January 2022 | Case of the Month Answer for Residency Program

January 2022 – Presented by Dr. Luke Dang (Mentored by Dr. Kurt Schaberg)

Discussion

Renal dysplasia is the most common pediatric cystic renal disease and occurs both sporadically (most commonly) as well as in association with a range of multi-malformation complexes and inherited syndromes. Clinically, this entity may be suspected in utero as 90% are associated with malformations including ureteropelvic obstruction (resulting in distal obstruction and possible ureteral stenosis or dilation, or bladder hypertrophy) or ureteral agenesis or atresia. Reported associations include VATER syndrome, MURC syndrome, caudal regression syndrome, prune belly syndrome, urorectal septum syndrome sequence, urogenital sinus syndrome, Dandy-Walker syndrome, Eljalde syndrome, Meckel-Gruber syndrome (typically with renal enlargement), thanatophoric dysplasia type 1 (a lethal dwarfism condition due to mutations in fibroblast growth receptor 3 (FGF3)), and a range of inherited metabolic disorders (including glutaric acidemia type II and carnitine palmitoyltransferase type II deficiencies). Maternal nutritional disturbances (malnutrition, iron deficiency, Vitamin A) and ACE inhibitor use have also been associated with increased risk of renal dysplasia. Given the clinical significance of the associated entities, when renal dysplasia is suspected clinically (often via ultrasound as small kidneys with noncommunicating hypoechogenic cysts), additional monitoring is appropriate, and presence of bilateral disease may additionally prompt further workup. If the dysplasia is unilateral, this condition may be asymptomatic, however based on the extent of involvement presenting symptoms may include failure to thrive, excessive thirst, hypertension, or salt wasting.

Based on either presenting symptoms or radiologic characterization, specimens submitted for histopathologic characterization may be accompanied by a clinical history of congenital renal abnormalities which may provide context for recognition of this entity. Gross findings commonly include the presence of a cystic component within an abnormal kidney with loss of corticomedullary differentiation (indistinct corticomedullary junction), and the collecting system may be absent (Figure 1). The gross morphology of dysplastic kidneys can be variable as involvement may be unilateral or bilateral and architecturally may range from large and multicystic to small and aplastic. Microscopically, disorganized parenchyma, large cysts with flattened lining and dysplastic or immature ducts with collarettes of positive spindle cells are seen (Figure 2). Less frequently (in ~30% of cases), immature cartilage (blastema-derived), islands of undifferentiated mesenchyma, or nodular blastema is also seen (Figure 3). Immature tubules and aberrant glomeruli or normal tubules and glomeruli may be present. Commonly, this process will involve the entire kidney, however segmental dysplasia may also be observed (occurring in individuals with duplex kidneys).

Importantly, dysplasia in this context refers to aberrant developmental anomalies, but does not refer to an association with neoplasia, so it is important that the presence of blastemal elements does not produce an assumption that the process is neoplastic in nature. The differential diagnosis may include renal hypoplasia (small, architecturally preserved kidneys with reduced nephrons), renal aplasia, or other polycystic kidney diseases (answer choice A, would lack dysplastic/mesenchymal elements). Neoplastic entities typically have a distinct clinical presentation and morphologic appearance: cystic Wilm’s tumor (answer choice A, peak incidence from 2-4 years, rare in infants under 6 months, typically demarcated from normal surrounding parenchyma), immature teratoma (answer choice D, typically large, solid, and encapsulated), cystic partially differentiated nephroblastoma (answer choice E, multiloculated tumor with thin septations with clusters of blastemal cells), or cystic nephroma (lacking mesenchymal component). The presence of primitive ducts lined by columnar to cuboidal epithelium, surrounded by mesenchyme is the characteristic finding of renal dysplasia. In this case, both the clinical presentation in a pediatric patient with congenital malformations and histopathologic features (disorganized parenchyma, immature tubules, focal immature cartilage) are classic for renal dysplasia.

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