Which histologic findings are characteristic of translocation-associated renal cell carcinomas (RCCs)?

Updated: May 17, 2017
  • Author: Angela J Wu, MD; Chief Editor: Liang Cheng, MD  more...
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In Xp11.2 translocation-associated renal cell carcinoma (RCC), cells typically have voluminous cytoplasm, which can range from eosinophilic and granular to clear. Cells may also exhibit bulging cell borders—a trait that has been referred to as "soap bubble" morphology. Within any tumor, nuclear size may vary, but uniformly, these tumors are of a high Fuhrman nuclear grade.

The hallmark of these tumors is architectural heterogeneity; within a given tumor, cells may be variably arranged in broad sheets, nests, trabeculae, true papillae, or pseudopapillae (see the first 3 images below). Another characteristic architectural feature found in many of these tumors is a pseudoalveolar pattern in which cells are arranged in alveolae with central cellular discohesion (see the fourth image below). Psammoma bodies and scattered xanthoma cells have been described in some tumors.

Xp11.2 translocation-associated renal cell carcino Xp11.2 translocation-associated renal cell carcinomas (RCCs) have heterogeneous morphology; at least focally, tumor cells often have abundant clear cytoplasm, mimicking clear cell RCC. Image courtesy of University of Michigan.
Xp11.2 translocation-associated renal cell carcino Xp11.2 translocation-associated renal cell carcinomas (RCCs) may have well-developed papillae, mimicking papillary RCCs. Image courtesy of University of Michigan.
In Xp11.2 translocation-associated renal cell carc In Xp11.2 translocation-associated renal cell carcinoma, tumor cells with abundant eosinophilic cytoplasm and high nuclear grade are often arranged in large nests with a delicate, intervening vascular stroma. Image courtesy of University of Michigan.
The nests of tumor cells in Xp11.2 translocation-a The nests of tumor cells in Xp11.2 translocation-associated renal cell carcinomas may become centrally discohesive, giving rise to a pseudoalveolar growth pattern. Image courtesy of University of Michigan.

Because of the architectural variation in these tumors, they often mimic, at least focally, the appearance of other RCC subtypes, such as clear cell RCC and papillary RCC. [2, 3, 10, 13, 14, 12] Heterogeneous architectural features, in which some foci within a single tumor resemble clear cell RCC and other foci resemble papillary RCC, as well as classically described features of translocation-associated RCC, such as high-grade cells with abundant clear to granular cytoplasm, prominent cell borders, and prominent psammoma bodies, are clues to the correct diagnosis.

Occasionally, a tumor will completely mimic a clear cell or papillary RCC, and the only clue to the diagnosis will be the patient's young age. Papillary and clear cell types each express cytokeratin and are negative for transcription factor E3 (TFE3). [3, 15]

Another interesting tumor that may potentially be confused with translocation-associated RCC is the clear cell papillary RCC. These tumors were originally described in end-stage kidneys but may also be seen in other settings. They typically occur in older patients. Most importantly, these lesions present as low-grade and low-stage tumors. Clear cell papillary RCC is strongly positive for cytokeratin 7 and negative for alpha-methylacyl-CoA racemase (AMACR) and TFE3.

Transcription factor EB (TFEB) RCC is characterized by polygonal cells that have abundant clear to eosinophilic cytoplasm with Fuhrman nuclear grade 3 nuclei arranged in nests with a delicate, intervening vascular network. Cell borders are typically prominent. A characteristic feature seen in most tumors is a second distinct population of cells that are smaller and epithelioid and that are clustered around hyaline basement membrane (see the image below). These tumors typically have low mitotic activity and are without necrosis. In a few cases, abortive papillae or psammoma bodies have also been described. [2, 10, 16]

Transcription factor EB (TFEB) renal cell carcinom Transcription factor EB (TFEB) renal cell carcinoma is characterized by polygonal cells that have abundant clear to eosinophilic cytoplasm and high nuclear grade arranged in nests with a delicate, intervening vascular network. A characteristic feature is a second distinct population of smaller, epithelioid cells clustered around hyaline basement membrane. Image courtesy of Dr. Pedram Argani, Johns Hopkins University, and Dr. Ming Zhou, Cleveland Clinic.

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