Mixed Endometrioid Adenocarcinoma and Müllerian Adenosarcoma of the Uterus and Ovary

Mullerian adenosarcoma is a biphasic neoplasm composed of benign or atypical Müllerian epithelium and a malignant mesenchymal component that is usually, but not always, of low grade. Focal architectural or cytologic atypia of the epithelial component resembling atypical hyperplasia may uncommonly be present and foci of adenocarcinoma have been rarely reported. Whether the coexistence of these 2 tumor components is a result of independent primaries (collision tumor), adenocarcinoma arising from the epithelial component of the adenosarcoma, an unusual form of carcinosarcoma or some other mechanism is uncertain. To establish the diagnostic criteria and clinical significance of the coexistence of adenocarcinoma in close association with Müllerian adenosarcoma, we conducted a multi-institutional study of these rare tumors. Twenty-six patients were identified with "mixed" adenosarcoma and adenocarcinoma; they ranged in age from 43 to 87 years (median: 66 y). Tumors occurred in the uterine corpus (n=22), ovary (n=2), and the pelvis (n=2). All but 6 had International Federation of Gynecology and Obstetrics (FIGO) stage I disease. All extrauterine tumors were associated with endometriosis. The tumor size ranged from 2 to 25 cm (median: 7.9 cm). The sarcomatous component was of low grade in 18 and high grade in 8 (the majority demonstrating rhabdomyoblastic differentiation); 9 had stromal overgrowth. Twenty-five carcinomas were endometrioid in type (23 FIGO grade 1; 3 FIGO grade 2) and 1 carcinoma was dedifferentiated with FIGO grade 1 endometrioid adenocarcinoma component; 33% of the uterine neoplasms were associated with adjacent endometrial hyperplasia. Next-generation sequencing in 2 tumors identified similar molecular abnormalities in the sarcomatous and carcinomatous components supporting a clonal relationship. Of 10 patients with available follow-up (median: 18 mo), 8 had no evidence of disease and 2 died of recurrent sarcoma at 7 and 8 months. Endometrioid adenocarcinomas that arise in close spatial association with Müllerian adenosarcoma appear to be clonally related to the sarcoma. Unlike carcinosarcomas, these tumors are usually early stage at presentation. The prognosis appears to be driven by the sarcomatous component. These tumors should be distinguished from carcinosarcomas, dedifferentiated endometrial carcinomas, and corded and hyalinized endometrioid carcinomas.