A 63-Year-Old Woman With Chronic Pelvic Pain

A 63-year-old woman presented with chronic pelvic pain refractory to medical treatment. Physical examination revealed a 12-week size fibroid uterus with normal tubes and ovaries. Hysterectomy with bilateral salpingo-oopherectomy was performed. Grossly, the uterus was bosselated and weighed 497 g. The myometrium showed multiple, circumscribed, tan nodules ranging in size from 0.5 to 11.0 cm in maximal diameters with tan, fish-flesh cut surface (Figure 1). Microscopic examination of the largest nodule showed a well-circumscribed tumor located within the myometrium (Figure 2). The tumor showed 2 different patterns, trabecular and whorled (Figure 3). The trabecular pattern consisted of epithelioid cells arranged in anastomosing cords (Figure 4, a). The whorled pattern consisted of spindle cells with fusiform nuclei and scant cytoplasm (Figure 4, b). No significant cellular atypia or mitotic activity was noted in both the spindle and epithelioid components of the tumor. The stroma varied from hyalinization to cellular fibroblastic proliferation. Immunohistochemistry results were positive for vimentin, CD10, CD99, and cytokeratin. Results for smooth muscle actin, epithelial membrane antigen, desmin, and inhibin were negative.What is your diagnosis?Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are an unusual group of stromal neoplasms exhibiting sex cord differentiation, which resemble ovarian granulosa or Sertoli cell tumors. The grossly well-circumscribed tumors microscopically consist of endometrial stroma and sex cord–like epithelial elements represented by anastomosing cords, nests, and trabecular ribbons. UTROSCTs are divided into 2 groups based on predominance of the stromal (group 1) or epithelial (group 2) component. Immunohistochemically, the tumor cells are generally positive for mesenchymal or stromal markers (vimentin, desmin, CD10, and estrogen and progesterone receptors), epithelial markers such as cytokeratin and epithelial membrane antigen, and sex cord differentiation markers (inhibin and CD99). The morphologic features and clinical information can be used to differentiate UTROSCT from low grade endometrial stromal sarcoma, adenosarcoma, carcinosarcoma, and metastatic ovarian sex cord tumor. UTROSCT, a low malignant potential neoplasm, can recur in approximately 15% of cases 2 to 12 years after hysterectomy.Uterine tumor resembling ovarian sex cord tumors (UTROSCTs) are rare tumors and were first described by Clement and Scully in 1976.1 Before the coining of this entity, such tumors were interpreted as granulosa cell tumor. In the original report, Clement and Scully performed a clinicopathologic evaluation of 14 cases. The cases were divided into 2 groups on the basis of predominance of the stromal or epithelial-like component. Those in group 1 (stromal predominance) were identical in appearance to endometrial stromal tumors except for the focal intratumorous presence of epithelial-like elements arranged in trabeculae, cords, nests, and tubules. Those in group 2 were predominantly or entirely epithelial in appearance, lacking an obvious stromal component and resembling ovarian sex cord tumors.1Clinically, UTROSCTs occur in middle-aged women; the average age is around 50 years. The main symptoms are abnormal bleeding or pelvic pain. Most patients have enlarged uteri or palpable uterine masses.2Macroscopically, UTROSCTs are solid, round, well-circumscribed masses (mean diameter, 5.7 cm). Occasional tumors are submucosal or subserosal and may be polypoid. Rare tumors are predominantly cystic. The cut surfaces are yellow, gray, or tan; soft; and fleshy without the whorled pattern of a leiomyoma.3The microscopic picture is variable. UTROSCTs are characterized by a variety of epithelial and stromal patterns resembling ovarian sex cord tumors, especially granulosa cell and Sertoli cell tumors including the retiform-type tumors. These patterns include anastomosing cords, small nests, and sertoliform tubular structures. Occasionally, Call-Exner–like bodies may be present. The neoplastic epithelioid cells in the sex cord–like areas range from small and round with scanty cytoplasm to large cells with abundant eosinophilic, clear, or foamy cytoplasm. The small uniform nuclei display rare or absent nuclear grooves and indistinct nucleoli. Mitotic figures are rare. The sex cord–like elements are separated by a scant to abundant stroma that may be hyalinized and vary from moderately cellular to hypocellular.3Immunohistochemically, UTROSCTs may express epithelial, stromal, and smooth muscle markers suggesting divergent differentiation.4 In a study by Baker et al5 to determine whether the sex cord–like elements of these tumors show immunohistologic evidence of sex cord differentiation, inhibin and CD99 expression were evaluated in 5 UTROSCTs. They found 100% (5/5) immunoreactivity for inhibin and CD99. Inhibin is a peptide hormone expressed by normal ovarian granulosa cells and ovarian sex cord neoplasms. CD99 is a protein expressed by granulosa cells, Sertoli cells, and some ovarian sex cord neoplasms. An immunohistochemical analysis of 7 UTROSCTs by Oliva et al6 showed less frequent inhibin expression in the sex cord–like elements than in other studies. Inhibin expression was positive only in 1 case, whereas CD99 expression was positive in 4 of 7. The other markers tested were desmin, positive in 5 of 7; h-caldesmon, negative in all; and CD10 and keratin, positive in 5 of 7. The absence of h-caldesmon in UTROSCT helps separate them from epithelioid smooth muscle tumors. CD10 is a reliable marker for normal endometrial stroma as well as for endometrial stromal nodules.4 Sullinger and Scully7 in one of the largest series of UTROSCTs reported 18 of 21 cases positive for vimentin and 13 of 20 positive for keratin. Hence to summarize, the tumor cells are generally immunoreactive for mesenchymal (eg, vimentin, desmin), epithelial markers (eg, cytokeratin, epithelial membrane antigen), sex cord differentiation markers (inhibin, CD99), CD10, and estrogen and progesterone receptors.3 Results for expression of epithelial membrane antigen are negative in sex cord neoplasms such as germ cell tumors and Sertoli cell tumors, and smooth muscle actin stain is classically negative in neoplasms of epithelial origin.The main differential diagnoses include low grade endometrial stromal sarcoma, adenosarcoma, carcinosarcoma, and metastatic ovarian sex cord stromal tumor. The low grade endometrial stromal sarcoma exhibits a unique infiltrative growth pattern and sometimes contains a few scattered glands that are less than 10% of the area under inspection. Adenosarcoma consists of numerous cystically dilated glands with a cambium layer evenly distributed throughout the lesion. Carcinosarcoma has a high grade stromal component with heterologous differentiation. The clinical picture can be of help in differentiating metastatic ovarian sex cord stromal tumors.8UTROSCTs are considered to be tumors with low malignant potential. Recurrence develops in approximately 15% of cases at intervals of 2 to 12 years after hysterectomy. Features predictive of recurrence include serosal rupture, vessel invasion, stromal predominance, and cytologic atypia.3