) Department of Clinical Pathology, State University of New York Health Science Center, 750 East Adams Street, Syracuse, NY 13210, USA, US (6) Barnes and Thornburg, Attorneys-at-Law, 2600 Chase Plaza, Chicago, IL, USA 60603, US

Byline: Megan K. Dishop (1), William N. O'Connor (1), Simon Abraham (2), Carol M. Cottrill (3) Keywords: Key words: lipoblastoma, cardiac tumor, pediatric, atrium Abstract: Lipoblastoma is a benign adipose tumor in children that has been described in various anatomic locations, most commonly the extremities. We describe the case of a 17-month-old boy diagnosed with cardiac lipoblastoma, a previously unreported primary cardiac tumor in children. Our patient presented with symptoms of coughing, wheezing, and hoarseness and was found to have a large mediastinal mass, which narrowed the left mainstem bronchus and compressed the right atrium and superior vena cava, causing superior vena cava syndrome. Surgical exploration revealed an intrapericardial soft tissue mass arising from the area of the posterior interatrial septum. Grossly, the resected mass was lobulated, pale yellow, and fatty with focal areas of gray myxoid tissue. Microscopically, the tumor consisted of both immature and mature adipocytes, with focal vascular myxoid areas containing lipoblasts, diagnostic of lipoblastoma. Two months after surgery, the patient was in good health without evidence of recurrence. Author Affiliation: (1) Department of Pathology and Laboratory Medicine, University of Kentucky Medical Center, MS 117, Lexington, KY 40536, USA, US (2) Division of Cardiothoracic Surgery, University of Kentucky Medical Center, C 204, Lexington, KY 40536, USA, US (3) Department of Pediatrics, University of Kentucky Medical Center, MN 478, Lexington, KY 40536, USA, US Article note: Received April 13, 2000 accepted August 17, 2000.

Byline: Ranganathan Sarangarajan (1), D. Ashley Hill (1), Peter A. Humphrey (1), Michael G. Hitchcock (2), Louis P. Dehner (1), John D. Pfeifer (1) Keywords: Key words: primitive neuroectodermal tumor, Ewing's sarcoma, viscera, Wilms' tumor, second malignancy Abstract: Primitive neuroectodermal tumor (PNET) is a prototypic malignant small round cell tumor of childhood that is characterized in most cases by t(11 22) resulting in an EWS-FLI1 gene fusion. Once thought to be uncommon, PNET now accounts for almost 20% of malignant soft tissue tumors in children. Increased recognition of PNET is partly due to advances in immunohistochemistry and molecular diagnostics, which have led to the identification of the tumor in non-classical sites. We report the clinical, histologic, immunohistochemical, and molecular findings of two visceral PNETs of the digestive system--one involving the small intestine and the other involving the hepatic duct. Histologically, each tumor was composed of malignant small cells growing in sheets, nests, and lobules the tumor cells of both cases showed characteristic immunoreactivity for vimentin and O13 (CD99). Reverse transcription-polymerase chain reaction (RT-PCR) analysis for t(11 22) using nested primers was performed with RNA extracted from paraffin-embedded, formalin-fixed tissue and demonstrated an EWS exon 7 to FLI1 exon 5 fusion in both cases, confirmed by Southern blot hybridization and DNA sequence analysis. These results illustrate the expanded clinicopathologic profile of PNET, and demonstrate that visceral PNETs, despite their unusual sites of presentation, maintain the characteristic immunohistochemical and genetic features of PNETs at more conventional sites. Author Affiliation: (1) Lauren V. Ackerman Laboratory of Surgical Pathology, Washington University Medical Center, St. Louis, MO 63110--1093, USA, US (2) Department of Pathology, Wake Forest University School of Medicine, Forsyth Medical Center, Winston-Salem, NC 27103, USA, US Article note: Received November 9, 1999 accepted February 28, 2000.

Byline: Shuji Ogino (1), Shigeki Kubo (2), Fadi W. Abdul-Karim (1), Mark L. Cohen (1) Keywords: Key words: atypical teratoid/rhabdoid tumor, choroid plexus tumor, ependymoma, insulin-like growth factor II, insulin-like growth factor receptor type 1, medulloblastoma Abstract: Insulin-like growth factor (IGF)-II is an important growth factor in development of the central nervous system. The purpose of this study was to evaluate expression of IGF-II and IGF receptor type 1 (IGFR1) in various pediatric brain tumors. Immunohistochemistry for IGF-II and IGFR1 was performed on 15 choroid plexus papillomas (CPPs) including 1 atypical CPP, 2 choroid plexus carcinomas (CPCs), 5 anaplastic ependymomas, 7 nonanaplastic ependymomas (simply referred to as 'ependymoma'), 5 medulloblastomas, 1 cerebral neuroblastoma, and 1 atypical teratoid/rhabdoid tumor (ATRT) along with 10 non-neoplastic choroid plexus and 3 non-neoplastic ependymal linings. All non-neoplastic choroid plexus, CPPs, CPCs, anaplastic ependymomas, ATRT, 71% of ependymomas, and 67% of non-neoplastic ependymal linings showed cytoplasmic positivity for IGF-II, whereas all medulloblastomas and the cerebral neuroblastoma were negative for IGF-II. In addition to cytoplasmic positivity for IGFR1, membranous positivity was observed in 73% of CPPs, both CPCs, the ATRT, 22% of non-neoplastic choroid plexus, 80% of anaplastic ependymomas, and 29% of ependymomas, but not in any medulloblastoma, cerebral neuroblastoma, or non-neoplastic ependymal lining. IGF-II and IGFR1 may play roles in the pathogeneses of CPP, CPC, anaplastic ependymoma, ependymoma, and ATRT. Immunohistochemical testing for IGF-II and IGFR1 may be useful in differentiating ATRT, CPC, and anaplastic ependymoma from medulloblastoma and cerebral neuroblastoma. Author Affiliation: (1) Department of Pathology, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH 44106, USA, US (2) Department of Neurosurgery, Takarazuka Municipal Hospital, Takarazuka-city, Hyogo, 665-0827, Japan, JP Article note: Received June 23, 1999 accepted September 30, 1999.

Byline: Arvind B. Kasaragod (1), M. Scott Lucia (2), Gary Cabirac (1), Gary R. Grotendorst (3), Kurt R. Stenmark (1) Keywords: Key words: angiogenesis, connective tissue growth factor, fibroblast, myofibroblast, myofibroblastic tumors, endothelial cells Abstract: Human connective tissue growth factor (CTGF) is a secreted cysteine-rich peptide and a member of the peptide family that includes serum-induced immediate gene products such as a v-src-induced peptide and a putative proto-oncogene, c-src. CTGF is secreted by endothelial cells, fibroblasts, smooth muscle cells, and myofibroblasts. Its expression is increased in various human and animal fibrotic diseases. We hypothesized that tumors with significant fibrous and vascular components would exhibit increased expression of CTGF. We examined the expression of CTGF mRNA by in situ hybridization in 12 pediatric tumors and tumor-like conditions, including angiofibroma, malignant fibrous histiocytoma, infantile myofibromatosis, and malignant hemangiopericytoma. All the tumors showed moderate to intense CTGF expression in tumor cells and/or endothelial cells of the associated vasculature. Angiofibromas expressed CTGF only in factor VIII--positive endothelial cells and vascular smooth muscle cells. In contrast, infantile myofibromatosis, malignant hemangiopericytomas, and fibrous histiocytomas expressed CTGF in both endothelial cells and in vimentin-positive tumor cells, particularly those around the blood vessels. CTGF mRNA was not detected in the inflammatory cells observed in many of the tumors. The presence of CTGF in the endothelial cells and tumor cells around blood vessels raises the possibility that CTGF is involved in the pathogenesis of these myofibroblastic tumors. Author Affiliation: (1) Division of Pediatric Critical Care and Developmental Lung Biology Laboratory, University of Colorado Health Sciences Center, 4200 E. Ninth Avenue, Denver, CO 80262, USA, US (2) Department of Pathology, University of Colorado Health Sciences Center, 4200 E. Ninth Avenue, Denver, CO 80262, USA, US (3) University of Miami School of Medicine, Department of Cell Biology and Anatomy, 1600 North West 10th Avenue, Miami, FL 33136, USA, US Article note: Received December 13, 1999 accepted May 23, 2000.

Byline: Maja Barnard (1), Jane Bayani (2), Ronald Grant (4), Ikuko Teshima (1), Paul Thorner (1), Jeremy Squire (1) Keywords: Key words: pleuropulmonary blastoma, spectral karyotyping, chromosome translocation Abstract: Pleuropulmonary blastoma (PPB) is a rare, malignant intrathoracic pediatric tumor. It arises from the lung, pleura, or mediastinum and its pathogenesis and relationship to other pediatric solid tumors is not well understood. In this study, a case of PPB in a 3-year-old girl was studied using a combination of molecular genetic methods and cytogenetics. Molecular analysis of the commonly encountered fusion translocation gene products of pediatric solid tumors failed to detect a rearrangement. Cytogenetic analysis, supplemented by multicolor spectral karyotyping (SKY), identified an unbalanced translocation between chromosomes 1 and X, resulting in additional copies of 1q, an extra copy of Xq, and loss of part of Xp. In addition, trisomy 8 was detected. The identification of new chromosomal alterations and confirmation of previously reported ones in this rare neoplasm helps to improve our understanding of its pathogenesis and association with other pediatric tumors. Author Affiliation: (1) Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8, CA (2) Ontario Cancer Institute, Princess Margaret Hospital, 610 University Avenue, University Health Network, Toronto, Ontario, Canada M5G 2M9, CA (3) Department of Laboratory Medicine and Pathobiology, Banting Institute Faculty of Medicine, University of Toronto, 100 College Street, Toronto, Ontario, Canada M5G 1L5, CA (4) Department of Pediatrics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8, CA Article note: Received April 8, 1999 accepted August 20, 1999.

Byline: R.M. Freedom (1), K.-J. Lee (1), C. MacDonald (2), G. Taylor (3) Keywords: Key words: Cardiac tumors -- Pediatrics Abstract: Considerable literature concerning cardiac tumors in infancy and childhood has accumulated summarizing the prevalence, histologic types, clinical presentation and outcome, and changing imaging algorithms [1, 7, 10, 14, 20, 24, 33, 37, 43, 48, 57, 58, 60--62, 67, 69, 70, 90, 105, 106, 110, 124, 139, 140, 142, 143, 149]. In this review, we focus on selected aspects of cardiac tumors in the neonate, infant, and child, with an emphasis on imaging modalities [6, 13, 15, 18, 21--23, 60, 71, 77, 80, 92, 98, 99, 103, 107, 112, 114, 119, 146]. Various types of primary cardiac tumors in childhood are discussed in this article. Author Affiliation: (1) Department of Pediatrics, University of Toronto Faculty of Medicine and Division of Cardiology, the Hospital for Sick Children, 555 University Avenue, Room 1503C, Toronto, Ontario M5G 1X8, Canada, CA (2) Department of Medical Imaging, University of Toronto Faculty of Medicine and Division of Cardiology, the Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada, CA (3) Department of Pathology, University of Toronto Faculty of Medicine and Division of Cardiology, the Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada, CA

Byline: Tara Marshall (1), Joe C. Rutledge (1) Keywords: Key words: flow cytometry, pediatric neoplasia, DNA ploidy, cell cycle, tumor, prognosis Abstract: Author Affiliation: (1) Department of Laboratory Medicine, Children's Hospital and Regional Medical Center, 4800 Sand Point Way NE, Seattle, WA 98105, USA, US (2) Department of Laboratory Medicine, University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, USA, US Article note: Received August 15, 1999 accepted December 3, 1999.

Byline: Charles G. Eberhart (1), Daniel J. Brat (2), Kenneth J. Cohen (3), Peter C. Burger (1) Keywords: Key words: brain neoplasms, pediatric tumors, primitive neuroectodermal tumors, rosette Abstract: We have encountered a series of seven unusual neuroblastic pediatric central nervous system (CNS) neoplasms with a unique constellation of histologic, immunohistochemical, and ultrastructural features. The tumors presented in five girls and two boys, ages 1 to 3 years. In six cases the lesions involved the frontoparietal region, in one case the tectal plate. The tumors consisted of small to medium-sized, round to oval, hyperchromatic cells with poorly defined cytoplasmic borders. Cells were found in clusters and cords set in a paucicellular fibrillar neuropil matrix. Distinctive, virtually anuclear regions of neuropil were scattered throughout the lesions. True rosettes with well-formed central lumens often filled with granular debris were present, along with perivascular pseudorosettes and occasional Homer-Wright rosettes. Mitoses and apoptosis were frequent, but large regions of confluent necrosis were absent. Immunohistochemically, the neuropil-like areas as well as the perinuclear cytoplasm of many embryonal tumor cells were positive for synaptophysin and neurofilament protein. Ultrastructurally, the tumor cells showed microtubule-containing neuronal processes, some with neurosecretory granules. While the lesions were largely glial fibrillary acidic protein (GFAP) negative, there was focal GFAP positivity consistent with divergent differentiation in one case. The clinical outcome was poor, with five patients dead from their disease 5 to 14 months after initial presentation and one patient with recurrent disease 7 months after resection and chemotherapy. The final patient is alive without recurrent disease 30 months after initial presentation. These lesions present distinctive histological features within the group of primitive neuroectodermal tumors. Author Affiliation: (1) Department of Pathology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA, US (2) Department of Pathology, Emory University School of Medicine, 1364 Clifton Road N.E., Atlanta, GA 30322, USA, US (3) Department of Oncology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA, US Article note: Received November 2, 1998 accepted September 9, 1999.

Byline: MARGARET J. EVANS (1), D.SCOTT A. SANDERS (2), JEREMY H.J. GRANT (3), KAREN BLESSING (3) Keywords: Key words: congenital nevi, Melan-A, Spitz nevi Abstract: The expression of the antibody Melan-A in 27 benign melanocytic skin lesions (10 congenital nevi, 10 Spitz nevi, and 7 pigmented spindle cell nevi) was compared to that of S100 protein and HMB-45. To evaluate the role of Melan-A in differentiating melanocytic and nonmelano-cytic lesions we assessed a number of benign nonmelano-cytic skin lesions including neurofibromas, granular cell tumors, and dermatofibromas. Melan-A had an identical staining pattern to S100 protein in the melanocyte population of all lesions, but had the advantage of only staining cells of melanocytic lineage and no other cell types. HMB-45, although staining the junctional components of all lesions with a junctional component, showed varied intensity and distribution in the dermal components. Melan-A is much cleaner than S100 protein, having no background staining, and in skin appears to be specific for melanocytes. The nonmelanocytic lesions did not express Melan-A. Author Affiliation: (1) Department of Paediatric Pathology, Royal Hospital for Sick Children, 2 Rillbank Terrace, Edinburgh EH9 1LF, UK, GB (2) Department of Pathology, University Department, The Medical School, Edgbaston, Birmingham B1S 2TT, UK, GB (3) Department of Pathology, Worthing Hospital, Park Avenue, Worthing, West Sussex BN11 2DH, UK, GB Article note: Received September 1, 1998 accepted April 26, 1999.

Byline: Glenn E. Dickey (1), Cirilo Sotelo-Avila (3) Keywords: Key words: juvenile fibromatosis, soft tissue tumor, fibrous tumor, myofibroblastic proliferation, immunohistochemistry, electron microscopy, hamartoma Abstract: 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. Author Affiliation: (1) Department of Prenatal, Perinatal and Placental Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA , US (2) Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA , US (3) Department of Pathology, Cardinal Glennon Children's Hospital, 1465 South Grand Boulevard and St. Louis University School of Medicine, St. Louis, MO 63104, USA , US Article note: Received March 2, 1998 accepted December 15, 1998.

Byline: Agnes S. Chan (1), Sue MacNeill (1), Paul Thorner (1), Jeremy Squire (2), Maria Zielenska (1) Keywords: Key words: desmoplastic small round cell tumor, variant EWS-WT1 chimeric product, translocation, chromosome 11, chromosome 22 Abstract: Chromosome translocations found in neoplasms often result in the creation of hybrid genes encoding chimeric proteins. Desmoplastic small round cell tumor (DSRCT) is a recently described aggressive malignancy associated with a unique chromosomal translocation t(11 22)(p13 q12). This translocation has recently been characterized, revealing the rearrangement and fusion of the WT1 gene on chromosome 11 to the EWS gene on chromosome 22. Fusion of these two genes results in the production of a putative oncogenic protein composed of the zinc finger DNA-binding domains of WT1 linked to the potential transcriptional regulatory domains of EWS. The typical chimeric transcript consists of the first 7 exons of EWS and the last 3 exons of WT1. We report here the first case of DSRCT with a variant EWS-WT1 chimeric product that includes 9 exons of EWS and 3 exons of WT1. Author Affiliation: (1) Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8 , CA (2) Department of Oncologic Pathology, The Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9 , CA (3) Graduate Department of Cellular and Molecular Pathology, University of Toronto, Toronto, Ontario, Canada M5G 1L5 , CA Article note: Received February 4, 1998 accepted June 4, 1998.

Byline: Paul Thorner (1), Jeremy Squire (2), Natasha Plavsic (1), Roland Jong (1), Mark Greenberg (3), Maria Zielenska (1) Keywords: Key words:WT1, polyphenotypic tumor, mesothelioma Abstract: The WT1 gene is normally expressed in fetal kidney and mesothelium, and its expression has been suggested as a marker for Wilms tumor and mesothelioma. We examined WT1 expression levels by reverse-transcriptase polymerase chain reaction (RT-PCR) in 38 childhood small-cell tumors including Wilms tumor, embryonal and alveolar rhabdomyosarcoma, Ewing sarcoma, lymphoma, desmoplastic small round-cell tumor (DSRCT), synovial sarcoma, extrarenal rhabdoid tumor, and two tumors that were atypical for this group of tumors. WT1 expression was only detected in Wilms tumor, rhabdoid tumor, and in these two cases of uncertain histogenesis. Both arose in the peritoneal cavity and by immunohistochemistry were diffusely positive for vimentin, keratin, and desmin. Tonofilaments were identified by electron microscopy in one of the cases. RT-PCR failed to detect the t(11 22) translocation associated with DSRCT in either case. Our results suggest that WT1 expression is an unusual feature of childhood non-Wilms tumors and, in the right setting, it may indicate a mesothelial origin. The expression of WT1 may play a role in mesodermal cells acquiring epithelial characteristics, a concept supported by the mixed epithelial and mesenchymal phenotype of these two cases. Author Affiliation: (1) Department of Pediatric Laboratory Medicine, Division of Pathology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8 , CA (2) Division of Cellular and Molecular Biology, The Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9 , CA (3) Department of Pediatrics, Division of Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8 , CA Article note: Received November 28, 1997 accepted May 7, 1998.