Glomerulocystic and Nephroblastomatosis

Diagnosis: Glomerulocystic Kidney Disease and Diffuse Nephroblastomatosis

Glomerulocystic kidney disease (GCKD) is a rare form of hereditary disease characterized by cystic dilation of Bowman's capsule and the initial proximal convoluted tubule. The dilated Bowman spaces are lined by a flattened epithelium and contain rudimentary glomerular tufts. GCKD is defined as two- to three-fold dilatation of Bowman’s space in more than 5% of identifiable glomeruli in the plane of a kidney section, and the glomerular cysts in primary GCKD are mainly localized to the subcapsular region of the kidney (Rasouly HM, et al. Loss of Zeb2 in mesenchyme-derived nephrons causes primary glomerulocystic disease. Kidney Int. 2016;90(6):1262-1273. [PubMed link]).

On ultrasonographic imaging, the kidneys can appear enlarged with increased echogenicity and loss of corticomedullary junction differentiation. Familial GCKD is typically identified with hypoplastic or normal-sized kidneys. However, in both sporadic and familial forms, the kidneys can be either hypoplastic, normal-sized, or enlarged. Punctate cysts can be seen and will differentiate this from the classical ARPKD findings on ultrasound. On computed tomography (CT) and magnetic resonance imaging (MRI), GCKD appears as numerous small cortical cysts. These do not enhance with gadolinium during MRI. Unlike other cystic kidney diseases, the tubules in GCKD usually remain unaffected. Given the inconsistent nature of GCKD, it is clinically difficult to diagnose and can only be established by renal biopsy (Lundquist AL. Hereditary Renal Cystic Diseases: Glomerulocystic Kidney Disease. In: Renal & Urology News: www.renalandurologynews.com... Accessed February 26th, 2019 [Link to the website]).

Glomerular cysts in association with tubular cysts can be found in several syndromes including tuberous sclerosis complex, orofaciodigital syndrome 1, and Meckel-Gruber syndrome. Glomerular cysts can also be found in patients with mutations in the UMOD and HNF1β genes, and in patients of autosomal dominant polycystic kidney disease with PKD1 mutations, other ciliopathies such as nephronophthisis, multicystic dysplastic kidney or urinary tract obstruction. However, the genetic basis of primary glomerulocystic kidney disease without tubular dilatation remains largely unknown (Rasouly HM, et al. Loss of Zeb2 in mesenchyme-derived nephrons causes primary glomerulocystic disease. Kidney Int. 2016;90(6):1262-1273. [PubMed link]).

Nephroblastomatosis refers to diffuse or multifocal involvement of the kidneys with nephrogenic rests (persistent metanephric blastema). Nephrogenic rests are found incidentally in 1% of infants. Nephrogenic rests are foci of metanephric blastema that persist beyond 36 weeks of gestation and have the potential for malignant transformation into Wilms tumor. It is currently believed that nephrogenic rests give rise to approximately 30-40% of Wilms tumors. Nephrogenic rests are found in up to 99% of bilateral Wilms tumors. There are two pathologic subtypes of nephrogenic rest, perilobar rest (90%) and intralobar rest (10%), the latter being more associated with Wilms tumor (Harvey, Radswiki, et al. Nephroblastomatosis. In: Radiopaedia.org: radiopaedia.org/articles/nephroblastomatosis - Accessed: June 26, 2021).

The coexistence of these two alterations in the same kidney could be etiologically related, but we do not know this possible etiology or a possible genetic association in this case. In a literature search, we were unable to find a description of similar cases.

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