Introduction
Congenital mesoblastic nephroma accounts for only 2–5% of all pediatric renal tumors, whereas it is the most common solid renal tumor in neonates [
1‐
5]. Approximately 75% of all cases are diagnosed in the first 6 months of life [
5]. Congenital mesoblastic nephroma is considered to arise perinatally; however, only 11–15% have been reported to be detected through prenatal imaging [
2,
6‐
8]. Congenital mesoblastic nephroma as a separate entity was first described by Bolande et al. and classified as a benign renal tumor [
9,
10]. Nevertheless, given limited reports of metastatic behavior, it is currently best classified as a mesenchymal tumor with low malignant potential [
2,
5,
11‐
14]. Morbidity and mortality are predominantly caused by associated polyhydramnios and other related paraneoplastic syndromes at presentation, whereas the tumor rarely metastasizes, mainly to the lungs, brain, liver, or bone [
11,
15‐
20]. Histologically, three subtypes have been described [
9]. The classic type consists of bland spindle cells, with few mitoses and no apparent hemorrhage and necrosis [
2,
7,
21‐
23]. In contrast, the cellular type shows a high mitotic index and invasive growth pattern with areas of hemorrhage and necrosis [
2,
3,
7,
17,
22]. In general, if both histological patterns are present, the lesion is classified as mixed type [
2,
23,
24].
In children older than 6 months of age who have a renal tumor, preoperative chemotherapy for Wilms tumor is standard of care within the current Renal Tumor Study Group of the International Society of Pediatric Oncology (SIOP-RTSG) 2016 UMBRELLA protocol. In general, children <3 months of age undergo an upfront nephrectomy, which is the standard treatment for congenital mesoblastic nephroma [
11,
25‐
27]. Wilms tumor is the most frequent pediatric renal tumor in the first decade of life, whereas neonatal cases are rare [
28,
29]. Rhabdoid tumor of the kidney and clear cell sarcoma of the kidney are also predominantly diagnosed in the first years of life [
2,
29‐
31]. As pediatric renal tumors preferably require different treatment approaches, and biopsies are not advocated by the SIOP-RTSG in young children, non-invasive discrimination through imaging is important in the diagnostic process, especially in infants >3 months of age [
11,
29]. While prenatal and antenatal ultrasound (US) are the first-line modalities for diagnosis, magnetic resonance imaging (MRI) plays an increasingly important role due to the excellent soft-tissue contrast without use of ionizing radiation, and is therefore advocated as preferred modality within the SIOP-RTSG [
6,
11,
28,
32].
Based on previous case reports and small retrospective studies, congenital mesoblastic nephroma is typically described as homogeneous and isointense to normal renal parenchyma [
4,
7,
12,
14,
33]. The cellular type seems to be more heterogeneous, making differentiation from malignant tumors more difficult [
3,
6,
8,
21,
28,
33‐
37]. Therefore, identification of specific MRI characteristics of congenital mesoblastic nephroma at diagnosis, especially in young children, is important for the discrimination from Wilms tumors and more aggressive non-Wilms tumor [
11,
29,
34,
38]. This study aims to identify MRI characteristics that may be specific for congenital mesoblastic nephroma at diagnosis through a retrospective international multicenter SIOP-RTSG cohort study in the largest number of described patients to date.
Discussion
Given the evidence-based SIOP-RTSG guidelines advocating against invasive procedures to determine histology at diagnosis in the majority of children with renal tumors, imaging plays an increasingly important role in the non-invasive discrimination of pediatric renal tumors [
8,
25,
34]. This retrospective multicenter study illustrates the MRI characteristics of congenital mesoblastic nephroma in an international cohort, focusing on its different subtypes and identifying potentially specific MRI characteristics of this rare neonatal pediatric renal tumor. Although we know congenital mesoblastic nephroma accounts for the majority of prenatal and neonatal renal tumors, and outcome is excellent with reported outcome rates of 95–100%, early recognition and discrimination from more malignant pediatric renal tumors is important, especially in children >3 months of age [
1,
3,
11,
15‐
17,
29]. T2W isointensity particularly, appears to be potentially discriminating in the differentiation of congenital mesoblastic nephroma from the often T2W hyperintense Wilms tumor. Nonetheless, while the classic type congenital mesoblastic nephroma often appears homogeneous on imaging, the cellular and mixed type show more overlapping imaging MRI characteristics with malignant pediatric renal tumors in the same age range, such as Wilms tumor, rhabdoid tumor of the kidney, and clear cell sarcoma of the kidney [
2,
3,
6,
8,
11,
21,
31,
37,
44].
Above the age of 3 months, a combination of certain clinical, radiological, and biochemical criteria are usually used to decide if a diagnostic cutting needle biopsy is indicated [
26,
27]. In general, some studies have indicated the incidence of congenital mesoblastic nephroma is higher in males than females, whereas we only saw a slight predominance of male patients in our study (57.7%) [
33,
45‐
47]. Metastases are described in approximately 2% of patients with the cellular type, which is in line with only one suspected metastatic case in this study [
11,
13,
15,
18,
21,
35,
37]. Although its malignant potential remains a topic of debate, the rarity of metastases may be a discriminating factor between congenital mesoblastic nephroma and malignant renal tumors, especially in case of the classic type [
5,
6,
8,
11,
14,
48]. Nonetheless, a total nephrectomy is the indicated treatment for all subtypes, especially given the increased likelihood of local recurrence in approximately 5% of the patients after a partial nephrectomy due to positive margins [
11,
13,
15,
18].
We found that the classic type congenital mesoblastic nephroma often appears as a solid, well-defined, and homogeneous tumor, showing isointensity compared to the renal parenchyma on T2W imaging. The homogeneous appearance is predominantly caused by a lack of hemorrhage, necrotic, and/or cystic changes, which is in line with previous studies [
23,
28,
34]. The concentric ring sign, also known as “double layer sign,” was present in more than half of our classic type cases. This recognizable ring pattern, appearing hypoechoic on the abdominal ultrasound, in contrast to the isoechoic tumor tissue, has been predominantly mentioned in the context of the classic variant, and is hypothesized to be caused by compressed kidney tissue and dilated blood vessels [
49‐
51]. Nevertheless, it does not appear to be specific to classic type congenital mesoblastic nephroma, as we also reported the characteristic in cellular and mixed cases in this study, in line with Daniel et al. [
3,
52].
In case reports and small series, the cellular type congenital mesoblastic nephroma is suggested to be more heterogeneous on MRI, due to cystic, hemorrhagic, and/or necrotic components, in general showing a more aggressive growth pattern compared to the classic variant, as well as a larger size [
3,
21,
23,
33,
36,
48]. Our study confirmed these findings, again stressing the difficulty to discriminate this variant from the often large, heterogeneous Wilms tumour [
6,
11,
13,
21,
28,
48]. Also, this cohort of patients with cellular and mixed type congenital mesoblastic nephroma seemed to be older, indicating an overlap in age with the malignant Wilms and non-Wilms tumors [
31,
34]. Nevertheless, Wilms tumors are often described as T2W hyperintense, which might indicate T2W isointensity as slightly discriminative for congenital mesoblastic nephroma in general [
21,
22,
24,
53]. Rhabdoid tumors of the kidney are reported to be small, mainly T2W hypointense and often show infiltrative and aggressive features, potentially discriminating them from congenital mesoblastic nephroma as well as from Wilms tumors [
44,
54]. Finally, no additional potentially discriminative MRI characteristics were identified for mixed type congenital mesoblastic nephroma, concerning both differentiation from the classic and cellular type and from other renal tumor types.
Whereas solid tumor characteristics and T1W and T2W imaging are predominantly used to identify abnormal and potentially specific characteristics of tumors, DWI and ADC values might contribute through the semi-quantification of cellularity [
6,
34,
50]. Nevertheless, very limited studies have reported ADC-values of congenital mesoblastic nephroma, and conclusions are limited to the presence or absence of diffusion restriction in general [
6,
48]. We showed ADC values for all subtypes to be approximately the same, with overall means ranging from 1.05 to 1.10×10
−3 mm
2/s, indicating moderate diffusion restriction in most tumors. ADC values around this range have also been described for clear cell sarcoma of the kidney, as well as stromal type Wilms tumor, whereas in general, more aggressive Wilms tumor subtypes show a higher diffusion restriction [
44,
55,
56].
Our study has several limitations, predominantly related to its international setting and retrospective nature. While this could lead to potential information bias and variability, there was excellent interrater agreement among the included radiologists, who are experts in the field of imaging of pediatric renal tumors [
44]. Also, the design of this study and related inclusion in different SIOP-RTSG protocols over the past decades affects the extent of national registration and center-specific choice of cross-sectional imaging modalities, which may have led to registration bias, potentially resulting in a disproportionate number of included patients per country, nonetheless also taking into consideration differences in population. Furthermore, in international studies, variability on the level of the patient and the MRI, reflected in the heterogeneity of reported scan parameters, has to be taken into consideration [
57]. While this might not influence the reported results, it limits the possibility for statistical analysis in DWI data, given non-comparable ADC maps based on a variety of
b-values [
58]. Concerning clinical characteristics of the patients, this study was not designed to report on prenatal imaging or outcome, therefore lacking information on prenatal diagnoses and survival of the included patients. Also, despite the international setting of this study, numbers remained low and distribution of subtypes may not be in line with percentages reported by for instance a review by Gooskens et al., who showed a higher percentage of cellular type congenital mesoblastic nephroma (42%) [
2]. Finally, statistical analysis of the discriminative value of MRI characteristics in the differentiation of subtypes of congenital mesoblastic nephroma was limited due to these relatively low numbers, while the differentiation from other pediatric renal tumors could not be analyzed based on the design of this predominantly descriptive study.
Conclusion
Early non-invasive diagnosis of congenital mesoblastic nephroma based on MRI, as well as increasing knowledge of potential indications for a cutting needle biopsy, could be beneficial for increasing outcome and reducing treatment-related toxicity in pediatric renal tumor patients. This study forms the basis for future studies which may focus on the validation of identified potentially specific MRI characteristics in the light of differentiating congenital mesoblastic nephroma from Wilms tumors and other non-Wilms tumors, further exploring the discriminative value of MRI in pediatric renal tumor patients (Table
3).
Table 3
Overview of identified potentially specific magnetic resonance imaging and diffusion-weighted imaging characteristics of congenital mesoblastic nephroma in light of the differentiation of subtypes and the differentiation from Wilms tumor
Classic type | • Age predominantly <3 monthsb • Concentric ring sign • Small tumor volume • T2W isointensity • Homogeneous enhancement • ADC-values around 1.05–1.10*10-3 mm2/s • Absence of metastases • Lack of (pseudo)capsule • Lack of venous invasion / tumor thrombus | • (Pseudo)capsule • Large, solid tumor • T1W hypointensity • T2W hyperintensity • Heterogeneous enhancement due to hemorrhagic/necrotic components • Varying ADC-values related to histopathology • Possible tumor thrombus • Pulmonary metastases • Bilateral disease |
Cellular type | • Potentially older children (up to 2 years of age)b • Large tumor volume • T2W isointensity • Heterogeneous enhancement due to potential presence of hemorrhage and/or necrosis • ADC-values around 1.05–1.10*10-3 mm2/s • Metastases are rare, but do occur • Lack of venous invasion / tumor thrombus |
Mixed type | • Characteristics similar to cellular type congenital mesoblastic nephroma |
Since MRI is the preferred imaging modality for children with a renal tumor within the SIOP-RTSG, MRI characteristics of the different potential diagnoses need to be further explored. This study describes the MRI features of congenital mesoblastic nephroma at initial diagnosis through international collaboration of the SIOP-RTSG radiology panel in the largest retrospective series so far. Although age appears to remain the most important clinical characteristic to discriminate congenital mesoblastic nephroma from other pediatric renal tumor types, this study showed that homogeneity and a concentric ring sign quite specifically indicate a classic type. The cellular type can be discriminated from the classic variant based on its heterogeneity and larger size, whereas the T2W isointensity of all subtypes of congenital mesoblastic nephroma could be taken into consideration in the discrimination from more malignant pediatric renal tumors. Finally, the role of DWI and ADC values has been further explored, showing an almost equal ADC value for all congenital mesoblastic nephroma subtypes, which for example, could be used to discriminate from more aggressive pediatric renal tumors with high cellularity.
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