Pediatric Renal Cell Carcinoma

Abstract

Renal cell carcinomas are rare in children, and they show significant differences in their histology and pathogenesis when compared to those common in adults. The most common subtypes seen preferentially in children are the translocation-associated tumors, papillary renal cell carcinoma, renal medullary carcinoma, and oncocytic renal cell carcinoma following neuroblastoma. The histological diagnosis of renal cell carcinoma is made difficult by the considerable heterogeneity within and overlap between each of the above subtypes and by similarities to other pediatric renal neoplasms. While no effective therapies have yet been identified, there is considerable promise that the new Children's Oncology Group protocol will provide knowledge that will guide the future therapy of these lesions.

Figure 1. Translocation-Renal Cell Carcinoma involving t(X;17)

A) Within an overall tubular or nested architecture, cells with clear or eosinophilic cytoplasm protrude into the luminal area and result in a pseudopapillary appearance. Nucleoli are commonly evident at low power. Microcalcifications may be identified. The nests, acini, and tubules are separated by fine fibrovascular septae. B) Extensive cytoplasmic eosinophilia may occur, and cytoplasmic granules are not uncommon. C) Nuclear staining for the TFE3 protein is seen in this RCC metastastic to the liver. Cytoplasmic staining may occasionally be evident but should not be interpreted as positivity.

Figure 1. Translocation-Renal Cell Carcinoma involving t(X;17)

A) Within an overall tubular or nested architecture, cells with clear or eosinophilic cytoplasm protrude into the luminal area and result in a pseudopapillary appearance. Nucleoli are commonly evident at low power. Microcalcifications may be identified. The nests, acini, and tubules are separated by fine fibrovascular septae. B) Extensive cytoplasmic eosinophilia may occur, and cytoplasmic granules are not uncommon. C) Nuclear staining for the TFE3 protein is seen in this RCC metastastic to the liver. Cytoplasmic staining may occasionally be evident but should not be interpreted as positivity.

Figure 1. Translocation-Renal Cell Carcinoma involving t(X;17)

A) Within an overall tubular or nested architecture, cells with clear or eosinophilic cytoplasm protrude into the luminal area and result in a pseudopapillary appearance. Nucleoli are commonly evident at low power. Microcalcifications may be identified. The nests, acini, and tubules are separated by fine fibrovascular septae. B) Extensive cytoplasmic eosinophilia may occur, and cytoplasmic granules are not uncommon. C) Nuclear staining for the TFE3 protein is seen in this RCC metastastic to the liver. Cytoplasmic staining may occasionally be evident but should not be interpreted as positivity.

Figure 2. Translocation-Renal Cell Carcinoma involving t(X;1)

The morphologic appearance of all translocation-RCC may be heterogeneous. Shown are three different areas from the same tumor containing the t(X;1). A) Areas are more compact, with less cytoplasm, resembling type 2 papillary renal cell carcinomas. B) All translocation-RCC may show areas with striking clear cell features that may result in an erroneous diagnosis of clear cell carcinoma of the kidney. C) Regions devoid of overt epithelial differentiation may resemble epithelioid angiomyolipoma.

Figure 2. Translocation-Renal Cell Carcinoma involving t(X;1)

The morphologic appearance of all translocation-RCC may be heterogeneous. Shown are three different areas from the same tumor containing the t(X;1). A) Areas are more compact, with less cytoplasm, resembling type 2 papillary renal cell carcinomas. B) All translocation-RCC may show areas with striking clear cell features that may result in an erroneous diagnosis of clear cell carcinoma of the kidney. C) Regions devoid of overt epithelial differentiation may resemble epithelioid angiomyolipoma.

Figure 2. Translocation-Renal Cell Carcinoma involving t(X;1)

The morphologic appearance of all translocation-RCC may be heterogeneous. Shown are three different areas from the same tumor containing the t(X;1). A) Areas are more compact, with less cytoplasm, resembling type 2 papillary renal cell carcinomas. B) All translocation-RCC may show areas with striking clear cell features that may result in an erroneous diagnosis of clear cell carcinoma of the kidney. C) Regions devoid of overt epithelial differentiation may resemble epithelioid angiomyolipoma.

Figure 3. Translocation-Renal Cell Carcinoma involving t(6;11), TFEB/ALPHA

A) TFEB-RCC also show a spectrum of histologic appearance varying from tubulopapillary to solid. Many lack overt epithelial differentiation and resemble epithelioid angiomyolipomas. This is complicated by the fact that both entities express melanocytic markers. B) TFEB-RCC may show clusters of small cells surrounding hyaline bodies composed of basement membrane material. Such foci may be quite infrequent and are not always identified in these tumors.

Figure 3. Translocation-Renal Cell Carcinoma involving t(6;11), TFEB/ALPHA

A) TFEB-RCC also show a spectrum of histologic appearance varying from tubulopapillary to solid. Many lack overt epithelial differentiation and resemble epithelioid angiomyolipomas. This is complicated by the fact that both entities express melanocytic markers. B) TFEB-RCC may show clusters of small cells surrounding hyaline bodies composed of basement membrane material. Such foci may be quite infrequent and are not always identified in these tumors.

Figure 4. Papillary Renal Cell Carcinoma

A) Type 1 lesions most commonly have cuboidal nuclei that lack pleomorphism and lack prominent nucleoli. Foamy histiocytes within the papillae are common. Type 1 lesions show diffuse positivity for cytokeratin 7. B) Type 2 lesions often contain eosinophilic cytoplasm with pseudostratification and prominent nucleoli. Type 2 lesions are often negative for cytokeratin 7.

Figure 4. Papillary Renal Cell Carcinoma

A) Type 1 lesions most commonly have cuboidal nuclei that lack pleomorphism and lack prominent nucleoli. Foamy histiocytes within the papillae are common. Type 1 lesions show diffuse positivity for cytokeratin 7. B) Type 2 lesions often contain eosinophilic cytoplasm with pseudostratification and prominent nucleoli. Type 2 lesions are often negative for cytokeratin 7.

Figure 5

Renal Medullary Carcinomas are composed of a tubular and cribriforming growth pattern accompanied by significant desmoplasia. The cells contain prominent eosinophilic cytoplasm, occasionally with rhabdoid-like inclusions. Nucleoli are often prominent.

Figure 6. Oncocytic Renal Cell Carcinoma following Neuroblastoma

Such tumors are identified a median of 8 years following the diagnosis of neuroblastoma and contain cells which have a highly variable amount of eosinophilic cytoplasm. The nuclei are characteristically irregular and often contain prominent nucleoli.