Submitted by Megan Zilla, MD PhD and Karen Schoedel, MD
Background
Low grade endometrial stromal sarcoma is a rare mesenchymal tumor of the uterus which resembles proliferative-phase endometrial stroma. It is differentiated from endometrial stromal nodule by its invasion of the myometrium, and from high grade endometrial stromal sarcoma by its histologic appearance, immunostaining profile, prolonged clinical course and, more recently, specific genetic alterations.
Case Presentation
The patient is a female in her 80s who, 18 years prior, at a different institution, underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a uterine low grade endometrial stromal sarcoma. The patient refused adjuvant chemotherapy and over the years underwent four subsequent resections of recurrent and metastatic sarcoma within the abdomen and pelvis. The fifth resection included a partial gastrectomy, partial ileocolectomy and two paracolic tumor nodules. Grossly, these masses were lobulated and well circumscribed and on cross section were tan, glistening, lobulated and displayed focal hemorrhage and cystic degeneration (Figure 1A). Histologically, the tumor was highly cellular and composed of sheets of monotonous ovoid to spindled cells arranged vaguely in fascicles with many interspersed thin-walled vessels (Figure 1B and 1C). By immunohistochemistry, the cells were diffusely positive for CD10 (Figure 1D) and estrogen receptor (Figure 1E), while negative for CyclinD1 (Figure 1F). These findings were consistent with metastatic low grade endometrial stromal sarcoma. Next generation sequencing studies demonstrated a novel fusion between PHF1 exon 11 (NM_024165) and NUTM2B exon 4 (NM_001278495). The fusion was subsequently verified by RNA sequencing.
Discussion
The most common fusion in low grade endometrial stromal sarcoma is JAZF1-SUZ12. However, a number of other fusions have been described in this tumor type, including JAZF1-PHF1, EPC1-PHF1, MEAF6-PHF1, MBTD1-EZHIP, BRD8-PHF1, EPC2-PHF1, and EPC1-SUZ12. Alternatively, the genetic alterations found in high grade endometrial stromal sarcomas include YWHAE-NUTM2A/NUTM2B, ZC3H7B-BCOR, EPC1-BCOR, JAZF1-BCORL1, and BRD8-PHF1 fusions as well as BCOR internal tandem duplications. To our knowledge, a PHF1-NUTM2B fusion has not been described in endometrial stromal sarcoma, or in any other tumor type. Due to the histologic appearance, immunohistochemical phenotype and protracted clinical course even without neoadjuvant chemotherapy, we propose that PHF1-NUTM2B fusion should be added to the growing list of genetic alterations found in low grade endometrial stromal sarcoma.
References
WHO Classification of Tumours Editorial Board. Female genital tumours. Lyon (France): International Agency for Research on Cancer; 2020. (WHO classification of tumours series, 5th ed.; vol. 4). https://publications.iarc.fr/592.
R.J. Kurman et al. (eds.), Blaustein’s Pathology of the Female Genital Tract. Cham (Switzerland) Springer, 2019, 7th Edition.