Intravenous leiomyomatosis: HMGA2 common, MED12 and FH loss rare

Design

Retrospective clinicopathological and molecular cohort

Population

89 intravenous leiomyomatoses, 106 conventional and 83 cellular leiomyomas

Primary outcome

HMGA2, MED12 and FH status

Effect

HMGA2 upregulated 87.5%; MED12 2.5%; FH deficient 2.4%

A Chinese series characterised 89 cases of intravenous leiomyomatosis alongside 106 conventional and 83 cellular leiomyomas, using immunohistochemistry, FISH, Sanger sequencing and whole-exome sequencing.

HMGA2 was upregulated in 87.5% of intravenous leiomyomatoses and strongly expressed in 40.9%. About half carried HMGA2 rearrangements, mostly HMGA2–RAD51B fusions. Collagen gene mutations appeared in 7 of 10 exomes, all with HMGA2 upregulation. MED12 hotspot mutations (2.5%) and fumarate hydratase deficiency (2.4%) were rare. Most patients were of reproductive age with prior uterine surgery.

For diagnosis, strong HMGA2 staining supports intravenous leiomyomatosis in a smooth muscle lesion with intravascular growth, while FH deficiency should prompt the usual consideration of hereditary disease rather than be expected.

• Consider HMGA2 immunohistochemistry when intravascular growth is seen in a uterine smooth muscle tumour
• Do not expect MED12 mutation as supporting evidence in this entity
• Treat FH deficiency as a separate finding that may need genetic referral
• Ask about prior uterine surgery when the pattern is suspected

Why it matters

It gives pathologists a usable marker for a rare tumour that can extend into the heart.

The statistics, in plain English

The collagen gene finding rests on only 10 exomes, so it is a lead rather than an established marker.

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