Pediatric cystic nephromas: distinctive features and frequent DICER1 mutations

Abstract

Cystic nephromas (CNs) are uncommon benign renal neoplasms that present with a bimodal age distribution, affecting either infants/young children or adult females. Although differences between these age groups have been suggested, large studies of pediatric CN have not been conducted. As a result, the nomenclature and diagnostic criteria for these lesions remain controversial. In addition, the morphological overlap seen between CN and cystic partially differentiated nephroblastoma (CPDN) can result in diagnostic dilemmas. This study reviews the morphologic and radiographic features of 44 pediatric CN prospectively enrolled on a Children's Oncology Group protocol from 2007 to 2013. Although the typical multicystic architecture with thin septa described in adult CN was present in all of our pediatric cases, differences were also identified. We report distinctive features that add to the morphological spectrum of CN in children. Of the 44 cases, 16 had been previously analyzed and reported for DICER1 mutation, and either loss of function or missense mutations or both were identified in 15 of 16. In contrast, we analyzed 10 cases of adult CN, and all were negative for DICER1 mutations; similarly, 6 CPDNs previously analyzed and reported were negative for DICER1 mutations. Therefore, the clinical, morphological, and genetic differences between pediatric and adult CN, as well as between CN and CPDN, suggest that these 3 lesions represent distinct entities.

Keywords: Cystic nephromas; DICER1; Pediatric renal tumors; Renal cystic lesions; Renal development.

Figure 1

Radiographic features of pediatric cystic nephromas. Well-circumscribed cystic mass with pseudocapsule as described in adult CN (A); some cases of pediatric CN lacked a pseudocapsule (B). Relationship of pediatric CN to renal pelvis: axial T2-weighted image shows the cystic mass abutting the renal pelvis without herniation (C); coronal T2-weighted image shows herniation of the cystic renal mass into the renal pelvis and proximal ureter (D). Co-existing pulmonary cysts at initial presentation of pediatric cystic nephroma: solitary pulmonary cyst in a 13 month old (E) who had bilateral lesions, and large cystic pulmonary mass in a 16 month old (F).

Figure 2

Involvement of pelvicaliceal structures by pediatric cystic nephromas, with direct extension of the lesion from the renal papillae (A, B) and renal pelvis (C, D).

Figure 3

Fibrous pseudocapsule (A) and simple architecture with thin septa (B) as described in adult cystic nephroma. Many cases of pediatric cystic nephroma lacked encapsulation and showed a direct interface with the adjacent normal parenchyma (C, D).

Figure 4

Areas of increased architectural complexity reminiscent of multicystic dysplasia seen in pediatric cystic nephromas, with thicker septa, greater variation in cyst size and shape with more numerous small cystic structures (A-C) and frequent pericystic stromal condensation (B, D).