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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 1  |  Page : 290-294

Ovarian sertoli–leydig cell tumors: A multicenter long-term clinicopathological analysis of 27 patients


1 Department of Obstetrics and Gynecology, Ege University Medical School, Izmir, Turkey
2 Department of Gynecologic Oncology, Tepecik Education and Research Hospital, Izmir, Turkey
3 Department of Division of Medical Oncology, Ege University Medical School, Izmir, Turkey
4 Department of Pathology, Ege University Medical School, Izmir, Turkey

Date of Web Publication13-Apr-2016

Correspondence Address:
Levent Akman
Department of Obstetrics and Gynecology, Ege University Medical School, Bornova, Izmir
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.158037

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 > Abstract 


Aim: Information on the clinical behavior of ovarian Sertoli–Leydig cell tumors (SLCTs) as well as its prognostic factors and optimal management is limited due to a substantially low incidence of the disease. Also, limited data is available regarding the role of chemotherapy in the management of SLCTs. The aim of the study is to evaluate clinicopathological features and outcome of patients with ovarian SLCTs.
Materials and Methods: Twenty-seven patients with SLCT treated at two centers were reviewed retrospectively during 21 years.
Results: The median age was 45 years (range, 16–81) and the mean follow-up time was 86 months (range, 16–181). Twenty-three patients had stage IA, three patients had IC, and one patient had stage II disease. Eleven tumors (41%) were well-differentiated and 16 (59%) tumors were intermediately differentiated. Nine patients underwent unilateral salpino-oophorectomy and one patient, with a history of infertility, underwent cystectomy for fertility preservation. Eight patients with intermediately differentiated types of SLCT received adjuvant systemic chemotherapy including the combination bleomycin, etoposide, and cisplatin (BEP). Recurrence occurred in one patient with intermediated differentiated type SLCT with heterologous elements. She received four cycles of BEP chemotherapy. Twelve months later, she underwent cytoreductive surgery and received six cycles of cisplatin plus carboplatin. She died 24 months after the initial diagnosis.
Conclusion: SLCTs of the ovary are usually in early stage, unilateral, and benign. Fertility-sparing surgery is the preferred option in young women. In the adjuvant treatment setting, although information about chemotherapy is limited, BEP is a commonly used regimen. The degree of differentiation and the presence of heterologous elements relate to a poor prognosis.

Keywords: Ovarian tumor, prognostic factors, Sertoli-Leydig cell tumor, sex-cord stromal tumor


How to cite this article:
Akman L, Ertas IE, Gokcu M, Terek MC, Sanci M, Sanli UA, Zekioglu O, Ozsaran AA. Ovarian sertoli–leydig cell tumors: A multicenter long-term clinicopathological analysis of 27 patients. J Can Res Ther 2016;12:290-4

How to cite this URL:
Akman L, Ertas IE, Gokcu M, Terek MC, Sanci M, Sanli UA, Zekioglu O, Ozsaran AA. Ovarian sertoli–leydig cell tumors: A multicenter long-term clinicopathological analysis of 27 patients. J Can Res Ther [serial online] 2016 [cited 2019 Dec 15];12:290-4. Available from: http://www.cancerjournal.net/text.asp?2016/12/1/290/158037




 > Introduction Top


Sertoli–Leydig cell tumors (SLCTs) of the ovary account for less than 1% of all primary ovarian neoplasms. These tumors are classified under sex cord-stromal tumors of the ovary.[1] SLCT occurs in all age groups, but most are common in young women with an average age of 25 years.[2],[3] Patients present with abdominal pain and hormone-related (androgenic or estrogenic) symptoms. The tumor is usually unilateral with sites varying from 0.8 to 30 cm. Macroscopic appearance is solid mass with smooth external surface; the mass may be slightly lobulated. The cut surface of the mass reveals yellow-tan to bright yellow in appearance.[4] SLCTs are characterized by presence of testicular structures that produce androgens. Androgens may cause virilization; however, not all these tumors are functionally active. SLCTs are divided into well-differentiated, intermediate differentiated, poorly differentiated, with heterologous elements, retiform, and mixed types.[5]

Surgery is the cornerstone of treatment for patients with SLCT. As these tumors are found at an early stage and in young women, fertility sparing surgery is usually preferred. The majority of these tumors are classified as stage I at the time of diagnosis. Stage and grade of the disease are important prognostic factors for disease recurrence. Postoperative platinum-based chemotherapy is indicated in metastatic tumors and in poorly differentiated SLCTs or SLCT with heterologous elements.[6]


 > Materials and Methods Top


The hospital records of patients with the diagnosis of ovarian SLCT in two centers (Ege University Medical School and Tepecik Education and Research Hospital) between January 1, 1991 and December 31, 2012 were reviewed retrospectively. The clinical data obtained from patients' records included age, type of surgery, histological type of tumor, adjuvant therapy, recurrence, treatment after recurrence, and mortality.

All patients were staged according to the older International Federation of Gynecology and Obstetrics (FIGO) 1998 staging system. Staging procedure for ovarian tumor included peritoneal washings for cytology, total hysterectomy with bilateral salpingo-oophorectomy, peritoneal biopsies, omentectomy, and pelvic and paraaortic lymph node dissection. Unilateral salpingo-oophorectomy or cystectomy is preferred for patients desiring fertility.


 > Results Top


Twenty-seven patients with SLCT were treated at two centers during 21 years. Clinical and pathological features are summarized in [Table 1]. The median age of the patients was 45 years (range, 16–81). Of the 27 patients, 14 (51%) were in the 2nd and 3rd decades of life. The most common symptom was pelvic pain or mass (57%) in these patients. Menstrual abnormality/postmenopausal vaginal bleeding occurred in nine patients (33%). Only four patients presented with virilization symptoms (14%). Serum CA-125 level was measured in all patients and elevated CA-125 level (> U/ml) was observed in four patients. Serum alpha-fetoprotein (AFP) levels were measured in 12 patients and found to be elevated in two patients (> ng/ml).
Table 1: Summary of clinical and pathological features of the patients

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Ten patients were older than 50 years and in postmenopausal period. Six patients had postmenopausal bleeding and preoperative endometrial curettage was performed. Histopathological examination of endometrial curettage specimens revealed simple hyperplasia without atypia in two patients, endometrial polyp in two patients, and endometrioid endometrial adenocarcinoma grade 1 in two patients. Endometrial hyperplasia and carcinoma were confirmed in the hysterectomy specimens after surgery.

All tumors occurred in one ovary (15 right ovary and 12 left ovary). Of the 27 patients; 23 patients had stage IA, three patients had IC, and one patient stage II of the disease. The mean tumor size was 10.7 cm (range, 1–35). Eleven tumors (41%) were well-differentiated and 16 (59%) tumors were intermediately differentiated. None of the patients had poorly differentiated tumors. Of the 16 patients with intermediate differentiated SLCT, three (11%) had heterologous elements and one (3%) retiform pattern. Heterologous elements were confined to the carcinoid component in one patient; gastrointestinal mucinous epithelium component in one patient; and mucinous, carcinoid, and cartilage components in one patient. Disgerminoma was synchronously found in one patient with heterologous element SLCT. Histopathological images showing heterologous components of SLCTs in [Figure 1].
Figure 1: Histopathological images showing heterologous components of SLCTs. (a) Neuroendocrine cells with hyperchromatic nucleus and narrow cytoplasm (H and E, ×20). (b) Heterologous elements with a chondroid matrix (H and E, ×10). (c and d) Mucinous epithelium showing intestinal-type glandular structure (H and E, ×10) and (H and E, ×4). SLCTs = Sertoli–Leydig cell tumors, H and E = hematoxylin and eosin

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Surgery was performed in all patients. Seventeen patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Ten of them underwent additional staging surgical procedures. Nine patients underwent unilateral salpingo-oophorectomy and four of them underwent additional surgical procedures. One patient with a history of infertility underwent cystectomy for fertility preservation.

Postoperatively, eight patients with intermediately differentiated types of SLCT received adjuvant systemic chemotherapy including the combination bleomycin, etoposide, and cisplatin (BEP). Two patients with SLCT who also had endometrial cancer received adjuvant pelvic radiotherapy.

The mean follow-up time was 86 months (range, 16–181). Recurrence took place in one patient. Total abdominal hysterectomy and bilateral salpingo-oophoretcomy had been performed during primary surgery. Final histopathological examination revealed stage II SLCT of intermediated differentiated with heterologous elements. Heterologous elements confined carcinoid, mucinous, and cartilaginous components. She received four cycles BEP chemotherapy. Twelve months later, cytoreductive surgery was performed due to pelvic recurrences including small bowel metastasis. Histopathological results revealed carcinoid component metastasis of the SCLT. After operation she received six cycles of cisplatin plus carboplatin. She died 24 months after the initial diagnosis.


 > Discussion Top


SLCTs of the ovary, account for less than 1% of all primary ovarian neoplasms. Information on the clinical behavior of SCLT, as well as its prognostic factors and optimal management, is limited due to the substantially low incidence of the disease.

SLCT is characterized by presence of testicular structures in its content that cause androgen production. SLCT's are unilateral in 98% of the patients. They commonly produce androgens and androgen precursors. They are generally associated with symptoms of androgen excess such as hirsutism, acne, seborrhea, and oligomenorrhea-amenorrhea. In more serious cases, clitoris hypertrophy, deepening of the voice, and a reduction in breast volume can be seen. At least one-third of the cases may experience these symptoms.[7] All of the patients in our series were unilateral. Hyperandrogenism-related complaints were present in 48% of patients. Of these patients, four (36%) had well-differentiated and nine (56%) had moderately differentiated tumors. Similar to the series of O'Hern et al.,[8] and Roth et al.,[2] virilizing changes increased in paralleled to the increase in differentiation. Virilizing changes with the degree of differentiation were reported conversely related in the series of Gui et al.,[9] while in some studies it was not even mentioned. Three patients who applied to the hospital for complaints of virilizing-hirsutism were in postmenopausal period. SLCT should be kept in mind for incipient virilizing complaints in postmenopausal period, as in our patient group. Rarely, these tumors may secrete both androgen and estrogen. In our series as well, endometrial cancer was identified in two cases. Moderately differentiated tumors were observed to have larger tumor diameter.

Patients usually present with abdominal pain and abdominal bloating, if no clinical hormonal symptoms occurred. In the majority of symptomatic patients, the mass can be palpated. It can reach larger sizes. In our series, there was a tumor 35 cm in diameter. Fifty-seven percent of patients also presented with the complaints of pelvic pain and pelvic mass. Therefore, SLCT should be considered in young women with complaints of oligomenorrhea-amenorrhea, especially when large pelvic mass is detected before the operation.

More than 90% of patients are stage 1 and the majorities are moderately differentiated tumors at time of diagnosis.[10] The study by Bhat et al.,[10] has reported the ratio of well- and moderately differentiated tumors in stage 1A as 85.7 and 75%, respectively. For poorly differentiated tumors, more than 50% of the cases are under stage 1C. In our series, poorly differentiated tumors were not detected. Similar to the case series in the literature, moderately differentiated tumors accounted for the majority of case in our series.[1],[6],[7],[9] Well-differentiated tumors were all stage 1. Moderately differentiated tumors comprised 68% of the patients, and 75% were in stage 1A. Retiform patterns were observed in one case of moderately differentiated SLCT, whereas heterologous elements were detected in three cases.

Diagnosis may be delayed in some patients due to asymptomatic or nonspecific clinical symptoms. Advanced imaging methods can be utilized, especially in patients with small tumor size. Serum testosterone levels should be checked in case of clinical suspicion. In some patients, concomitant other ovarian tumors may occur simultaneously. In our series, simultaneous dysgerminoma was detected in one case.

Although there is no standard guideline in therapy, the gold standard is surgical removal of the mass. Well-differentiated tumors are almost always benign and unilateral; therefore unilateral salpingo-oophorectomy is adequate, especially in patients who would like to preserve fertility.[10],[11] For moderately and poorly differentiated tumors, standard staging surgery should be performed.[10] In these tumors, lymph node metastasis is very rare. Therefore, the need for pelvic lymphadenectomy is controversial. It is recommended in the literature, not to include lymphadenectomy in staging if intraoperative frozen section diagnosis was achieved.[9] Usually laparotomy is the favored surgical procedure. However, today, a laparoscopic approach can be considered in the management of early stage ovarian cancers as well. In some studies, increased cysts rupture and related disease-free survival (DFS) and overall survival (OS) decreases are reported with a laparoscopic surgery approach.[12],[13],[14] However, some studies have indicated no difference regarding ruptured cysts by laparoscopic surgery, which can provide better visibility and comparable lymph node sampling success in comparison to laparotomy.[15],[16],[17],[18] Litta et al.,[19] have reported no recurrence and port site metastasis in 3-year follow-up of their SCLT patients with laparoscopic surgery. In their 21 cases of SCLT, Sigismondi et al.,[6] have performed laparoscopic surgery in five patients and observed port site metastasis in one case.

Information on using adjuvant chemotherapy after surgery of SLCT is limited. The benefits of adjuvant chemotherapy have not been shown in clinical trials, and the most appropriate treatment regimen is still uncertain. Although there is no standard postoperative regimen, platinum-based chemotherapy is recommended in the National Comprehensive Cancer Network (NCCN) guidelines.[20] Adjuvant chemotherapy is recommended for patients other than stage 1, with moderately or poorly differentiated tumors or tumors containing heterologous elements. Currently BEP chemotherapy is frequently used as an adjuvant therapy in SLCT. In the series by Gui et al.,[9] DFS showed no significant difference between patients with moderately or poorly differentiated tumors whether chemotherapy was given or not. Moreover, their two patients with recurrence, were part of the group receiving chemotherapy. Therefore, benefit of adjuvant chemotherapy is limited, with the most benefit to patients with recurrences.[9] Because of the rarity of the disease, there is lack of consensus on management of recurrent SLCT. In cases with evidence of local recurrence, further surgery should be considered which, in cases with metastasis, should be followed by chemotherapy or irradiation. Lim et al.,[21] reported that tumors completely responded to second-line chemotherapy with paclitaxel and carboplatin after recurrence. In our case, 12 months later, cytoreductive surgery was performed due to pelvic recurrences including small bowel metastasis. After the operation, she received six cycles of cisplatin plus carboplatin. She died 24 months from the initial diagnosis.

The rate of transformation into malignancy was 11% in the poorly differentiated, while 59% in moderately differentiated tumors.[22] In our series, three moderately differentiated cases were determined as stage 1C, and one case as stage II. In SLCT, recurrence usually occurs during the 1st year, only 7% of recurrences can be observed after 5 years. Major sites of recurrence are abdominal cavity and retroperitoneal lymph nodes.[23]

The degree of differentiation of the tumor and whether it contains heterologous components or not is important prognostic factors. A variety of heterologous elements can be observed in 20% of SLCT cases.[1],[2] The most common heterologous element observed in SLCT is benign gastrointestinal-type epithelium.[2] In addition, the tumor may contain carcinoid tumor, endodermal elements, and mesenchymal elements, that are mainly immature skeletal muscle or cartilage.[2],[24],[25],[26] The presence of immature skeletal muscle cells and to a lesser degree immature cartilage appears to be a poor prognostic variable.[26] Prat et al.,[25] in their series with heterologous mesenchymal elements containing skeletal muscle and/or cartilage elements, have reported rapid pelvic and abdominal recurrence (3–15 months), and most of these patients died in the postoperative 5 months to 7 years period. In our series, recurrence was observed only in one patient (3%) having moderately differentiated tumor containing heterologous elements of mucinous, carcinoid, and cartilage components. Recurrence was determined in pelvis within 12 months and the patient died 24 months after the initial diagnosis. Besides this case, there was no case of death due to tumoral process in our cohort.

As a result, SCLT are substantially rare tumors that can produce hormones. They are usually in early-stage, unilateral, and benign. Therefore, fertility-sparing surgery is the preferred option in young women. In the adjuvant treatment setting, although information about chemotherapy is limited, BEP is a commonly used regimen. The degree of differentiation and the presence of heterologous elements are related with poor prognosis.

 
 > References Top

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Prat J, Young RH, Scully RE. Ovarian Sertoli-Leydig cell tumors with heterologous elements. II. Cartilage and skeletal muscle: A clinico pathologic analysis of twelve cases. Cancer 1982;50:2465-75.  Back to cited text no. 25
    
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