Unusual morphological features of uterine leiomyomas treated with progestogens

BACKGROUND: Uterine leiomyomas are extremely common in surgical pathology practice and in the vast majority there are no issues in diagnosis. Progestogens are widely prescribed drugs for a variety of indications, including abnormal uterine bleeding, and are often given to women with leiomyomas but the pathological features of leiomyomas treated with progestogens are poorly described. METHODS: We report the pathological features in eight cases of uterine leiomyomas in women who had been treated with oral progestogens or a progestogen-containing intrauterine device; all cases were received in consultation because the features raised concern for leiomyosarcoma, smooth muscle tumour of uncertain malignant potential or a benign leiomyoma with unusual features. Additionally, we reviewed a series of cases of uterine leiomyomas (n=99) in women who exhibited progestogenic effects in the endometrium. RESULTS: The morphological features in the consult cases, which were widespread and marked and which varied somewhat from case to case, included small and/or large areas of infarct-type necrosis (sometimes mimicking coagulative tumour cell necrosis) with surrounding increased cellularity, mitotic activity, nuclear pyknosis, cytoplasmic eosinophilia, epithelioid morphology, stromal oedema, haemorrhage, and myxoid change and infiltration by CD56 positive granulated lymphocytes. Sometimes the features resulted in an almost deciduoid appearance. Similar features were present to a minor degree in significant numbers of the additional series of cases. CONCLUSIONS: Pathologists should be aware of these progestogen-associated features when reporting uterine leiomyomas whether or not the clinician has indicated that the woman is taking progestogens since otherwise a diagnosis of leiomyosarcoma or smooth muscle tumour of uncertain malignant potential may be rendered. Useful features in suggesting a benign leiomyoma, in addition to recognition of the morphological features described which, in combination, are characteristic of progestogens, are the lack of true nuclear atypia and the low mitotic activity away from the abnormal areas.