Malignant non-epithelial tumors of the ovary include germ cell tumors and mesenchymal tumors of the sex cords, which are distinctly different from malignant epithelial tumors of the ovary. Most are young patients, most are early at presentation, and most are unilateral, have significant tumor markers or produce variable amounts of steroid hormones, and are mostly sensitive to chemotherapy. Fertility preserving surgery involves unilateral adnexal resection (or in some cases, ovarian cyst removal) with preservation of the normal contralateral ovary and/or uterus and is suitable for most young patients. These tumors are most often early in presentation and rarely metastasize to lymph nodes, making a full staging procedure that does not include pelvic lymph node dissection feasible. Although these tumors are sensitive to chemotherapy, there is no consensus on whether to supplement adjuvant chemotherapy directly after surgery or to wait for recurrence before receiving chemotherapy in early stage patients due to the immediate and long-term toxic side effects of chemotherapy, and further research is needed. Malignant non-epithelial tumors of the ovary account for no more than 10% of all malignant tumors of the ovary, with germ cell tumors most commonly seen in adolescents with an annual incidence of approximately 3.7 per million women and interstitial tumors of the sex cords most commonly seen in adults with an annual incidence of approximately 2.1 per million women. Primary non-epithelial tumors are most often seen in specific cells from the ovary (germ cells, granulosa cells, vesicular cells, mesenchymal cells, and steroid cells), whereas other gonadal tumors arise from non-specific cells of the ovary. Regardless of the type of tumor, the surgical management of young patients with pelvic masses focuses on frozen section examination of ovarian tumors, which should most satisfactorily be available to an experienced gynecologic pathologist, although, of course, the most specialized pathologists may not always be able to provide an accurate frozen section diagnosis. However, frozen section examination can provide the surgeon with specific decisions to be made during the procedure, especially in younger patients. Fertility-preserving procedures involving unilateral adnexal resection (or ovarian cyst removal in some cases) with preservation of the normal contralateral ovary and/or uterus are appropriate for most young patients with a recent diagnosis. Malignant germ cell tumors of the ovary of any stage, interstitial tumors of the sex cords of any stage, tumors of low malignant potential of any stage, and epithelial ovarian cancer of stage IA are suitable for fertility-preserving surgery. The choice of surgical procedure usually depends on what is seen on the preoperative examination. If the mass is small and there are no other abnormalities on imaging or physical examination, a less invasive laparoscopic procedure may be chosen. Of course, it is possible to switch from laparoscopy to open surgery if there are any intraoperative indications. On the other hand, if the ovarian mass is large or if there is an obvious extra-ovarian tumor suggesting advanced disease, open surgery should be chosen at the outset. However, the choice of surgical approach should take into account the possibility of tumor rupture and the possibility of converting stage IA to stage IC, thus potentially requiring adjuvant therapy. Regardless of the surgical approach, during surgery, a careful laparotomy is required. Staged surgery includes a large omental resection + biopsy of the diaphragmatic apex peritoneum, lateral colonic sulcus, and pelvic peritoneum + retention of abdominal irrigation fluid, and there is no consensus on whether to perform pelvic lymph node dissection. However, in patients with significant lymph node abnormalities, lymph node dissection should be performed. Malignant germ cell tumors of the ovary Malignant germ cell tumors of the ovary can be divided into 2 categories: anaplastic and non-anaplastic, the latter including yolk cystic tumors, immature teratomas, mixed germ cell tumors, choriocarcinoma, embryonal carcinoma, and gonadoblastoma, see Table 1. germ cell tumors are almost always unilateral, except for anaplastic tumors, which are bilateral in 10%-15% of cases. Because of the sensitivity of these tumors to chemotherapy and the increasing use of fertility-preserving surgery, a correct pathologic diagnosis is critical. Again, because of the rare nature of these tumors, it is always necessary for an experienced pathologist to re-read the pathology slides to confirm the diagnosis. Table 1. Classification of malignant germ cell tumors (MOGCTs) of the ovary Asexual cell tumor dysgerminoma Endodermal sinus tumor Immature teratoma Mixed germ cell tumor Choriocarcinoma Choriocarcinoma Embryonal carcinoma Polyembryomas Gonadoblastoma Gonadoblastoma MOGCTs At diagnosis, 60% to 70% are early stage, and stage I patients have an excellent prognosis, with long-term disease-free survival in the upper 90%. The recurrence rate in this group of patients is relatively low, about 15-25%, and successful treatment is also more often obtained when recurrence occurs. The prognosis for patients with advanced disease is relatively poor, with a treatment failure rate of at least 25-30%. Because MOGCTs are extremely sensitive to chemotherapy and easily amenable to fertility-preserving surgery, conservative treatment with unilateral adnexal resection and/or surgical staging is appropriate, and most gynecologic oncologists do not routinely remove apparently normal lymph nodes. For bilateral tumors, rather than performing bilateral adnexal resection, it may be better to consider an oophorectomy on one side and cyst excision on the other or bilateral ovarian cyst excision in an attempt to preserve a portion of the normal ovary. It has been suggested that treatment guidelines include collection of ascites or peritoneal washings for cytology, examination of the peritoneal surface and retroperitoneal lymph nodes, and sampling or excision of the abnormal area. This consideration is particularly relevant to the management of patients who are seen by gynecologic oncologists after inappropriate surgical staging. One study reported three patients with apparently stage IA pure anaplastic cell tumors who had recurrence after inappropriate staging and no adjuvant chemotherapy, all of whom were cured with remedial therapy, which seems to suggest that close surveillance is a reasonable alternative to surgical restaging. Whether this approach can be extrapolated to the management of other subtypes of MOGCTs remains unclear. Certainly, the deciding factor between restaging surgery or close monitoring should be the findings on imaging. Stage IA anaplastic cell tumors can be cured by surgery alone. stage IA highly differentiated immature teratomas do not require further adjuvant chemotherapy after appropriate surgical staging; the need for adjuvant chemotherapy in patients with stage IA intermediate-low differentiation and stage IB-IC is controversial. Some published data suggest that immature teratomas of any differentiation can be followed closely after surgical treatment to preserve reproductive function, and only those patients with proven recurrence after surgery are then treated with chemotherapy. However, this idea has not been widely accepted. Overall, the therapeutic role of chemotherapy in stage IA-IB anaplastic cell tumor-like ovarian GCTs remains controversial. The rationale for caution in postoperative chemotherapy is to avoid the myriad of acute reactions, as well as the long-term side effects after chemotherapy, including secondary leukemia or premature ovarian failure. Chemotherapy itself has been reported to cause premature ovarian failure in up to 30% of cases. For patients with a moderate risk of relapse requiring chemotherapy, it is feasible to consider starting chemotherapy at the time of relapse in order to avoid the side effects of chemotherapy. Chemotherapy is most often used with the BEP regimen. Even in patients with advanced disease, fertility-preserving surgery can be performed with a cure rate of >95%. Because the tumor is highly sensitive to chemotherapy, it is not necessary to perform overly extensive surgical operations, although the maximum possible removal of the naked eye tumor should be performed. BEP is the most commonly used chemotherapy regimen and the duration of treatment is controversial, but, usually, 3 courses of chemotherapy are possible in patients with complete tumor removal; for patients with residual naked eye tumor still present, 4-5 courses of chemotherapy are appropriate. Only after 3 courses, bleomycin (BLM) should be discontinued to reduce pulmonary toxicity. Asexual cell tumors are extremely sensitive to radiotherapy; however, because radiotherapy impairs fertility, it is only indicated for select patients. Of 64 patients with stage I-III malignant germ cell tumors treated with conservative surgery and chemotherapy, 38 attempted pregnancy, of which 29 (76.3%) had at least 1 pregnancy. Overall, for patients with MOGCTs, unilateral adnexal resection with preservation of the contralateral ovary and uterus is now considered to be the appropriate surgical treatment. Even in patients with advanced disease, unilateral adnexal resection with preservation of the contralateral ovary and uterus is appropriate due to the chemotherapy sensitivity of this tumor. Ovarian biopsy is not required when there are no abnormal findings on visual examination of the contralateral ovary. The stage of the disease is an important prognostic factor; however, the prognosis is good even for advanced disease due to sensitivity to chemotherapy. Interstitial tumors of the ovarian gonads and steroid cell tumors The classification of interstitial tumors of the gonads and steroid cell tumors is shown in Table 2. they produce unequal amounts of steroids, those with a gonadal component are malignant, and granulosa cell tumors are the most common histologic type. Most of the pure ovarian mesenchymal tumors are benign, and more than 50% are fibroids. Unlike GCTs, SCSTs and SCTs have a wider age range of onset, mostly in the perimenopausal and postmenopausal periods, however, there is often a more restricted age range of onset for specific tumor types. Because most patients are often young and most have unilateral lesions, a correct diagnosis is necessary for any patient with a fertility requirement in order to decide on treatment and preserve fertility. Table 2 Classification of interstitial tumors of the sex cord and steroid cell tumors Ovarian stromal tumors with sex cord elements Adult granulosa cell tumor Juvenile granulosa cell tumor cell tumor Support-testis type mesenchymal cell tumors Sertoli-Leydig cell tumors Gynandroblastoma Gynandroblastoma Sex cord tumor with annular tubules OtherOthers Pure mesenchymal tumors stromal tumors Follicular meningioma thecoma plain typetypical lutenized nuclear division active mitotically active fibrosarcoma plain typetypical cellular nuclear division active mitotically active fibrosarcoma fibrosarcoma Other ovarian stromal tumors Ovarian stromal tumor with minor sex cord elements Sclerosing stromal tumor Signet-ring stromal tumor Microcystic stromal tumor Ovarian mucinous tumor Ovarian myxoma Mesenchymal-testicular stromal cell tumor Steroid cell tumors Mesenchymal luteoma Stromal luteoma Testicular-type mesenchymal cell tumor Leydig cell tumor Steroid cell tumor Steroid cell tumor 60% to 95% of the disease is early at diagnosis. There is a general consensus in the management of SCSTs that lymph node dissection is not routinely required in the initial surgery because the chances of retroperitoneal lymph node metastasis in early stage patients are extremely low. Unilateral adnexal resection and surgical staging are appropriate treatments for women of childbearing age, and lymph node dissection can be omitted during staging. For patients with early SCSTs, there has been controversy as to whether to proceed with postoperative treatment. To date, the relative benefit of adjuvant chemotherapy has not been demonstrated, and some authors suggest that adjuvant therapy is recommended for stage IC with a high mitotic index, and that 3 to 4 courses of platinum-based chemotherapy (most commonly BEP regimens) may be considered, but that combination chemotherapy only moderately improves the prognosis of malignant disease. In patients with granulosa cell tumors, endometrial curettage must be performed to exclude endometrial carcinoma. prognosis after surgical treatment of granulosa cell tumors in stage IA is excellent and no adjuvant therapy is required postoperatively. The typical features of juvenile granulosa are the young age of the patient at diagnosis (80% of patients are younger than 20 years at diagnosis), the unilateral nature of the lesion, and the excellent overall prognosis when the lesion is confined to the ovary. Most patients are stage IA or IB at diagnosis, and unilateral adnexal resection and conservative staging are recommended. Support-mesenchymal cell tumors are often of low malignancy, but postoperative adjuvant chemotherapy should be performed in patients with stage I hypodifferentiation or with a heterogeneous component. Postoperative chemotherapy should also be administered to steroid cell tumors that are pleomorphic, have an active nuclear division count, large tumor size, or are advanced. Patient’s age, stage of disease and tumor size are factors that affect the survival of SCSTs; young and early is the most important factor to improve the prognosis, and tumor ≥10 cm is a poor prognostic factor. We had 40 cases of ovarian support-mesenchymal cell tumors (SLCTs) with a median age of 28 years, all tumors were confined to the unilateral ovary, including 1 cystectomy, 27 unilateral adnexal resections (13 of which underwent complete staging: omentectomy + appendectomy + pelvic lymph node dissection), and 12 total hysterectomy with double adnexa. 57.5% of the patients (23/40) received postoperative chemotherapy, and no cases were treated. 57.5% (23/40) of the patients received postoperative chemotherapy, and no case recurred. Except for one patient who died of diabetic nephropathy and three who were lost to follow-up, only two patients with stage IC hypofractionation relapsed and achieved complete remission again after reoperation and chemotherapy. The results of this study suggest that SLCTs have a good prognosis, that conservative surgery is acceptable for young patients who wish to preserve their fertility, and that tumors that are large (>10 cm in diameter), ruptured (stage Ic) and hypofractionated without endocrine changes may have a higher biological behavior of malignancy. Highly differentiated SLCTs were benign and recurrence-free; the malignancy rates were 11% and 59% for moderately and poorly differentiated, respectively, with 10-year survival rates of 87% and 41%, respectively. Response assessment and follow-up Serum tumor markers (hCG, AFP, LDH, CA125, and inhibin) may be associated with tumor response during chemotherapy. In particular, inhibin is secreted by granulocytic tumors and is a useful tumor marker with decreased levels after tumor resection and, also, a marker of tumor recurrence. CA125 is not high in GCTs but, sometimes, is useful in finding recurrence in patients within the normal range of AFP/b-hCG. Pelvic-abdominal and thoracic CT and pelvic ultrasound are the most common and useful imaging tests to assess chemotherapy response in patients with measurable disease. Approximately 75% of recurrences of GCTs occur within the first year after initial treatment; the most common site is the abdominal cavity, with retroperitoneal lymph nodes being less common. Conversely, SCSTs with a lazy nature tend to relapse late (median time to relapse of 4-6 years) and require long-term follow-up. Recurrences of up to 37 years have been reported more than 20 years after diagnosis. The most common sites of recurrence are the upper abdominal cavity (55% to 70%) and the pelvis (30% to 45%). Follow-up includes history, physical examination, pelvic examination and measurement of tumor markers every 3 months for 2 years and then every 6 months for life or until recurrence. For patients who have undergone fertility preserving surgery, pelvic ultrasound should be performed every 6 months, however, the need for CT of the pelvic and abdominal cavity is often determined based on clinical indications. The use of PET scans for outcome assessment or follow-up is inconclusive.