CT, MRI, and FDG-PET imaging findings of low-grade extrauterine endometrial stromal sarcoma arising from the mesentery: A case report

A 49-year-old woman with increasing lower abdominal pain was referred to our institution 4 months after undergoing a medical check-up with reported ovarian enlargement. Ultrasonography detected a solid polycystic mass measuring 12 × 12 cm. She had no medical history other than depression, and no family history of malignancies, except for her father, who had prostate cancer. Laboratory analysis was not significant except for a slight increase in CA-125 of 42 U/mL (normal range, 0-35 U/mL). Contrast-enhanced computed tomography (CT) revealed a 13 cm solid and cystic mass with contrast enhancement ( Fig. 1 ). The dorsal edge of the mass was ill-defined, and internal walls were found within the mass. The mesenteric vein, which was suspected to be the drainage vein, was located at the periphery of the mass ( Fig. 1 B). On magnetic resonance imaging (MRI), the solid part of the tumor showed heterogeneous intensity on T2-weighted imaging (T2WI) and T1-weighted imaging (T1WI) with restricted diffusion ( Fig. 2 ). No abnormality was suspected in the uterus, other than typical leiomyomas, and both ovaries were normal. 18F-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) was also performed, on which FDG accumulated in the solid part of the tumor with a maximum standardized uptake value (SUVmax) of 4.5 and 5.9 at 1 and 2 h after isotope injection, respectively ( Fig. 3 ). No metastasis was observed. Fig. 1 (A) A 13 cm solid and cystic mass with contrast enhancement (arrow); (B) the mesenteric vein is located at the periphery of the mass (arrowhead) Fig 1 Fig. 2 The solid part of the mass (arrows) shows heterogeneous signal intensity on axial (A), coronal (B), and sagittal T2-weighted imaging (T2WI) (C), and axial T1-weighted imaging (T1WI) (D); the dorsal edge of the mass is ill-defined; diffusion is restricted in the solid part with apparent diffusion coefficient (ADC) of 1.04 × 10 −3 mm 2 /s (E and F) Fig 2 Fig. 3 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) shows abnormal FDG uptake in the solid part (arrows); the maximum standardized uptake value (SUVmax) was 4.5 at 1 h after (A) and 5.9 at 2 h after isotope injection (B). Fig 3 (A) A 13 cm solid and cystic mass with contrast enhancement (arrow); (B) the mesenteric vein is located at the periphery of the mass (arrowhead) The solid part of the mass (arrows) shows heterogeneous signal intensity on axial (A), coronal (B), and sagittal T2-weighted imaging (T2WI) (C), and axial T1-weighted imaging (T1WI) (D); the dorsal edge of the mass is ill-defined; diffusion is restricted in the solid part with apparent diffusion coefficient (ADC) of 1.04 × 10 −3 mm 2 /s (E and F) 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) shows abnormal FDG uptake in the solid part (arrows); the maximum standardized uptake value (SUVmax) was 4.5 at 1 h after (A) and 5.9 at 2 h after isotope injection (B). Malignancies, including gastrointestinal stromal tumors, were considered for the differential diagnosis, and laparotomy was performed. Direct visual inspection during surgery revealed that the uterus and ovaries were intact, and the mass was confirmed to arise from the mesentery ( Fig. 4 ), after which it was removed. No metastasis or dissemination was observed. Fig. 4 Operative view of the tumor (arrow) arising from the mesentery (arrowhead) Fig 4 Operative view of the tumor (arrow) arising from the mesentery (arrowhead) Macroscopically, the tumor was polycystic with a soft, yellow-white solid component. Histologically, diffuse proliferation of cells with ovoid- to spindle-like nuclei and clear cytoplasm was observed ( Fig. 5 ). Cell density was high in a few regions of hemorrhage, edema, and necrosis. The tumor was covered with a fibrous capsule, and the margins were negative. Several foci of venous invasion were observed. Ki-67 was positive in approximately 20% of cells. Immunohistochemically, proliferating cells were positive for cluster of differentiation 10 (CD10) and estrogen receptor (ER). The recombination of the JAZF1 gene was identified by fluorescence in situ hybridization (FISH), and the tumor was diagnosed as low-grade EESS. No PHF1 gene recombinations were observed. Because uterine involvement was highly suspected, hysterectomy and bilateral salpingo-oophorectomy were performed; however, no malignancy or endometriosis was observed. After discharge, the patient was regularly attended follow-up visits. Fig. 5 Microscopic view of the resected specimen (×100 each); (A) Hematoxylin and eosin (HE) stain shows diffuse proliferation of cells with ovoid- to spindle-like nuclei with a few regions of hemorrhage, edema, and necrosis; immunohistochemical staining with (B) cluster of differentiation 10 (CD10) and (C) ER was positive. Fig 5 Microscopic view of the resected specimen (×100 each); (A) Hematoxylin and eosin (HE) stain shows diffuse proliferation of cells with ovoid- to spindle-like nuclei with a few regions of hemorrhage, edema, and necrosis; immunohistochemical staining with (B) cluster of differentiation 10 (CD10) and (C) ER was positive.

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We have reported herein a case of low-grade EESS originating from the mesentery, without uterine ESS or evidence of endometriosis, which was formally diagnosed through FISH. CT, MRI, and FDG-PET/CT imaging showed a 13 cm mainly polycystic mass containing a contrast-enhanced solid component with restricted diffusion and mild FDG uptake. A large cystic component may be a characteristic feature of EESS, given the low pressure of the surrounding tissues, although further investigation is necessary.

We have reported herein a case of low-grade EESS originating from the mesentery. A few other authors have reported cases of EESS originating from extrauterine organs, such as the colon [6] , small bowel [7] , stomach [8] , round ligament [9] , ovary [10] , vagina [11] , peritoneum [12] , lung [5] , and mesentery [13] , [14] , [15] , [16] ; however, to the best of our knowledge, only four cases of EESS originating from the mesentery have been reported in the available English literature, and the present case is the first to report all of CT, MRI, and FDG-PET/CT findings. According to a study by Masand et al. [17] , which summarized 63 cases of ESS with extrauterine involvement, the median age was 50 years (range, 27-87 years), and the most frequent symptoms reported were abdominal and pelvic masses, pain, genital bleeding, and gastrointestinal symptoms. Endometriosis was noted in 30/63 cases. LGESS generally has an indolent clinical course with a median overall survival of 80 months [18] . Lan et al. [19] speculated that EESS of endometrioid origin might be more prone to dissemination, as the incidence of dissemination was 76.9% in low-grade EESS arising from endometriosis, and 31% in uterine LGESS. In the present case, there was no history of endometriosis nor were there findings suggestive of endometriosis at the time of surgery. Although it is possible that the EESS originated from subclinical endometriosis, the absence of disseminated lesions in the present case may be related to the absence of coexisting endometriosis. Preoperative diagnosis of EESS is considered challenging, especially in the absence of uterine ESS, as in the present case, because of the rarity of the condition and the radiological similarities with other tumors, such as leiomyoma, leiomyosarcoma, and gastrointestinal stromal tumor. Radiologically, uterine LGESS forms a polypoidal endometrial mass with a well-defined or infiltrative border [ 20 , 21 ]. MRI typically shows heterogeneous isointensity on T1WI and heterogeneous hyperintensity on T2WI [21] , but the signal intensity on T2WI may vary depending on the degenerative changes [22] . Several characteristic MRI features of LGESS have been reported as follows: a worm-like nodular extension [21] indicates lymphatic and vascular invasion into the myometrium; and T2WI hypointense bands [22] , indicating the preserved normal myometrium surrounded by the tumor, and the extension along with the ligaments [23] . LGESS is typically moderately enhanced after contrast enhancement, and restricted diffusion with a mean ADC value of 1.09 [ 24 , 25 ]. The reported SUVmax of LGESS was 5.41 [26] and 13.28 [27] . However, there are very few reports available on the imaging features of low-grade EESS. Almost nothing is known about the differences in imaging features between uterine ESS and EESS because of the rarity of these tumors. The large polycystic part of the tumor was a major characteristic of the present case. We speculated that the cystic components of EESS might tend to be larger than those in uterine ESS, given the lower pressure from the surrounding tissues in the uterine myometrium. However, very few studies have focused on this issue. Khan et al. [14] reported two EESS cases (the grade was low in one patient but undescribed for the other), in which CT imaging showed large tumors occupying the right lobe of the liver, and most of the tumors had large cystic components in both cases. Kim et al. [7] reviewed 16 EESS cases, including the 2 cases reported by Khan et al. [14] , and 4 EESS cases contained cystic parts macroscopically, although the grade was unknown in 3 of them. In a review of low-grade EESS by Xie et al. [28] , 2 out of 9 included cystic parts macroscopically; however, information about the size of the cystic components was unavailable. For uterine LGESS, although cystic change is frequent (up to 70%), cystic components tend to be small as seen in the study by Park et al. [29] , in which the mean size of 10 LGESS cases including 7 cystic components was 2.8 cm (range, 1.3-4.5 cm). EESS may therefore be characterized by a tendency to have a larger cystic component compared to uterine ESS. To confirm this, further investigation with a larger number of patients is needed. Pathological findings of low-grade EESS are similar to those of uterine LGESS [4] . Macroscopically, LGESS is circumscribed, solid, and multinodular. It is composed of monotonous cells with scant cytoplasm and minimal atypia [30] . Immunohistochemically, ESS is positive for CD10, ER, and progesterone receptor, and may also be positive for smooth muscle markers, including H-cardesmon and desmin [31] . Ki-67 index and p53 immunoreactivity were lower than those of HGESS. LGESS frequently involves fusion of two zinc finger genes between chromosomes 7 and 17, JAZF1/SUZ12 and/or JAZF1/PHF1, which is useful for differentiating LGESS from HGESS [32] . These pathological features were also found in the present case, including the recombination of the JAZF1 gene seen in FISH. The management of EESS usually follows that of uterine ESS [33] , where the first-line treatment is hysterectomy and adnexectomy, followed by adjuvant hormonal therapy [34] . In cases of EESS, resection of the EESS is also required. The benefits of adjuvant hormonal therapy for EESS may be limited, however, especially in cases of advanced or metastatic disease [33] .

Endometrial stromal sarcoma (ESS) is a rare uterine mesenchymal neoplasm, accounting for < 10% of uterine sarcomas and 0.2% of all primary malignant tumors of the uterus [1] . In the 2020 World Health Organization (WHO) “Classification of Tumours of Female Reproductive Organs,” endometrial stromal tumors and related tumors were classified into four categories: benign endometrial stromal nodules, low-grade ESS (LGESS), high-grade ESS (HGESS), and undifferentiated uterine sarcoma [2] . Extrauterine ESS (EESS) is an even rarer entity, thought to originate from foci of endometriosis [3] . Most reports on EESS involve cases of LGESS, few cases of HGESS [ 4 , 5 ], and no cases of benign endometrial stromal nodules or undifferentiated uterine sarcoma, which is in-line with the frequency of each category in uterine ESS. Here, we present a case of low-grade EESS in the mesentery with no evidence of primary uterine ESS or endometriosis.