Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ®)–Health Professional Version - National Cancer Institute

Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ®)–Health Professional Version

Congenital Mesoblastic Nephroma

General Information About Congenital Mesoblastic Nephroma

Mesoblastic nephroma comprises about 5% of childhood kidney tumors, and more than 90% of cases appear within the first year of life. More than 15% of the cases are detected prenatally.[1] It is the most common kidney tumor found in infants younger than 6 months.[2] The median age of diagnosis is 1 to 2 months. Twice as many males as females are diagnosed. The diagnosis should be questioned when applied to individuals older than 2 years.[1]

When patients are diagnosed in the first 7 months of life, the 5-year event-free survival rate is 94%, and the overall survival (OS) rate is 96%.[3] In a report from the United Kingdom of 50 children with mesoblastic nephroma studied on clinical trials and 80 cases from the national registry in the same time period, there were no deaths.[1] However, in a comprehensive review of the literature, 12 deaths were reported; of these 12 deaths, 7 were from surgical complications in infants.[4][Level of evidence: 3iiiDii]

Grossly, mesoblastic nephromas appear as solitary, unilateral masses indistinguishable from nephroblastoma. Microscopically, they consist of spindled mesenchymal cells. Mesoblastic nephroma can be divided into the following three histologic subtypes:

Classic.[5]
Cellular. The cellular subtype is identical to infantile fibrosarcoma.[6]
Mixed. The mixed subtype (<10%) is a mixture of classic and cellular patterns.[7]

A frequent genetic alteration is the translocation t(12;15)(q13;q25), resulting in a fusion of the ETV6 and NTRK3 genes on 15p15 that occurs almost exclusively in the cellular type of mesoblastic nephroma. In a cohort of 79 mesoblastic nephromas analyzed for the translocation, all classical (n = 38) and mixed (n = 12) mesoblastic nephromas were translocation negative.[8] The same translocation was initially described in infantile fibrosarcoma, and besides the similar morphologic appearance, cases of cellular mesoblastic nephroma and infantile fibrosarcoma share other genetic changes such as gains of chromosome 11.[9]

The risk of recurrence for patients with mesoblastic nephroma is closely associated with the presence of a cellular subtype and with stage III disease.[5] In an International Society of Pediatric Oncology (SIOP) series of 79 patients with congenital mesoblastic nephromas, patients within the cellular subgroup who had translocation-positive tumors had a significantly superior relapse-free survival (RFS) rate when compared with patients who did not have the gene fusion (100% vs. 73%, respectively).[8]

(Refer to the Clinical Features of Wilms Tumor and Diagnostic and Staging Evaluation for Wilms Tumor sections of this summary for more information about the clinical features and diagnostic evaluation of childhood kidney tumors.)

Treatment of Congenital Mesoblastic Nephroma

The OS of patients with congenital mesoblastic nephroma is excellent; however, reported causes of death in about one-half of the cases are treatment related, and most of these patients were very young (median age, <1 year).[4] This underscores the special attention that infants with renal tumors require, with respect to timing and type of treatment and the importance of a dedicated expert pediatric oncology setting.

Standard treatment options for stages I and II (80% of patients) and stage III (classic and mixed subtypes) congenital mesoblastic nephroma include the following:

Nephrectomy only.

Treatment options for stage III (cellular subtype) congenital mesoblastic nephroma include the following:

Nephrectomy.
Chemotherapy.

Nephrectomy

Evidence (nephrectomy):

In a SIOP/Gesellschaft für Pädiatrische Hämatologie und Onkologie (GPOH) nephroblastoma study, 111 patients with congenital mesoblastic nephromas demonstrated a 5-year RFS rate of 93.2% and a 5-year OS rate of 96.8%.[8]
- Sixty-seven patients had classical congenital mesoblastic nephromas (60%), 29 patients had the cellular subtype (26%), and 15 patients had the mixed subtype (14%). The 5-year RFS rate was significantly superior for the classical type (98%) compared with the cellular type (89%, P = .039) or mixed type (80%, P = .002). There was no significant difference in OS by tumor types.
- Tumor stage consisted of stage I (35%), stage II (50%), and stage III (15%).
- Ninety-one patients were treated with surgery alone, and 19 patients were treated with chemotherapy in addition to surgery (12 preoperatively and 11 postoperatively).
- Seven patients relapsed (five local and two combined) and three patients died because of local relapse (one of each histologic type).
- Tissue was available for translocation analysis from 79 of the 111 tumors. Within the group of cellular congenital mesoblastic nephromas, patients who had translocation-positive tumors had a significantly improved RFS compared with the patients who had translocation-negative tumors (5-year RFS rate, 100% vs. 73%).

Adjuvant chemotherapy

Adjuvant chemotherapy has been recommended for patients with stage III cellular subtype mesoblastic nephromas who are aged 3 months or older at diagnosis.[5] In a study of stage III cellular type congenital mesoblastic nephroma, 7 of 12 patients who were treated with surgery only suffered from a relapse, while 4 of 14 patients who were treated with adjuvant chemotherapy (primarily dactinomycin/vincristine and sometimes doxorubicin) developed a relapse.[1,5,10] Cyclophosphamide and ifosfamide have been combined with these agents and have shown activity.[11]

Infants younger than 2 months with incompletely resected, stage III disease may not need chemotherapy.[1]

(Refer to the Treatment of Recurrent Congenital Mesoblastic Nephroma section of this summary for information about recurrent disease.)

Treatment options under clinical evaluation for congenital mesoblastic nephroma

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.

The following is an example of a national and/or institutional clinical trial that is currently being conducted:

ADVL1823 (NCT03834961) (Larotrectinib in Treating Patients With Previously Untreated TRK Fusion Solid Tumors and TRK Fusion Relapsed Acute Leukemia): This is a phase II trial to study how well larotrectinib works in treating patients with previously untreated TRK fusion solid tumors and TRK fusion acute leukemia that has come back. Larotrectinib is a highly selective oral small molecule inhibitor of the TRK family of tyrosine kinases (TRKA, TRKB, and TRKC), which are encoded by the NTRK genes. Larotrectinib will be administered twice daily on a continuous dosing schedule.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References

England RJ, Haider N, Vujanic GM, et al.: Mesoblastic nephroma: a report of the United Kingdom Children's Cancer and Leukaemia Group (CCLG). Pediatr Blood Cancer 56 (5): 744-8, 2011. [PUBMED Abstract]
Jehangir S, Kurian JJ, Selvarajah D, et al.: Recurrent and metastatic congenital mesoblastic nephroma: where does the evidence stand? Pediatr Surg Int 33 (11): 1183-1188, 2017. [PUBMED Abstract]
van den Heuvel-Eibrink MM, Grundy P, Graf N, et al.: Characteristics and survival of 750 children diagnosed with a renal tumor in the first seven months of life: A collaborative study by the SIOP/GPOH/SFOP, NWTSG, and UKCCSG Wilms tumor study groups. Pediatr Blood Cancer 50 (6): 1130-4, 2008. [PUBMED Abstract]
Gooskens SL, Houwing ME, Vujanic GM, et al.: Congenital mesoblastic nephroma 50 years after its recognition: A narrative review. Pediatr Blood Cancer 64 (7): , 2017. [PUBMED Abstract]
Furtwaengler R, Reinhard H, Leuschner I, et al.: Mesoblastic nephroma--a report from the Gesellschaft fur Pädiatrische Onkologie und Hämatologie (GPOH). Cancer 106 (10): 2275-83, 2006. [PUBMED Abstract]
El Demellawy D, Cundiff CA, Nasr A, et al.: Congenital mesoblastic nephroma: a study of 19 cases using immunohistochemistry and ETV6-NTRK3 fusion gene rearrangement. Pathology 48 (1): 47-50, 2016. [PUBMED Abstract]
Argani P, Ladanyi M: Recent advances in pediatric renal neoplasia. Adv Anat Pathol 10 (5): 243-60, 2003. [PUBMED Abstract]
Vokuhl C, Nourkami-Tutdibi N, Furtwängler R, et al.: ETV6-NTRK3 in congenital mesoblastic nephroma: A report of the SIOP/GPOH nephroblastoma study. Pediatr Blood Cancer 65 (4): , 2018. [PUBMED Abstract]
Knezevich SR, Garnett MJ, Pysher TJ, et al.: ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma. Cancer Res 58 (22): 5046-8, 1998. [PUBMED Abstract]
Bayindir P, Guillerman RP, Hicks MJ, et al.: Cellular mesoblastic nephroma (infantile renal fibrosarcoma): institutional review of the clinical, diagnostic imaging, and pathologic features of a distinctive neoplasm of infancy. Pediatr Radiol 39 (10): 1066-74, 2009. [PUBMED Abstract]
McCahon E, Sorensen PH, Davis JH, et al.: Non-resectable congenital tumors with the ETV6-NTRK3 gene fusion are highly responsive to chemotherapy. Med Pediatr Oncol 40 (5): 288-92, 2003. [PUBMED Abstract]

Ewing Sarcoma of the Kidney

General Information About Ewing Sarcoma of the Kidney

Ewing sarcoma (previously known as neuroepithelial tumor) of the kidney is extremely rare and demonstrates a unique proclivity for young adults. It is a highly aggressive neoplasm, more often presenting with large tumors and penetration of the renal capsule, extension into the renal vein, and in 40% of cases, evidence of metastases.[1-3]

Ewing sarcoma of the kidney is characterized by CD99 (MIC-2) positivity and the detection of EWS/FLI-1 fusion transcripts. In Ewing sarcoma of the kidney, focal, atypical histologic features have been seen, including clear cell sarcoma, rhabdoid tumor, malignant peripheral nerve sheath tumors, and paraganglioma.[1,4] (Refer to the PDQ summary on Ewing Sarcoma Treatment for more information.)

Treatment of Ewing Sarcoma of the Kidney

There is no standard treatment option for Ewing sarcoma of the kidney. However, treatment with chemotherapy and radiation therapy and an aggressive surgical approach seem to be associated with a better outcome than previously reported.[2] Consideration should also be given to substituting cyclophosphamide for ifosfamide in patients after they have undergone a nephrectomy. [2,3]

Treatment according to Ewing sarcoma protocols should be considered.[1]

Current Clinical Trials

References

Parham DM, Roloson GJ, Feely M, et al.: Primary malignant neuroepithelial tumors of the kidney: a clinicopathologic analysis of 146 adult and pediatric cases from the National Wilms' Tumor Study Group Pathology Center. Am J Surg Pathol 25 (2): 133-46, 2001. [PUBMED Abstract]
Tagarelli A, Spreafico F, Ferrari A, et al.: Primary renal soft tissue sarcoma in children. Urology 80 (3): 698-702, 2012. [PUBMED Abstract]
Rowe RG, Thomas DG, Schuetze SM, et al.: Ewing sarcoma of the kidney: case series and literature review of an often overlooked entity in the diagnosis of primary renal tumors. Urology 81 (2): 347-53, 2013. [PUBMED Abstract]
Ellison DA, Parham DM, Bridge J, et al.: Immunohistochemistry of primary malignant neuroepithelial tumors of the kidney: a potential source of confusion? A study of 30 cases from the National Wilms Tumor Study Pathology Center. Hum Pathol 38 (2): 205-11, 2007. [PUBMED Abstract]

Primary Renal Myoepithelial Carcinoma

General Information About Primary Renal Myoepithelial Carcinoma

Myoepithelial carcinomas are aggressive malignancies primarily affecting soft tissues with occasional visceral origin. Approximately 20% of all reported cases have been described in children and are associated with a particularly unfavorable outcome, frequent development of metastases, and short overall survival.[1]

Two cases of primary renal myoepithelial carcinoma have occurred in children, and both cases had a translocation involving EWSR1 and the novel fusion partner KLF15, a transcription factor uniquely functioning within the kidney. Helpful features to establish the diagnosis include coexpression of cytokeratins, S-100, and smooth muscle markers, and the documentation of EWSR1 rearrangements.[2]

Treatment of Primary Renal Myoepithelial Carcinoma

Although no standard therapy has been established, surgical resection of the primary tumor and pulmonary nodules (if present) has been used in addition to chemotherapy and radiation therapy.[2]

References

Gleason BC, Fletcher CD: Myoepithelial carcinoma of soft tissue in children: an aggressive neoplasm analyzed in a series of 29 cases. Am J Surg Pathol 31 (12): 1813-24, 2007. [PUBMED Abstract]
Cajaiba MM, Jennings LJ, Rohan SM, et al.: Expanding the Spectrum of Renal Tumors in Children: Primary Renal Myoepithelial Carcinomas With a Novel EWSR1-KLF15 Fusion. Am J Surg Pathol 40 (3): 386-94, 2016. [PUBMED Abstract]