Anaplastic sarcoma of the kidney (DICER1-sarcoma of the kidney): A report from the International Pleuropulmonary Blastoma/DICER1 Registry

Abstract

Background: Anaplastic sarcoma of the kidney (ASK) is a DICER1-related neoplasm first identified as a distinctive tumor type through the evaluation of unusual cases of putative anaplastic Wilms tumors. Subsequent case reports identified the presence of biallelic DICER1 variants as well as progression from cystic nephroma, a benign DICER1-related neoplasm. Despite increasing recognition of ASK as a distinct entity, the optimal treatment remains unclear.

Methods: Individuals with known or suspected DICER1-related tumors including ASK were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry. Additionally, a comprehensive review of reported cases of ASK was undertaken, and data were aggregated for analysis with the aim to identify prognostic factors and clinical characteristics to guide decisions regarding genetic testing, treatment, and surveillance.

Results: Ten cases of ASK were identified in the Registry along with 37 previously published cases. Staging data, per Children's Oncology Group guidelines, was available for 40 patients: 13 were stage I, 12 were stage II, 10 were stage III, and five were stage IV. Outcome data were available for 37 patients. Most (38 of 46) patients received upfront chemotherapy and 14 patients received upfront radiation. Two-year event-free survival (EFS) for stage I-II ASK was 81.8% (95% confidence interval [CI]: 67.2%-99.6%), compared with 46.6% EFS (95% CI: 24.7%-87.8%) for stage III-IV (p = .07). Two-year overall survival (OS) for stage I-II ASK was 88.9% (95% CI: 75.5%-100.0%), compared with 70.0% (95% CI: 46.7%-100.0%) for stage III-IV (p = .20). Chemotherapy was associated with improved EFS and OS with hazard ratios of 0.09 (95% CI: 0.02-0.31) and 0.08 (95% CI: 0.02-0.42), respectively.

Conclusion: ASK is a rare DICER1-related renal neoplasm. In the current report, we identify clinical and treatment-related factors associated with outcome including the importance of chemotherapy in treating ASK. Ongoing data collection and genomic analysis are indicated to optimize outcomes for children and adults with these rare tumors.

Keywords: DICER1; anaplastic sarcoma of the kidney; childhood cancer; cystic nephroma; pleuropulmonary blastoma; renal sarcoma.

FIGURE 1

Anaplastic sarcoma of kidney in a 14-year-old female (Case 9, Supplemental Table 2). A. Nest of pleomorphic and anaplastic cells. B. Nodule of atypical cartilage surrounded by nests of undifferentiated round and spindle cells. C. Cysts lined by low cuboidal epithelial cells representing remnants of cystic nephroma surrounded by undifferentiated spindle cells. D. Diffuse intense nuclear p53 immunostaining in nests of anaplastic and pleomorphic tumor cells. E. Anaplastic sarcoma of kidney. A partially hemorrhagic, greyish-tan, mucoid mass in the right kidney of a 6-year-old female (Case 4, Supplemental Table 2).

FIGURE 2

Kaplan-Meier survival curves by stage at diagnosis and use of chemotherapy. A. EFS by stage I-II versus III-IV; B. OS by stage I-II versus III-IV. C. EFS in stage I and II by use of chemotherapy; D. OS in stage I and II by use of chemotherapy.