Treatment of congenital mesoblastic nephroma at pediatric oncology unit of Gabriel Toure teaching hospital

Fousseyni Traore1*, Belco Maiga1, Konimba Diabaté2, Yacaria Coulibaly3, Hawa Diall1, Pierre Togo1, Oumar Coulibaly1, Issa Amadou3, Karamoko Sacko1, Abdoul Karim Doumbia1, Abdoul Aziz Diakite1, Bakary Kamaté4, Fatoumata Dicko-Traoré1, Mariam Sylla1, Boubacar Togo1 1Gabriel Toure hospital, department of pediatrics, Bamako-Mali 2National hospital of Mali, Radiation therapy service, Bamako-Mali 3Gabriel Toure hospital, pediatric surgery service, Bamako-Mali 4Hospital of Point G, department of histopathology, Bamako-Mali


Introduction
Congenital Mesoblastic Nephroma (CMN) is a renal tumor of the newborn and young infant.This tumor was first described by Bolande in 1967 as a distinct tumor from nephroblastoma by its histological, therapeutic and prognostic features 1 .It is classically considered benign, and most often, only the surgical treatment is enough for its management.CMN occurs in 90% of cases before one year of age and in 60% of cases before 4 months 2 .It accounts for 3% to 4% of pediatric renal tumors 3 .Obstetric ultrasound permits to make in utero diagnosis 4 .Histologically, there are three variants of this tumor: the classical form, the cellular and mixed form (Fig. 1).Abdominal ultrasound and CT scan are commonly used radiological examinations.Ultrasound appearance can vary depending on the pathological variant.In general it is a well-defined mass with low-level homogeneous echoes.The abdominal CT scan shows a solid hypoattenuating renal lesion with variable contrast enhancement (Fig. 2).The clinicalhistological correlation and the prognosis of the disease have not been demonstrated 5,6 .And in Africa, in general, few studies have been carried out on CMN.In this study, we report our experience on the management of this tumor at the pediatric oncology unit of teaching hospital Gabriel Toure.

Objectives
This retrospective study aimed at evaluating the epidemiological, therapeutic and evolutive aspects of children treated for CMN.

Patients and methods
The study was performed retrospectively from 01 January 2005 to 31 December 2016 (duration 11 years), in the pediatric-oncology unit of Gabriel Touré Teaching Hospital.Were included, patients with histologically proven CMN.Parents or legal guardian consent has been obtained.All patients had a complete clinical oncology evaluation combined with CBC (complete blood count) routine check, echocardiography, renal and hepatic function tests, HIV (human immunodeficiency virus), HbsAg (hepatitis B virus), Rhesus grouping, serum electrolytes, and haemoglobin electrophoresis.The Z-score on WHO's growth standards (weight-height score according to age of children) was used to evaluate the nutritional status of the patients.Abdominal computed tomography (CT scan) with contrast was also performed on all patients.The data was collected from medical records.Patient monitoring after surgery was done with a thoraco-abdominal CT scan, performed at 6 months, 1 year, and once a year for 3 years.

Statistical analysis:
The follow-up time for each patient was counted from inclusion in the study to the latest information.For overall survival (OS), all deaths were counted regardless of the cause and the survival times of the living patients were censored at the time of closure.Data from the included patient medical records was analyzed on SPSS version 20 (SPSS Inc., Chicago, IT).

Results
Eight cases of CMN were included.It accounted for 3% of renal tumors (n=251) during the same period.The median age was 4.5 months (1 month-6 months) with a sex ratio of 0.33 (M = 2, F = 6).Sixty-two percent of the patients had a low socioeconomic status; twenty-five percent of patients had medical insurance (n = 2).Antenatal ultrasonography was normal in all patients.Abdominal mass was the most common physical sign (n = 7; 87%).One patient presented the association of abdominal mass and hematuria (n = 1; 12.5%).Computed tomography was performed in five patients (62%) and abdominal ultrasonography in three patients (37%).There was no difference according to the laterality (right kidney, n = 4; left kidney, n = 4).Three patients with significant tumor volume have received neoadjuvant chemotherapy (37%).Five patients received primary nephro-ureterectomy (n=5; 62%).The surgery was performed without incident in 75% of the cases.CMN with the classic histological form was confirmed in all patients (n = 8, The histological stages were as follows: stage 1 (n = 4; 50%), stage 2 (n = 2; 25%), unspecified (n = 2; 25%).Two patients have received adjuvant chemotherapy (25%), with 11% toxicity (18 courses): neutropenia grade 3 (n = 2) and anemia grade 3 (n = 2).All patients were in complete remission after the treatment and no relapse has been noticed.Overall survival was 100% with a median follow-up of 8 years (6 -10 years).The characteristics of the patients are summarized in Table 1.

Discussion
CMN is a renal tumor considered as benign, occurring in 90% of cases before the age of one year.It represents 3% to 4% of pediatric renal tumors 7 , which are found in our series.The median age in our series is 4.5 years with female predominance.Exceptionally the tumor can be diagnosed in the old child and sometimes even in the adult.The male sex is predominant in several series 8,9 .The presence of an abdominal mass of renal origin remains the major symptom in CMN 10 .Antenatal diagnosis is currently feasible from the second trimester of pregnancy 11 .None of our patients had an antenatal diagnosis.The diagnosis in neonate or in infant is most often made after the palpation of an abdominal mass.The etiological research of arterial hypertension in the infant can often lead to the diagnosis.Radiographically, ultrasound and CT-scan have an important role 12,13 .CT-scan provides a better understanding of the extent of the disease (abdomen, lungs and brain).Sixty-two percent of our patients had CT-scan.Concerning laterality, there was no difference in our patients.This identical distribution is found in the studies of Bayindir and England RJ 14,15 .Surgery remains the main therapeutic option of the CMN.Neoadjuvant chemotherapy remains exceptional in the CMN.Its goal is to obtain a tumor reduction to facilitate excision.Thirty-seven percent of our patients with significant tumor volume at diagnosis received neoadjuvant chemotherapy.Neoadjuvant chemotherapy has been indicated in patients with significant tumor volume at diagnosis.It allowed tumor reduction, allowing enlarged nephrectomy without any surgical complications.Bayindir and England RJ have reported 20% and 4% preoperative chemotherapy respectively in their series 14,15 .Nephroureterectomy was performed in all our patients.The precision of the surgical and histological stage is crucial for further postoperative treatment.Adjuvant chemotherapy has been performed on two patients (25%) due to unclear surgical and histological stage in our series.Sandstedt reports 17% postoperative chemotherapy in 29 patients treated for CMN 16 .The classic histological form was found in all our patients (100%).It remains predominant in the literature and is made of fusiform cells, of the fibroblast and myofibroblast types, intertwined 17 .Genetic abnormalities related to CMN have been reported.These abnormalities are found in chromosomes 8, 11, 17 and 20.In the cellular form of CMN, a translocation (12; 15) was found, resulting in the formation of an ETV6-NTRK3 fusion gene 18,19,20 .The genetic study of our cases has not been done for lack of means.The overall survival of our patients is 100% with a median follow-up of 8 years (6 -10 years).This result is similar to those found in other series 14,15,21 Treatment strategy: Enlarged uretero-nephrectomy was indicated in all included patients.Patients with significant tumor volume at abdominal CT-scan and those with no staging at surgery and imprecise histologic stage, received neoadjuvant (Vincristine 1, 5 mg/m² IV, once a week, during 4 weeks; Actynomycin-D 45 γ /kg IV, on week 1 and 4) and adjuvant chemotherapy (Vincristine 1, 5 mg/ m² IV, once a week, during 8 weeks; Actynomycin-D 45 γ / kg IV, on weeks 3 and 7), respectively.The chemotherapy regimen is based on "GFA Nephro 2005" of the Franco-African Group of Pediatric Oncology (GFAOP).Definition of the response criteria: Complete remission was defined as the disappearance of any clinical and biological signs with imagery without signs of tumor in progression.Relapse has been defined as the reappearance of the tumor regardless of the site.