Congenital mesoblastic nephroma: a single-centre series.

BACKGROUND: Congenital mesoblastic nephroma is a rare disease. Treatment is surgical in the first instance. Chemotherapy has traditionally been thought not to have a role. Recent literature suggests a 50% mortality rate for recurrent/metastatic disease. MATERIALS AND METHODS: This study is a retrospective case review of prospectively collected data. Demographics, histopathology, treatment, outcomes and follow up were reviewed. RESULTS: Nine patients, 6 male and 3 female, were included. The median age at presentation was one month (range 0-7 months); follow-up was for a median of 21.5 months (range 16-79 months). Two patients had mixed and classical subtypes and the other five had the cellular subtype. Surgery was completed by an open procedure in eight patients and laparoscopically in one. There were three recurrences; two were local and one was pulmonary. Recurrences were treated with a combination of chemotherapy, radiotherapy and surgery. One patient with recurrent disease died from acute-on-chronic respiratory failure secondary to lung irradiation but was disease free. The other eight are disease free, alive and well with no sequelae at latest follow-up. CONCLUSIONS: Surgery remains the mainstay of management with chemo- and radiotherapy reserved for unresectable tumours or adjuvant management of recurrent disease. Specimen-positive margins are not an indication for instituting chemotherapy. The tyrosine kinase pathway seems to be a potential target for future chemotherapeutic agents although it is too early to assess how that will impact on the management of congenital mesoblastic nephroma.

ETV6-NTRK3 in congenital mesoblastic nephroma: A report of the SIOP/GPOH nephroblastoma study.

BACKGROUND: Congenital mesoblastic nephroma (MN) is a rare pediatric renal tumor representing approximately 5% of all pediatric renal tumors. Three different types of MN are distinguished histologically: classical, cellular, and mixed. A frequent genetic alteration is the translocation t(12;15) resulting in a fusion of the ETV6 gene on 12p13 and the NTRK3 gene on 15p15 that occurs almost exclusively in cellular MN. The aim of this study was to determine translocation status of a large cohort of MN with respect to tumor subtype and outcome. PROCEDURE: In total, clinical data from 111 patients were available. Sixty-seven tumors were classical MN (51%), 29 cellular MN (31%), and 15 were mixed MN (18%). From these 111 cases, 79 were analyzed by FISH and RT-PCR. RESULTS: All classical and mixed MN were translocation negative. Seventeen out of 29 (58%) cellular MN harbored the ETV6-NTRK3 translocation. Five-year relapse-free survival (RFS) and overall survival (OS) were 93.2% and 96.8% for the complete cohort. All seven relapses occurred in translocation negative tumors. Five-year RFS was significantly inferior for cellular and mixed MN compared to classic MN (89%, 80%, and 98%), whereas 5-year OS was similar (93%, 96%, and 98%). Within the group of cellular MN, patients having translocation-positive tumors had a significantly superior RFS (5-year RFS: 100% vs. 73%). CONCLUSION: The majority of cellular MNs harbor the ETV6-NTKR3 gene fusion, whereas all classic- and mixed-type MNs were translocation negative. Within the cellular subgroup, patients having translocation-positive tumors had a significantly superior RFS.

Current Management of Fetal and Neonatal Renal Tumors.

Fetal and neonatal renal tumors are rare. Nevertheless, in-depth understanding of their features can lead to early recognition and appropriate treatment, ultimately benefiting outcome. Despite the many obvious similarities, important distinctions exist between these tumors and their counterparts in older children. Likewise, some important distinctions exist between fetal tumors on the one hand and neonatal tumors on the other. In this article, we review the pertinent features of fetal and neonatal renal tumors and specifically point out the important individualities in their clinical management.

Nefroma mesoblástico congênito subtipo celular: relato de caso / Cellular congenital mesoblastic nephroma: case report

INTRODUÇÃO: Nefroma Mesoblástico Con-gênito é uma rara neoplasia renal pediátrica. Apresenta dois subtipos histológicos, clássico e celular, sendo o último de pior prognóstico e responsável por aproximadamente dois terços dos casos. Esse tumor ainda é um desafio diagnóstico aos patologistas devido à similaridade com outras neoplasias pediátricas renais mais frequentes. RELATO DO CASO: Criança do gênero feminino, 2 anos e 9 meses de idade, foi encaminhada a serviço médico com referência em oncologia apresentando massa renal à esquerda. Após nefrectomia, o estudo do espécime mostrou, macroscopicamente, extensa área tumoral granular, brancoacinzentada, ocupando aproximadamente todo o rim, invadindo seio renal, cápsula e gordura perirrenal, com áreas de hemorragia e necrose. Histologicamente, caracterizava-se pela presença de células fusiformes e mitoses, sem atipias celulares. O diagnóstico foi de Nefroma Mesoblástico Congênito subtipo celular e a paciente foi submetida a quimioterapia. Durante o primeiro ano de tratamento, houve recidiva do tumor, apresentando-se irressecável e sem resposta a nova quimioterapia. A paciente foi a óbito aos 4 anos de idade. DISCUSSÃO: O subtipo celular do nefroma mesoblástico tende a ser mais agressivo, apresentando uma taxa de sobrevivência de 85 por cento, comparada com 100 por cento para a variante clássica. Geralmente, a recorrência ocorre no primeiro ano de tratamento, principalmente quando o subtipo é o celular.

INTRODUCTION: Congenital Mesoblastic Nephroma (CMN) is a rare pediatric renal tumor. It comprises two histological subtypes, namely classic and cellular, with the second accounting for two thirds of all cases and being more often associated with poor prognosis. It remains a diagnostic challenge for pathologists due to its similarity with other more frequent pediatric kidney neoplasms. CASE REPORT: We describe the case of a 2-year- old girl who presented with a left renal mass. After nephrectomy, the specimen analysis showed, on gross examination, an extensive, granular and whitish tumor lesion occupying almost the entire kidney, invading the renal sinus, capsule and perirenal fat, with areas of hemorrhage and necrosis. Histologically, it was characterized by ovoid spindle cells, mitoses and no cell atypia, which led to a diagnosis of cellular mesoblastic nephroma. Adjuvant chemotherapy was carried out, but tumor recurrence occurred in the first year, presenting as an unresectable tumor that did not respond to adjuvant chemotherapy and the patient died at 4 years of age. DISCUSSION: The cellular variant tends to be more aggressive, with a survival rate of 85 percent versus 100 percent for the classic variant. Recurrence generally occurs in the first year, particularly with the cellular variant.

[Management of antenatal fetal abdominal tumors. Clues for the diagnosis of a congenital mesoblastic nephroma]. / Conduite à tenir obstétricopédiatrique devant la découverte anténatale d'une masse hyperéchogène rétropéritonéale. Arguments en faveur d'un néphrome mésoblastique congénital.

The prenatal diagnosis of abdominal mass poses the problem of its origin. Renal tumors are rarer than neuroblastoma but they are most often congenital mesoblastic nephroma. The congenital mesoblastic nephroma has a good forecast in spite of a sonographic impressive aspect. MRI can help to locate tumor but cannot tell difference between the different kinds of renal tumor. Prenatal forecast is especially linked with hydramnios and hydrops fetalis. Histolological study of the tumor is important for the prognosis. Two morphological subtypes are currently distinguished: the classic type with a good forecast and the atypical or cellular type. Distant metastases have been related only to the cellular form but especially in infants aged more than 3 months and never in the newborns. The diagnosis of the tumor does not change the mode of delivery except in case of an important volume. Complications are searched during the first days of life: hypertension, hypercalcemia, vomiting, hyperreninemia. Radical nephrectomy is performed after the end of the first week. In case of a classic form, the healing is always obtained. In case of cellular form, distant metastases are searched. In any rate, the follow-up is recommended until the end of the growth.

Mesoblastic nephroma--a report from the Gesellschaft fur Pädiatrische Onkologie und Hämatologie (GPOH).

BACKGROUND: Surgery alone is the appropriate first-line treatment for patients with mesoblastic nephroma (MN). Nevertheless, there are reports of local recurrences and metastasis, especially in the cellular subtype. The authors evaluated the outcome of patients with MN who were enrolled in either the International Society of Pediatric Oncology (SIOP) 93-01/GPOH or the SIOP 2001/GPOH Nephroblastoma Study and Trial. METHODS: In total, 50 patients with MN were analyzed. Eleven patients were suspected antenatally of having a renal tumor. The median age at diagnosis was 18.5 days. Central pathologic review was performed for all specimens. The median observation time was 4.2 years. RESULTS: Forty-five patients underwent initial surgery. Five patients older than 6 months received preoperative chemotherapy. Twenty-nine tumors were classic MN, and 21 tumors were cellular MN. Nine patients had a Stage III MN, 5 of those patients had tumor ruptures, and 8 had positive surgical margins. After they underwent nephrectomy, 40 patients received no further treatment. For the entire group, event-free survival (EFS) (94%) and overall survival (OS) (95%) were excellent. Patients with a cellular MN, patients with age 3 months or older, and patients with Stage III MN had lower EFS. Three patients developed recurrent disease, and 2 of those patients died. Metastases to the brain, lung, and liver were observed in 1 patient. CONCLUSIONS: Radical nephrectomy with accurate surgical-pathologic staging is the standard of care for children with MN. Nonetheless, a subgroup of patients with MN (Stage III cellular MN in patients age 3 months or older) tends to develop recurrences more often. Further prospective studies will be needed to verify this finding and should help determine whether these patients may benefit from adjuvant therapy.

Results of the SIOP 93-01/GPOH trial and study for the treatment of patients with unilateral nonmetastatic Wilms Tumor.

BACKGROUND: The treatment of Wilms Tumor is integrated into clinical trials since the 1970's. In contrast to the National Wilms Tumor Study Group (NWTSG) the SIOP trials and studies largely focus on the issue of preoperative therapy to facilitate surgery of a shrunken tumor and to treat metastasis as early as possible. PATIENTS AND METHODS: In the SIOP 93-01/GPOH trial and study 1 020 patients with a newly diagnosed renal tumor were registered. 847 of them had a histological proven Wilms Tumor, of whom 637 were unilateral localized, and 173 tumors had an other histology [40 congenital mesoblastic nephroma (CMN), 51 clear cell sarcoma (CCSK), 24 rhabdoid tumor (RTK) and 58 other tumors]. Preoperative chemotherapy in benign tumors was given to 1.3 % of the patients. The main objective of the trial was the randomized question, if the postoperative two drug chemotherapy for stage I in intermediate risk or anaplasia can be reduced from conventional 3 courses to an experimental 1 course without loss of efficacy. RESULTS: 519 patients with unilateral nonmetastatic Wilms did receive preoperative chemotherapy. The histology in this group of patients was of intermediate risk in 469 (90 %) patients, 14 (3 %) tumors were low risk and 36 (7 %) high risk. The stage distribution of the tumors was stage I in 315 (61 %), stage II N- in 126 (24 %), stage II N+ in 25 (5 %) and stage III in 36 (7 %) patients. In 17 (3 %) patients the tumor stage remained unclear. Tumor volume was measured in 487 patients before and in 402 after preoperative chemotherapy. The median tumor volume did shrink from 353 to 126 ml. The amount of volume reduction depends on the histological subtype. The event free survival (EFS) after 5 years was 91 % for all patients with unilateral Wilms tumor without distant metastasis. Randomisation was done in 43.7 % for stage I patients and there was no difference in EFS for both treatment arms (90 versus 91 %). The EFS is identical for patients with stage I and II N- (0.92), as well as for stage II N+ and III (0.82). The tumor volume after chemotherapy is a prognostic factor for intermediate risk tumors with the exception of epithelial and stromal predominant tumors. These two subtypes often present as large tumors, they do not shrink during preoperative chemotherapy but they still have an excellent prognosis. On the other hand the prognosis of patients with blastemal predominant subtype after preoperative chemotherapy is worse than in any other patient group of intermediate risk tumors. There are less blastemal predominant tumors compared to primary surgery, but they are chemotherapeutic resistant selected by the preoperative chemotherapy. CONCLUSION: Patients with unilateral Wilms tumor without metastasis have an excellent prognosis. The post-operative chemotherapy in stage I can be reduced to 4 weeks without worsening treatment outcome. The reduction of the tumor volume could be identified as a helpful marker for stratification of post-operative treatment. Post-chemotherapy blastemal predominant subtype of Wilms tumor has to be classified as high risk tumor. Focal anaplasia has a better prognosis than diffuse anaplasia and will be classified as intermediate risk tumor.

Flow cytometric nuclear DNA content analysis of renal tumors in children: prognostic significance of nuclear DNA ploidy.

We studied, by flow cytometry, the DNA contents of paraffin-embedded tumor specimens from 90 infants and children with kidney tumors, and analyzed the relationship of DNA ploidy with histological types and prognosis. Data of adequate quality were obtained from 90 cases: 65 tumors with favorable histology, 5 congenital mesoblastic nephromas and 20 tumors with unfavorable histology. The 90 cases had nuclear DNA histogram patterns that were classified as DNA diploid in 64 tumors, aneuploid in 19 and tetraploid in 7. There were no significant correlations between DNA ploidy and histological types or clinical stages. Survival rates for patients with diploidy were 80 and 70% at 2 and 5 years, respectively, and those of patients with aneuploidy were 72 and 61% at 2 and 5 years, respectively. On the other hand, patients with a DNA tetraploid pattern had significantly worse survival rates of 43 and 29% at 2 and 5 years, respectively. Among patients with aneuploidy or tetraploidy, the S-phase fractions in those who died (mean +/- SD: 10.3 +/- 4.1 and 22.1 +/- 11.6%, respectively) appear to be greater than those in their surviving counterparts (8.8 +/- 4.0 and 12.1 +/- 2.8%). Hence, although the differences between diploid and aneuploid DNA patterns were not correlated with differential prognosis in children with kidney tumors, a tetraploid pattern clearly indicates a poor prognosis, especially in combination with histological types and clinical stages.

Outcome of solid renal tumours in children at the University Hospital of the West Indies.

Of the twenty-nine children with solid renal tumours treated at the University Hospital of the West Indies (UHWI) between January, 1972 and December, 1991, there were twenty-eight cases of nephroblastoma and one of mesoblastic nephroma. Peak incidence was between the ages of two and four years. Twenty-five children had radical nephrectomy while one had bilateral partial nephrectomy. In thirteen cases, pre-operative chemotherapy +/- radiotherapy was used. Post-operative chemotherapy and radiotherapy were used in 24 and 13 cases, respectively. Stage of the tumour was the most decisive factor influencing the outcome. Whereas there was a 100% cure rate in Stages I and II, Stage III had only a 55.5% survival rate and none of the Stage IV survived. Bilateral (Stage V) tumours are curable if individual tumours are localised, as in one of the two cases. The benign mesoblastic nephroma, in a one-month-old infant, was cured by nephrectomy alone. While the present therapy of radical nephrectomy along with combination chemotherapy is satisfactory for early stages, more aggressive adjuvant therapy is needed for improving the results in Stages III and IV.