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ORIGINAL ARTICLE
Year : 2019  |  Volume : 56  |  Issue : 4  |  Page : 335-340
 

Utility of YWHAE fluorescent in-situ hybridisation in mesenchymal tumors of uterus- An initial experience from tertiary oncology centre in India


1 Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
2 Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
3 Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India

Date of Web Publication11-Oct-2019

Correspondence Address:
Santosh Menon
Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_722_18

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 » Abstract 


Background: Endometrial stromal sarcoma (ESS) is a common uterine mesenchymal malignancy. According to World Health Organisation (WHO) 2014 classification, ESSs are further subdivided into low-grade ESS (LGESS) and high-grade ESS (HGESS). HGESS is defined by the presence of YWHAE gene rearrangement and has a poorer prognosis compared to LGESS.
METHODS: Twenty-four cases comprising of 16 endometrial stromal sarcoma and 8 lesions mimicking ESS were retrieved from the archives of the Department of Pathology and subjected to fluorescent in situ hybridization (FISH) analysis for YWHAE gene rearrangement. Immunohistochemistry for CD10, ER, PR, Cyclin D1, SMA, H-Caldesmon, Desmin, Ki-67, and Pan Cytokeratin was performed.
RESULTS: Two cases with histological features similar to HGESS were positive for YWHAE gene rearrangement while 1 was indeterminate. No cases of LGESS and histological mimics of ESS were positive for this rearrangement.
CONCLUSIONS: HGESSs are defined by the presence of YWHAE rearrangement. These tumors present at higher stage and have poorer prognosis. They may not respond to hormonal therapy and may be treated with chemotherapy. Cyclin D1 though not specific remains a sensitive tool to triage endometrial stromal sarcomas for this FISH study.


Keywords: Cyclin D1, endometrial stromal sarcoma, high grade, YWHAE


How to cite this article:
Verma A, Menon S, Rekhi B, Pai T, Maheshwari A, Ghosh J, Gupta S, Deodhar K. Utility of YWHAE fluorescent in-situ hybridisation in mesenchymal tumors of uterus- An initial experience from tertiary oncology centre in India. Indian J Cancer 2019;56:335-40

How to cite this URL:
Verma A, Menon S, Rekhi B, Pai T, Maheshwari A, Ghosh J, Gupta S, Deodhar K. Utility of YWHAE fluorescent in-situ hybridisation in mesenchymal tumors of uterus- An initial experience from tertiary oncology centre in India. Indian J Cancer [serial online] 2019 [cited 2019 Nov 22];56:335-40. Available from: http://www.indianjcancer.com/text.asp?2019/56/4/335/268963





 » Introduction Top


Endometrial stromal sarcoma (ESS) is the second most common uterine mesenchymal malignancy.[1] ESSs are further subdivided into low-grade ESS (LGESS) and high-grade ESS (HGESS) based on the histological, immunohistochemical, and molecular findings.[2] The World Health Organization (WHO) in 2003 had excluded the term HGESS in favor of undifferentiated endometrial sarcoma (UES).[3] However, it was soon realized that a category of ESSs with intermediate prognosis and histological features do exist.[4],[5],[6] This subset of ESS has recently been described to harbor a recurrent chromosomal translocation, t(10:17), which involves the characteristic YWHAE-NUTM2A/B juxtaposition and shows a biological behavior intermediate to that of LGESS and UES.[7] These tumors on histology show high-grade features generally not associated with LGESS as well as endometrial stromal differentiation which is not seen in UES.[7] Hence, HGESS was reintroduced in WHO 2014 to address and classify such tumors.[2] Sarcomas not showing endometrial stromal differentiation were reclassified from UES to undifferentiated uterine sarcoma (UUS).[2] It is important to identify HGESS as they have prognostic and therapeutic implications.[7],[8],[9] In this study, we evaluate YWHAE translocation in ESS and its close differential diagnoses.


 » Materials and Methods Top


This was an observational study on retrospective cases. Twenty four cases were selected for the study from the archives of the Pathology department (2012--2016). The selected cases were comprised of 16 cases of ESS and 8 malignant and benign tumors which were morphologically close differential diagnoses/mimickers of ESS (3 cases of leiomyosarcoma, 3 cases of UUS, and 1 case each of undifferentiated carcinoma and cellular leiomyoma).

Fluorescence in situ hybridization (FISH) was performed using ZytoLight SPEC YWHAE Dual Colour Break Apart Probe, ZytoVision, Germany on 4 μm thick formalin fixed paraffin sections. The procedure was performed on whole sections and tissue micro array. ESS cases were randomly selected for FISH analysis on whole sections or TMA. The histological mimickers of ESS were analyzed using TMA. All uninterpretable and indeterminate cases were repeated on whole sections. At least 50 tumor nuclei were evaluated in all the cases. Signals ≥3 diameters apart were considered as split signals. Cases showing split signals in more than 20% of the cells were considered positive.[10]

Results of immunohistochemistry (IHC) results including CD10, ER, PR, Cyclin D1, SMA, H-Caldesmon, Desmin, Ki-67, Pan Cytokeratin, and other necessary IHC like EMA, calretinin, inhibin, C-kit, DOG1, synaptophysin, chromogranin, and HMB 45 were collated. These IHC tests had been performed on whole sections using automated Ventana Benchmark XT. The details of IHC are given in [Table 1].
Table 1: Details of antibodies

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 » Results Top


The summary of clinical and pathological details of all the cases is given in [Table 2]. Of the 16 cases of ESS, 7 cases were of conventional LGESS while the remaining 9 cases were ESS with suggestion of high-grade features like necrosis, increased mitotic activity, atypia, epithelioid cells, and round cells. All the 24 cases underwent evaluation for YWHAE gene rearrangement by FISH. Rearrangement was seen in 2 cases (Case 4 and Case 19) and was indeterminate/border-line in 1 case (Case 18). Rearrangement was negative in 16 cases while it was uninterpretable (No signal seen) in the remaining 5 cases. Both the FISH positive cases are described in detail as follows:
Table 2: Summary of all the study cases

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Case 4

A 20 year old woman complaining of abnormal per vaginal (PV) bleeds underwent myomectomy elsewhere following an ultrasonography which was suggestive of fibroid. Paraffin blocks reviewed at our institute showed a cellular blue tumor composed of oval cells with uniformly interspersed arterioles. The tumor cells had pale ovoid nuclei resembling endometrial stroma. Sparse mitotic figures were noted. Necrosis was not seen. The tumor widely infiltrated the myometrium. The tumor was labelled as LGESS. Following myomectomy, the patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy with bilateral pelvic lymph node dissection. On gross examination, a 10 cm tumor deeply invading myometrium was seen. On histology, a tumor similar to that seen in the previously submitted paraffin blocks was present. In addition, there were juxtaposed areas with high-grade morphology displaying epithelioid cells with moderate cytoplasm arranged around small vessels and capillaries. Necrosis was noted while the mitotic count was 2-3/10hpf. Myxoid and fibrous changes were also seen. Bilateral pelvic lymph nodes showed metastasis (two out of four). The low-grade areas showed positivity for CD10, ER, and PR while the high-grade areas showed diffuse and strong positivity for Cyclin D1. AE1/AE3, EMA, SMA, Desmin, Calretinin, and Inhibin were negative. A morphological diagnosis of HGESS had been rendered and the FISH study for rearrangement of the YWHAE gene confirmed split signals in 62% cells [Figure 1]. The patient underwent adjuvant chemotherapy with 4 cycles of paclitaxel and carboplatin followed by radiotherapy. At present, the patient is disease-free at 8 months follow- up.
Figure 1: (a) Low grade myopermeative areas resembling conventional Endometrial Stromal Sarcoma (10×), (b and c) High grade areas composed of epithelioid and round cells (10×, 40×), (d) Very focal CD10 (10×), (e) Diffuse Cyclin D1 (10×), (f) Focal moderate Cyclin D1 in low grade (star) and diffuse strong in high grade (arrow) areas (10×), (g) Positive PR in low grade (star) and negative in high grade (arrow) areas (10×), (h) Fluoroscent In-situ Hybridisation for YWHAE rearrangement showing split signals

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Case 19

The patient was a 28-year-old lady with complaints of continuous PV bleeding. She underwent dilatation and curettage (D&C) followed by hysterectomy which showed a tumor of 1.5 cm tumor in the isthmus and endocervix. The paraffin blocks of the D&C and hysterectomy specimens showed an invasive sarcomatous tumor predominantly, having high nucleus to cytoplasmic ratio resembling round cells (suspected high grade areas). Along with these high-grade areas, tumor with cells arranged around blood vessels resembling LGESS were also seen. Necrosis was not seen and occasional mitotic figures were noted (1 per 10 high power field). The tumor was diffusely positive for Cyclin D1 and PR and focally for CD10 and p16. Epithelial and smooth muscle markers were negative. FISH study for rearrangement of the YWHAE gene showed split signals in 22% cells [Figure 2]. No adjuvant therapy was offered to this patient. She is disease-free at present and is on follow-up for the past 4 months.
Figure 2: (a) Low grade areas invading muscle deeply (10×), (b) High grade areas showing round cells (20×), (c) Diffuse Cyclin D1 (10×), (d) Fluoroscent In-situ Hybridisationfor YWHAE rearrangement showing split signals

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Other cases of endometrial stromal sarcoma with suspected high grade areas

Of the other seven cases of ESS showing high-grade areas, 3 were negative, 3 were uninterpretable, and 1 was indeterminate (12% cells with split signals) for YWHAE gene rearrangement. In the indeterminate case, FISH was repeated on a whole section. These cases showed areas resembling LGESS with high-grade sarcomatous areas. Epithelioid or round tumor cells as seen in high-grade areas of FISH positive cases were prominently seen in 3 cases while 1 case showed bizarre giant tumor cells. All the cases showed presence of necrosis. Mitotic activity varied from as low as 2--3/10 hpf in one of the cases to 15/10 hpf. CD10 was positive in 2 cases, focally in 4 cases, and negative in 1 case. Smooth muscle markers were negative. PR was positive in a single case. Cyclin D1 showed diffuse and strong positivity in 3 cases, weak to moderate positivity in 3 cases, and was negative in 1 case. Ki-67 labelling was high in all the cases ranging from 30% to 100%. The indeterminate case (case 18) and the 2 uninterpretable cases (case 7 and case 15) resembled the other 2 positive cases in showing LGESS areas along with high-grade round cell areas. These 3 tumors also showed an immunoprofile similar to that of cases with positive rearrangement.

Low-grade endometrial stromal sarcoma

YWHAE gene rearrangement was negative in 5 cases and uninterpretable in 2 cases of LGESS. All the cases of LGESS on histology showed a cellular tumor composed of spindle to oval cells with small nuclei arranged around delicate small arterioles with a tongue-like pattern of myometrial invasion. Two cases presented as extrauterine masses (case 3 presented as a mass in the mesentery of the small intestine and case 9 presented as an abdominal wall mass). One of the cases showed sex cord-like areas (case 17). Mitotic activity was significantly increased in only 1 case (Case 14; 20/10 hpf). Focal necrosis was noted in a single case (case 23). This case also showed nuclear staining for Cyclin D1 with strong intensity in 80% of the cells but was negative for YWHAE gene rearrangement. Other cases showed negative to weak staining for Cyclin D1. CD10 was diffusely positive in 4 cases and focally in 3 cases. PR was positive in 4 cases while SMA showed focal positivity in a single case. Extrauterine cases were negative for CKIT, DOG1, Synaptophysin, and Chromogranin. Ki-67 was approximately 35--40% in one case while it ranged between 8 and 15% in the other cases.

Undifferentiated uterine sarcoma, leiomyosarcoma, undifferentiated carcinoma, cellular leiomyoma

All 3 cases of UUS were negative for YWHAE gene rearrangement and did not resemble any particular sarcoma on histology. Increased mitotic activity was seen in all the cases while necrosis was seen in one case. Focal CD10 positivity was seen in one case with all the cases being negative for smooth muscle markers. PR and Cyclin D1 showed only focal and weak positivity. Ki-67 was on the higher side (approximately 90%) while one case was diffusely and strongly positive for p53. All the cases of leiomyosarcoma fulfilled the histological criteria of presence of necrosis, increased mitotic count (4--30 per 10 high power field), and cytological atypia. One of the 3 cases of leiomyosarcoma had epithelioid morphology. Smooth muscle markers showed focal to diffuse positivity while Cyclin D1 was only focal and weak. All the cases of leiomyosarcoma were negative for YWHAE gene rearrangement. The single case of undifferentiated carcinoma which was also negative for YWHAE gene rearrangement showed a malignant tumor composed of epithelioid and oval cells arranged in sheets. The tumor showed areas of necrosis and mitotic activity of 18--20/10hpf. The tumor was positive for AE1/AE3 and focally for CD10 and EMA. SMA, desmin, and inhibin were negative. Diffuse and strong positivity for Cyclin D1 was also noted [Figure 3]. Cellular leiomyoma showed a cellular spindle cell tumor arranged in sheets and fascicles which was diffusely positive for H-Caldesmon and Desmin and was negative for CD10. Ki-67 labelling index was <1%.
Figure 3: (a) Undifferentiated carcinoma (10×), (b) AE1/AE3 positivity in undifferentiated carcinoma (20×) (c) Negative CD10 (10×), (d) Diffuse Cyclin D1 (10×)

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 » Discussion Top


ESSs are uncommon uterine mesenchymal malignancies, second only to leiomyosarcoma and represent approximately 7--15% of uterine mesenchymal tumors.[11],[12] Prior to 2003, ESSs were divided into LGESS and HGESS based on mitotic count. However, it was realized that increased mitotic activity can be seen in proliferative endometrial stroma and also mitoses alone did not have any prognostic significance.[1],[13] ESS were thus classified by the WHO 2003 as LGESS and UES based on histological resemblance to proliferative endometrial stroma.[3] LGESS deeply permeates the myometrium and resembles endometrial stroma while UES has no resemblance but shows cytological atypia and nuclear pleomorphism.[3] It was important to differentiate the two as 5-year survival of LGESS is approximately 85% and is <50% for UES.[1],[14],[15],[16],[17],[18] Chang et al. recognized that a subset of ESS showed high mitotic activity and atypia in LGESS and suggested that such cases should not be labelled as LGESS.[1] Kurihara et al. then further divided UES as those showing nuclear uniformity (UES-U) and those showing nuclear pleomorphism (UES-P) based on nuclear features implying that UES was a very heterogeneous group.[4] Sciallis et al. in their analysis of ESS reported that even UES-U are heterogeneous not only histologically but also immunohistochemically and genetically.[19] Cases showing low-grade and high-grade sarcomatous areas have also been reported in the literature.[5],[6] Lee et al. in their seminal paper described that some of such cases are associated with YWHAE-NUTM2A/B t(10;17) translocation.[7] They found that these tumors present at an advanced stage and have an aggressive behavior compared with JAZF1 mutated LGESS.[7] Thus, based on this translocation, the term HGESS was reintroduced in the WHO 2014 classification.[2],[7]

In the study by Lee et al. and Croce et al., cases with YWHAE-NUTM2A/B translocation had an average age of 50 years (range 28--67 years), while both of our positive cases and the indeterminate case were comparatively younger.[7],[10] The sizes of the tumors reported have ranged from 3 to 9 cm with a median size of 7.5 cm. On microscopy, these tumors are myopermeative and show a biphasic pattern consisting of conventional LGESS -like areas admixed with high-grade areas. The high-grade areas are composed of cellular uniform round cells with scanty cytoplasm or epithelioid cells with moderate cytoplasm and irregular and angulated nuclear contours and nuclei approximately twice the size of the low-grade areas.[7],[19] Pseudoglandular, pseudopapillary, and sex-cord- like areas have also been described.[7] Although high mitotic rate and necrosis are commonly noted in these tumors, both of our cases did not show increased mitotic activity while necrosis was noted only in 1 case.[7],[19] Low-grade areas may show fibrocollagenous to fibromyxoid areas as seen in one of our cases.[7] Vascular invasion is commonly seen.[7] Immunohistochemistry may show a dichotomous staining pattern. The low-grade areas are stained strongly by ER, PR, and CD10 while the high-grade areas are negative to weak and focal with these markers. Cyclin D1 on the other hand stains the high-grade areas strongly while the low-grade areas are negative or may stain weakly.[7],[10],[19],[20],[21],[22] A cutoff of 70% strong nuclear staining in tumor nuclei has been recommended for labelling cyclin D1 postivity.[20] Kurihara et al., were the first to describe diffuse Cyclin D1 expression in UES uniform type.[23] As seen in one of our case, initial specimen may show only low-grade areas and IHC test for Cyclin D1 is useful in such instance as an indicator for HGESS. Hence, Cyclin D1 has been suggested as a surrogate marker for HGESS with YWHAE gene rearrangement. Butdiffuse and strong Cyclin D1 can also be seen in UUS and undifferentiated carcinoma as seen in one of our cases.[24],[25] In presence of diffuse Cyclin D1, an undifferentiated carcinoma must be hence ruled out by using epithelial markers, as ESSs are not known to show positivity for EMA and cytokeratin.[24],[25] It may be noted that one of our LGESS also showed diffuse positivity for Cyclin D1. CKIT shows a staining pattern similar to Cyclin D1 while DOG1 is consistently negative.[26] P53 diffuse positivity may be seen in UUS, unlike in HGESS, even one of our UUS case showed diffuse strong positivity.[4],[24] Proliferative Ki-67 index is on the higher side in the high-grade areas.[7],[27] Histology and immunoprofile were similar in both our positive cases alongwith 2 cases with uninterpretable FISH and the only indeterminate case.

t(10;17) translocation results in fusion between YWHAE and 1 of 2 highly homologous gene NUTM2A/2B, formerly known as FAM22A/22B.[7],[24] This fusion gene results in 14-3-3 oncoprotein probably promoting oncogenesis.[28] This translocation was first described in clear cell sarcoma of kidney (CCSK), a rare pediatric renal tumor.[29] YWHAE-NUTM2A/B fusion rearrangement has also been found in these tumors.[30] Interestingly, CCSK and the high-grade areas of HGESS are similar on histology.[7] t(10;17) translocation in ESS was first described by Leunen et al., in a 28-year-old patient with postpartum hemorrhage.[31] Amant et al., described neuroectodermal differentiation in ESS with t(10;17) translocation.[32] Neuroectodermal component described by them probably represented the high-grade areas of ESS.[32] JAZF1-SUZ12 t(7;17) translocation was the first and the most common genetic alteration described in LGESS.[24],[33] Later various translocations like JAZF1-PHF1, EPC1-PHF1, MEAF6-PHF1, and MBTD1-CXorf67 have been found to be associated with LGESS.[24]

Croce et al. recommended a cautious threshold of 30% cells showing split signals to consider a FISH test positive.[10] However, in their study, best concordance between FISH and RT-PCR was observed at a threshold of 20%.[10] The only discordant case in their study, which was positive by RT-PCR and negative by FISH, did not resemble ESS on histology.[10] Compared with PCR, FISH may help in detection of YWHAE rearrangement with other fusion partners hitherto undescribed in literature. PCR may be helpful to detect cases with cryptic rearrangements that are too small to be detected by FISH.[10] PCR would have been helpful in our indeterminate case to confirm its YWHAE gene status. Some of our ESS with high-grade areas lacking YWHAE-NUTM2A/B translocation could be harboring another recently described ZC3H7B-BCOR translocation but not yet included in the WHO classification. These tumors show haphazard fascicles of spindle cells with mild to moderate nuclear atypia and high mitotic count. These tumors show a myxoid and collagenous background. These tumors are also known to present with a high stage disease, have poorer prognosis compared with LGESS tumors and must be treated as a HGESS.[34]

It is necessary to identify HGESS as they have a significant bearing on the choice of adjuvant therapy. Patients with LGESS are treated with hysterectomy followed by hormonal therapy like aromatase inhibitors.[8],[35],[36],[37],[38] Removing ovaries may also offer some benefit as a part of hormonal therapy.[8] However, some recent studies have shown that retaining ovaries does not worsen the survival and it is particularly important in young females.[16],[39],[40] HGESS cases are also treated with surgery but are unlikely to respond to hormonal therapy, as they are negative for ER and PR; hence, adjuvant chemotherapy and radiotherapy has been suggested in these patients.[8],[9],[41],[42],[43] Due to paucity of experience, there is no consensus on preservation of the ovaries, especially in a low stage premenopausal woman. Even though HGESSs do not show CKIT and PDGFR α mutations, they are known to express CKIT and PDGFRβ and may benefit from Imatinib therapy.[9],[44] Role of lymphadenectomy in clinically node negative ESS and UUS still remains controversial.[16],[39],[45],[46]

Although only a subset of ESS with aggressive features show YWHAE-NUTM2A/B translocation they may still harbor ZC3H7B-BCOR or hitherto undescribed genetic changes. Tumors with YWHAE-NUTM2A/B translocation are characterized by peculiar histological and immunohistochemical features. Cyclin D1 though not specific is a sensitive tool to test for YWHAE rearrangement. It is important to test for these translocations as these cases are aggressive compared to low grade ESS. As the incidences of these cases are low, pooled data from multicentric studies may aid in knowledge comprehending their biologic behaviour and developing optimal treatment strategies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Chang KL, Crabtree GS, Lim-Tan SK, Kempson RL, Hendrickson MR. Primary uterine endometrial stromal neoplasms. A clinicopathologic study of 117 cases. Am J Surg Pathol 1990;14:415-38.  Back to cited text no. 1
    
2.
Oliva E, Carcangiu ML, Carinelli SG, Ip P, Loening T, Longacre TA, et al. Mesenchymal tumours. In: Kurman RJ, Carcangiu ML, Herrington CS, Young RH, editors. WHO Classification of Tumours of Female Reproductive Organs. Lyon: International Agency for Research on Cancer; 2014. p. 135-47.  Back to cited text no. 2
    
3.
Hendrickson MR, Tavassoli FA, Kempson RL, McCluggage WG, Haller U, Kubik-Huch RA. Mesenchymal tumours and related lesions. In: Tavassoli FA, Devilee P, editors. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon: International Agency for Reasearch on Cancer; 2003. p. 233-44.  Back to cited text no. 3
    
4.
Kurihara S, Oda Y, Ohishi Y, Iwasa A, Takahira T, Kaneki E, et al. Endometrial stromal sarcomas and related high-grade sarcomas: Immunohistochemical and molecular genetic study of 31 cases. Am J Surg Pathol 2008;32:1228-38.  Back to cited text no. 4
    
5.
Amant F, Woestenborghs H, Vandenbroucke V, Berteloot P, Neven P, Moerman P, et al. Transition of endometrial stromal sarcoma into high-grade sarcoma. Gynecol Oncol 2006;103:1137-40.  Back to cited text no. 5
    
6.
Ohta Y, Suzuki T, Omatsu M, Hamatani S, Shiokawa A, Kushima M, et al. Transition from low-grade endometrial stromal sarcoma to high-grade endometrial stromal sarcoma. Int J Gynecol Pathol 2010;29:374-7.  Back to cited text no. 6
    
7.
Lee CH, Marino-Enriquez A, Ou W, Zhu M, Ali RH, Chiang S, et al. The clinicopathologic features of YWHAE-FAM22 endometrial stromal sarcomas: A histologically high-grade and clinically aggressive tumor. Am J Surg Pathol 2012;36:641-53.  Back to cited text no. 7
    
8.
Amant F, Floquet A, Friedlander M, Kristensen G, Mahner S, Nam EJ, et al. Gynecologic Cancer InterGroup (GCIG) consensus review for endometrial stromal sarcoma. Int J Gynecol Cancer 2014;24:S67-72.  Back to cited text no. 8
    
9.
Cuppens T, Tuyaerts S, Amant F. Potential therapeutic targets in uterine sarcomas. Sarcoma 2015;2015:243298.  Back to cited text no. 9
    
10.
Croce S, Hostein I, Ribeiro A, Garbay D, Velasco V, Stoeckle E, et al. YWHAE rearrangement identified by FISH and RT-PCR in endometrial stromal sarcomas: Genetic and pathological correlations. Mod Pathol 2013;26:1390-400.  Back to cited text no. 10
    
11.
Nordal RR, Thoresen SO. Uterine sarcomas in Norway 1956-1992: Incidence, survival and mortality. Eur J Cancer 1997;33:907-11.  Back to cited text no. 11
    
12.
Koivisto-Korander R, Martinsen JI, Weiderpass E, Leminen A, Pukkala E. Incidence of uterine leiomyosarcoma and endometrial stromal sarcoma in Nordic countries: Results from NORDCAN and NOCCA databases. Maturitas 2012;72:56-60.  Back to cited text no. 12
    
13.
Evans HL. Endometrial stromal sarcoma and poorly differentiated endometrial sarcoma. Cancer 1982;50:2170-82.  Back to cited text no. 13
    
14.
Abeler VM, Royne O, Thoresen S, Danielsen HE, Nesland JM, Kristensen GB. Uterine sarcomas in Norway. A histopathological and prognostic survey of a total population from 1970 to 2000 including 419 patients. Histopathology 2009;54:355-64.  Back to cited text no. 14
    
15.
Bartosch C, Exposito MI, Lopes JM. Low-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma: A comparative analysis emphasizing the importance of distinguishing between these two groups. Int J Surg Pathol 2010;18:286-91.  Back to cited text no. 15
    
16.
Chan JK, Kawar NM, Shin JY, Osann K, Chen LM, Powell CB, et al. Endometrial stromal sarcoma: A population-based analysis. Br J Cancer 2008;99:1210-5.  Back to cited text no. 16
    
17.
D'Angelo E, Spagnoli LG, Prat J. Comparative clinicopathologic and immunohistochemical analysis of uterine sarcomas diagnosed using the World Health Organization classification system. Hum Pathol 2009;40:1571-85.  Back to cited text no. 17
    
18.
Denschlag D, Masoud I, Stanimir G, Gilbert L. Prognostic factors and outcome in women with uterine sarcoma. Eur J Surg Oncol 2007;33:91-5.  Back to cited text no. 18
    
19.
Sciallis AP, Bedroske PP, Schoolmeester JK, Sukov WR, Keeney GL, Hodge JC, et al. High-grade endometrial stromal sarcomas: A clinicopathologic study of a group of tumors with heterogenous morphologic and genetic features. Am J Surg Pathol 2014;38:1161-72.  Back to cited text no. 19
    
20.
Lee CH, Ali RH, Rouzbahman M, Marino-Enriquez A, Zhu M, Guo X, et al. Cyclin D1 as a diagnostic immunomarker for endometrial stromal sarcoma with YWHAE-FAM22 rearrangement. Am J Surg Pathol 2012;36:1562-70.  Back to cited text no. 20
    
21.
Isphording A, Ali RH, Irving J, Goytain A, Nelnyk N, Hoang LN, et al. YWHAE-FAM22 endometrial stromal sarcoma: Diagnosis by reverse transcription-polymerase chain reaction in formalin-fixed, paraffin-embedded tumor. Hum Pathol 2013;44:837-43.  Back to cited text no. 21
    
22.
Stewart CJ, Leung YC, Murch A, Peverall J. Evaluation of fluorescence in-situ hybridization in monomorphic endometrial stromal neoplasms and their histological mimics: A review of 49 cases. Histopathology 2014;65:473-82.  Back to cited text no. 22
    
23.
Kurihara S, Oda Y, Ohishi Y, Kaneki E, Kobayashi H, Wake N, et al. Coincident expression of beta-catenin and cyclin D1 in endometrial stromal tumors and related high-grade sarcomas. Mod Pathol 2010;23:225-34.  Back to cited text no. 23
    
24.
Lee CH, Nucci MR. Endometrial stromal sarcoma--the new genetic paradigm. Histopathology 2015;67:1-19.  Back to cited text no. 24
    
25.
Shah VI, McCluggage WG. Cyclin D1 does not distinguish YWHAE-NUTM2 high-grade endometrial stromal sarcoma from undifferentiated endometrial carcinoma. Am J Surg Pathol 2015;39:722-4.  Back to cited text no. 25
    
26.
Lee CH, Hoang LN, Yip S, Reyes C, Marino-Enriquez A, Eilers G, et al. Frequent expression of KIT in endometrial stromal sarcoma with YWHAE genetic rearrangement. Mod Pathol 2014;27:751-7.  Back to cited text no. 26
    
27.
Gremel G, Liew M, Hamzei F, Hardell E, Selling J, Ghaderi M, et al. A prognosis based classification of undifferentiated uterine sarcomas: Identification of mitotic index, hormone receptors and YWHAE-FAM22 translocation status as predictors of survival. Int J Cancer 2015;136:1608-18.  Back to cited text no. 27
    
28.
Lee CH, Ou WB, Marino-Enriquez A, Zhu M, Mayeda M, Wang Y, et al. 14-3-3 fusion oncogenes in high-grade endometrial stromal sarcoma. Proc Natl Acad Sci U S A 2012;109:929-34.  Back to cited text no. 28
    
29.
Punnett HH, Halligan GE, Zaeri N, Karmazin N. Translocation 10;17 in clear cell sarcoma of the kidney. A first report. Cancer Genet Cytogenet 1989;41:123-8.  Back to cited text no. 29
    
30.
O'Meara E, Stack D, Lee CH, Garvin AJ, Morris T, Argani P, et al. Characterization of the chromosomal translocation t (10;17)(q22;p13) in clear cell sarcoma of kidney. J Pathol 2012;227:72-80.  Back to cited text no. 30
    
31.
Leunen K, Amant F, Debiec-Rychter M, Croes R, Hagemeijer A, Schoenmakers EF, et al. Endometrial stromal sarcoma presenting as postpartum haemorrhage: Report of a case with a sole t(10;17)(q22;p13) translocation. Gynecol Oncol 2003;91:265-71.  Back to cited text no. 31
    
32.
Amant F, Tousseyn T, Coenegrachts L, Decloedt J, Moerman P, Debiec-Rychter M. Case report of a poorly differentiated uterine tumour with t(10;17) translocation and neuroectodermal phenotype. Anticancer Res 2011;31:2367-71.  Back to cited text no. 32
    
33.
Koontz JI, Soreng AL, Nucci M, Kuo FC, Pauwels P, van Den Berghe H, et al. Frequent fusion of the JAZF1 and JJAZ1 genes in endometrial stromal tumors. Proc Natl Acad Sci U S A 2001;98:6348-53.  Back to cited text no. 33
    
34.
Lewis N, Soslow RA, Delair DF, Park KJ, Murali R, Hollmann TJ, et al. ZC3H7B-BCOR high-grade endometrial stromal sarcomas: A report of 17 cases of a newly defined entity. Mod Pathol 2018;31:674-84.  Back to cited text no. 34
    
35.
Amant F, Coosemans A, Debiec-Rychter M, Timmerman D, Vergote I. Clinical management of uterine sarcomas. Lancet Oncol 2009;10:1188-98.  Back to cited text no. 35
    
36.
Rauh-Hain JA, del Carmen MG. Endometrial stromal sarcoma: A systematic review. Obstet Gynecol 2013;122:676-83.  Back to cited text no. 36
    
37.
Pink D, Lindner T, Mrozek A, Kretzschmar A, Thuss-Patience PC, Dorken B, et al. Harm or benefit of hormonal treatment in metastatic low-grade endometrial stromal sarcoma: Single center experience with 10 cases and review of the literature. Gynecol Oncol 2006;101:464-9.  Back to cited text no. 37
    
38.
Altman AD, Nelson GS, Chu P, Nation J, Ghatage P. Uterine sarcoma and aromatase inhibitors: Tom Baker Cancer Centre experience and review of the literature. Int J Gynecol Cancer 2012;22:1006-12.  Back to cited text no. 38
    
39.
Shah JP, Bryant CS, Kumar S, Ali-Fehmi R, Malone JM Jr, Morris RT. Lymphadenectomy and ovarian preservation in low-grade endometrial stromal sarcoma. Obstet Gynecol 2008;112:1102-8.  Back to cited text no. 39
    
40.
Li AJ, Giuntoli RL 2nd, Drake R, Byun SY, Rojas F, Barbuto D, et al. Ovarian preservation in stage I low-grade endometrial stromal sarcomas. Obstet Gynecol 2005;106:1304-8.  Back to cited text no. 40
    
41.
Pautier P, Nam EJ, Provencher DM, Hamilton AL, Mangili G, Siddiqui NA, et al. Gynecologic Cancer InterGroup (GCIG) consensus review for high-grade undifferentiated sarcomas of the uterus. Int J Gynecol Cancer 2014;24:S73-7.  Back to cited text no. 41
    
42.
Reed NS, Mangioni C, Malmstrom H, Scarfone G, Poveda A, Pecorelli S, et al. Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: An European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874). Eur J Cancer 2008;44:808-18.  Back to cited text no. 42
    
43.
Pautier P, Floquet A, Gladieff L, Bompas E, Ray-Coquard I, Piperno-Neumann S, et al. A randomized clinical trial of adjuvant chemotherapy with doxorubicin, ifosfamide, and cisplatin followed by radiotherapy versus radiotherapy alone in patients with localized uterine sarcomas (SARCGYN study). A study of the French Sarcoma Group. Ann Oncol 2013;24:1099-104.  Back to cited text no. 43
    
44.
Salvatierra A, Tarrats A, Gomez C, Sastre JM, Balana C. A case of c-kit positive high-grade stromal endometrial sarcoma responding to Imatinib Mesylate. Gynecol Oncol 2006;101:545-7.  Back to cited text no. 44
    
45.
Dos Santos LA, Garg K, Diaz JP, Soslow RA, Hensley ML, Alektiar KM, et al. Incidence of lymph node and adnexal metastasis in endometrial stromal sarcoma. Gynecol Oncol 2011;121:319-22.  Back to cited text no. 45
    
46.
Amant F, De Knijf A, Van Calster B, Leunen K, Neven P, Berteloot P, et al. Clinical study investigating the role of lymphadenectomy, surgical castration and adjuvant hormonal treatment in endometrial stromal sarcoma. Br J Cancer 2007;97:1194-9.  Back to cited text no. 46
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]



 

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