GPNMB is sensitive for uterine PEComa but shows up in its main mimics

Design

Retrospective immunohistochemical study of archived tumours

Population

115 uterine mesenchymal tumours, including 9 PEComas and 19 leiomyosarcomas

Primary outcome

Diffuse moderate-to-strong GPNMB positivity by tumour type

Effect

PEComa 9/9 (100%); leiomyosarcoma 9/19 (47%); undifferentiated uterine sarcoma 2/5 (40%)

This study stained 115 uterine mesenchymal tumours for GPNMB, a lysosomal protein proposed as a surrogate marker for TFE3, TFEB and mTOR-driven tumours such as PEComa. Nine were PEComas; the rest covered leiomyosarcoma, STUMP, leiomyoma, endometrial stromal sarcomas, adenosarcoma and rare entities. A case counted as positive only with diffuse (over 75% of cells) moderate to strong staining.

All nine PEComas (100%) were positive. So were 9 of 19 leiomyosarcomas (47%), 2 of 5 undifferentiated uterine sarcomas (40%), 2 of 3 inflammatory myofibroblastic tumours (67%) and 1 of 18 low-grade endometrial stromal sarcomas (6%). Focal or weak staining was common in the remaining tumours (60 of 92), which supports using the strict scoring rule.

The authors conclude that GPNMB lacks the specificity to separate PEComa from its main mimics and should be read with morphology and a wider panel. Only nine PEComas were studied, so sensitivity is uncertain.

• Do not diagnose PEComa on GPNMB positivity alone.
• Apply the strict rule: diffuse staining in over 75% of cells at moderate to strong intensity.
• Expect positivity in some leiomyosarcomas, so keep smooth muscle markers in the panel.
• Treat focal or weak staining as negative.
• Add TFE3 or other testing where the differential includes a translocation-associated tumour.

Why it matters

A marker proposed as a shortcut would misclassify a large share of leiomyosarcomas if used alone.

Don't overread it

Nine PEComas and a single-study cohort; it does not give a validated cut-off for routine practice.

The statistics, in plain English

A sensitivity of 9 of 9 sounds perfect, but with only nine cases the lower confidence limit is far below 100%. Specificity is the problem here: nearly half of the leiomyosarcomas also met the positive threshold.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.