- Design
- retrospective single-institution case series with review, immunohistochemistry and sequencing of one case
- Population
- 26 breast adenomyoepitheliomas: 54% benign, 27% atypical, 12% special salivary gland-like, 8% malignant
- Primary outcome
- reclassification on review, and disease-free survival
- Effect
- 35% reclassified; malignant median 27.5 mm vs 12-18 mm for others; disease-free survival 89% at median 44 months
Twenty-six breast adenomyoepitheliomas were reviewed across the full spectrum: benign in 54%, atypical in 27%, special salivary gland-like in 12% and malignant in 8%. Thirty-five per cent were reclassified overall.
Two features stratified the spectrum. Benign, atypical and special subtypes had median sizes of 12 to 18 mm with lobulated or multilobulated contours; malignant lesions were larger, median 27.5 mm, and infiltrative. Cytological atypia and mitoses predominated in the atypical and malignant subtypes. Aberrant myoepithelium — loss or heterogeneous p63 and calponin expression — was present in 19%, which is the trap: the myoepithelial markers used to confirm the biphasic nature of the lesion can themselves behave abnormally in it.
The misdiagnoses are instructive because of what they were called instead. Excision corrected six core biopsy misinterpretations: three read as nodular adenosis-like, one unrecognised, one as a tubular adenoma-like lesion, and one atypical adenomyoepithelioma read as an infarcted papilloma. Retrospective review upgraded two benign lesions to atypical on cytological atypia with mitoses, and corrected a metastatic malignant adenomyoepithelioma that had been called a papilloma with ductal carcinoma in situ. Sequencing of that metastatic case found AKT1 E17K and GNAS R844C shared between primary and pulmonary metastasis, confirming clonality.
Disease-free survival was 89% over a median 44 months, with one benign local recurrence at 29 months and one pulmonary metastasis at 134 months — a reminder that the clock on these runs long. The authors' recommendation follows directly from the 35% reclassification rate: an adenomyoepithelioma-like lesion on core biopsy should go to excision, particularly above 20 mm.
- Recommend excision for an adenomyoepithelioma-like lesion on core biopsy, particularly above 20 mm
- Record size and border character explicitly — infiltrative and larger than about 25 mm shifted these towards malignant
- Do not rely on p63 and calponin alone; aberrant or heterogeneous myoepithelial staining occurred in about one in five
- Look specifically for cytological atypia with mitoses, which separated atypical from benign on review
- Keep adenomyoepithelioma in the differential for a lesion reported as nodular adenosis, tubular adenoma or an infarcted papilloma
Why it matters
The commonest error here was not calling the lesion the wrong grade but not recognising it as an adenomyoepithelioma at all.
Don't overread it
A 26-case series assembled for diagnostic difficulty cannot give the true frequency of any subtype or the real misclassification rate in routine practice.
The statistics, in plain English
Twenty-six cases is a small series from one practice, and the subtype proportions — 8% malignant, for instance — are only two cases, so those percentages should not be quoted as frequencies. The 35% reclassification rate is a property of this review process, not a measure of how often the diagnosis is wrong generally; a series assembled because the entity is difficult will over-represent difficulty. The 89% disease-free survival rests on two events in 26 patients and a median follow-up shorter than the interval at which one of them occurred.
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