Diagnostic Utility of the JAZF1/JJAZ1 Gene Fusion in Endometrial Stromal Sarcomas and Their Histologic Variants

Endometrial stromal tumor is an uncommon uterine tumor comprising <10% of all uterine mesenchymal neoplasms. The diagnosis of low-grade endometrial stromal sarcoma (LGESS) is based on characteristic histopathological features showing diffuse growth of uniform stromal cells resembling those of proliferative phase endometrium and uniformly distributed small spiral arterioles and it is not problematic in most LGESS cases. However, it is often difficult when the tumor displays diverse histological differentiation. A variety of histological differentiation types, including smooth muscle cells, fibromyxoid tissue, ovarian sex cord-like/epithelioid features, endometrioid glandular structures, atypical bizarre nuclei, rhabdoid or clear cell phenotype, adipose tissue or skeletal muscle, and predominant cystic changes have been described in the literature. When differentiation occurs, it frequently obscures the characteristic features of stromal cells and vascular pattern of LGESS, causing diagnostic difficulties. In contrast, undifferentiated endometrial sarcoma (UES) does not histologically exhibit endometrial stromal differentiation, thus, the origin of UES can be controversial, however, combined LGESS and UES cases clearly suggest that at least a subset of UES is of endometrial stromal origin. The diagnosis of UES should only be made after excluding histologically similar tumors including poorly differentiated carcinoma, leiomyosarcoma, carcinosarcoma, and other specific sarcomas of the uterus by adequate sampling and immunohistochemical staining. Various ancillary techniques have been employed to facilitate the diagnosis of LGESS, including immunohistochemical staining for estrogen receptor (ER) and progesterone receptor (PR), smooth muscle actin (SMA), β-catenin, and h-caldesmon. However, their value in the differential diagnosis has not been determined. JAZF1/JJAZ1, derived from the fusion of two zinc-finger genes (JAZF1 located at chromosome 7p15 and JJAZ1 at 17q21), Diagnostic Utility of the JAZF1/JJAZ1 Gene Fusion in Endometrial Stromal Sarcomas and Their Histologic Variants