Design: Diagnostic comparison study
Population: 16 TFEB-altered renal carcinomas and 225 control renal tumours
Primary outcome: Sensitivity and specificity of IHC and RNA-ISH markers
Effect: TFEB RNA-ISH positive in 16/16 cases and 0 controls

TFEB-altered renal cell carcinoma is rare and easily mistaken for other tumours. FISH is the reference test but is not widely available. This study compared light-microscopy methods in 16 molecularly confirmed TFEB-altered carcinomas against more than 220 control tumours, including five TFE3-rearranged carcinomas.

TFEB immunohistochemistry was variable across three antibody clones, with the Bethyl clone the most reliable. Cathepsin K and GPNMB were sensitive but not specific, labelling 40% and 50% of TFE3-rearranged tumours and some common renal tumours. TRIM63 RNA-ISH was positive in all TFEB-altered tumours but also in TFE3-rearranged ones.

TFEB RNA-ISH was positive in all 16 TFEB-altered carcinomas and negative in every control, including the TFE3-rearranged tumours.

The numbers are small, as they must be for a rare tumour. Where FISH is not available, TFEB RNA-ISH looks like the best single light-microscopy test, with confirmation still advised where it can be obtained.

Consider TFEB-altered carcinoma in a renal tumour that does not fit a common subtype.
Do not rely on cathepsin K or GPNMB alone; both stained TFE3-rearranged tumours.
TFEB RNA-ISH was positive in all 16 TFEB-altered tumours and no controls.
TFEB immunohistochemistry varied by clone; validate your clone locally.
Confirm with FISH or molecular testing where it is available.

Why it matters

It offers laboratories without molecular testing a way to make a diagnosis that otherwise depends on FISH.

The statistics, in plain English

Sixteen positives is a small number, so the true sensitivity could be lower than 100%. Specificity against more than 220 controls is better supported.