Molecular Testing Improves Accuracy in Kidney Cancer Diagnosis

Molecular testing can help doctors distinguish between aggressive and indolent kidney cancer types, explained Dr. Shuanzeng “Sam” Wei of Fox Chase Cancer Center.

Subtypes like papillary renal cell carcinoma may require major surgery, while mucinous tubular spindle cell carcinoma is often less aggressive. Wei’s team showed chromosomal microarray analysis can reveal key differences that routine pathology may miss, helping avoid misdiagnosis.

Accurate diagnosis guides treatment decisions and spares patient’s unnecessary surgery. Wei encouraged patients to ask their care team about molecular testing to ensure the right care plan.

Wei is an associate professor in the Department of Pathology, director of cytopathology, and medical director of the Clinical Genomics Laboratory at Fox Chase Cancer Center.

CURE: For patients who have newly diagnosed kidney cancer, could you explain what molecular testing involves and why it can be critical in distinguishing between certain types of renal cell carcinoma?

Wei: For renal cell carcinoma diagnosis, it’s simple for carcinoma, but for the subtypes of renal cell carcinoma, sometimes it’s difficult. For example, in this study, we mentioned papillary renal cell carcinoma and mucinous tubular spindle cell carcinoma. Sometimes it’s hard to distinguish them on a small biopsy or a fine needle aspiration, which only gives us very small tissue, maybe just tumor cells.

How does accurately identifying whether a tumor is one type of renal cell carcinoma or another effect treatment decisions and outcomes for patients?

For example, papillary carcinoma can be aggressive. Often, you may need to remove the tumor, either by radical nephrectomy, which is taking out the whole kidney, or partial nephrectomy, which is only removing the tumor portion. It’s a big surgery. On the other hand, most mucinous tubular spindle cell carcinomas are relatively indolent. For elderly patients or those with other comorbidities, you may not need such a big surgery. That’s why accurate diagnosis is critical.

In this study, we used molecular testing, specifically a chromosomal microarray, which works like a “sniper array.” It can identify chromosomal changes, not just single alterations but the overall pattern in renal cell carcinoma. For instance, papillary renal cell carcinoma often has specific changes like three copies of chromosomes 7 and 17, whereas mucinous tubular spindle cell carcinoma may only have single copies of chromosomes 1, 4, 6, 9, 8, 13, 14, 15 and 22.

This makes molecular testing very useful because sometimes routine H&E staining isn’t enough. In our study, we found five cases of mucinous tubular spindle cell carcinoma that all had papillary formations. If you relied only on morphology, you might misdiagnose them as papillary carcinoma.

How often might misdiagnosis occur without molecular testing?

This tumor, mucinous tubular spindle cell carcinoma, is rare. Over 20 years, our institution only had five cases. Even so, one case came as a consultation from a well-known institution, and they had diagnosed it as papillary renal carcinoma. With molecular testing, specifically looking at chromosomal losses, we correctly identified it as mucinous tubular spindle cell carcinoma. Misdiagnosis isn’t uncommon, especially with small biopsies that provide very limited tissue.

How may ongoing research help patients better understand their diagnosis and treatment options in the coming years?

Since this tumor is rare, we are still collecting more cases. Most tumors are indolent, but some can transform to high-grade disease. We are studying both morphology and molecular features, like chromosomal microarrays and next-generation sequencing, to find reliable markers. The goal is to achieve accurate diagnosis even from small biopsies. Molecular testing can help not just with these two subtypes, but other renal cell carcinomas as well.

For patients navigating kidney cancer care, what steps can they take to ensure they are getting the most accurate diagnosis, and how can they discuss this with their care team?

Right now, smaller biopsies are preferred to avoid large surgeries, which is good for patients. But small biopsies give less tissue, which can make accurate diagnosis harder. It’s important for clinicians to consider obtaining larger specimens when needed and to use advanced technologies, like chromosomal microarrays and next-generation sequencing, to help pathologists reach an accurate diagnosis. Accurate diagnosis is the first step in patient management, whether it’s deciding on observation, surgery, chemotherapy, or immunotherapy.

Transcript has been edited for clarity and conciseness.

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