Encyclopedia of Pathology

Living Edition
| Editors: J.H.J.M. van Krieken

Nephroblastic Tumors

  • Anna Caliò
  • Diego Segala
  • Guido MartignoniEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-28845-1_4861-1

Definition

Nephroblastic tumors include nephroblastoma, the most common, and cystic partially differentiated nephroblastoma.

Synonyms

Clinical Features

  • Incidence

    Nephroblastoma is a malignant tumor which comprises more than 85% of pediatric renal tumors and 5% of childhood cancers.

  • Age

    It is usually found in children 2–4 years old, it is relatively uncommon in the first 6 months of life and in children older than 6 years, whereas it is rare in the neonatal period. Nephroblastoma rarely occurs in adults.

  • Sex

    There is no gender predilection.

  • Site

    Five percent of the tumors are multicentric and bilateral.

  • Treatment

    Tumor resection followed by chemotherapy or adjuvant chemotherapy and surgical treatment are the two different protocols of therapy.

  • Outcome

    Despite the different managements, the overall survival currently is more than 90%.

The associations with cryptorchidism, hypospadias, other genital anomalies, hemihypertrophy, and aniridia are well-recognized and described in different genetic syndromes such as Beckwith-Wiedemann, Wilms-aniridia-genital anomaly-retardation (WAGR), and Denys-Drash syndromes due to different genetic alterations.

Macroscopy

It presents as a mass usually larger than 5 cm with solid, soft, and grayish or pinkish, resembling brain tissue. Hemorrhage and necrosis are frequently present. The tumor is usually surrounded by a prominent pseudocapsule composed of compressed renal and perirenal tissues. Cystic tumors macroscopically indistinguishable from cystic nephroma which present small foci of blastema, immature appearing stromal cells, and primitive epithelium are classified as cystic partially differentiated nephroblastoma (Beckwith et al. 1990).

Microscopy

Nephroblastoma is typically triphasic being composed of variable admixtures of blastema, epithelium, and stroma (Fig. 1). However in some neoplasms only two or occasionally only one component is present. The blastemal component can grow in three different patterns: nodular, serpentine, and diffuse. The blastemal cells are small and densely packed and show oval to elongated nuclei with numerous mitoses. The epithelial component usually consists of small tubules lined by primitive columnar cells and abortive glomeruli. The stromal component can differentiate along the lines of almost any type of soft tissue; loose myxoid, fibroblastic spindle cell stroma, and skeletal muscle are the most common. Based on the absence or presence of anaplasia, nephroblastomas are divided into two categories: favorable and unfavorable histologies. Anaplasia has been defined as the combination of cells with very large hyperchromatic nuclei and multipolar mitotic figures. Anaplasia is found in approximately 6% of nephroblastomas; it is rare in patients younger than 1 year, and more than 80% of patients are older than two. Even small foci of anaplasia can be associated with an adverse outcome (Faria et al. 1996). Thus, it is important to sample the specimens extensively.
Fig. 1

An example of nephroblastoma showing blastemal component (a) intermixed with epithelial tubules (b)

Immunophenotype

The blastema component is usually positive for WT1 and may label for desmin and not for the other muscular markers. The epithelial components are positive for WT1 and cytokeratins, including CK7.

Molecular Features

The WT1 gene located on chromosome 11p13 is involved in the pathogenesis of the WAGR (Wilms tumor associated with aniridia, genital anomalies, and mental retardation) and the Denys-Drash (pseudohermaphroditism, severe glomerulopathy, and Wilms tumor) syndromes. The WT1 gene is mutated in approximately 20% of sporadic nephroblastomas. Nephroblastomas demonstrating loss of heterozygosity for chromosomes 1p and 16q have been shown to have a poor prognosis (Huang et al. 2009).

Differential Diagnosis

The differential diagnosis includes small blue cell tumors (neuroblastoma, rhabdomyosarcoma, and primitive neuroectodermic tumor), immature teratoma, metanephric adenoma, and papillary renal cell carcinoma. The differential diagnosis is based on the morphological features in association with an immunohistochemical panel such as WT1, CD99, CD57, myogenin, and chromogranin.

Nephrogenic Rests

Nephrogenic rests are abnormally persistent foci of embryonal cells that are potentially able of developing into nephroblastoma (Wilms tumor). Nephrogenic rests can be found adjacent to nephroblastoma or in the surrounding renal parenchyma (Beckwith et al. 1990).

References and Further Reading

  1. Beckwith, J. B., Kiviat, N. B., & Bonadio, J. F. (1990). Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms’ tumor. Pediatric Pathology, 10, 1–36.CrossRefGoogle Scholar
  2. Faria, P., Beckwith, J. B., Mishra, K., et al. (1996). Focal versus diffuse anaplasia in Wilms tumor – new definitions with prognostic significance: A report from the National Wilms Tumor Study Group. The American Journal of Surgical Pathology, 20, 909–920.CrossRefGoogle Scholar
  3. Huang, C. C., Gadd, S., Breslow, N., et al. (2009). Predicting relapse in favorable histology Wilms tumor using gene expression analysis: A report from the Renal Tumor Committee of the Children’s Oncology Group. Clinical Cancer Research, 15, 1770–1778.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Diagnostic and Public Health, Section of PathologyUniversity of VeronaVeronaItaly
  2. 2.Department of PathologyPederzoli Hospital, Peschiera del GardaPeschiera del GardaItaly