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.

Congenital Bilateral Wilms Tumor: A Case Report.

Compare to congenital mesoblastic nephroma in fetus, congenital wilms tumor is extremely rare. Herein we report a case of congenital bilateral solid masses on antenatal ultrasound. The mass was evaluated by ultrasonography and contrast computed tomography scan in postnatal period, and the patient was undergoing tumor enucleation separately in short period after neoadjuvant chemotherapy. The diagnosis was confirmed by histology analysis for each side, and the treatment was taken according to the International Society of Pediatric Oncology.

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.

The clinical presentation, imaging features and differential diagnoses of congenital Wilms tumour.

Solid fetal renal masses are a rare finding on antenatal ultrasound, with hydronephrosis and cystic disease of the kidney usually being the most common causes for fetal renal enlargement. Herein we report a case of a solid fetal renal mass which was detected on third trimester antenatal ultrasound scanning. This renal mass was evaluated by MRI in the postnatal period and diagnosis confirmed by histological analysis, after surgical excision. Also discussed are the differential diagnoses and imaging features of other solid fetal renal masses, including congenital mesoblastic nephroma, nephroblastomatosis, renal sarcoma and angiomyolipoma.

Specific computed tomography imaging characteristics of congenital mesoblastic nephroma and correlation with ultrasound and pathology.

INTRODUCTION: Congenital mesoblastic nephroma (CMN) is a common solid renal tumor in the neonate. Congenital mesoblastic nephroma can be divided into classic, cellular, and mixed types. The prognosis of CMN is very optimistic. But CMN can easily be misdiagnosed as the other malignant renal tumors by radiology. However, no studies have described the computed tomography (CT) imaging appearance of CNM in detail. The objective of this study is retrospective analyses of the multislice CT characteristics of CMN and their corresponding ultrasound findings and pathology. METHODS: This retrospective study reviewed the enhanced CT images of the CMNs and other renal tumors in children younger than 1 year in the past 10 years from the First Affiliated Hospital of Sun Yat-sen University. Two radiologists had noted the CT imaging characteristics of these images. t-test and Fisher's exact test were used in the comparison of imaging characteristics between the CMNs and other renal tumors. RESULTS AND DISCUSSION: Compared with other malignant renal tumors, the CMNs tend to appear as smaller round masses without clear coverage or clear boundary with the kidney in CT images (P < 0.01). The intratumor pelvis and the double-layer sign are the specific characteristics of CMNs (P < 0.01). The gender, quality of tumor (solid or solid-cystic), character of enhancement (homogeneous or heterogeneous enhancement), peri-renal hemorrhage, or peripheral lymph node enlargement showed no statistical significance (P > 0.05) between CMNs and other renal tumors. The appearances of CMN with classic components in the CT images are relevant to the pathological findings. The intratumor pelvis is caused by the classic components of CMN growing to encapsulate the pelvis. The double-layer sign in CT image correlates with the specific hypoechoic ring in ultrasound, which is caused by the slow blood flow and delay contrast agent filling in the blood sinus located in the peripheral part of the tumor. The differential diagnosis of CMN should include the other solitary renal tumors such as Wilms' tumor, clear-cell sarcoma of the kidney, and rhabdoid tumor of the kidney. CONCLUSION: The unclear coverage and unclear boundary with the kidney, the intratumor pelvis, and double-layer sign after contrast were specific CT imaging characteristics of CMN.

Recurrent EML4-NTRK3 fusions in infantile fibrosarcoma and congenital mesoblastic nephroma suggest a revised testing strategy.

Infantile fibrosarcoma and congenital mesoblastic nephroma are tumors of infancy traditionally associated with the ETV6-NTRK3 gene fusion. However, a number of case reports have identified variant fusions in these tumors. In order to assess the frequency of variant NTRK3 fusions, and in particular whether the recently identified EML4-NTRK3 fusion is recurrent, 63 archival cases of infantile fibrosarcoma, congenital mesoblastic nephroma, mammary analog secretory carcinoma and secretory breast carcinoma (tumor types that are known to carry recurrent ETV6-NTRK3 fusions) were tested with NTRK3 break-apart FISH, EML4-NTRK3 dual fusion FISH, and targeted RNA sequencing. The EML4-NTRK3 fusion was identified in two cases of infantile fibrosarcoma (one of which was previously described), and in one case of congenital mesoblastic nephroma, demonstrating that the EML4-NTRK3 fusion is a recurrent genetic event in these related tumors. The growing spectrum of gene fusions associated with infantile fibrosarcoma and congenital mesoblastic nephroma along with the recent availability of targeted therapies directed toward inhibition of NTRK signaling argue for alternate testing strategies beyond ETV6 break-apart FISH. The use of either NTRK3 FISH or next-generation sequencing will expand the number of cases in which an oncogenic fusion is identified and facilitate optimal diagnosis and treatment for patients.

Congenital mesoblastic nephroma: a study of 19 cases using immunohistochemistry and ETV6-NTRK3 fusion gene rearrangement.

Mesoblastic nephroma (MN) is the most common renal tumour in the first 3 months of life and accounts for 3-5% of all paediatric renal neoplasms. To further understand the morphological variants of MN, we identified 19 cases of MN (five classic, eight cellular and six mixed) and examined each case for markers known to be important in urogenital embryological development (PAX8, WT1 and RCC), stem cell associated markers (Oct 4, CD34 and c-kit), muscle/myofibroblastic markers (muscle specific actin, calponin and h-caldesmon), aberrant transcription factors, cell cycle regulation and other oncogenic proteins (p16, cyclin D1 and beta-catenin). Fluorescence in situ hybridisation (FISH) testing for ETV6-NTRK3 gene fusion/rearrangement revealed further differentiation between the subtypes with ETV6-NTRK3 gene fusion detected in 0/5 of the classic MN, 8/8 of the cellular MN and 5/6 of the mixed MN cohorts, respectively. Our results conclude that cyclin D1 and beta-catenin may be useful markers for differentiating between cellular MN and classic MN when the histology is not conclusive. The absence of expression of stem cell markers and markers involved in urogenital development suggests that MN is not a nephroma and most likely represents a soft tissue tumour, with congenital infantile fibrosarcoma representing cellular MN with a predilection to arise in the kidney. In addition, the immunophenotype and genetic fingerprint of mixed MN most likely represents a heterogenous group of tumours that are mostly cellular type, with areas that are phenotypically less cellular.

Congenital Mesoblastic Nephroma Presenting With Hematuria in a Neonate: A Case Report.

Congenital mesoblastic nephroma (CMN) is the most frequent renal neoplasm of newborns and young infants. Four cases presenting with hemorrhagic manifestations have been reported in the English literature (Hu et al, 2006; Bolande et al, 1967). We report the unusual clinical and radiographic findings of a 2-day-old neonate with hematuria secondary to a CMN. The first ultrasound was equivocal. Repeat ultrasound followed by magnetic resonance imaging confirmed the diagnosis. He underwent a right nephroureterectomy with histopathology revealing a cellular variant of CMN without classical translocation (t12:15). Neonates presenting with hematuria require close follow-up and serial imaging to rule out occult renal tumors. Classical translocation may not be demonstrable in all the cases.

Congenital renal tumor: metanephric adenoma, nephrogenic rest, or malignancy?

We report a renal tumor detected by prenatal ultrasound and resected at 2 months of age. This 9-cm, solid mass was composed of tubular and papillary structures lined by small, uniform epithelial cells. There was local invasion into renal parenchyma and a tumor deposit in a hilar lymph node. The tumor was immunopositive for WT1, pankeratin, and CD10; focally positive for CK7; and negative for EMA and TFE3. Based on morphology and immunophenotype, the favored diagnosis was metanephric adenoma over Wilms tumor, renal cell carcinoma, and nephrogenic rest. However, metanephric adenoma only occasionally occurs in children and has never been reported prenatally. Alternatively, this tumor might be a congenital Wilms tumor that differentiated completely. Although the nature of the tumor remains unconfirmed, resection appears to have been curative; the patient remains disease-free 18 months following surgery alone.

Congenital multifocal rhabdoid tumor: a case with peculiar biological behavior and different response to treatment according to location (central nervous system and kidney).

Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system and malignant rhabdoid tumor of the kidney (MRTK) may present with different responses to chemotherapy and outcomes. We describe the case of an infant with multifocal rhabdoid tumor with different behavior and response to treatment, depending on the anatomic site.

Synchronous congenital malignant rhabdoid tumor of the orbit and atypical teratoid/rhabdoid tumor--feasibility and efficacy of multimodal therapy in a long-term survivor.

Among infant malignancies, congenital tumors, especially those of the central nervous system (CNS), constitute a rather unique subgroup. Poor survival rates (28% in CNS tumors) may be attributed to the aggressive biology as well as specific therapeutic limitations innate to the young age of affected patients. Our patient developed synchronous congenital tumors: an atypical teratoid/rhabdoid tumor (AT/RT) localized in the right lateral ventricle of the brain and a malignant rhabdoid tumor (MRT) in the soft tissue of the right orbit. A de novo germline chromosomal deletion in 22q encompassing the SMARCB1 gene was detected, prompting the diagnosis of a de novo rhabdoid tumor predisposition syndrome 1 (RTPS1). The patient was reported to the European Rhabdoid Registry (EU-RHAB) and treated according to the Rhabdoid 2007 recommendation. Despite the very young age of the patient, the initially desperate situation of RTPS1, and the synchronous localization of congenital rhabdoid tumors, intensive chemotherapy was well tolerated; the child is still in complete remission 5 years following diagnosis. In conclusion, RTPS1 with congenital synchronous MRTs is not necessarily associated with a detrimental outcome. Intensive multidrug chemotherapy, including high dose chemotherapy, may be feasible and justified.

Congenital mesoblastic nephroma in a premature neonate: a case report and review of literature.

Congenital mesoblastic nephroma (CMN) is a renal stromal neoplasm of infancy. It comprises 3-10% of all pediatric renal tumors. We report a case of CMN in a 30 week old premature female neonate seen at autopsy who was born to a 26-year-old woman by emergency cesarean section on account of polyhydramnios.

Cellular mesoblastic nephroma with liver metastasis in a neonate: prenatal and postnatal diffusion-weighted MR imaging.

Congenital mesoblastic nephroma (CMN) is the most common renal tumor in the first year of life. Here, we present unique findings of cellular variant CMN seen on prenatal and postnatal MRI with diffusion-weighted imaging (DWI).The mass was well-visualized on prenatal MR DWI with diffusion restriction in the solid portions. After excision of the mass, follow-up whole body MRI with DWI helped identify local tumor recurrence with suspicious liver metastasis. This hepatic lesion also showed diffusion restriction.

Cellular Mesoblastic Nephroma with Liver Metastasis in a Neonate: Prenatal and Postnatal Diffusion-Weighted MR Imaging

Congenital mesoblastic nephroma (CMN) is the most common renal tumor in the first year of life. Here, we present unique findings of cellular variant CMN seen on prenatal and postnatal MRI with diffusion-weighted imaging (DWI).The mass was well-visualized on prenatal MR DWI with diffusion restriction in the solid portions. After excision of the mass, follow-up whole body MRI with DWI helped identify local tumor recurrence with suspicious liver metastasis. This hepatic lesion also showed diffusion restriction.

Congenital mesoblastic nephroma in a young basset hound dog.

An 18-month-old male basset hound was presented with vomiting, diarrhoea and depression. Abdominal ultrasonography revealed a mass in the left kidney. An ultrasound-guided core-biopsy indicated aggregates of spindle cells, but did not allow a definitive diagnosis. Nephrectomy was performed after a period of six months, when ultrasound examination revealed a slight increase in mass dimensions. Histologically the mass was composed of neoplastic spindle cells forming interlacing fascicles, bundles and whorls, within a loose myxoid to dense collagenous stroma. Immunohistochemically neoplastic cells were positive for vimentin and smooth muscle actin. Based on these findings the tumour was diagnosed as a congenital mesoblastic nephroma, classical variant. After a two-and-a-half-year follow-up the dog was clinically healthy, indicating a benign behaviour. To the authors' knowledge, this report describes the first case of canine congenital mesoblastic nephroma successfully treated surgically, with a reasonable postsurgical follow-up.

[Fibrosarcoma in children and adolescents: different entities for the same name]. / Les « fibrosarcomes ¼ de l'enfant et de l'adolescent : un même nom pour différentes entités.

Fibrosarcomas (FS) are rare malignant tumors in pediatrics, classified in the heterogeneous non-rhabdomyosarcomas group of malignant mesenchymal tumors. Infantile FS are found typically in children less than 2 years of age, and include congenital FS usually occurring in infants in the first 3 months of life. Histological diagnosis can be difficult; and confirmed with detection by molecular biology of the ETV6-NTRK3 fusion protein. FS is most often a localized disease at diagnosis, with involvement of an extremity. The management of these patients must be multidisciplinary, to define the different phases of treatment and avoid mutilating surgery. Cellular or atypical mesoblastic nephroma (MN) is a subtype of malignant pediatric renal tumors, most often present in children of less than 3 months. Histopathological characteristics of the cellular MN are very close to the congenital FS due to a fusion transcript common to both diseases. Treatment schedule is defined by initial local stage of the disease. FS called "adult-type" found exceptionally in childhood occur most often after 10 years old. Adult FS differ from infantile FS in their clinical presentation because of a strong local aggressiveness and problematic appearance of metastasis in 50% of cases, sometimes late. These three diseases present therefore histological similarities. Both have a common name but different clinical presentation and outcome: infantile FS and adult FS. Two have different names and initial location but similar histology, chromosomal rearrangement, sensitivity to chemotherapy and outcome: the congenital FS and cellular mesoblatic nephroma. Authors present a review of the literature of these entities.

Renal and hepatic tumors in the neonatal period.

Renal and hepatic tumors in neonates are extremely rare. Nevertheless it is important for clinicians to be familiar with them. Both renal and hepatic neonatal tumors are heterogeneous collections of several tumor types. Some renal and hepatic tumors are benign and may require no interventions whereas others can be associated with significant morbidity and even mortality and may require multimodality treatment. Early diagnosis and initiation of the proper treatment plan is crucial for achieving the best outcomes for these rare tumors in this vulnerable population.

[Hereditary cutaneous leiomyomatosis]. / Hereditäre kutane Leiomyomatose.

The occurrence of multiple cutaneous leiomyomas can be indicative of hereditary cutaneous leiomyomatosis. This autosomal dominant disorder is due to germline mutations in the fumarate hydratase (FH) gene. Associations with uterine myomas and renal cell carcinomas have been described and are referred to as Multiple Cutaneous and Uterine Leiomyomas (MCUL) or Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC), respectively. A 34-year-old man presented with multiple red-brown papules and nodules. After histopathologic confirmation of piloleiomyomas, we made the diagnosis of hereditary cutaneous leiomyomatosis. Taking into consideration the aforementioned complications, close interdisciplinary management of these patients and regular screening examinations within affected families are mandatory.