Design: Retrospective immunohistochemical study
Population: 115 uterine mesenchymal tumours including 9 PEComas
Primary outcome: Diffuse moderate-to-strong GPNMB positivity by tumour type
Effect: PEComa 9/9; leiomyosarcoma 9/19 (47%); IMT 2/3; UUS 2/5

This study stained 115 uterine mesenchymal tumours for GPNMB, a marker proposed for TFE3/TFEB-driven and mTOR-activated tumours, including PEComa. Positivity was strictly defined as moderate-to-strong staining in more than 75% of tumour.

All 9 PEComas were positive. So were 9 of 19 leiomyosarcomas (47%), 2 of 5 undifferentiated uterine sarcomas, 2 of 3 inflammatory myofibroblastic tumours and 1 of 18 low-grade endometrial stromal sarcomas. Leiomyomas, STUMP, high-grade endometrial stromal sarcoma and adenosarcoma were negative by the strict definition, though focal or weak staining was common (65% of non-positive tumours).

In practice, a negative GPNMB makes PEComa unlikely, but a positive result does not confirm it. The strict scoring rule matters: counting focal or weak staining would produce many more false positives.

Use GPNMB as a sensitive screen for uterine PEComa; strong diffuse negativity argues against it.
Do not diagnose PEComa on GPNMB positivity alone; leiomyosarcoma, undifferentiated sarcoma and inflammatory myofibroblastic tumour also stained.
Score strictly: count only moderate-to-strong staining in more than 75% of tumour.
Pair GPNMB with melanocytic markers, smooth muscle markers and, where needed, TFE3 or TSC testing.

Why it matters

Calling a leiomyosarcoma a PEComa, or the reverse, changes prognosis and eligibility for mTOR inhibitors.

The statistics, in plain English

Sensitivity here is 9 of 9, which sounds perfect but rests on only nine PEComas. Specificity is the problem: nearly half of leiomyosarcomas were also positive, so a positive stain cannot tell the two apart.