Two Synchronous Neonatal Tumors: An Extremely Rare Case.

We report a case of a newborn with two synchronous tumors-sialoblastoma and hepatoblastoma-diagnosed at 20 weeks of gestation by magnetic resonance imaging (MRI) and ultrasonography (US). The aim of this study was to describe the management of this case together with a review of the literature. Our patient had a large facial tumor associated with extremely high alpha-fetoprotein levels. Diagnosis of the tumors was made by surgical biopsy, showing typical features in both. Sialoblastoma is a potentially aggressive tumor. In our case, the Ki67 index in the sialoblastoma was between 20 and 30%, indicating a possibly unfavorable behavior. The infant underwent surgery and chemotherapy in different steps. Complete surgical resection with clean margins is considered to be the best treatment option for sialoblastoma. Only four similar cases were previously reported. Timely management by a multidisciplinary team is essential in these difficult cases. In our patient, outcome was good at the time of this report.

Immune response to racotumomab in a child with relapsed neuroblastoma.

Immunotherapy targeting ganglioside antigens is a powerful tool for the treatment of high risk neuroblastoma. However, only treatment with anti-GD2 antibodies has been used in clinical practice and other options may be pursued. We report the use of racotumomab, an anti-idiotype vaccine against N-glycolyl neuraminic acid (NeuGc)- containing gangliosides, eliciting an immune response in a child with relapsed neuroblastoma expressing the NeuGcGM3 ganglioside.

Tailgut cyst (Retrorectal hamartoma): report of a pediatric case.

Tailgut cyst (TGC) is an uncommon congenital lesion, located in the retrorectal/presacral space. We report a 12-year-old girl with lumbar pain and a retrorectal mass. She had mental retardation, hypothyroidism, didelphus uterus, sacrum vertebrae, and coccyx agenesis, without chromosomic anomalies. Three surgeries were performed for the complete excision of the tumor. Microscopically, the mass consisted of cystic spaces lined by a wide variety of epithelia and a stroma composed of fibrous tissue containing bundles of smooth muscle fibers. According to these findings, the diagnosis was TGC. This is a rare congenital lesion that usually presents as a multiloculated cyst in the retrorectal space of young women; TGC requires complete surgical excision to prevent recurrences, infections, and malignant transformation. This case was unique because of the association of TGC with other malformative features and concomitant disease in a pediatric patient.

Liver infiltrating mononuclear cells in children with type 1 autoimmune hepatitis.

OBJECTIVE: To investigate infiltrating cells in the liver of children with type 1 autoimmune hepatitis (AH-1). METHODS: liver biopsies from 24 untreated AH-1 patients (14 children, 10 adults), five patients with hepatitis C virus related chronic hepatitis (HCV), and 10 control liver specimens (CL) were processed for immunohistochemical cell characterisation. RESULTS: Two different cell distribution patterns were detected in the liver of patients with AH-1: (1) CD4(+) and CD20(+) cells were found in the central areas of the portal tracts (portal distribution); (2) CD8(+) cells were observed at the periphery of the portal space (periportal distribution). Some cell subsets, like CD56, CD57, Fas-L, and Bak, showed a non-defined distribution pattern. The presence of two well defined patterns of cell distribution was not observed in HCV and CL (CD4(+), CD20(+), and CD8(+) cells were uniformly distributed in the portal space). In AH-1 and CL, the NK markers CD56 and CD57 were found scattered throughout the liver parenchyma. However, in HCV biopsies, CD56(+) cells were also clearly increased in both the portal and the periportal areas. Biopsies of AH-1 and HCV patients showed a uniform distribution of Fas-L and Bak in the portal and periportal areas, with Bak staining also detected in the hepatic parenchyma. CONCLUSIONS: Despite clinical and genetic differences, there was a similar distribution of liver infiltrating mononuclear cells in children and adults with AH-1. These results raise the possibility of reclassifying cryptogenic chronic hepatitis by immunohistochemical analysis of infiltrating liver cells.

Evolución de niños post-trasplante hepático luego del primer año de sobrevida / Evolution of children one year post liver transplant

Orthotopic liver transplantation is the only definitive mode of therapy for children with end-stage liver disease. However, it remains challenging because of the necessity to prevent long-term complications. The aim of this study was to analyze the evolution of transplanted patients with more than one year of follow up. Between November 1992 and November 2001, 238 patients underwent 264 liver transplantations. A total of 143 patients with more than one year of follow up were included. The median age of patients +/- SD was 5.41 years +/- 5.26 (r: 0.58-21.7 years). All children received primary immunosuppression with cyclosporine. The indications for liver replacement were: fulminant hepatic failure (n: 50), biliary atresia (n: 38), cirrhosis (n: 37), chronic cholestasis (n: 13) and miscellaneous (n: 5). The indications for liver re-transplantation were: biliary cirrhosis (n: 7), hepatic artery thrombosis (n: 4) and chronic rejection (n: 3). Reduced-size liver allografts were used in 73/157 liver transplants, 14 of them were from living-related donors and 11 were split-livers. Patient and graft survival rates were 93% and 86% respectively. Death risk was statistically higher in retransplanted and reduced-size grafted patients. Growth retardation and low bone density were recovered before the first 3 years post-transplant. The incidence of lymphoproliferative disease was 7.69%. De novo hepatitis B was diagnosed in 7 patients (4.8%). Social risk did not affect the outcome of our population. The prevention, detection and early treatment of complications in the long-term follow up contributed to improve the outcome.

Evolución de niños post-trasplante hepático luego del primer año de sobrevida / Evolution of children one year post liver transplant

Orthotopic liver transplantation is the only definitive mode of therapy for children with end-stage liver disease. However, it remains challenging because of the necessity to prevent long-term complications. The aim of this study was to analyze the evolution of transplanted patients with more than one year of follow up. Between November 1992 and November 2001, 238 patients underwent 264 liver transplantations. A total of 143 patients with more than one year of follow up were included. The median age of patients +/- SD was 5.41 years +/- 5.26 (r: 0.58-21.7 years). All children received primary immunosuppression with cyclosporine. The indications for liver replacement were: fulminant hepatic failure (n: 50), biliary atresia (n: 38), cirrhosis (n: 37), chronic cholestasis (n: 13) and miscellaneous (n: 5). The indications for liver re-transplantation were: biliary cirrhosis (n: 7), hepatic artery thrombosis (n: 4) and chronic rejection (n: 3). Reduced-size liver allografts were used in 73/157 liver transplants, 14 of them were from living-related donors and 11 were split-livers. Patient and graft survival rates were 93% and 86% respectively. Death risk was statistically higher in retransplanted and reduced-size grafted patients. Growth retardation and low bone density were recovered before the first 3 years post-transplant. The incidence of lymphoproliferative disease was 7.69%. De novo hepatitis B was diagnosed in 7 patients (4.8%). Social risk did not affect the outcome of our population. The prevention, detection and early treatment of complications in the long-term follow up contributed to improve the outcome.(AU)

Retinoblastoma patients with high risk ocular pathological features: who needs adjuvant therapy?

AIMS: To describe the outcome of patients with non-metastatic unilateral retinoblastoma with high risk histopathological features after primary enucleation, and to clarify the need and results of adjuvant therapy. PATIENTS AND METHODS: From 1980 to 2001 adjuvant therapy was recommended only to patients with scleral involvement, post-laminar optic nerve involvement (PLONI) with either a positive margin or associated choroidal involvement, or (before 1994) isolated PLONI. RESULTS: 108 of 224 patients had at least one high risk feature (choroidal, scleral, anterior chamber, and/or PLONI). Patients with isolated choroidal (n = 55) or anterior chamber (n = 2) invasion, and most with PLONI without other risk factors (n = 21) were not treated; three relapsed but are long term survivors after intensive therapy. Four with isolated PLONI received adjuvant chemotherapy and none relapsed. Three of 11 with PLONI and concomitant choroidal or scleral involvement who received adjuvant therapy relapsed, versus two of four not treated. Two of five with scleral disease relapsed. All 12 with cut end involvement received adjuvant treatment and none relapsed. In the total group, all four patients who relapsed after adjuvant therapy died. CONCLUSIONS: Relapsing patients can be rescued with intensive therapy. Those with isolated choroidal or PLONI have a good prognosis without adjuvant therapy. Patients with PLONI with a positive margin have a good prognosis if treated with combined therapy. Those with scleral involvement or PLONI with concomitant choroid disease may benefit from adjuvant therapy.

Small cells in hepatoblastoma lack "oval" cell phenotype.

Hepatoblastoma, a childhood tumor of the liver, is composed of epithelial and mesenchymal elements in varying proportions and at various stages of differentiation. The epithelial element recapitulates the stages of hepatocyte development from the primitive blastema through embryonal hepatocytes to fetal hepatocytes. The blastemal or undifferentiated cells have been postulated to represent neoplastic hepatocyte progenitor cells. In this study, we examine the immunophenotype of the various epithelial cells of hepatoblastoma with special emphasis on the small undifferentiated cell component and compare it with that of adult hepatocytes and hepatic stem (oval) cells. Putative stem cells in the liver can express all of the following markers: alpha-feto protein, CK19 (OV-6), chromogranin A, Bcl-2, HepPar-1, and alpha1 microglobulin. The latter, like alpha-feto protein, is a plasma protein synthesized by hepatocytes. Both alpha1 microglobulin and HepPar-1 are expressed in fetal liver cells as early as 7 weeks of intrauterine life. They are also expressed in hepatocellular carcinoma and in hepatocytic cell lines derived from normal fetal or adult liver. Formalin-fixed, paraffin-embedded archival tissues from 10 predominantly epithelial hepatoblastomas were immunostained with antibodies directed against CD 34, alpha1 microglobulin, Bcl-2, HepPar 1, and CK19 using the avidin-biotin-peroxidase method. The undifferentiated small cell component did not express any of the markers studied, namely, Bcl-2, HepPar-1, alpha(1) microglobulin, CD34, or CK19. Hepatocyte-like cells were alpha1 microglobulin- and HepPar-1-positive, with the intensity of staining correlating with the degree of hepatocytic differentiation. Bcl-2 expression was restricted to areas of ductular differentiation. CK19 was detected in foci that showed duct formation. The small cells of hepatoblastoma did not express HepPar-1, Bcl-2, CK19, alpha1 microglobulin, or CD34, markers that characterize the immunophenotype of hepatic stem cells ("oval" cells). Thus, this observation raises the following questions: (1) is "hepatoblastoma" a misnomer? (2) is the expression of tumor antigens dysregulated in hepatoblastoma? (3) does the liver have two different types of progenitor cells, oval cells and blastemal cells, with differing immunophenotypes? and (4) do the blastemal cells, rather than oval cells, represent the more primitive progenitor cells of the liver?

Microlitiasis testicular en pediatria / testicular microlithiasis in pediatric care

La microlitiasis testicular(MT)es una entidad rara,caracterizada ultrasonográficamente por la presencia de múltiples focos ecogénicos pequeños(más de cinco por campo de corte ecográfico)sin sombra acústica,generalmente bilaterales,los cuales corresponden a microcalcificaciones localizadas dentro de los túbulos seminíferos.La MT se ha asociado con patologías benignas,algunos síndromes y tumores de células germinales.Describimos 21 pacientes con Mt detectados entre julio de 1996 y Marzo de 1999,evaluamos los factores predisponentes y tratamos de establecer criterios de seguimiento.Utilizamos transductos de 7.5-10 Mhz.En todos los pacietnes se determinaron niverls de alfa-fetroproteínay betagonadotrofina coriónica humana.En 7 de ellos,se praticó biopsia testicular.Desde el momento del diagnóstico se realizó un seguimiento ecográfico semestral.De los 21 pacientes detectados con criterio ecográficos de MT,de acuerdo a su localización fueron:bilateral(n=16)unilateral(n=1)en testículo único(n=4)Las edades oscilaron entre 6 y 23 años(m=14,4 años)Los antecedentes clínicos que originaron el examen Us se agruparon en:criptoquidia corregida quirurgicamente(n=11)orquiepidimitis(n=2)traumatismo testicular(n=2)sindrómicos(n=2)torsión testicular(n=2)sindrómicos(n=2)tosion testicular operada(n=1)torsión de hidátide operada(n=1)asimetría testicular(n=1)control de leucemia(n=1)Los marcadores tumorales resultaron normales en todos los pacientes.las biopsias realizadas,5 evidenciaron cuerpos calcoficados,lamelados concentricamente,intratubulares,típicos de Mt y 2(los pacientes síndromicos)tumor de células de sertoli grandes calcificadas.La MT es un hallazgo ecográfico de patogenia desconocida.Se ha descripto asociado a tumores malignos.La evolución clínica y ecográfica es incierta.De no existir cambios clínicos evidentes,es conveniente un seguimiento ecográfico anual de los pacientes,con el fin de detectar cambios morfológicos que justifiquen la biopsia.En los casos sindromáticos,en los cuales hay asociación conocida con tumores,se debe realizar biopsia y control semestral

Acute lymphoblastic leukemia presenting as acute hepatic failure in childhood.

We report a 7-year old white girl who was admitted because of acute severe hepatic failure. Her complete blood count revealed pancytopenia and a bone marrow aspiration was consistent with acute lymphoblastic leukemia (ALL). Blasts cells were positive for cytoplasmic CD3 and cell surface T-associated markers. Viral, metabolic, immune and toxic causes for hepatic failure were ruled out. Treatment pre-phase with prednisone was started and liver function tests clearly improved after one-week therapy. However, due to her hepatic insufficiency, daily etoposide was administered orally during 15 days. On day 33 complete remission was achieved and hepatic function was normal, except for an increase in the bilirubin level which normalized on day 72. She received our current treatment for intermediate risk ALL and is still receiving continuation phase therapy, currently, with normal liver function and good tolerance to chemotherapy + 8 months after achieving complete remission.

[Barrett's esophagus: diagnosis and coexistent diseases in childhood]. / Esófago de Barrett: diagnóstico y enfermedades coexistentes en la edad pediátrica.

From 1990 to 1998, 12 patients with columnar metaplasia of the lower esophagus were diagnosed. Only 4 of them displayed a Barrett's epithelium (BE) with a specialized columnar epithelium and globet cells. As it is already published, a male predominance was observed. In three of these patients some predisposing factor to develop BE was detected (i.e. severe central nervous system damage, chronic pulmonary disease, esophageal atresia and chemotherapy). All patients had severe gastroesophageal reflux (GER) with abnormal pH probe. Diagnosis was suggested by characteristic endoscopy images in 2 patients and was confirmed by biopsy in all cases. All patients had been primary treated with proton-bomb inhibitors. Two patients were treated by a Nissen fundoplication, 4 and 6 month after diagnosis, respectively. One patient with severe neurological damage will undergo the same surgery soon. In another patient with caustic esophageal injury, the affected esophagus will be resected, restoring continuity with stomach or colon. In view of the potential oncogenous transformation of BE, the importance of not overlooking this anomaly in all patients with severe GER is highlighted. All cases with predisposing factors to develop BE should be closely followed by periodic examination and multiple biopsies.

Retinoblastoma with low risk for extraocular relapse.

OBJECTIVE: To define a subgroup of patients with retino-blastoma and low risk of extraocular relapse through histopathological and clinical variables. PATIENTS AND METHODS: Inclusion criteria consisted of stage I (intraocular disease), stage IIb1 (without concomitant choroid and/or scleral invasion), and nonenucleated patients (according to the Grabowski-Abramson classification). A total of 112 consecutive patients admitted to Hospital JP Garrahan from 1987 to 1997 were evaluable. Treatment included enucleation or local therapy and no chemotherapy. RESULTS: Forty-one patients had stage Ia (intraretinal), 8 stage Ib (prelaminar optic nerve invasion), 40 stage Ic (uveal invasion), and 12 stage IIb1 (postlaminar optic nerve invasion and cut end free of tumor). Eleven patients had neither eye enucleated. Median follow-up was 60 months. Only two events occurred: one patient had progressive disease in the contralateral globe and died of CNS metastasis and another had an orbital relapse that was successfully treated. Both had choroidal invasion. Five-year pEFS and pOS were 0.97 and 0.98, respectively. Neither length of the optic nerve stump, tumor size, anterior chamber invasion, degree of differentiation, nor degree of ocular coat invasion correlated with increased risk of metastasis. CONCLUSIONS: A subset of patients with retinoblastoma with low risk of relapse can be determined using histopathological evaluation of the invasion of ocular coats. Adjuvant chemotherapy is not warranted for patients with intraretinal extension and prelaminar optic nerve invasion. It is also probable that those patients with isolated choroidal invasion and those with postlaminar optic nerve extension with surgical margins clear of tumor do not need chemotherapy.

Short-term cyclosporine induces a remission of autoimmune hepatitis in children.

BACKGROUND/AIMS: The current immunosuppressive treatment of patients with autoimmune hepatitis consists of prednisone and azathioprine. High doses of prednisone used to obtain the remission of the disease are associated with serious adverse effects. To avoid harmful consequences of prednisone therapy, we proposed to treat patients with oral cyclosporine to obtain the remission of the inflammatory process. METHODS: This is a pilot, multinational, multicenter, clinical trial involving children with autoimmune hepatitis. Thirty-two children were recruited, who according to international criteria were considered as having definite autoimmune hepatitis. Cyclosporine alone was administered for 6 months, followed by combined low doses of prednisone and azathioprine for 1 month, after which cyclosporine was discontinued. Biochemical remission of the disease was established by the follow-up of serum transaminase activity levels. Growth parameters and adverse effects of the treatment were recorded. RESULTS: Two patients were withdrawn from the study: one for non-compliance and the other for liver failure which did not improve with cyclosporine. Of the 30 remaining patients, 25 normalized alanine aminotransferase activity levels by 6 months and all the patients by 1 year of treatment. Z-scores for height showed a trend towards improvement during treatment. Adverse effects of cyclosporine were mild and disappeared during weaning off the medication. CONCLUSIONS: Cyclosporine induced the biochemical remission of the hepatic inflammatory/necrotic process in children with autoimmune hepatitis, with few and well-tolerated adverse effects.

Immunohistochemical evaluation of hepatoblastomas with use of the hepatocyte-specific marker, hepatocyte paraffin 1, and the polyclonal anti-carcinoembryonic antigen.

The distinction of hepatoblastoma, especially the embryonal type, from other small, round-cell tumors of childhood can sometimes be difficult. Polyclonal anticarcinoembryonic antigen (pCEA) and Hepatocyte Paraffin 1 (Hep Par 1) are immunohistochemical markers that are useful in the diagnosis of hepatocellular carcinomas. We immunohistochemically studied pCEA, monoclonal CEA (mCEA), and Hep Par 1 on 12 hepatoblastomas (3 fetal type, 2 embryonal type, and 7 mixed epithelial type). In addition, we studied the expression of Hep Par 1 on 27 other selected childhood tumors, including 1 hepatocellular carcinoma, 5 germ-cell tumors, 4 peripheral neuroectodermal tumors/Ewing's sarcomas, 3 rhabdomyosarcomas, 5 neuroblastomas, 2 rhabdoid tumors, 3 lymphomas, and 4 Wilms' tumors. All of the hepatoblastomas expressed Hep Par 1 with a characteristic granular intracytoplasmic pattern that was generally less intense in embryonal-type than in fetal-type hepatoblastomas, perhaps reflecting the degree of hepatocyte differentiation. All of the fetal-type hepatoblastomas expressed pCEA with both an intracytoplasmic and bile canalicular pattern. Embryonal type hepatoblastomas were more likely to be pCEA negative or to show focal or no canalicular pattern of expression, again possibly reflecting the degree of hepatocyte differentiation. All of the hepatoblastomas were mCEA negative. All of the nonhepatoblastomas were Hep Par 1 negative, except for the one hepatocellular carcinoma in this study, which was Hep Par 1 positive. We conclude that Hep Par 1 and pCEA are useful markers for hepatoblastomas, as they have been shown to be in hepatocellular carcinomas.

Results of a stage-based protocol for the treatment of retinoblastoma.

PURPOSE: To describe the treatment of retinoblastoma at a single institution using a prospective protocol based on histopathologic staging. PATIENTS AND METHODS: We included 116 consecutive patients (101 eligible, 46 bilateral) from August 1987 to December 1993. Treatment was enucleation or conservative therapy for intraocular disease (stage I patients). Stage II patients (orbital or postlaminar invasion) received vincristine, cyclophosphamide, and doxorubicin for 57 weeks. Patients with orbital mass and extension beyond the cut end of the optic nerve also received orbital radiotherapy (45 Gy). The latter received intrathecal therapy. In those with CNS (stage III) or hematogenous metastasis (stage IV), cisplatin and etoposide were added along with cranial (in patients with a CNS mass and prophylactically in stage IV) or craniospinal (in patients with positive CSF) radiotherapy. RESULTS: The median follow-up time was 39 months (range, 12 to 84). The overall survival rate was 0.84. Survival rates according to stage were as follows: stage I probability of overall survival [pOS] = 0.97) (alive/total), 59 of 60; stage II (pOS = 0.85) including patients with scattered episcleral cells, three of three; orbital mass, one of one; postlaminar invasion up to and beyond the cut end of optic nerve, 10 of 11 and 11 of 14, respectively; of stage III (pOS = 0), zero of six; and stage IV (pOS = 0.50), three of six. Only those patients with preauricular adenopathy as the only metastatic site survived in the latter group. Acute toxicity was mild. CONCLUSION: Chemotherapy is not warranted to prevent systemic metastasis for intraocular disease. Patients with extraocular orbital disease and had a good outcome with this therapy. Patients with metastatic disease fared poorly, except for those with isolated malignant preauricular adenopathy.