Diagnosing RMC Requires IHC, Not Just NGS

In an interview with Targeted Oncology, Pavlos Msaouel, MD, PhD, of The University of Texas MD Anderson Cancer Center clarifies the critical role of immunohistochemistry panels in diagnosing renal medullary carcinoma, or RMC. Although academic centers often automatically perform such testing on high grade kidney tumors with suspicious morphology, community oncologists must specifically request it when clinical suspicion is high.

A major pitfall is that most next-generation sequencing assays fail to detect the underlying genetic mechanisms of SMARCB1 loss. Approximately half of RMC cases involve inactivating translocations of one allele combined with deletion of the second, and another 16% show deletion of both alleles.

These alterations are notoriously difficult to capture with standard DNA sequencing. Only about 15% of cases have detectable small insertions, deletions, or nonsense mutations.

Consequently, it is common to see complete loss of SMARCB1 protein by immunohistochemistry alongside a clean next-generation sequencing report. This discrepancy frequently confuses even academic oncologists, who may mistakenly rule out RMC based on negative sequencing results.

Adding to the confusion is terminology: clinicians should use the term “loss” rather than “positive” or “negative,” as RMC is defined by absence of SMARCB1 expression at the tissue level. The protein itself goes by multiple names, including INI1, SNF5, BAF47, and SMARCB1, all referring to the same entity. Therefore, requesting an INI1 or SMARCB1 immunohistochemistry stain is essential for accurate diagnosis.