The clinical, morphological, and genetic heterogeneity of endometrial stromal sarcoma

Excerpt

Uterine sarcomas are rare tumors, the majority of which consist of leiomyosarcoma and endometrial stromal tumors. The latter consist of endometrial stromal nodule, low-grade endometrial stromal sarcoma (LG-ESS), and high-grade ESS (HG-ESS). ESS characteristically harbors various fusion genes, including t(7;17)(p15;q11) JAZF1-SUZ12, t(6;7)(p21;p15) JAZF1-PHF1, t(6;10)(p21;p11) EPC1-PHF1, t(1;6)(p34;p21) MEAF6-PHF1, and t(X;17)(p11; q21) CXorf67-MBTD1 fusions in LG-ESS and t(10;17)(q22;p13) YWHAE-NUTM2 fusion in HG-ESS [1‐3]. A novel MEAF6-SUZ12 fusion was recently described in LG-ESS [4]. The t(X;22)(p11; q13) ZC3H7B-BCOR fusion, initially regarded to be a feature of LG-ESS, was recently recognized, together with internal tandem duplication of the BCOR gene, to be associated with more aggressive clinical behavior than the majority of LG-ESS, and this finding is consequently considered to be a feature of HG-ESS lacking the YWHAE-NUTM2 fusion [2, 5]. A substantial number of undifferentiated uterine sarcoma (UUS) appear to harbor the YWHAE-NUTM2 fusion or BCOR rearrangement, suggesting that they may in fact be undiagnosed HG-ESS [6]. In contrast to LG-ESS, HG-ESS is characterized by a variety of histological features, which may complicate the diagnostic procedure. Therefore, in particular for tumors with a spindle cell pattern, a complex diagnostic algorithm assisted by immunohistochemical and molecular analysis with special emphasis on gene fusions has been proposed [7]. …