Congenital mesoblastic nephroma is the most common solid renal tumor in neonates. Therefore, patients <3 months of age are advised to undergo upfront nephrectomy, whereas invasive procedures at diagnosis in patients ≥3 months of age are discouraged by the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG). Nevertheless, discriminating congenital mesoblastic nephroma, especially from the more common Wilms tumor, solely based on imaging remains difficult. Recently, magnetic resonance imaging (MRI) has become the preferred modality. Studies focusing on MRI characteristics of congenital mesoblastic nephroma are limited.
This study aims to identify diagnostic MRI characteristics of congenital mesoblastic nephroma in the largest series of patients to date.
In this retrospective multicenter study, five SIOP-RTSG national review radiologists identified 52 diagnostic MRIs of histologically proven congenital mesoblastic nephromas. MRI was performed following SIOP-RTSG protocols, while radiologists assessed their national cases using a validated case report form.
Patients (24/52 classic, 11/52 cellular, and 15/52 mixed type congenital mesoblastic nephroma, 2/52 unknown) had a median age of 1 month (range 1 day-3 months). Classic type congenital mesoblastic nephroma appeared homogeneous with a lack of hemorrhage, necrosis and/or cysts, showing a concentric ring sign in 14 (58.3%) patients. Cellular and mixed type congenital mesoblastic nephroma appeared more heterogeneous and were larger (311.6 and 174.2 cm3, respectively, versus 41.0 cm3 for the classic type (P<0.001)). All cases were predominantly T2-weighted isointense and T1-weighted hypointense, and mean overall apparent diffusion coefficient values ranged from 1.05-1.10×10-3 mm2/s.
This retrospective international collaborative study showed classic type congenital mesoblastic nephroma predominantly presented as a homogeneous T2-weighted isointense mass with a typical concentric ring sign, whereas the cellular type appeared more heterogeneous. Future studies may use identified MRI characteristic of congenital mesoblastic nephroma for validation and for exploring the discriminative non-invasive value of MRI, especially from Wilms tumor.

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.
METHODS: 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%).
CONCLUSIONS: 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.

The most common nonencapsulated solid renal tumor in the neonatal period is congenital mesoblastic nephroma. Mesoblastic nephroma is a solid lesion originating within or extending from the renal parenchyma. These tumors proliferate rapidly, typically within 3-6 months after birth. Mesoblastic nephromas are stratified by classification as either classical (benign) or atypical (malignant); masses composed of both benign and malignant cells are also reported. The hallmark clinical manifestation of mesoblastic nephroma is a palpable abdominal mass, which may be accompanied by hypertension, hypercalcemia, hematuria, and polyuria. Differentiating between benign and malignant renal tumors is essential to invoke a timely, evidence-based management and treatment plan. With appropriate surgical intervention in a timely manner, prognosis is excellent and mesoblastic nephroma is considered curable. We present a case involving a premature infant with congenital mesoblastic nephroma with discussion of embryology, pathophysiology, diagnostic, management, and prognostic implications for the neonate and family.

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.

Infantile fibrosarcoma (IFS; also known as cellular congenital mesoblastic nephroma, CMN, when in the kidney) is a rare, undifferentiated tumour often characterized by the ETV6-NTRK3 fusion transcript. Our goal was to identify downstream pathways, diagnostic markers and potential therapeutic targets for IFS/CMN. Global gene expression, reverse-phase protein array and ETV6-NTRK3 fusion analyses were performed on 14 IFS/CMN and compared with 41 other paediatric renal tumours. These analyses confirm significant receptor tyrosine kinase (RTK) activation, with evidence of PI3-Akt, MAPK and SRC activation. In particular, GAB2 docking protein, STAT5-pTyr-694, STAT3-pSer-729 and YAP-pSer-127 were elevated, and TAZ-pSer-89 was decreased. This provides mRNA and proteomic evidence that GAB2, STAT activation and phosphorylation of the Hippo pathway transcription co-activators YAP and TAZ contribute to the RTK signal transduction in IFS/CMN. All IFS/CMN tumours displayed a distinctive gene expression pattern that may be diagnostically useful. Unexpectedly, abundant ETV6-NTRK3 transcript copies were present in only 7/14 IFS, with very low copy number in 3/14. An additional 4/14 were negative by RT-PCR and absence of ETV6-NTRK3 was confirmed by FISH for both ETV6 and NTRK3. Therefore, molecular mechanisms other than ETV6-NTRK3 fusion are responsible for the development of some IFS/CMNs and the absence of ETV6-NTRK3 fusion products should not exclude IFS/CMN as a diagnosis.

The authors present an atypical case of MEST uncovered in 12-year-old girl diagnosed with recurrent pyuria and persistent albuminuria with concomitant hypertension. Urine changes persisted despite the antibiotics therapy and they were accompanied with aseptic urine cultures. While investigating these changes, USG, urography, CT and MRI were performed and these manifested tumor-like change in the right kidney. Right-side nefrectomy was performed. Microscopically MEST was found while infection was found in parenchyma. Mixed epithelial and stromal tumor is a very rare kidney tumor that occurs almost exclusively in perimenopausal women or women after a long-term estrogen replacement. There are only few cases of this tumor in premenarcheal girls described in literature.

暂无摘要。

Congenital mesoblastic nephroma (CMN) accounts for approximately 5% of paediatric renal tumours with the highest peak of incidence during the first 3 postnatal months. CMN almost always has a favourable prognosis. Therefore, CMN needs to be correctly diagnosed and differentiated, principally histologically, from other pediatric neoplasms. We present a clinicopathologic study of 5 cases of CMN.

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.
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.
CONCLUSIONS: 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.

OBJECTIVE: Rhabdoid tumor of the kidney (RTK) is unique among childhood renal neoplasms in its frequent association with primary or metastatic CNS lesions. Previous reports suggest that RTK has characteristic CT features. It has been proposed that if CT could accurately predict the correct diagnosis of RTK preoperatively, then imaging protocols might be modified during the examination to include imaging of the brain. We wished to determine if RTK could be reliably distinguished from other renal neoplasms of early childhood.
METHODS: We retrospectively reviewed clinical, radiologic, and pathologic records of 21 patients with RTK. The study group included 13 males and eight females who were newborn to 36 months old (mean, 11 months). The study group was compared with 153 patients who were 3 years old or younger and who had solid renal masses. From the comparison group a subset of 54 patients 1 year old and younger was also selected for comparison with 13 (62%) of the 21 patients in the study group who were 1 year old or younger. Both comparison groups consisted of patients whose case material was consecutively added to the radiologic pathology archives at our institution. Diagnoses of the group of 153 patients were Wilms\' tumor (n = 93), mesoblastic nephroma (n = 44), clear cell sarcoma of the kidney (n = 12), renal cell carcinoma (n = 3), and undifferentiated sarcoma (n = 1).
RESULTS: A prominent eccentric crescent with the attenuation of fluid, representing sub-capsular renal hemorrhage or peripheral tumor necrosis adjacent to tumor lobules, was revealed on CT scans in 15 (71%) of the 21 patients with RTK and in seven (54%) of the 13 patients with RTK who were 1 year old or younger. Nineteen (12%) of 153 patients in the larger comparison group, representing patients with all tumor types, had CT features identical to those of the RTK group, including six (4%) patients with pathologic confirmation of sub-capsular renal hematomas. Six (11%) of the 54 comparison patients 1 year old and younger had CT features identical to those of the RTK group, and all proved to have mesoblastic nephroma. Associated CNS lesions were seen on CT or MR imaging in 11 (52%) of the 21 patients with RTK but none was seen in the comparison group of patients.
CONCLUSIONS: On CT, a peripheral crescent with the attenuation of fluid is characteristic of RTK. However, 12% of renal neoplasms that occur more commonly than RTK in children had CT findings indistinguishable from those of RTK. Because the prevalence of RTK is relatively low, and because the CT findings are not pathognomonic, a renal mass seen on CT in a child is unlikely to represent RTK regardless of its CT features. We therefore conclude that the routine addition of CT of the brain for pediatric patients with renal masses that show a peripheral crescent of fluid attenuation is not justified. Supplemental imaging of the brain should be based on clinical findings or tissue diagnosis.