Uterine tumors with sex cord-like elements: a clinicopathologic study of 19 cases

The clinicopathological features of the nine UTROSCTs, seven LGESS, two AS, and one CHEC case are summarized in Table  2 . Patient age ranged from 27 to 88 years (median and mean ages: 49 and 48.2 years, respectively). Six patients were postmenopausal. Three patients showed increased serum CA-125 levels at initial diagnosis. None of the patients had any history of tamoxifen use. Ultrasound revealed “leiomyoma” in four UTROSCT and six LGESS cases, “leiomyoma with abnormal endometrial echo” in one UTROSCT and one LGESS case, “endometrial polyp” in one UTROSCT case, and “intrauterine space-occupying mass” in the other six cases. Frozen section biopsy was performed for 14 patients. Follow-up information was available for 18 patients over a period of 3–79 months (median: 25.5 months and mean: 25.9 months). With the exception of one patient with LGESS relapse 25 months after the initial operation, all other patients were alive without recurrence or metastasis at the last follow-up. Table 2 Clinicopathological features of uterine tumors with sex cord-like elements Case Category Main symptoms Surgical method Location Tumor size(cm) Borderline Necrosis Mitotic activity (Sex cord-like area) Lymphovascular invasion Sex cord-like proportion Polygonal cells FIGO stage Follow-up 1 UTROSCT No Tumorectomy Near uterine isthmus 1.2 Invasive No 2/10HPF No - Absent - 29 months ANED 2 Menostaxis and abdomen pain Hysterectomy and bilateral adnexectomy with pelvic lymph nodes Uterine body 10 Invasive Yes 10/10HPF No - Present - 29 months ANED 3 No Hysterectomy and bilateral salpingectomy Near uterine isthmus 5.5 Invasive No <1/10HPF No - Present - 79 months ANED 4 No Hysterectomy Uterine body 3 Clear No 2/10HPF No - Absent - 24 months ANED 5 No Tumorectomy Uterine body 4.5 Clear No 7/10HPF No - Absent - NA 6 Irregular vaginal bleeding Hysterectomy and bilateral adnexectomy Uterine body 4.5 Invasive No <1/10HPF Yes - Absent - 48 months ANED 7 Irregular vaginal bleeding Hysterectomy and bilateral adnexectomy Near uterine fundus 2.5 Invasive No 2/10HPF No - Absent - 29 months ANED 8 Irregular vaginal bleeding Hysterectomy and bilateral adnexectomy Uterine body 1 Invasive No <1/10HPF No - Absent - 20 months ANED 9 Irregular vaginal bleeding Hysterectomy and bilateral adnexectomy Near uterine fundus 1.5 Invasive No 9/10HPF No - Absent - 8 months ANED 10 LGESS Profuse menstruation Tumorectomy Uterine body 6.5 Invasive No <1/10HPF No 40% Absent ⅠB 25 months Relapse 11 Profuse menstruation and abdomen pain Hysterectomy and bilateral adnexectomy Near uterine isthmus 5.5 Invasive No 1/10HPF No 10% Absent ⅠB 22 months ANED 12 Abdomen discomfort Hysterectomy and bilateral adnexectomy with pelvic lymph nodes Uterine body 7 Invasive No <1/10HPF Yes 20% Absent ⅠB 3 months ANED 13 Menostaxis Hysterectomy and bilateral adnexectomy Uterine body 3 Invasive No <1/10HPF Yes 30% Absent ⅠA 27 months ANED 14 Irregular vaginal bleeding Hysterectomy and bilateral adnexectomy Uterine body 4 Invasive No <1/10HPF Yes 80% Absent ⅠA 27 months ANED 15 Menostaxis Hysterectomy and bilateral adnexectomy Uterine body 11 Invasive No <1/10HPF Yes 10% Absent ⅠB 26 months ANED 16 Menostaxis Hysterectomy and bilateral adnexectomy Uterine body 7 Invasive Yes <1/10HPF No 30% Absent ⅠB 9 months ANED 17 Adenosarcoma Irregular vaginal bleeding Hysterectomy and bilateral adnexectomy with pelvic and para-aortic lymph nodes Near uterine isthmus 2.7 Invasive No <1/10HPF No 15% Absent ⅠB 45 months ANED 18 Irregular vaginal bleeding Hysterectomy and bilateral adnexectomy with pelvic lymph nodes and omentum Uterine body 10 Invasive Yes 7/10HPF No 80% Present ⅠB 5 months ANED 19 CHEC Irregular vaginal bleeding Hysterectomy and bilateral adnexectomy with pelvic lymph nodes and omentum Near uterine isthmus 4.6 Invasive No <1/10HPF No 40% No ⅠA 11 months ANED ANED Alive with no evidence of disease, CHEC Corded and hyalinized endometrioid carcinoma, LGESS Low grade endometrial stromal sarcoma, NA Not available, UTROSCT Uterine tumor resembling ovarian sex cord tumor Clinicopathological features of uterine tumors with sex cord-like elements ANED Alive with no evidence of disease, CHEC Corded and hyalinized endometrioid carcinoma, LGESS Low grade endometrial stromal sarcoma, NA Not available, UTROSCT Uterine tumor resembling ovarian sex cord tumor For UTROSCTs (Fig.  1 A-B), tumor size ranged from 1.0 to 10.0 cm (median: 3.0 cm and mean: 3.7 cm). With the exception of two cases, microscopically, these tumors showed an invasive border joined to the myometrium. The morphological patterns of sex cord-like elements included clusters or nests (6/9 cases, 66.7%), sheets (6/9 cases, 66.7%), cords or trabeculae (4/9 cases, 44.4%), tubules (2/9 cases, 22.2%), and retiform (1/9 cases, 11.1%) growth. Two cases showed hyalinization, and four cases showed edematous degeneration in the stroma. For LGESS (Fig.  1 C-D), tumor size ranged from 3.0 to 11.0 cm (median: 6.5 cm and mean: 6.3 cm). Sex cord-like elements account for 10–80% of these tumors. The main pattern was clusters or nests in two cases and cords or trabeculae in the other five cases. Cord or trabecular patterns were observed in the sex cord-like elements of LGESS (6/7 cases, 85.7%) with stromal hyalinization commonly observed in 5/7 cases (71.4%). For the two AS (Fig.  1 E-F), sex cord-like elements, specifically cords or trabeculae and clusters or nests accounted for 15% and 80% of cases, respectively. One patient with AS showed a sarcomatous overgrowth. For CHEC (Fig.  1 G-H), sex cord-like elements accounted for 40% of cases, typically with cord or trabecular patterns. Fig. 1 Hematoxylin-eosin staining pictures of selected cases. A Uterine tumor resembling ovarian sex cord tumor (UTROSCT); ( B ) UTROSCT with polygonal cells; ( C - D ) Low grade endometrial stromal sarcoma; ( E - F ) Adenosarcoma; ( G - H ) Corded and hyalinized endometrioid carcinoma. (A, B, D, F, H: ×100; C, G: ×40; E: ×20) Hematoxylin-eosin staining pictures of selected cases. A Uterine tumor resembling ovarian sex cord tumor (UTROSCT); ( B ) UTROSCT with polygonal cells; ( C - D ) Low grade endometrial stromal sarcoma; ( E - F ) Adenosarcoma; ( G - H ) Corded and hyalinized endometrioid carcinoma. (A, B, D, F, H: ×100; C, G: ×40; E: ×20) The tumor cells of sex cord-like elements showed two features. In most cases, the tumor cells were similar to the cells of adult granulosa cell tumors, whereas in two UTROSCT cases and one AS case, polygonal cells were observed focally or diffusely (Fig.  1 B). The immunohistochemical features of the sex cord-like elements are summarized in Tables  3 , 4 and 5 . Among the three categories of non-UTROSCTs, the immunohistochemical features of sex cord-like elements in AS were most similar to those in UTROSCTs. AS cells were exclusively positive for CK (AE1/AE3), calretinin, Melan A, and SF-1 (Fig.  2 ). With the exception of one LGESS case (that exhibited weak and focal expression), LGESS and CHEC cases were negative for α-inhibin. Most cases highly expressed CD56, indicating low marker specificity. Among all markers, Melan A exhibited the lowest expression rate in the study cohort, and its expression tended to be present in polygonal cells. Among the six sex cord markers, calretinin was the only marker that showed statistically significant differential expression between the UTROSCT and non-UTROSCT groups ( p  = 0.005). The sensitivity and specificity for calretinin were 88.9% and 80.0%, respectively. Table 3 Immunohistochemical profile of sex cord-like elements Case Category CK (AE1/AE3) EMA Vimentin ER PR CD10 WT1 Desmin SMA Ki67 1 UTROSCT + + + + + - + + + 10% 2 + - + + + - + + + 30% 3 + - NA + + - NA - + 10% 4 + NA NA + + - NA - + <1% 5 + - NA + + + NA + + 20% 6 + - + + + + + - - 15% 7 + NA + + + + + + - 2% 8 + NA NA + + - + + + <1% 9 + NA NA + + - + + - 30% 10 LGESS - - NA + + + NA - + 20% 11 - NA NA + + + NA - - 10% 12 - NA NA + + + - - + 5% 13 - NA NA + + + + + + NA 14 - NA NA + - + + + + 5% 15 NA NA NA + + + + + + 5% 16 NA NA NA + + + - + - 10% 17 Adenosarcoma + NA + + + - NA NA NA 5% 18 + + + + + - + + - 50% 19 CHEC - - + - - + + - + 15% CHEC Corded and hyalinized endometrioid carcinoma, EMA Epithelial membrane antigen, ER Estrogen receptor, LGESS Low grade endometrial stromal sarcoma, NA Not available, PR Progesterone receptor, SMA Smooth muscle actin, UTROSCT Uterine tumor resembling ovarian sex cord tumor, WT1 Wilms tumor 1 protein Immunohistochemical profile of sex cord-like elements CHEC Corded and hyalinized endometrioid carcinoma, EMA Epithelial membrane antigen, ER Estrogen receptor, LGESS Low grade endometrial stromal sarcoma, NA Not available, PR Progesterone receptor, SMA Smooth muscle actin, UTROSCT Uterine tumor resembling ovarian sex cord tumor, WT1 Wilms tumor 1 protein Table 4 Immunohistochemical expression of sex cord markers between UTROSCT and non-UTROSCT Antibodies In total(n(%)) Category p UTROSCT(n(%)) Non-UTROSCT(n(%)) Calretinin  Positive 10(52.6%) 8(88.9%) 2(20.0%) 0.005  Negative 9(47.4%) 1(11.1%) 8(80.0%) α-inhibin  Positive 9(47.4%) 6(66.7%) 3(30.0%) 0.179  Negative 10(52.6%) 3(33.3%) 7(70.0%) CD56  Positive 17(94.4%) 7(87.5%) 10(100.0%) 0.444  Negative 1(5.6%) 1(12.5%) 0(0.0%) Melan A  Positive 2(14.3%) 1(14.3%) 1(14.3%) 1.000  Negative 12(85.7%) 6(85.7%) 6(85.7%) CD99  Positive 14(87.5%) 8(100.0%) 6(75.0%) 0.467  Negative 2(12.5%) 0(0.0%) 2(25.0%) SF-1  Positive 5(33.3%) 3(50.0%) 2(22.2%) 0.329  Negative 10(66.7%) 3(50.0%) 7(77.8%) SF-1 Steroidogenic factor-1, UTROSCT Uterine tumor resembling ovarian sex cord tumor Immunohistochemical expression of sex cord markers between UTROSCT and non-UTROSCT SF-1 Steroidogenic factor-1, UTROSCT Uterine tumor resembling ovarian sex cord tumor Table 5 Semiquantitative analysis of the expression of sex cord markers between UTROSCT and non-UTROSCT Antibodies UTROSCT (Case No.) Non-UTROSCT (Case No.) p 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Calretinin  Intensity score 3 3 1 3 0 2 3 3 3 0 0 0 0 0 0 0 3 3 0  Extent score 4 1 2 4 0 4 4 4 1 0 0 0 0 0 0 0 2 1 0  Final score 12 3 2 12 0 8 12 12 3 0 0 0 0 0 0 0 6 3 0 0.003 α-inhibin  Intensity score 0 3 2 0 0 3 3 2 1 0 0 0 0 0 0 1 2 3 0  Extent score 0 1 1 0 0 1 2 2 4 0 0 0 0 0 0 1 1 2 0  Final score 0 3 2 0 0 3 6 4 4 0 0 0 0 0 0 1 2 6 0 0.084 CD56  Intensity score 3 3 3 3 3 0 3 3 NA 3 3 3 3 3 3 2 3 3 3  Extent score 4 4 4 1 4 0 4 3 NA 4 4 4 4 4 4 4 4 4 1  Final score 12 12 12 3 12 0 12 9 NA 12 12 12 12 12 12 8 12 12 3 0.399 Melan A  Intensity score 0 2 0 0 0 0 0 NA NA 0 0 0 NA 0 NA NA 0 3 0  Extent score 0 1 0 0 0 0 0 NA NA 0 0 0 NA 0 NA NA 0 4 0  Final score 0 2 0 0 0 0 0 NA NA 0 0 0 NA 0 NA NA 0 12 0 0.917 CD99  Intensity score 3 3 1 3 1 1 2 1 NA 0 1 2 NA 0 1 NA 3 3 3  Extent score 3 4 4 4 1 1 4 4 NA 0 4 4 NA 0 4 NA 4 2 4  Final score 9 12 4 12 1 1 8 4 NA 0 4 8 NA 0 4 NA 12 6 12 0.708 SF-1  Intensity score 0 2 2 2 0 0 NA NA NA 0 0 0 NA 0 0 0 1 3 0  Extent score 0 1 4 2 0 0 NA NA NA 0 0 0 NA 0 0 0 1 3 0  Final score 0 2 8 4 0 0 NA NA NA 0 0 0 NA 0 0 0 1 9 0 0.293 SF-1 Steroidogenic factor-1, UTROSCT Uterine tumor resembling ovarian sex cord tumor Semiquantitative analysis of the expression of sex cord markers between UTROSCT and non-UTROSCT SF-1 Steroidogenic factor-1, UTROSCT Uterine tumor resembling ovarian sex cord tumor Fig. 2 Calretinin, α-inhibin, Melan A and steroidogenic factor-1 (SF-1) expression in uterine tumor resembling ovarian sex cord tumor (UTROSCT) and adenosarcoma (AS). A Diffuse calretinin expression in UTROSCT; ( B ) Dot-like α-inhibin expression in UTROSCT; ( C ) Polygonal cells in UTROSCT showed Melan A positive; ( D ) SF-1 expression in UTROSCT; ( E - H ) Calretinin, α-inhibin, Melan A and SF-1 expression in AS. (×200) Calretinin, α-inhibin, Melan A and steroidogenic factor-1 (SF-1) expression in uterine tumor resembling ovarian sex cord tumor (UTROSCT) and adenosarcoma (AS). A Diffuse calretinin expression in UTROSCT; ( B ) Dot-like α-inhibin expression in UTROSCT; ( C ) Polygonal cells in UTROSCT showed Melan A positive; ( D ) SF-1 expression in UTROSCT; ( E - H ) Calretinin, α-inhibin, Melan A and SF-1 expression in AS. (×200)

This study was approved by the Ethics Board of The Second Hospital of Jilin University (Approval number: 2021106). We retrospectively collected the medical data of patients with primary uterine tumors showing sex cord-like features who attended The Second Hospital of Jilin University between 2009 and 2024. In total, nine cases of UTROSCTs, seven cases of low-grade endometrial stromal sarcomas (LGESS), two cases of adenosarcomas (AS), and one case of corded and hyalinized endometrioid carcinoma (CHEC) were retrieved. Clinicopathological parameters including patient age, main symptoms, laboratory results, ultrasound manifestations, surgical methods, and follow-up data were extracted from the original medical records. The pathological diagnoses were confirmed by two pathologists (PL.S. and M.J.) based on morphological descriptions outlined in the 2020 WHO Classification and coincidental immunohistochemical expression guidelines [ 10 ]. The diagnosis of UTROSCTs was made based on morphological features with no recognizable endometrial stromal component, and was supported by positive staining of at least two markers that are commonly positive in ovarian sex cord-stromal tumors (calretinin, α-inhibin, CD56, Melan A, CD99, or SF-1) (4, 6). Sex cord-like elements were defined as areas in which tumor cells were arranged in cords, trabeculae, tubules, clusters, sheets, or retiform patterns. Selected tumors were staged according to the criteria proposed by the International Federation of Gynecology and Obstetrics for carcinomas and sarcomas of the corpus uteri [ 11 , 12 ]. Immunohistochemistry was performed using the PT Link Pre-Treatment system (DAKO, CA, USA), the Autostainer Link 48 system (DAKO), and the Roche Benchmark XT system (Ventana, AZ, USA). CK (AE1/AE3), epithelial membrane antigen, vimentin, estrogen receptor, progesterone receptor, CD10, Wilms tumor 1 protein, desmin, smooth muscle actin, Ki67, calretinin, α-inhibin, CD56, Melan A, CD99, and SF-1 expression data, used for initial diagnosis, were retrieved from patient medical records, and some immunohistochemical staining was performed again. Detailed information on the antibodies used is presented in Table  1 . Table 1 Detailed information of antibodies Antibody Clone Source City Country Platform ER SP1 Ventana AZ USA Ventana Ki67 30-9 Ventana AZ USA Ventana PR 1E2 Ventana AZ USA Ventana CK (AE1/AE3) AE1/AE3 DAKO CA USA DAKO EMA E29 DAKO CA USA DAKO SMA 1A4 DAKO CA USA DAKO Vimentin V9 DAKO CA USA DAKO WT1 6F-H2 DAKO CA USA DAKO α-inhibin R1 DAKO CA USA DAKO Calretinin Polyclonal Zhongshan Golden Bridge Biotechnology LLC Beijing China DAKO CD10 UMAB235 Zhongshan Golden Bridge Biotechnology LLC Beijing China DAKO CD56 UMAB83 Zhongshan Golden Bridge Biotechnology LLC Beijing China DAKO CD99 HO36-1.1 Zhongshan Golden Bridge Biotechnology LLC Beijing China DAKO Desmin ZC18 Zhongshan Golden Bridge Biotechnology LLC Beijing China DAKO Melan A A103 Zhongshan Golden Bridge Biotechnology LLC Beijing China DAKO SF-1 OTI1H2 Zhongshan Golden Bridge Biotechnology LLC Beijing China DAKO EMA Epithelial membrane antigen, ER Estrogen receptor, PR Progesterone receptor, SF-1 Steroidogenic factor-1, SMA Smooth muscle actin, WT1 Wilms tumor 1 protein Detailed information of antibodies EMA Epithelial membrane antigen, ER Estrogen receptor, PR Progesterone receptor, SF-1 Steroidogenic factor-1, SMA Smooth muscle actin, WT1 Wilms tumor 1 protein Marker expression was quantified based on the extent of staining (graded on a scale of 0–4 as follows: 0, no staining; 1, 1–25% positive tumor cells; 2, 26–50%; 3, 51–75%; and 4, 76–100%) and the intensity of staining (graded on a scale of 0–3 as follows: 0, no staining; 1, weak staining; 2, moderate staining; and 3, strong staining). The final score was obtained by multiplying the extent and intensity of staining grades. Positive cases were defined as those with final scores not equal to 0. All specimens were evaluated under light microscopy by two independent pathologists (MY.L. and JM.L.). The results were analyzed exclusively for sex cord-like elements. Statistical analyses were performed using the Statistical Package for Social Sciences software, version 22.0, for Windows (SPSS, Chicago, IL, USA). Fisher’s exact test and the Mann–Whitney U test were used to analyze the differences in immunohistochemical expression between the UTROSCTs and non-UTROSCTs. A p value of < 0.05 was considered statistically significant.

Sex cord-like elements, in which tumor cells are arranged in cords, trabeculae, tubular, clustered, sheet, and retiform patterns, are rarely observed in primary tumors of the uterine corpus. In most cases, this unique morphological feature is indicative of a uterine tumor resembling an ovarian sex cord tumor (UTROSCT). In rare cases, the sex cord-like element may be a concomitant component of various non-UTROSCTs [ 1 ]. UTROSCTs are associated with uncertain biological behavior, whereas the prognosis of non-UTROSCTs is predictable and tumor-type dependent. Hence, it is important to distinguish UTROSCTs from non-UTROSCTs based on sex cord-like elements, particularly when the sex cord-like element is observed in a biopsy/curettage specimen without a conventional component. The morphological features of sex cord-like elements among different tumors are similar; thus, routine hematoxylin-eosin staining-based diagnosis is challenging. Consequently, immunohistochemical staining and genetic detection results play important roles in a differential diagnosis. According to recent studies [ 2 – 5 ], UTROSCTs characteristically harbor recurrent NCOA1-3 rearrangements with partner genes ESR1 or GREB1, and thus may have potential value in an UTROSCT diagnosis. However, molecular testing is time-consuming and expensive. Thus, the immunohistochemical profiles of sex cord-like elements among different tumors may highlight specific markers which may aid in making a differential diagnosis. The immunohistochemical profile of UTROSCTs has been previously described [ 6 – 8 ]. Compared with most uterine tumors, UTROSCTs express markers frequently expressed in ovarian sex cord-stromal tumors, including calretinin, α-inhibin, Melan-A, CD99, CD56, steroidogenic factor-1 (SF-1), and FOXL2. Nevertheless, the expression of these markers in non-UTROSCTs with sex cord-like elements remains underexplored. In 2016, Stewart et al. demonstrated that SF-1 immunochemistry is useful in differentiating between UTROSCTs and non-UTROSCTs, with 50% sensitivity and 100% specificity [ 9 ]. However, this finding was based on a small sample size, and statistical semi-quantitative analysis of marker expression was not performed. Therefore, in this study, we aimed to elucidate the clinicopathological features of UTROSCTs and non-UTROSCTs. Here, we report a series of uterine cases with sex cord-like elements, including nine UTROSCTs and non-UTROSCTs, and semi-quantitatively analyze the expression of immunohistochemical markers.

A variety of uterine tumors and non-tumorous lesions exhibit sex cord-like features. Owing to the non-specificity and rarity, sex cord-like features lead to diagnostic confusion, especially in biopsy/curettage specimens. In the current study, we described the clinicopathological features of nine UTROSCTs and ten non-UTROSCTs and semi-quantitatively analyzed the immunohistochemical expression of sex cord markers in these tumors. Immunohistochemical features of the sex cord elements in AS were most similar to those in UTROSCTs. Meanwhile, calretinin was differentially expressed between UTROSCTs and non-UTROSCTs, with higher expression in UTROSCTs. These results further revealed the immunohistochemical features of sex cord-like elements in primary uterine tumors and indicated their potential significance in differential diagnosis. UTROSCTs are associated with uncertain biological behavior. In 2017, Moore and McCluggage reported 34 cases of UTROSCTs and summarized the clinical outcomes of these patients [ 8 ]: 23.5% of the cases developed extrauterine metastasis, and the presence of necrosis and significant mitotic activity correlated with malignant behavior. Compared to UTROSCTs, the prognosis of non-UTROSCTs with sex cord-like elements is predictable. Various non-UTROSCTs exhibit sex cord-like features, including benign lesions (such as adenomyosis, endometrial polyps, and leiomyoma) and malignant tumors (such as endometrial stromal sarcoma, AS, CHEC, leiomyosarcoma, sertoliform endometrioid carcinoma, and mesonephric and mesonephric-like adenocarcinoma) [ 13 – 19 ]. The sex cord-like elements in these lesions manifest as a unique morphological pattern but do not significantly affect prognosis. The clinical outcomes of non-UTROSCTs depend on their pathological classifications. Thus, when sex cord-like elements are the only microscopically observed findings, especially in a biopsy/curettage specimen, differential diagnosis is important for subsequent treatment and prognostic prediction. Calretinin is a calcium-binding protein commonly used for the diagnosis of mesothelioma or ovarian sex cord-stromal tumors. In UTROSCTs, calretinin is positively expressed [ 6 , 20 ]; however, calretinin-negative cases have also been reported [ 21 ]. In non-UTROSCTs with sex cord-like elements, calretinin is positively expressed in AS [ 9 , 22 – 26 ], endometrial stromal tumors [ 6 , 9 , 27 ], and sertoliform endometrioid adenocarcinoma [ 15 ]. Interestingly, based on these previous reports, the positive rate of calretinin expression in the sex cord-like elements of AS is uniquely high compared with that in the other two categories [ 1 ]. Similar results were observed in the current study; in the non-UTROSCT cohort, calretinin was exclusively positive in AS. Among the six sex cord markers, calretinin was the only marker that demonstrated a statistically significant differential expression between UTROSCTs and non-UTROSCTs. This result suggests that calretinin serves as a potential marker in the differential diagnosis between UTROSCTs and non-UTROSCTs. SF-1, a nuclear transcription factor, regulates genes involved in steroidogenesis, the development of the gonads and adrenal glands, sexual differentiation, reproduction, and metabolism [ 28 ]. In 2009, Zhao et al. reported that SF-1 is the most sensitive sex cord-stromal marker among the most common types of ovarian sex cord-stromal tumors [ 28 ]. However, the expression of this marker in uterine tumors with sex cord-like elements remains poorly understood. According to previous studies, the expression rate of SF-1 ranges from 50.0% to 57.9% in UTROSCTs [ 9 , 29 ]. Consistently, in the current study, 50.0% of UTROSCT cases were SF-1 positive. The expression of SF-1 has rarely been studied in non-UTROSCTs with sex cord-like elements. In 2016, Stewart et al. analyzed the immunohistochemical expression of six UTROSCT and 10 non-UTROSCT lesions with sex cord-like elements, and demonstrated that none of the non-UTROSCT lesions were SF-1 positive [ 9 , 29 ]. Based on this finding, Stewart et al. indicated that SF-1 is a specific marker for differential diagnosis. However, in the current study, SF-1 was strongly positive in the sex cord-like elements of AS. Thus, SF-1 expression may not accurately distinguish UTROSCTs from non-UTROSCTs with sex cord-like elements. In the current study, we found that the immunohistochemical profile of sex cord-like elements in AS was similar to that in UTROSCT. UTROSCT and AS were exclusively positive for CK (AE1/AE3), calretinin, Melan A and SF-1. The stromal elements of Müllerian AS in the uterine corpus, cervix, and ovary may present with sex cord-like features, and in some cases, the sex cord-like elements may show extensive overgrowth [ 9 , 22 – 26 , 30 , 31 ]. Based on previous reports, in most cases, calretinin and inhibin are positively expressed in sex cord-like elements. This finding is similar to that of the current study. Molecularly, a part of UTROSCTs harbor an ESR1-NCOA2 rearrangement [ 2 , 3 ]. This rearrangement was also observed in one AS with sex cord-like elements [ 32 ]. Although the number of studies is limited, the observed similarities between UTROSCTs and AS warrant further exploration. Our study has some limitations. First, this was a single-center study, which might have resulted in poor representativeness. Second, because uterine tumors with sex cord-like elements are rarely observed, the sample size in the present study was small. The limited sample size may have introduced biases and affected the accuracy of the obtained results. Nonetheless, we demonstrated that calretinin expression is significantly higher in UTROSCTs than in non-UTROSCTs. This finding suggests that calretinin serves as a potential key marker in the differential diagnosis of UTROSCTs and non-UTROSCTs. However, so far, no single immunohistochemical marker could distinguish UTROSCT from other non-UTROSCT tumors with sex cord-like elements specifically. Accurate diagnosis relies on thorough histological examination and the expression of series-related markers. However, for some indeterminate cases, molecular tests for specific genes may be conclusive for the diagnosis. We also demonstrated that the immunohistochemical profile of sex cord-like elements in AS is similar to that in UTROSCTs. This finding indicates a possible connection between these two tumor types. Considering the rarity of sex cord-like elements in uterine tumors, further studies with larger sample sizes are needed to confirm the current study results.