We used, for the first time, data registered in the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST)-Greece to estimate incidence/time trends of the rare childhood (0–14 years) non-Wilms tumors (non-WT), and compared the results of malignant non-WT to those from the Surveillance, Epidemiology, and End Results Program (SEER)-USA.
Fifty-five cases (n = 33 malignant-only) were extracted from NARECHEM-ST (2001–2020) and 332 malignant cases from SEER (1990–2017). To allow between-country comparisons, age-standardized incidence rates (AIR) of malignant-only non-WT were calculated, and temporal trends were evaluated using Poisson and joinpoint regressions.
In NARECHEM-ST, malignant and non-malignant non-WT accounted for 22.6% of all renal tumors. Among malignant tumors, the AIR was 1.0/10 6 children in Greece, similar to that calculated for SEER, USA (AIR=0.9/10 6 ). The proportion of infant malignant and non-malignant non-WT was 27% (20% before 6 months) in NARECHEM-ST. Most common non-WT in Greece were congenital mesoblastic nephromas (CMN) diagnosed mainly in infancy (CIR=7.2/10 6 ). The proportion of infant malignant non-WT was 20% in SEER (AIR infancy =2.5/10 6 ), mainly attributed to rhabdoid tumors (CIR=1.6/10 6 ). The male-to-female (M:F) ratio of malignant non-WT was 0.9 in NARECHEM-ST vs. 1.2 in SEER, whereas boys outnumbered girls with clear cell sarcoma in NARECHEM-ST (M:F=4.0). Lastly, significantly increasing trends in incidence rates were noted in NARECHEM-ST [+ 6.8%, 95% confidence intervals (CI): 0.5, 13.3] and in SEER (+7.3%, 95%CI: 5.6, 9.0).
Observed incidence, time trends and sociodemographic variations of non-WT may reflect differential registration practices and healthcare delivery patterns including differences regarding surveillance, coding and treatment practices.
- • The proportion of non-WT among all renal tumors was 22.6% in Greece.
- • The AIR of malignant non-WT was similar in Greece (1.0/10 6 ) and SEER, USA (0.9/10 6 ).
- • The non-WT incidence was higher during infancy than in later age in SEER, USA.
- • There is need for common registration and coding standards and monitoring of the occurrence of these rare entities to improve quality and comparability of international data.
Renal tumors are the second most common abdominal tumors in children (0–14 years), following abdominal neuroblastomas. Wilms’ tumor (WT), an embryonal type of renal cancer also called nephroblastoma, is by far the most common renal neoplasm accounting for 85–95% of all pediatric renal malignancies . While the incidence patterns of childhood WTs have been extensively studied , less is known about the incidence of non-Wilms’ tumors (non-WT), which are infrequent in childhood representing approximately 10% of primary renal neoplasms and less than 1% of all childhood malignancies .
The diagnosis and thus estimation of incidence of non-WTs is challenging due to their rarity, the large heterogeneity of histological subtypes and their variable malignant potential . In addition, incidence variations by age, gender and ethnicity have been reported for non-WTs . The differential diagnosis of these tumors includes a large variety of epithelial, mesenchymal, neuroectodermal, and hematopoietic neoplasms , as well as benign disorders . Of note is that non-neoplastic renal masses, such as hydronephrosis and multicystic dysplastic kidney should also be taken into consideration in the differential diagnosis, especially in certain age groups; i.e., only 20% of renal masses in the first year of life are true neoplasms . The diagnosis of non-WTs can be suspected on the basis of their clinical and imaging features; however, radiology findings are not pathognomonic due to the non-specific morphology and the lack of specific radiological criteria . Notably, in treatment centers where a tissue diagnosis is not a prerequisite to initiating treatment, misdiagnosis is possible and a significant proportion of patients may not receive optimal treatment, at least initially. Moreover, the rarity of this group of tumors poses additional challenges to the accurate diagnosis. Sociodemographic and clinical characteristics, such as the specific age distribution of each tumor subtype, the presence of nephroblastoma associated stigmata or genetic predisposition syndromes, the laboratory findings as well as the presence and the type of metastases can be helpful in the differential diagnosis . Immunohistochemistry and molecular diagnostic approaches are nowadays mandatory to differentiate non-WTs and to establish a precise tissue diagnosis, but misdiagnosis may occur even in pathology reviews, including differences in initial histology and pathologic staging . Discrepancies in risk stratification between pathology laboratories are identified in a substantial number of cases indicating the crucial contribution of central pathology review .
We aimed to estimate, for the first time in Greece, the incidence rates and trends of primary non-WTs overall and by histological subtype, as well as their distribution by demographic and clinical characteristics using data from the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST). We thereafter compared the data of malignant non-WT to those from the Surveillance, Epidemiology, and End Results Program (SEER), USA. The ratio of WT to non-WT in NARECHEM-ST, Greece was also calculated.