Kidney

This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2021, Case 19, and is Nephroblastoma (Wilms tumor) in the kidney.

The information provided in this case was accurate and correct at the time of publication in 2021. Any changes in terminology since the time of publication may not be reflected in this case

Histologic examination shows a triphasic tumor with a dominant blastemal component composed of small overlapping cells with scant cytoplasm and small nucleoli. Epithelial differentiation is characterized by small tubules and scattered primitive glomeruli. The stromal component is composed of oval to spindled cells in a loose stroma. Foci of necrosis are present in some sections. The histologic features are consistent with nephroblastoma (Wilms tumor).

Nephroblastoma is the most common malignant renal neoplasm in the pediatric population and accounts for up to 80% of renal tumors in children. The average age at presentation is 3 to 4 years, with nearly all cases diagnosed in children less than 10 years of age. The most common clinical presentation is an abdominal mass, although some patients experience abdominal pain, hypertension, or hematuria. A minority of cases are syndromic and may be a component of WAGR syndrome (Wilms tumor, Aniridia, Genitourinary anomalies, intellectual disability [formerly referred to as mental Retardation]), Beckwith–Wiedemann syndrome, and Denys–Drash syndrome.

Grossly, nephroblastoma is most commonly unifocal, but multifocal and bilateral tumors are seen in approximately 5% of patients. Tumors are often multinodular and well-circumscribed, with a fibrous pseudocapsule. Cut surfaces are typically pale gray to tan and soft. Cysts and regions of necrosis may be present.

Nephroblastoma characteristically shows a triphasic growth pattern, with epithelial, blastemal, and stromal elements. The blastemal component is characterized by small cells with scant cytoplasm, frequent mitoses, and small nucleoli. The epithelial component is most commonly composed of tubules or glomeruloid structures. The stromal component appears as primitive mesenchyme or may show a more differentiated appearance, most commonly smooth muscle or fibroblastic differentiation. Some tumors show heterologous differentiation, including squamous or mucinous epithelium, skeletal muscle, adipose tissue, cartilage, bone, and neuroglial tissue. ​​​​A fibrous pseudocapsule is present at the periphery of the tumor. In the setting of preoperative chemotherapy, there may be necrosis, xanthomatous change, hemosiderin, and/or fibrosis. Preoperative treatment may also lead to maturation of one or more components of the tumor, most commonly seen as striated muscle differentiation.

Adequate sampling of the tumor typically shows regions with the characteristic triphasic pattern, and ancillary studies are not required for diagnosis. Other tumors in the differential diagnosis of nephroblastoma do not show this triphasic morphology. If immunohistochemistry is needed, the blastemal and epithelial components are positive for WT1 and variably positive for pancytokeratin. Desmin may be focally positive.

Nephroblastoma is classified as unfavorable histology when focal or diffuse anaplasia is present. Anaplasia is identified in nearly 10% of tumors and is defined as large hyperchromatic nuclei (at least three times the length of nonanaplastic nuclei) and atypical, multipolar mitotic figures.

The most important adverse prognostic factors are high stage and the presence of anaplasia. Additionally, identification of loss of heterozygosity for chromosomes 1p and 16q has been shown to be associated with a worse prognosis. Molecular studies are increasingly important for risk stratification and may prompt more intensive chemotherapy in some patients.

B-lymphoblastic lymphoma involving the kidney may appear similar to blastemal-predominant nephroblastoma but can be distinguished by immunohistochemistry. B-lymphoblastic lymphoma will be positive for CD45, TdT, and CD20.

Cellular congenital mesoblastic nephroma (CMN) is composed of sheets of ovoid to spindle cells and may resemble nephroblastoma with a dominant blastemal component or with a densely cellular stromal component. By immunohistochemistry, CMN is negative for WT1. Additionally, the majority of cellular CMN show t(12;15)(p13;q25) with ETV6::NTRK3 gene fusion.

Ewing sarcoma is composed of sheets of round cells with a small amount of clear cytoplasm and may appear similar to the blastemal component of nephroblastoma. Expression of CD99 and NKX2.2 and identification of a characteristic translocation involving EWSR1, most commonly t(11;22)(q24;q12) with EWSR1::FLI1 gene fusion, are helpful in making a diagnosis of Ewing sarcoma.

Neuroblastoma involving the kidney is most often a result of extension from the adjacent adrenal gland, but primary intrarenal neuroblastoma has been reported. Blastemal-predominant nephroblastoma may appear similar to neuroblastoma, especially in poorly differentiated or undifferentiated tumors. The presence of neuropil and lack of a triphasic growth pattern are helpful in confirming a diagnosis of neuroblastoma. If immunohistochemistry is needed, neuroblastoma is positive for synaptophysin and PHOX2B and negative for WT1.

1. Which of the following is the most common malignant renal neoplasm in children?
   
   
   1. B-lymphoblastic lymphoma
   2. Cellular congenital mesoblastic nephroma
   3. Ewing sarcoma
   4. Nephroblastoma (Wilms tumor)
   5. Neuroblastoma
2. In addition to large, hyperchromatic nuclei, which of the following histologic features is included in the criteria for anaplasia in nephroblastoma?
   
   
   1. Atypical, multipolar mitotic figures
   2. Geographic necrosis
   3. Hypercellularity
   4. Large, prominent nucleoli
   5. Small, primitive cells with scant cytoplasm
3. Which of the following would be most helpful in confirming a diagnosis of neuroblastoma?
   
   
   1. Absence of neuropil
      
   2. Positive PHOX2B immunohistochemistry
   3. Positive WT1 immunohistochemistry
   4. Presence of t(11;22)(q24;q12) EWSR::FLI1 fusion
   5. Triphasic growth pattern

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1. Nephroblastoma (Wilms tumor) (d)
2. Atypical, multipolar mitotic figures (a)
3. Positive PHOX2B immunohistochemistry (b)