Guess the Leiomyoma Subtype: FH-Deficient vs Bizarre Nuclei, Cellular and Mitotically Active Leiomyoma, With MCQs

Subtitle: Image quiz: guess the leiomyoma subtype from morphology. FH-deficient leiomyoma vs leiomyoma with bizarre nuclei, cellular and mitotically active leiomyoma, MED12 and HMGA2, FH and 2SC IHC, HLRCC and 8 MCQs.

Author: PathologyMCQ Editorial Board

Category: Female Genital Pathology

Last Updated: October 2026

Read Time: 5 minutes

At-a-Glance

FH-deficient: eosinophilic nucleoli with halos, staghorn vessels, rhabdoid-like inclusions; FH loss, 2SC positive; think HLRCC.
Bizarre nuclei: focal pleomorphic, smudged nuclei; low mitoses; no tumour cell necrosis.
Cellular: more cellular than adjacent myometrium; HMGA2 in a subset.
Mitotically active: high mitoses without atypia or necrosis.
Usual leiomyoma: MED12 mutations (~70%).

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Image Quiz

Look at the images and guess the type of leiomyoma from the morphology alone.

Leiomyoma, nuclear detail — Focus on the nuclei.

Leiomyoma with prominent eosinophilic nucleoli and perinucleolar halos — Spindle to oval nuclei with bright eosinophilic nucleoli surrounded by a halo.

Leiomyoma with eosinophilic cytoplasmic inclusions — Note the rhabdoid-like eosinophilic cytoplasmic inclusions.

What type of leiomyoma is this? A. Leiomyoma with bizarre nuclei · B. Fumarate hydratase-deficient leiomyoma · C. Cellular leiomyoma · D. Mitotically active leiomyoma

Show answer

B. Fumarate hydratase-deficient leiomyoma. Prominent eosinophilic nucleoli with perinucleolar halos and eosinophilic cytoplasmic inclusions are classic clues.

A: Bizarre nuclei show smudged, hyperchromatic nuclei without the halo-ringed eosinophilic nucleoli. C: Cellular leiomyoma is simply more cellular than the adjacent myometrium. D: Mitotically active leiomyoma shows increased mitoses (often 10 or more per 10 HPF) without atypia or necrosis.

FH-Deficient vs Bizarre Nuclei

FH-deficient leiomyoma vs leiomyoma with bizarre nuclei

Feature	FH-deficient	Bizarre nuclei
Nuclei	Ovoid; chain-like arrangement; eosinophilic nucleoli with perinucleolar halos	Scattered large, pleomorphic, hyperchromatic, smudged nuclei; pseudoinclusions
Cytoplasm	Eosinophilic rhabdoid-like globules	Usually unremarkable
Stroma and vessels	Staghorn vessels, alveolar-pattern oedema	Usual
Mitoses	Low	Low (may include karyorrhectic figures)
IHC	FH loss, 2SC positive	FH retained (most); p16 and p53 may be positive
Significance	Screen for HLRCC (germline FH)	Benign; exclude leiomyosarcoma

FH-deficient leiomyoma versus leiomyoma with bizarre nuclei — Summary card: leiomyoma with bizarre nuclei vs FH-deficient leiomyoma.

Leiomyoma Subtypes

Leiomyoma subtypes and genetics

Subtype	Key feature	Genetics
Usual	Fascicles of bland smooth muscle	MED12 (~70%)
Cellular / highly cellular	More cellular than myometrium	HMGA2 in a subset
Mitotically active	High mitoses, no atypia or necrosis	—
With bizarre nuclei	Focal bizarre nuclei, low mitoses	TP53/RB1 pathway alterations in some
FH-deficient	Nucleoli with halos, staghorn vessels	FH (somatic or germline)
Lipoleiomyoma	Mature fat admixed	HMGA2
Diffuse leiomyomatosis	Innumerable small nodules	COL4A5/COL4A6 (Alport)

Test Yourself: 8 MCQs

Leiomyoma subtypes: 8 MCQs

FH-deficient, bizarre nuclei, cellular and mitotically active leiomyoma, with instant explanations.

Score: 0 / 8

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Exam Pearls

Eosinophilic nucleoli with halos = think FH deficiency.
FH loss + 2SC positive; refer for HLRCC testing.
Bizarre nuclei with low mitoses and no necrosis = benign.
MED12 = usual leiomyoma; HMGA2 = cellular and lipoleiomyoma.

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