Alveolar soft part sarcoma of the female genital tract: a clinicopathological and molecular genetic study of 26 cases

AIMS: Occurrence of alveolar soft part sarcoma (ASPS) in the female genital tract is extremely rare. We report 26 cases of ASPS arising in the female genital tract to further characterize its clinicopathological and molecular features, differential diagnosis and biological behaviour. METHODS AND RESULTS: Twenty-six cases of ASPS in the female genital tract were retrieved from our pathology archives. Patient age ranged from 11 to 69 years (median = 30 years). Tumours involved the uterus (n = 22), vagina (n = 3), and broad ligament (n = 1), with a median size of 3.3 cm (1.5-8.5 cm). Histologically, the tumours were predominantly composed of large epithelioid or round cells with abundant eosinophilic-to-clear cytoplasm, round nuclei and prominent nucleoli. Architecturally, tumour cells were arranged mostly in diffuse sheets or solid nests, while classic pseudoalveolar structures were rarely observed. All tumours showed strong TFE3 nuclear expression (100%), with variable immunoreactivity for ER (10/11, 90.9%) and PR (9/9, 100%). Twenty-one tested tumours demonstrated TFE3 rearrangement or ASPSCR1::TFE3 fusion by fluorescence in situ hybridization or targeted RNA sequencing. Among 21 patients' available follow-up data (range, 17-151 months; median, 30 months), 2 of 3 vaginal ASPS patients developed disease progression (1 local recurrence, 1 lung metastasis), whereas all 18 patients with uterine ASPS (range = 17-151 months; median = 30.5 months) remained disease-free. CONCLUSIONS: Female genital tract ASPS most commonly affects the uterus of young women. Uterine ASPS may have a relatively favourable prognosis. Distinguishing ASPS from its morphological mimickers, especially perivascular epithelioid cell tumour (PEComa), is of clinical importance to avoid inappropriate treatment and inaccurate prognosis assessment.