| Written | 2013-04 | Arnold-Jan Kruse, Sabrina Croce, Roy FPM Kruitwagen, Robert G Riedl, Brigitte FM Slangen, Toon Van Gorp, Koen K Van de Vijver |
| | GROW, School for Oncology, Developmental Biology (AJK, RFPMK, BFMS, TVG), Departments of Obstetrics, Gynaecology (AJK, RFPMK, BFMS, TVG), Pathology (RGR), Maastricht University Medical Center, Maastricht, The Netherlands, Department of Pathology, Institut Bergonie (SC), Bordeaux, France, Department of Pathology (KKVdV), The Netherlands Cancer Institute, Amsterdam, The Netherlands |
| Note | The tumour is derived from endometrial stromal cells. |
| Epidemiology | Rare tumour whose true frequency is unknown, as tumours previously considered undifferentiated uterine sarcoma may belong to this category. |
| Clinics | A total of 20 patients with YWHAE-NUTM2 ESS are identified thus far (Lee et al, 2012, Croce et al, 2013, Kruse et al, 2014). The median age of the patients was 50 years (range 28-67 years) which is in line with the median age in conventional ESS (Tavassoli et al, 2003).The most common symptoms of YWHAE-NUTM2 ESS were abnormal vaginal bleeding, and an enlarged uterus presenting as a pelvic mass, symptoms which occur also frequently in women with conventional ESS. Stage was known for 17 patients, including 6 patients with stage I, 6 with stage II, 4 with stage III, and 1 patient with stage IV disease. |
| Pathology | The clinic-pathological features of YWHAE-NUTM2 ESS have been described by Lee et al (Lee et al, 2012, Lee et al, 2012). In the recently published 2014 WHO classification, ESS are subdivided into low-grade and high-grade ESS, in which the high-grade ESS typically harbours the YWHAE-NUTM2 genetic fusion (Kurman et al, 2014). Although it has been found that FISH analysis demonstrated absolute specificity of this genetic fusion for high-grade ESS, a considerable number of high-grade ESS is negative according to the literature (5 of 12 cases (42%)) (Lee et al, 2012). In the 2014 WHO classification, high-grade ESS has been defined as a malignant tumour of endometrial stromal derivation with high-grade, round cell morphology sometimes associated with a low-grade spindle cell (fibroblastic) component that is most commonly fibromyxoid.. Immunohistochemistry may be of help to differentiate between conventional ESS and YWHAE-NUTM2 ESS, reviewed recently (Chiang et al, 2013). The neoplastic cells of low-grade ESS are immunoreactive for CD10 and at least focally for actin. They are usually, but not always negative for desmin and h-caldesmon. Low-grade ESS is almost always positive for both estrogen and progesterone receptors. The spindle cell component of YWHAE-NUTM2 ESS is typically diffusely positive for CD10, ER, and PR, similar to the immunoprofile of conventional low-grade ESS, whereas the round cell component is consistently CD10-negative and shows absent to only focal, weak to moderate ER and PR staining. The cyclin D1 immunostain is quite discriminatory in this context (Lee et al, 2012), and recently Lee et al. found frequent expression of KIT in the high-grade round cell component, but lacking KIT hotspot mutations (Lee et al, 2014). The high-grade component shows strong membranous/cytoplasmic KIT staining and strong diffuse nuclear cyclin D1 positivity in more than 70% of tumour cells. The low-grade spindle cell component shows weak cytoplasmic KIT staining and weak to variable, heterogeneous cylin D1 expression. Conventional ESSs are typically negative for cyclin D1 expression. |
| Treatment | Total abdominal hysterectomy with bilateral salpingo-oophorectomy, and debulking if applicable. |
| Prognosis | Follow-up information was available for 16 patients of the 20 abovementioned patients. Three patients died of their disease within 24 months, 1 patient had no evidence of disease, 4 patients developed recurrent disease, within 6, 12, and 18 months respectively. Four patients were alive with disease, no further information was available. Patients with high-grade ESS appear to have a prognosis that is intermediate between low-grade endometrial stromal sarcomas and undifferentiated sarcoma. |
| YWHAE rearrangement identified by FISH and RT-PCR in endometrial stromal sarcomas: genetic and pathological correlations |
| Croce S, Hostein I, Ribeiro A, Garbay D, Velasco V, Stoeckle E, Guyon F, Floquet A, Neuville A, Coindre JM, MacGrogan G, Chibon F |
| Mod Pathol 2013 Oct;26(10):1390-400 |
| PMID 23599159 |
| |
| Aggressive behavior and poor prognosis of endometrial stromal sarcomas with YWHAE-FAM22 rearrangement indicate the clinical importance to recognize this subset |
| Kruse AJ, Croce S, Kruitwagen RF, Riedl RG, Slangen BF, Van Gorp T, Van de Vijver KK |
| Int J Gynecol Cancer 2014 Nov;24(9):1616-22 |
| PMID 25244606 |
| |
| World Health Organization Classification of Tumours of Female Reproductive Organs. |
| Kurman RJ, Carcangiu ML, Herrington CS, Young RH. |
| Lyon: IARC Press; 2014. |
| |
| Cyclin D1 as a diagnostic immunomarker for endometrial stromal sarcoma with YWHAE-FAM22 rearrangement |
| Lee CH, Ali RH, Rouzbahman M, Marino-Enriquez A, Zhu M, Guo X, Brunner AL, Chiang S, Leung S, Nelnyk N, Huntsman DG, Blake Gilks C, Nielsen TO, Dal Cin P, van de Rijn M, Oliva E, Fletcher JA, Nucci MR |
| Am J Surg Pathol 2012 Oct;36(10):1562-70 |
| PMID 22982899 |
| |
| Frequent expression of KIT in endometrial stromal sarcoma with YWHAE genetic rearrangement |
| Lee CH, Hoang LN, Yip S, Reyes C, Marino-Enriquez A, Eilers G, Tao D, Chiang S, Fletcher JA, Soslow RA, Nucci MR, Oliva E |
| Mod Pathol 2014 May;27(5):751-7 |
| PMID 24186140 |
| |
| The clinicopathologic features of YWHAE-FAM22 endometrial stromal sarcomas: a histologically high-grade and clinically aggressive tumor |
| Lee CH, Mariño-Enriquez A, Ou W, Zhu M, Ali RH, Chiang S, Amant F, Gilks CB, van de Rijn M, Oliva E, Debiec-Rychter M, Dal Cin P, Fletcher JA, Nucci MR |
| Am J Surg Pathol 2012 May;36(5):641-53 |
| PMID 22456610 |
| |
| 14-3-3 fusion oncogenes in high-grade endometrial stromal sarcoma |
| Lee CH, Ou WB, Mariño-Enriquez A, Zhu M, Mayeda M, Wang Y, Guo X, Brunner AL, Amant F, French CA, West RB, McAlpine JN, Gilks CB, Yaffe MB, Prentice LM, McPherson A, Jones SJ, Marra MA, Shah SP, van de Rijn M, Huntsman DG, Dal Cin P, Debiec-Rychter M, Nucci MR, Fletcher JA |
| Proc Natl Acad Sci U S A 2012 Jan 17;109(3):929-34 |
| PMID 22223660 |
| |
| Dynamic interactions between 14-3-3 proteins and phosphoproteins regulate diverse cellular processes |
| Mackintosh C |
| Biochem J 2004 Jul 15;381(Pt 2):329-42 |
| PMID 15167810 |
| |
| World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. |
| Tavassoli FA, Devilee P. |
| Lyon: IARC Press; 2003. |
| |
