Severe neonatal hypercalcemia revealing congenital mesoblastic nephroma: A case report and management of neonatal hypercalcemia: Severe neonatal hypercalcemia revealing congenital mesoblastic nephroma.

Congenital mesoblastic nephroma is a rare pediatric renal tumor and has been reported in patients presenting with palpable abdominal mass, arterial hypertension, hematuria, polyuria, or hypercalcemia. Here we present the case of a 1-month-old neonate with suspected parathyroid hormone (PTH)-related peptide (PTH-rp)-mediated severe hypercalcemia revealing congenital mesoblastic nephroma. Preoperatively, hypercalcemia was corrected with hydration, furosemide, pamidronate, and low-calcium infant formula. Unilateral nephrectomy led to the resolution of hypercalcemia, transient hyperparathyroidism, and transient vitamin D and mineral supplementation. We conclude that congenital mesoblastic nephroma can secrete PTH-rp that can cause severe hypercalcemia.

Simultaneous detection of anti-C1q and anti-double stranded DNA autoantibodies in lupus nephritis: predictive value for renal flares.

Clinical difficulties in predicting systemic lupus erythematosus (SLE) renal flares are still encountered. Biological markers such as autoantibodies (aAbs) may be of major interest for clinicians in the follow-up of SLE patients. The aim of our study was to investigate the clinical utility of one of these biological markers, anti-C1q aAbs, in predicting renal flares of SLE nephritis in comparison with the 'gold standard' anti-double stranded DNA (anti-dsDNA) aAbs. Anti-C1q aAbs and anti-dsDNA aAbs were analysed through a longitudinal retrospective study of 23 SLE patients presenting with one or more renal flares. Anti-C1q and/or anti-dsDNA aAbs were found in 20 (87%) of 23 patients, of whom 16 (69%) displayed both. Thirty-three renal flares occurred during the course of the study, and anti-C1q aAbs and anti-dsDNA aAbs were positive in 25 (76%) and 24 (73%) of these flares respectively. The sensitivity of anti-C1q and/or anti-dsDNA aAbs in predicting renal flares reached 85%. The specificity of anti-C1q aAbs was 84%, of anti-dsDNA aAbs 77% and of both aAbs 97%. Positive and negative predictive values were as follows: 56% and 70% for anti-C1q aAbs, 53% and 72% for anti-dsDNA aAbs. The combination of both aAbs had the highest positive predictive value (69%), whereas absence of both aAbs was associated with the highest negative predictive value (74%). In conclusion, our results confirm that anti-C1q aAbs are present in a significant percentage of SLE patients with active renal involvement, suggesting that these aAbs could be a useful additional marker. The presence of anti-C1q and anti-dsDNA aAbs was associated with a high risk of renal flare, whereas the absence of both aAbs excluded such an event. These data confirm that systematic detection of anti-C1q and anti-dsDNA aAbs is of interest for the follow-up in SLE patients with renal involvement.

Genotype-phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease.

The prognosis of autosomal recessive polycystic kidney disease is known to correlate with genotype. The presence of two truncating mutations in the PKHD1 gene encoding the fibrocystin protein is associated with neonatal death while patients who survive have at least one missense mutation. To determine relationships between genotype and renal and hepatic abnormalities we correlated the severity of renal and hepatic histological lesions to the type of PKHD1 mutations in 54 fetuses (medical pregnancy termination) and 20 neonates who died shortly after birth. Within this cohort, 55.5% of the mutations truncated fibrocystin. The severity of cortical collecting duct dilatations, cortical tubule and glomerular lesions, and renal cortical and hepatic portal fibrosis increased with gestational age. Severe genotypes, defined by two truncating mutations, were more frequent in patients of less than 30 weeks gestation compared to older fetuses and neonates. When adjusted to gestational age, the extension of collecting duct dilatation into the cortex and cortical tubule lesions, but not portal fibrosis, was more prevalent in patients with severe than in those with a non-severe genotype. Our results show the presence of two truncating mutations of the PKHD1 gene is associated with the most severe renal forms of prenatally detected autosomal recessive polycystic kidney disease. Their absence, however, does not guarantee survival to the neonatal period.

Clinical management of adolescents and young adults suffering from sarcoma in the French Rhône-Alpes region: A prospective exhaustive cohort with 10 years follow up.

INTRODUCTION: Survival of adolescents and young adults (AYA) with sarcoma is lower than in younger patients. The objective of this study was to describe the regional healthcare circuits, the differences in the management between adult, paediatric and mixed units and to assess the prognostic impact of compliance with clinical practice guidelines (CPGs) on overall survival (OS) and on relapse free survival (RFS). MATERIALS AND METHODS: Retrospective analysis of the management and long term follow-up of all 13-25 year old patients with a sarcoma diagnosed in the Rhône-Alpes area between 2000 and 2005. RESULTS: 140 patients satisfied inclusion criteria and were selected. The majority of 13-25 year old patients were treated in paediatric units. Joint management resulted in a higher rate of discussion in multidisciplinary tumour board, inclusion in clinical trials, and fertility preservation. Non-compliance with guidelines was observed in 65% of cases. Overall compliance was not reported to correlate to survival. Compliance of radiotherapy with CPG's seemed associated with a better prognosis for OS (HR = 0.20, 95% CI = [0.10-0.40]; p < 0.0001) and RFS (HR = 0.18, 95% CI = [0.09-0.37; p < 0.0001) as well as compliance of surgery for OS (HR = 0.43, 95% CI = [0.23-0.81]; p = 0.01). Multivariate Cox regression analysis revealed other independent predictors of OS like age at diagnosis, stage and histological subtype. CONCLUSIONS: Management of AYA in joint units seems to improve the quality of care. Compliance of surgery and radiotherapy with CGP's seems to improve survival.

Campomelic dysplasia: echographic suspicion in the first trimester of pregnancy and final diagnosis of two cases.

OBJECTIVE: Campomelic dysplasia (CD) is a rare skeletal dysplasia characterized by marked femoral and tibial angulations, hypoplasic scapulae, normal upper limbs and sex reversal in 3/4 of 46,XY fetuses. Most cases are lethal in the neonatal period. Heterozygous mutations in the SOX9 gene are responsible for CD. The diagnosis is not usually made until the mid-second trimester or later. METHODS: We describe 2 cases of CD suspected by ultrasonography in the first trimester. RESULTS: The 2 cases presented with hygroma colli along with anomalies in the lower but not the upper limbs. Terminations of pregnancy were obtained at 14+3 and 20+6 gestational weeks. Fetopathological examinations confirmed sonographic findings. CONCLUSION: When first trimester hygroma colli is accompanied by specific findings of the lower limbs, the diagnosis of CD can be investigated through SOX9 mutation analysis.

[Renal tubular dysgenesis and mutation in the renin gene]. / Dysgénésie tubulaire proximale et mutation du gène de la rénine.

Renal tubular dysgenesis is a severe and rare disorder of the renal development characterized by fetal anuria, oligohydramnios and early death from pulmonary hypoplasia and refractory arterial hypotension. We report on a female patient who presented with anuria in the neonatal period, requiring peritoneal dialysis until 5 months of age with unexpected diuresis recovery at 2 months of age. Clinical, histological and pathophysiological issues are discussed for this disease related to a mutation in the renin gene.

[Disseminated actinomycosis treated with clindamycin]. / Actinomycose disséminée traitée par clindamycine.

Actinomycosis is a rare bacterial disease caused by Actinomyces spp., an anaerobic bacteria from the oropharynx, digestive, and female genital tracts. Initial clinical presentation often mimics malignancy, which can lead to a delay in diagnosis. Cervico-facial, genitourinary, digestive, and respiratory features are the most frequent. Few cases are reported in children and risk factors are not well known in this population. We report on the case of an 8-year-old boy with disseminated actinomycosis with cervico-facial, pulmonary, and bone involvement caused by Actinomyces israelii. The infiltrative appearance initially suggested malignancy and the patient was started on chemotherapy for presumed histiocytosis. Evaluation of subsequent tissue samples demonstrated the presence of filamentous structures consistent with fungal or filamentous bacterial infection. Prolonged culture yielded the correct diagnosis. The patient had a severe allergic reaction to piperacillin/tazobactam and was therefore transitioned to clindamycin to complete a 9-month course. This treatment, which has not been reported in children, led to a favorable clinical, biological, and radiological response, with a good clinical tolerance.

[Standards and Options for the use of radiation therapy in the management of patients with osteosarcoma. Update 2004]. / Recommandations pour la pratique clinique: Standards et Options 2004 pour la prise en charge par radiothérapie des patients atteints d'ostéosarcome. Mise à jour.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the 20 French regional cancer centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVE: To update the SOR recommendations for the use of radiation therapy in the management of patients with osteosarcoma. This work was performed in collaboration with the French society against cancers in children and adolescent (SFCE). METHODS: Data have been identified by literature search using Medline (from January 1992 to October 2003). In addition several Internet sites were searched in October 2003. RESULTS: The 3 mains standards are: 1) local and exclusive curative irradiation is not indicated as primary treatment for osteosarcoma or for local and operable recurrence, except for lesion in inaccessible sites or if the patient refuses surgery; 2) local and prophylactic adjuvant irradiation is not indicated for the treatment of osteosarcoma after chemotherapy (neoadjuvant and/or adjuvant) and complete macro or microscopic surgery, except for non-operable R1 or R2 surgical resection; 3) whole-lung prophylactic irradiation is not indicated in non-metastatic osteosarcoma. Systemic metabolic radiotherapy for pain treatment, using samarium-153 ethylenediaminetetramethylene phosphonic acid (Sm-153-EDTMP) can be offered to patients with painful metastatic osteosarcoma or in case of recurrent bone sites inaccessible to local therapies (surgery, external irradiation).

[Macrophage activation syndrome and autoimmunity due to visceral leishmaniasis]. / Syndrome d'activation macrophagique et auto-immunité cortico-sensible révélateurs d'une leishmaniose viscérale.

Hemophagocytic syndromes are a heterogeneous group of diseases characterized by an excessive immune response, mediated by activated cytotoxic T cells and macrophages. Among hemophagocytic syndromes, genetic and secondary forms can be distinguished. We report on the case of a male newborn who presented with macrophage activation syndrome associated with lymphoproliferation with favorable outcome under prednisone and cyclosporin. Hemopathy, infection, or genetic lymphohistiocytosis were initially ruled out. Severe autoimmunity was suspected because of positive antinuclear antibodies and Farr test associated with anemia and a positive Coombs test as well as cytolytic hepatitis with anti-liver, kidney microsome (LKM) antibodies. Treatment was therefore intensified by adding mycophenolate mofetil. This led to an unexpected deterioration of general health and lab exam results with recurrence of fever and inflammation. The initial investigations were revisited and completed by a liver biopsy, which revealed the presence of numerous leishmania parasites at the amastigote stage, enabling the diagnosis of visceral leishmaniasis. The patient's condition dramatically improved under liposomal amphotericin B treatment. Our observation shows that visceral leishmaniasis can present as lupus-like syndrome with lymphoproliferation. Moreover, the lack of leishmania on marrow aspiration cannot rule out the diagnosis of visceral leishmaniasis. Detection of leishmania by serological or molecular tests is mandatory in case of hepatosplenomegaly with hemophagocytic syndrome together with autoantibodies, in order to avoid useless and life-threatening exposure to immunosuppressive treatments.

Does nephroblastomatosis influence the natural history and relapse rate in Wilms' tumour? A single centre experience over 11 years.

The presence of multifocal or diffuse nephrogenic rests (NRs) in one or both kidneys is termed nephroblastomatosis (Nbm). Nbm may be a predisposing factor for Wilms' tumour (WT). The aim of this retrospective study was to evaluate the impact of Nbm on the outcome of WT in children. We assessed the outcome of 81 children with Wilms tumours and practical implications of Nbm in the treatment and follow-up. All the pathology slides have been reviewed in 1997. 63 had WT without Nbm (group A) and 18 had WT associated with Nbm (group B). There was no statistical difference between the two groups according to the age at diagnosis and histology. Clinical abnormalities were more frequent in group B (33 versus 8%). There was no statistical difference between the percentage of stage IV in both groups, but bilaterality (stage V) was present only in the group B. Relapse was observed in 20/81 patients (25%): 11 (17%) in group A and 9 (50%) in group B. Mean delay of relapse was longer (25 months) in group B than in group A (10 months). For the whole population, with a median follow-up of 9 years, the event-free survival (EFS) and the overall survival (OS) probabilities were respectively 74%+/-10 and 83%+/-9 at 120 months. The difference in EFS between groups A (82+/-9%) and B (38%+/-29) was significant (P=0.004). The discovery of Nbm in the non-tumoral part of the kidney with WT can be an adverse factor and in particular favours the subsequent development of a new Wilms tumour. It justifies separate follow-up guidelines.

Epstein-Barr virus-related lymphoproliferative disease complicating childhood acute lymphoblastic leukemia: no recurrence after unrelated donor bone marrow transplantation.

A 16-year-old boy in complete remission of ALL, undergoing oral maintenance therapy, developed intestinal perforation related to EBV-associated lymphoproliferative disease (LPD). He was successfully managed with surgical resection, acyclovir, immunoglobulins and discontinuation of maintenance therapy. Leukemic marrow relapse occurred 3 months later, treated by polychemotherapy followed by unmanipulated BMT from a matched unrelated EBV seropositive donor. Donor lymphocytes were infused twice after transplant because of delayed immunologic recovery and severe CMV colitis. This was followed by acute GVHD requiring prolonged immunosuppressive treatment. Despite intensive and prolonged immunosuppression, recurrence of LPD was not observed. Following EBV-related LPD, allogeneic BMT can be performed if indicated. Selection of an EBV seropositive donor is of major importance for the prevention of LPD recurrence as the recipient may be protected by passive transfer of EBV-specific cytotoxic T cells.

Juvenile granulosa cell tumor of the ovary in infants: a clinicopathologic study of three cases and review of the literature.

The clinical and pathological features of three cases of juvenile granulosa cell tumors occurring in infants were studied. Precocious pseudopuberty developed in two patients and acute abdominal symptoms related to the rupture of the tumor developed in one. Surgery was the only treatment in each case and no adjuvant therapy was delivered. No patient experienced relapse. Histological examination showed a predominantly diffuse pattern with prominent luteinization. Call-Exner bodies were absent. Two tumors had multilocular thin walled cysts containing large amounts of estradiol, the third one contained rudimentary microfollicles. The prognosis of juvenile granulosa cell tumors in infancy appears more favorable than those occurring in older patients. No case of tumor recurrence has been reported in infancy so far. Surgery appears to be the state-of-the-art treatment of these tumors and additional therapy (chemotherapy or radiotherapy) must be discussed with caution, even in advanced stages.

[Rectal localization of Burkitt's lymphoma]. / Lymphome de Burkitt de localisation rectale.

BACKGROUND: Rectal tumors are rare in childhood and among them malignant tumors are even less common. Only eight cases of primary rectal lymphomas were reported in children, with various presenting signs and histology. Burkitt's lymphomas are among these cases. CASE REPORT: A five-year-old child presented with hematochezia and unusual constipation. The rectal examination showed a voluminous intra rectal mass. Radiographic and pathologic examinations led to the diagnostic of Burkitt's lymphoma with medullary involvement. Complete remission was obtained after initial chemotherapy but a local relapse occurred and the child died eight months later. CONCLUSION: Hematochezia associated with unusual constipation impose a rectal examination. Early diagnosis of a rectal tumor may allow patients survival.

[Renal biopsy in the elderly]. / La biopsie rénale chez le sujet âgé.

Fifty years after the first percutaneous needle biopsies of the kidney, enough results have been obtained to evaluate indications in elderly patients, a population group we define as over 75 years of age. In approximately 50% of the patients in this group, the indication for renal biposy is a nephrotic syndrome. The lesions usually observed involve extramembranous glomerulonephritis or minimal change glomerulopathy. The biopsy may also reveal amylosis. Chronic renal failure is the predominant reason for nephrology consultation in the elderly. Although all of these patients do not undergo biopsy, in our experience, results show chronic glomerulopathies, mainly IgA, in about half of the case as well as chronic interstitial nephritis and nephroangiosclerosis. The aging process also leads to acute renal failure in many patients. Biopsy would not be indicated in case of shock, drug toxicity or obstruction but in approximately 10% of the cases histology can reveal a specific parenchymal lesion. The technique for renal biopsy is the same in elderly patients as in younger adults. Renal biopsy can be considered as a safe diagnostic tool of considerable importance when ordered by a nephrologist, performed by an experienced operator and read by a well-trained pathologist. In many cases it is essential to in order to provide patients over 75 with the same quality care as younger adults.

[Pediatric seizures and end-stage renal disease]. / État de mal convulsif révélateur d'une ostéodystrophie rénale.

Neonates and infants with hypocalcemia usually present with seizures, whereas this is less common in older children and teenagers. We report on a case of hypocalcemic seizures in a 16-year-old girl with undiagnosed end-stage renal disease with progressive growth retardation and bone deformations. We highlight the value of checking serum calcium, phosphate, and creatinine in children with growth retardation, seizures, and/or unexplained bone deformations. We also discuss the clinical consequences of pediatric renal osteodystrophy.

Kidney biopsy in the critically ill patient, results of a multicentre retrospective case series.

BACKGROUND: The impact of a contributive result of kidney biopsy on the management of patients in the intensive care unit (ICU) has not been extensively investigated yet. METHODS: This was a retrospective study conducted between 2000 and 2011 in five French ICUs. The study included 56 patients. They had at least one non-renal organ failure, as defined by a Sequential Organ Failure Assessment (SOFA) score ≥3 on ICU admission, and kidney biopsy was performed during ICU stay. Kidney samples were obtained by percutaneous (N.=55) or transjugular biopsy (N.=1). RESULTS: The mean Simplified Acute Physiology Score II and total SOFA scores on ICU admission were 52±19 years and 10.3±3.6, respectively. ICU mortality was 23%. The median (interquartile range) time between ICU admission and kidney biopsy was 9 days (5-21). Pathologic findings in the 54 analyzable kidney biopsies were acute tubular necrosis (N.=26), glomerulonephritis (N.=14), acute vascular nephritis (N.=11), acute interstitial nephritis (N.=6), and deposit disease (N.=3). Kidney biopsy was contributive to the management of 40 patients. In 23 of these, new treatments were started, in 13 ongoing treatments were stopped, including four life-sustaining therapies, and in 13 it was decided to start chronic renal replacement. Severe bleeding was observed in 7 patients, with fatal outcome in one case. CONCLUSION: Kidney biopsy may have a significant impact on the management of critically ill patients. Further studies should be done to identify the groups of ICU patients likely to benefit from the procedure with minimum risk.

Osteoid osteoma transformation into osteoblastoma: fact or fiction?

BACKGROUND: Osteoid osteoma and osteoblastoma are rare, benign, bone-forming tumours. The clinical presentation, imaging study findings, and course indicate clearly that these two tumours are distinct entities. CLINICAL REPORTS: We report two cases suggesting transformation of osteoid osteoma into osteoblastoma and therefore inviting a discussion of the links between these two tumours. An 11-year-old girl with a small metaphyseal lesion of the proximal tibia was given a diagnosis of osteoid osteoma. Over the next few weeks, worsening pain and marked tumour growth prompted a biopsy, which was consistent with an aggressive osteoblastoma. A review of the case suggested primary osteoblastoma at the earliest stage of development. In a 14-year-old boy, en-bloc excision was performed to remove a 1cm defect located within the femoral shaft cortex and typical for osteoid osteoma. An asymptomatic recurrence measuring 20mm along the long axis was removed 18 months later. Reassessment of the histological slides indicated recurrence of an incompletely excised osteoid osteoma. DISCUSSION: The histological similarities between osteoid osteoma and osteoblastoma, together with the lesion size criterion, may result in confusion. Collaboration between the clinician and pathologist is crucial and should take the tempo of evolution into account. CONCLUSION: The histopathological differences between these two tumour types deserve to be emphasized. The data reported here challenge the concept that osteoid osteoma can transform into osteoblastoma. These two tumours are distinct entities that should no longer be differentiated based on size, as was long done in the past.