[Xanthelasma and juvenile xanthogranuloma in a 7-year-old boy]. / Xanthélasmas et xanthogranulomes juvéniles chez un garçon de sept ans.

BACKGROUND: Palpebrum xanthelasma is the most common type of xanthoma seen in adults but it is extremely rare in children. We report an original case of bilateral xanthelasma palpebrarum associated with juvenile xanthogranuloma (JXG) in a 7-year-old child. Only two cases of xanthelasma in children have been described to date. The association of xanthelasma and JXG has never been described. PATIENTS AND METHODS: A 7-year-old boy presented xanthelasmas on both eyelids. At the same time, pinkish JXG papules appeared on the child's trunk. The boy had been diagnosed at the age of 10 months with myelogenous leukaemia, which was in remission. He also had a familial history of hypercholesterolaemia. The skin lesions were removed and microscopic examination confirmed the diagnosis of xanthelasmas and JXG. DISCUSSION: This patient's presentation is unusual in several respects: the presence of xanthelasma in a child, appearance of JXG at an advanced age, and the association of these two diseases in a child with a past history of leukaemia. The occurrence of these skin lesions did not appear to be linked to the history of malignant blood disease in this patient.

[Infantile fibrosarcoma mimicking rapidly involuting congenital haemangioma (RICH)]. / Fibrosarcome infantile simulant un hémangiome type rapidly involuting congenital hemangioma (RICH).

BACKGROUND: While haemangioma is common, an unusual appearance or course should alert the clinician's concern. Congenital haemangioma, particularly rapidly involuting congenital haemangioma (RICH), may carry a risk of misdiagnosis as congenital malignant tumours such as infantile fibrosarcoma (also known as congenital infantile fibrosarcoma). In this case, histological diagnosis may prove inconclusive, as in the case reported herein. PATIENTS AND METHODS: At birth, a newborn baby presented angiomatous lesions on the sole of the left foot that was initially considered as congenital haemangioma. Histopathological examination suggested highly remodelled immature infantile haemangioma. After surgery, the tumour increased in size within eight weeks. Reanalysis of the histology slides resulted in a diagnosis of infantile fibrosarcoma. This diagnosis was confirmed by the presence of a specific translocation seen in infantile fibrosarcoma (ETV6/NTRK3). CONCLUSION: There is a risk of erroneous diagnosis in newborn infants between angiomatous tumour in RICH and malignant congenital tumours (particularly infantile fibrosarcoma). Clinicians should be attentive for this type of lesion and take all necessary diagnostic measures.

Incidence and prognostic value of tumour cells detected by RT-PCR in peripheral blood stem cell collections from patients with Ewing tumour.

To retrospectively evaluate the incidence of tumour cell contamination of peripheral blood stem cell (PBSC) collections and to correlate these data with the clinical outcome after high-dose chemotherapy (HDCT) with stem cell rescue in patients with a high-risk Ewing tumour. Peripheral blood stem cell collections obtained from 171 patients were analysed. Tumour contamination was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). The files of 88 patients who underwent HDCT followed by PBSC reinfusion were reviewed in detail, and their outcome compared to the PBSC RT-PCR results. Seven of 88 PBSC collections (8%) contained tumour cells as detected by RT-PCR. Peripheral blood stem cells were collected after a median of five cycles of chemotherapy. No clinical factor predictive of tumour cell contamination of PBSC harvest could be identified. Event-free survival (EFS) and overall survival (OS) of the whole study population were 45.3 % and 51.8 % at 3 years from the date of the graft, respectively. Forty-five patients relapsed with a median time of 15 months after graft, only four of whom had tumour cell contamination of the PBSC harvest. Tumour cell contamination of PBSC collection is rare and does not seem to be associated with a significantly poorer EFS or OS in this high-risk population.

Topotecan as a radiosensitizer in the treatment of children with malignant diffuse brainstem gliomas: results of a French Society of Paediatric Oncology Phase II Study.

BACKGROUND: The current Phase II study was conducted to evaluate the survival and toxicity observed in children with newly diagnosed brainstem gliomas who were treated with the daily radiotherapy with topotecan used as a radiosensitizer. METHODS: Eligible patients were those ages 3-18 years with previously untreated tumors arising in the pons diagnosed within the previous 6 months. Histologic confirmation was not mandatory provided that the clinical and magnetic resonance imaging findings were typical for a diffusely infiltrating brainstem lesion. Treatment was comprised of a 6-week course of topotecan administered intravenously at a dose of 0.4 mg/m(2)/day over 30 minutes within 1 hour before irradiation. Radiotherapy was comprised of a once-daily treatment of 1.8 grays (Gy) per fraction to a total dose of 54 Gy. RESULTS: Thirty-two patients were included in the current study between August 2000 and October 2002. All patients completed the combined treatment in accordance with the treatment design. Only partial responses were observed, occurring in 40% of the patients. The 9-month and 12-month survival rates were 34.4% +/- 8% and 25.5% +/- 8%, respectively. The median duration of survival for these 32 patients was 8.3 months. An intratumoral cystic/necrotic change was observed in five patients, with clinical impairment noted in two patients. One intratumoral hemorrhage occurred during radiotherapy, and was associated with transitory neurologic impairment. CONCLUSIONS: The findings of the current study regarding newly diagnosed brainstem glioma patients treated with topotecan given as a radiosensitizing agent did not reproduce the encouraging results obtained in preclinical studies. Therefore, the concomitant combination of topotecan and radiotherapy at this schedule and these doses cannot be recommended for the treatment of patients with brainstem gliomas.

Treatment of childhood acute myeloblastic leukemia: dose intensification improves outcome and maintenance therapy is of no benefit--multicenter studies of the French LAME (Leucémie Aiguë Myéloblastique Enfant) Cooperative Group.

From 1989 to 1998, 341 children were included in the French multicentric LAME (Leucémie Aiguë Myéloblastique Enfant) trials. A total of 309 children were registered in the LAME 89/91 protocol. This intensive regimen included an induction phase (mitoxantrone plus cytarabine), two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase and amsacrine; 276 (90%) achieved a CR. The 5-year overall survival (OS) and event-free survival (EFS) were 60+/-4 and 48+/-4%, respectively. From 1997, timed-sequencing of the LAME SP induction chemotherapy led to an unacceptable frequency of consolidation delay; future improvements are unlikely to come from further increases in intensity. The role of allogenic bone-marrow transplantation from an HLA-identical sibling in CR1 was examined. The disease-free survival (DFS) was 52+/-4% for non-allografted patients and 57+/-7% for allografted patients (P=NS); a better OS for allografted patients was shown and could be related either to allo-BMT early in CR1 or to a second allo-BMT in CR2. For the complete responders after consolidation therapy, the 5-year OS was significantly better in patients randomized for no maintenance therapy (MT-) than in patients randomized for MT (77.6+/-8 vs 59+/-8%; P=0.05), while the 5-year DFS was not significantly different. Exposure to low-dose MT might contribute to clinical drug resistance and treatment failure in relapsing patients.

Adverse outcome of infants with metastatic neuroblastoma, MYCN amplification and/or bone lesions: results of the French society of pediatric oncology.

To assess the relevance of MYCN amplification and bone lesions in stage 4 neuroblastoma (NB) in infants aged <1 year, 51 infants with stage 4 NB were enrolled. Three groups of patients were defined according to the type of metastases and the resectability of the primary tumour. Group I comprised 21 infants with radiologically detectable bone lesions, Group II 22 patients with an unresectable primary tumour and Group III eight patients with only metaiodobenzylguanidine (MIBG) skeletal uptake. MYCN oncogene content was assayed in 47/51 tumours and found to be amplified in 17 (37%). The 5-year event-free survival (EFS) rate of these 51 infants was 64.1% (+/- 7.1%). In a univariate analysis, bone lesions, MYCN amplification, urinary vanillylmandelic/homovanillic acid ratio and serum ferritin levels adversely influenced outcome. In the multivariate analysis, radiologically detectable bone lesions were the most powerful unfavourable prognostic indicator: the EFS rate was 27.2% for these infants compared to 90% for infants without bone lesions (P<0.0001). Our data emphasize the poor prognosis of infants affected by stage 4 NB with bone lesions, especially when associated with MYCN amplification. Given the poor results in this group whatever the treatment, new therapeutic approaches need to be investigated in the future.

Improving survival in recurrent medulloblastoma: earlier detection, better treatment or still an impasse?

Early detection of relapse has been advocated to improve survival in children with recurrent medulloblastoma. However, the prognostic factors and the longer term outcome of these patients remains unclear. Pattern of recurrences were analysed in three consecutive protocols of the Société Française d'Oncologie Pédiatrique (1985-91). A uniform surveillance programme including repeated lumbar puncture combined with computerized tomography (CT) or magnetic resonance imaging (MRI) scan was applied for all registered patients. Forty-six out of 116 patients had progressive or recurrent disease. The median time from diagnosis to recurrence was 10.5 months and 76% relapses occurred during the first 2 years. Seventeen patients had asymptomatic relapses that were detected by the surveillance protocol. Forty-one patients were treated at time of progression. Twenty-three responded to salvage therapy and 11 achieved a second complete remission. The median survival time after progression was 5 months (<1-41 months), and only two patients remained alive at time of follow-up. Length of survival is primarily related to some specific patterns of relapse (time from diagnosis to recurrence, circumstances of relapse, extent of relapse) and to the response to salvage therapy. No evidence of long-term benefit appeared from any form of treatment.

Nonmetastatic intracranial germinoma: the experience of the French Society of Pediatric Oncology.

BACKGROUND: Standard treatment of localized intracranial germinoma is focal irradiation of the primary tumor (45-50 grays [Gy]) combined with craniospinal radiotherapy (RT). To decrease late effects related to extensive fields of RT, the French Society of Pediatric Oncology decided in 1990 to replace prophylactic RT with chemotherapy (CT) and to deliver focal RT at 40 Gy. METHODS: Twenty-nine patients with localized, biopsy proven germinoma were included in this study between January 1990 and December 1994. CT consisted of 2 cycles of carboplatin 600 mg/m2 on Day 1, etoposide 150 mg/m2 on Days 1-3, ifosfamide 1.8 g/m2 on Days 22-26, and etoposide 150 mg2 on Days 22-24, followed by RT delivered to the initial tumor volume (40 Gy). RESULTS: The median age of the 19 boys and 10 girls was 12.8 years; 25 patients had a unifocal tumor in the pineal (13), suprasellar (10), or thalamic (2) area, and 4 patients had a bifocal tumor. Three patients initially had complete surgery. Of the 26 patients evaluable for CT response, 11 had a small amount of tumor residue and 15 no residue; no patient underwent surgery after CT or RT. One patient recurred 3 years after diagnosis and is in his second complete remission. Twenty-eight patients are in their first complete remission after a median follow-up of 32 months (range, 7-68 months); 9 of the 28 have a small amount of tumor residue that is considered nonevolving. Overall survival at 4 years is 100% and event free survival is 93.3% (+/- 6%) after a median follow-up of 32 months. CONCLUSIONS: This treatment strategy avoids craniospinal RT and reduces focal RT, with results equivalent to those achieved with extensive RT. Thus, the authors consider it a valid treatment of nonmetastatic germinoma.

Nephrotic syndrome and Hodgkin disease in children: a report of five cases.

UNLABELLED: This report documents the occurrence of a nephrotic syndrome in five children with Hodgkin disease. In two cases the nephrotic syndrome predated the diagnosis of lymphoma by 6 months and 12 months respectively, while in the other three, the two disorders occurred simultaneously. The nephrotic syndrome resolved in four cases during effective treatment for active Hodgkin disease, while proteinuria remained unchanged in the fifth case with partial control of the lymphoma. The occurrence of a nephrotic syndrome as a manifestation of active Hodgkin disease suggests that some immunological abnormalities play a role in the pathogenesis of the association. CONCLUSION: The possibility of glomerular dysfunction although rare must be considered and actively looked for in all cases of Hodgkin disease. Similarly, any unusual sign or symptom noted in patients with nephrotic syndrome, particularly receiving or having received immunosuppressants, requires thorough investigation to determine the presence or absence of lymphoma.

[Melanoma in children: a case]. / Mélanome de l'enfant: un cas.

INTRODUCTION: Melanoma is rare in children. We report a new case. CASE REPORT: A black tumor on the medial aspect of the right thigh was removed at the age of 5 years. Histologic diagnosis was melanoma. One year later, a metastasic inguinal lymph node appeared in the right inguinal fold. Exeresis with curetage was performed followed with chemotherapy. Outcome has been favourable to date. DISCUSSION: The diagnosis of melanoma is difficult in children and is usually mistaken. In this case, the histologic diagnosis appears to have been exact and chemotherapy was performed. The rationale and modalities have been discussed.

Treatment of non-metastatic, non-seminomatous malignant germ-cell tumours in childhood: experience of the "Société Française d'Oncologie Pédiatrique" MGCT 1985-1989 study.

The members of the French Society of Pediatric Oncology treated, between January 1985 and June 1989, 67 cases of non-metastatic, non-seminomatous malignant germ cell tumours (nSGCT) in sites other than the brain. They used a clinical pre- and postsurgical TNM-type classification in order to standardize the treatment regardless of tumour site. The intensity of the treatment was decreased in comparison with the previous regimen (elimination of adriamycin, reduction in the length of treatment). The actuarial 2-year disease-free survival rate is 80%; results are excellent for patients with clinical stage I and II tumours and permit cure with moderate chemotherapy, avoiding undesirable late effects. On the other hand it is inadequate for patients with stage III suggesting that the initial chemotherapy should be intensified for these latter patients in future protocols.

Etoposide and carboplatin in neuroblastoma: a French Society of Pediatric Oncology phase II study.

PURPOSE: A phase II study of etoposide (VP 16) and carboplatin (CBDCA) was performed in patients with metastatic neuroblastoma (NB). The aim of the study was to find an alternative treatment for induction with different toxicities than the VP 16/cisplatin (CDDP) combination. PATIENTS AND METHODS: Forty-seven patients who were from 6 months to 16 years of age, with either relapsed (29) or primary resistant (18) NB, were included in a cooperative multicenter phase II study of the French Society of Pediatric Oncology (SFOP). The schedule consisted of 5 consecutive days of VP 16 100 mg/m2/d and CBDCA 160 mg/m2/d. RESULTS: The response rate for the 39 assessable patients was 43%; there were four complete remissions and 13 partial remissions. Neither the status of the patients nor the total dose of CDDP that was received previously influenced response. Hematologic toxicity was marked and caused considerable delay between courses (median interval, 39 days). In these heavily pretreated patients, 16% had a more than 50% decrease in creatinine clearance and a 22% World Health Organization (WHO) grade 2 ototoxicity. CONCLUSION: This VP 16/CBDCA combination deserves further evaluation for efficacy and toxicity in newly diagnosed patients, and the combination of both drugs should be considered for high-dose therapy with bone marrow transplantation.

Structural rearrangements of chromosome 13 as additional abnormalities in Burkitt lymphoma and type 3 acute lymphoblastic leukemia.

We report three cases of chromosome 13 rearrangements as additional abnormalities in two patients with Burkitt lymphoma (BL) and one with type 3 acute lymphoblastic leukemia (ALL). Involvement of chromosome 13 has been reported most often as 13q+, without identification of the supplementary chromosomal material; in our three cases with 13q+, we identified two duplications: dup(13)(q13q22) and dup(13)(q21q22).

Ifosfamide is an active drug in Wilms' tumor: a phase II study conducted by the French Society of Pediatric Oncology.

Twenty-one patients with advanced Wilms' tumor entered a phase II study with high-dose ifosfamide (3 g/m2 over two days every 15 days). Mesna and hyperhydration were associated with minimal bladder toxicity. After two courses, five partial responses and six complete responses were observed. Ten patients did not respond. The median duration of response was 2 months (range, 1 to 7). Therapy was delayed because of leukopenia for 1 or 2 weeks in only three cases. Fever and infection were not observed. Seven patients presented with hematuria, three of whom were among the 17 patients coadministered mesna, which did not interfere with subsequent therapy.

[Metastatic neuroblastoma: consolidation treatment with 2 courses of high-dose chemotherapy followed by a bone marrow autograft]. / Neuroblastomes métastatiques: traitement de consolidation par deux cures de chimiothérapie lourde suivies d'autogreffe médullaire.

Among 62 children over 1 year of age at diagnosis who were treated for stage IV neuroblastoma, 33 entered remission after conventional therapy. They received high-dose chemotherapy and in vitro purged bone marrow transplantation as consolidation therapy. Fifteen patients received one course and 18 two courses. At present, 16/33 grafted patients are alive in CR with a median follow-up of 28 months. Toxicity of this regimen was tolerable. Under this treatment, actuarial disease free survival is improved compared with that observed under conventional therapy.

Repeated high-dose chemotherapy followed by purged autologous bone marrow transplantation as consolidation therapy in metastatic neuroblastoma.

Among 62 children over 1 year of age at diagnosis, who were treated for stage IV neuroblastoma, 33 entered complete remission (CR) or good partial remission (GPR) after conventional therapy and received high-dose chemotherapy (HDC) with in vitro purged autologous bone marrow transplantation (ABMT) as consolidation therapy. The HDC was a combination of carmustine (BCNU), teniposide (VM-26), and melphalan. Thirty-three patients received one course of this regimen, and 18 received two courses. At present, 16 of the 33 grafted patients are alive in continuous CR, with a median follow-up of 28 months. Toxicity of this regimen was tolerable, principally marked by bone marrow depression and gastrointestinal (GI) tract complications. Four complication-related deaths were observed. Relapse post-ABMT occurred most often in the bone marrow. Under this treatment, actuarial disease-free survival is improved compared with that observed under conventional therapy.