A Distinctive DICER1-Related Wilms-Like Uterine Tumor: A Report of Eight Cases

The presence of DICER1 mutations associated with overlapping morphologic features in tumors arising at different sites has been suggested to define an emerging category of DICER1-related neoplasms. We undertook a clinicopathologic and molecular characterization of uterine tumors originally diagnosed as Wilms tumors to ascertain if they belong to the spectrum of DICER1-related neoplasms. Of 8 patients with a median age of 36.5 (17-69) years, 5 underwent hysterectomy, 2 endometrial curettings, and 1 polypectomy. Most tumors were centered in the endometrium, and 6 were polypoid with a median size of 8 (3.5-16) cm. All showed a variable admixture of primitive mesenchyme and epithelial-like elements set in a hypocellular, edematous to focally myxoid stroma. The epithelial-like elements were the most extensive component, showing a lobular arrangement, including variably sized and shaped primitive tubules with focal confluent/solid growth and cribriforming, as well as glomeruloid and rosette-like structures. Some primitive tubules had intraluminal projections in 3 tumors, imparting an adenosarcoma-like appearance. Scattered glands with fetal-type epithelium were seen in 7 tumors. Rhabdomyosarcomatous differentiation was present in 6 tumors, and neuroectodermal differentiation and fetal-type cartilage in 3 tumors each (including 2 with both features). DICER1 sequencing was successful in 5 of 6 tumors tested, with 4 harboring DICER1 mutations, including all 3 with neuroectodermal differentiation and adenosarcoma-like foci. Fetal-type cartilage was present in 2 of 4 DICER1-mutant tumors and 1 tumor with unknown DICER1 status. Follow-up was available for 6 patients. The patient with DICER1 wild-type tumor (associated with low-grade endometrial endometrioid carcinoma and KRAS mutation) died of disease at 9 months. Of 4 patients with DICER1-mutant tumors, 1 recurred at 7.5 months, 2 were alive without disease at 12 and 38 months, respectively, and 1 was alive with unknown disease status at 31 months. Another patient with unknown DICER1 status was alive at 196 months. Uterine tumors diagnosed as Wilms tumors belong to the spectrum of DICER1-related neoplasms at this site and are best described as a "DICER1-related Wilms-like uterine tumor." These unique tumors are likely part of the larger category of "DICER1-related primitive polyphenotypic neoplasm," warranting further studies.