Arch Gynecol Obstet DOI 10.1007/s00404-014-3293-6
Review
Sertoli–Leydig cell tumor in a 12‑year‑old girl: a review article and case report Fernanda Cabrera‑Cantú · Marta Urrutia‑Osorio · Fernando Valdez‑Arellano · Liliana Rivadeneyra‑Espinoza · Alejandro Papaqui · Elena Soto‑Vega
Received: 7 April 2014 / Accepted: 21 May 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract Background The Sertoli and Leydig cell tumor is an unusual neoplasm that belongs to the sex cord-stromal tumors. Generally these tumors are associated with good prognosis. These tumors usually present virilizing symptoms such as oligomenorrhea or amenorrhea, hirsutism, voice raucity, laryngeal protuberance and clitoromegaly. Case presentation A 12 year old girl referred acute abdominal pain with no other clinical manifestations. An abdominal ultrasound showed a semisolid mass suggestive of ovarian tumor. The diagnosis was confirmed by a computed tomography. A unilateral salpingo oophorectomy was performed and the pathologist reported a Sertoli-Leydig tumor with intermediate differentiation. The outcome was excellent. Conclusions These tumors represent a rare condition in children. However, they can occur at any age, therefore it is important to acknowledge the clinical manifestations, diagnostic approach and therapeutic options. In this case the patient presented unusual symptoms which makes it more interesting.
F. Cabrera‑Cantú · M. Urrutia‑Osorio · F. Valdez‑Arellano Facultad de Medicina, Universidad Popular Autónoma del Estado de Puebla, Puebla, Puebla, Mexico L. Rivadeneyra‑Espinoza · E. Soto‑Vega (*) Research Department, Facultad de Medicina, Universidad Popular Autónoma del Estado de Puebla, 21 sur 1103, Col. Barrio de Santiago, 72410 Puebla, Puebla, Mexico e-mail: [email protected] A. Papaqui Pediatrics Department, Hospital Ángeles de Puebla, Puebla, Puebla, Mexico
Keywords Sertoli–Leydig cell tumor · Ovarian tumor · Virilizing symptoms · Ovarian cancer · Sex cord-stromal tumors
Introduction The National Cancer Institute estimated in 2012 that there were 22,280 new cases of ovarian cancer in the United States [1]. The most common ovarian tumors are surface epithelial-stromal tumors that account for 60 % of the ovarian tumors [2], followed by germ cells tumors that constitute 30 % of primary ovarian tumors and finally the sex cord-stromal tumors, accounting for about 8 % of ovarian neoplasms [3]. Sertoli and Leydig cell tumors (SLCTs) constitute 0.5 % of ovarian tumors and they represent about 1 % of sex cordstromal tumors [4]. Intermediate and poorly differentiated SLCTs are the most common histological forms [3]. These tumors can occur in women of all ages but they are most commonly presented in young women, with an average age of 25. However, it is rare to find these neoplasms before menarche or after menopause [5]. Sertoli–Leydig cell tumor has the same stage classification of all ovarian tumors. Based on FIGO classification (Table 1), over 97 % of these tumors are unilateral and only 2–3 % of tumors can metastasize [3]. Origin of the cells Sertoli cells Evidence suggests that Sertoli cells are derived from the coelomic epithelium or from mesonephros, which are potential contributors of sex cord elements in the ovary.
13
Arch Gynecol Obstet
Table 1 FIGO stage classification for ovarian cancer Stage 1 The tumor is confined to the ovary or ovaries IA IB Ovarian capsule intact Both ovaries affected by tumor Only one ovary affected No ascites
Ovary capsule intact No tumor on the external surfaces
IC Tumor stage IA or IB on the surface of one or both ovaries Ovary capsule ruptured Ascites or peritoneal washings contain malignant cells
No tumor on the external surfaces No ascites Stage 2 The tumor involves one or both ovaries and has extended into the pelvis 2A 2B The tumor has extended and/or metastasized The tumor has extended to another pelvic into the uterus and/or the fallopian tubes tissue
2C Tumor stage 2A or 2B and malignant cells are detected in the ascites or peritoneal washings Capsule ruptured Stage 3 The tumor involves one or both ovaries with microscopically confirmed peritoneal metastases outside the pelvis and/or regional lymph node metastasis. Includes liver capsule metastases 3A 3B 3C Microscopic peritoneal metastasis beyond Microscopic peritoneal metastasis beyond the Microscopic peritoneal metastasis beyond the the pelvis pelvis 2 cm Negative nodes Negative nodes Positive retroperitoneal or inguinal nodes Stage 4 The tumor involves one or two ovaries with distant metastasis beyond the peritoneal cavity. And liver parenchymal metastasis Consulted in: Heintz et al. [24]
However, there are some similarities with testicular Sertoli cells, such as the presence of anti-müllerian hormone and inhibin. Testicular Sertoli cells have three subunits of inhibin one A and two B subunits, whereas SLCTs only express two subunits: bA and bB [6]. Leydig cells The origin of Leydig cells in the SLCT is due to the formation of neoplastic cells from Leydig cells found in the normal ovary, which have a mesonephric origin. Interstitial cells in the hilar region are analogs to the testicular Leydig cells. Both cell types produce androgens, insulin growth factor family called relaxin-like factor and also a calciumbinding protein called calretinin [6]. The main theories about the histogenesis of SLCTs propose that they arise either from the gonadal mesenchyme of the ovary or from remnants in the hilum [7]. Imaging According to imaging, this tumor can be a solid, cystic, or solid/cystic mass or even papillary on ultrasound, magnetic resonance imaging (MRI), or computed tomography (CT) [3]. The best imaging test for ovarian tumors is ultrasound, and color Doppler is used to characterize SLCTs because these tumors tend to be well vascularized [8]. CT scans of SLCTs show a well-defined mass with an intratumoral cyst. This study also helps to detect distant
13
metastases; despite the fact that metastases are a rare phenomena in these tumors and are only seen in a 2–3 % of the cases. MRI images demonstrate a hypointense area with multiple variables and cystic areas. In T2 the tumor has low signal intensity and the fibrous stroma is seen as weighted imaging. Signal and intensity at MRI reflect the extent of fibrous stroma. In SLCTs with heterologous elements, multicystic areas are observed [9]. In SLCTs patients with virilizing symptoms, the tumors tend to be smaller and are difficult to detect, even by transvaginal ultrasound [10]. Histology Sertoli and Leydig cell tumors originate from the sex cordstroma and are composed by Sertoli and Leydig cells. Sertoli cells are small cells that form a tubular structure with a central lumen. Leydig cells are numerous and they are usually located in the stroma in the tubular structure of the Sertoli cells, which are polygonal with distinct cytoplasmic borders and eosinophilic cytoplasm that may be solid or feathery, with a dense central nucleus with nuclear membrane and sometimes with prominent nucleoli. Reinke crystalloids found only rarely in SCLTs of the ovary are pathognomonic of testicular Leydig cells. These crystalloids are large, bright, eosinophilic, intracytoplasmatic and best seen with PAS stain or trichrome [6]. Histologically these tumors show uniform, rounded cells arranged in nests, cords, and trabeculae. The cytoplasm is clear in these cells and it is vacuolated.
Arch Gynecol Obstet
It is important to define the histological type in SLCTs; therefore it has been classified into six categories: well-differentiated, intermediate differentiated, poorly differentiated, retiform, heterologous, and mixed forms [11]. Well-differentiated SLCTs (Meyer type I) present Sertoli cells in tubules, which are opened or closed with a lack of nuclear atypia or mitotic activity. There is a delicate fibrous stroma, in which Leydig cells are forming small clusters (this is a very helpful characteristic of these tumors) [12]. In intermediate differentiated SLCTs (Meyer type II), the cellular lobules are compounded of hyperchromatic gonadal spindle-shaped stroma, separated by indistinct cytoplasm of edematous stroma. Leydig cells are found in clusters at the periphery of the lobules or mixed with other elements; these cells may have Reinke crystals, lipofuscin or can be vacuolated. Mitoses are rare in Leydig cells; there may be a range of 5–10 fields. The poorly differentiated tumors (Meyer type III) are typically larger than the two forms listed above. It is common to find necrosis and/or hemorrhages in some areas, mainly in the center of the tumor. Histologically, they are much like fibrosarcoma [11]. SLCTs with heterologous elements are present in 20 % of the SLCTs. They are present in some intermediate or poorly differentiated SLCTs, presenting predominantly as cystic tumors [12]. These tumors contain tissue that does not belong to sex cord-like elements and they are mostly mucinous epithelial, usually bland intestinal-type gastric epithelium or sometimes with malignant changes. Retiform SLCTs are present in 10–15 % of all SLCTs and tend to be larger tumors [12]. They are composed by 90 % of slit-shaped spaces similar to the rete testis. Tumors with more than 10 % but I [17].
A 12-year-old girl presented with acute abdominal pain in the right lower abdomen. On examination the patient had no findings of hormonal clinical manifestations. Abdominal ultrasound was indicated; a semisolid mass with defined
13
Fig. 1 Macroscopic view of the tumor
Arch Gynecol Obstet
measures 8.0 × 6.0 × 6.4 cm with cystic areas was seen. Contrast-enhanced computed tomography of the abdomen reported a well-defined 7.4 × 9.5 cm cystic-solid tumor with small irregular areas of necrosis. Lactic dehydrogenase, alpha-fetoprotein, chorionic gonadotropin and carcinoembryonic antigen were normal. A unilateral salpingo oophorectomy was practiced trough laparoscopy. Macroscopic examination revealed an encapsulated smooth, graybrown, shiny tumor of 10 × 7 × 6 cm weighing 256 g 8 (Fig. 1). Cut-section was solid with soft myxoid material with a well-defined yellow area. Microscopic examination showed a tumor with neoplastic cells forming sheets of small to medium cells which were forming cords. Some tumor cells have eosinophilic cytoplasm. Immunohistochemical stains showed reactive for androgen receptors and weak and multifocal to inhibin and calretinin. The cytoplasmic CD99 was intensely positive neoplastic cells, while EMA and cytokeratin 7 were negative. The final diagnosis was a Sertoli–Leydig tumor with intermediate differentiation (Meyer type 2) without vascular or capsular invasion (stage 1 FIGO classification). The patient was evaluated by the oncologist who did not recommend chemotherapy. The first follow-up was 2 months after surgery and the patient did not present any pain or other symptoms suggestive of surgical complications or recurrence. There was no evidence of recurrence in the first year of follow-up. It was recommended to continue with regular pediatric evaluations according to her age.
Discussion Sertoli and Leydig cell tumor is a rare neoplasm that constitutes 0.5 % of ovarian tumors and only about 1 % of sex cord-stromal tumors [3]. SLCT represents up to 4 % of ovarian tumors in female subjects under 20 years of age [21]. SLCT is rare in children. In 75 % of cases, age at diagnosis is 30 years [22]. This is the first report in Mexico of a Sertoli and Leydig Cell tumor on a 12-year-old girl, and one of the few cases reported worldwide at this age. The presentation of SLCT is rare in the first decade of life, so it is usually not initially suspected at the time of clinical diagnosis. In our case there was no suspicion of an ovarian tumor due to the age of the patient and the absence of typically androgen manifestations. The girl did not presented amenorrhea, hirsutism, voice raucity, laryngeal protuberance, or clitoromegaly even the patients did not has the estrogen excess manifestations as nearly 50 % of the patients. She only had abdominal pain. This was the reason for performing imaging studies like TC, which reported a cystic-solid tumor with small irregular areas of necrosis. Pain, commonly chronic and dull, is probably due to compression of visceral structures in the vicinity, in this case pain was acute, but no
torsion or bleeding was found. Because the cornerstone of the treatment is surgery, the age of the patient, the unilateral tumor with the capsule intact (stage 1 according to the FIGO), and the desire of the parents to preserve fertility, the recommended treatment was unilateral salpingo oophorectomy. The chemotherapy was not indicated because the stage IA has good prognosis and the Meyer type 2 of our patient usually are benign because only 11 % of intermediately differentiations are malignant [23]. The immunohistochemical stains showed reactive inhibin and calretinin, as are most of the SLCTs, however, given it was positive to inhibin we can exclude an epithelial tumor. The cytoplasmic CD99 was intensely positive neoplastic cells, while EMA and cytokeratin 7 were negative. These two last ones suggest the tumor had no mucinous elements, otherwise it should have stained positive. The highlight of this case is the age of presentation. It is important that clinicians take into account the possibility of the presence of SLCTs in young patients. Due to the low incidence of SLCTs, the diagnosis can pass unnoticed, making a late diagnosis and therefore making the treatment less effective. If those tumors are diagnosed in the early stages, treatment merely requires conservative surgery and monitoring after surgery. The overall survival rate is up to 92.3 % for stage one and the recurrence rate is low, so a very good prognosis will be highly probable in this patient. Acknowledgments Vania Smith-Oka and Amy Klopfenstein form Notre-Dame University for their valuable collaboration. Conflict of interest We have no conflict of interest to declare.
References 1. National Cancer Institute (2012) Available at: http://www.cancer. gov/cancertopics/types/ovarian. Accessed 4 Aug 2013 2. Chen VW, Ruiz B, Killeen JL et al (2003) Pathology and classification of ovarian tumors. Cancer 97:2631–2642 3. Tavassoli FA, Devilee P (2003) Tumors of the ovary and peritoneum. In: Kleihues P, Sobin L (eds) Tumors of the brest and female genital organs. IARC Press, Lyon, pp 113–120 4. Chakrabarti I, De A, Gangopadhyay M, Bera P (2010) Sertoli– Leydig cell tumour of ovary with heterologous elements: a case report. Internet J Gynecol Obstet 13(1) 5. Bhat RA, Lim YK, Chia YN, Yam KL (2013) Sertoli–Leydig cell tumor of the ovary: analysis of a single institution database. J Obstet Gynaecol Res 39:305–310 6. Nouriani M, Felix JC, Dubeau L (2002) Histogenesis and histopathological characteristics of Sertoli–Leydig cell tumors. CME. 7:114–120 7. Roth LM, Anderson MC, Chir B et al (1981) Sertoli–Leydig cell tumors: a clinicopathologic study of 34 cases. Cancer 48:187–197 8. Zanotti KM (2002) The clinical manifestations and diagnosis of Sertoli–Leydig cell tumors of the ovary. CME 7:129–133 9. Jung SE, Rha SE, Lee JM et al (2005) CT and MRI findings of sex cord-stromal tumor of the ovary. Am J Roentgenol 185:207–215
13
10. Tanaka YO, Tsunoda H, Kitagawa Y et al (2004) Functioning ovarian tumors: direct and indirect findings at MR imaging. Radiographics 1:S147–S166 11. Soleimanpour H, Shirian S, Oryan A et al (2011) Cytologic, immunocytologic, histopathologic and immunohistologic diagnosis of the poorly differentiated Sertoli–Leydig cell tumor. Acta Cytol 55:382–386 12. Young RH (2005) Sex cord-stromal tumors of the ovary and testis: their similarities and differences with consideration of selected problems. Mod Pathol 18:S81–S98 13. Demidov VN, Lipatenkova J, Vikhareva O et al (2008) Imaging of gynecological disease (2): clinical and ultrasound characteristics of sertoli cell tumors, Sertoli–Leydig cell tumors and Leydig cell tumors. Ultrasound Obstet Gynecol 31:85–91 14. Zhao C, Vinh TN, McManus K et al (2009) Identification of the most sensitive and robust immunohistochemical markers in different categories of ovarian sex cord-stromal tumors. Am J Surg Pathol 33:354–366 15. Al-Agha OM, Huwait HF, Chow C et al (2011) FOXL2 is a sensitive and specific marker for sex cord-stromal tumors of the ovary. Am J Surg Pathol 35:484–494 16. Gui T, Cao D, Shen K et al (2012) A clinicopathological analysis of 40 cases of ovarian Sertoli–Leydig cell tumors. Gynecol Oncol 127:384–389
13
Arch Gynecol Obstet 17. Sigismondi C, Gadducci A, Lorusso D et al (2012) Ovarian Sertoli–Leydig cell tumors. A retrospective MITO study. Gynecol Oncol 3:673–676 18. Weng CS, Chen MY, Wang TY et al (2013) Sertoli Leydig cell tumors of the ovary: a Taiwanese gynecologic oncology group study. Taiwan J Obstet Gynecol 52:66–70 19. Abu-Zaid A, Azzam A, Abdulhamid L et al (2013) Poorly differentiated ovarian Sertoli–Leydig cell tumor in a 16-year-old single woman: a case report and literature review. Case Rep Obstet Gynecol 2013:1–6 20. Thrall MM, Paley P, Pizer E et al (2011) Patterns of spread and recurrence of sex cord-stromal tumors of the ovary. Gynecol Oncol 122:242–455 21. Kawatra V, Mandal S, Khurana N, Aggarwal SK (2009) Retiform pattern of Sertoli–Leydig cell tumor of the ovary in a 4-year-old girl. J Obstet Gynaecol Res 35:176–179 22. Persechini ML, Motton S, Lequevaque P et al (2011) Virilising ovarian tumour: a case associating a Sertoli–Leydig cell tumour and a brenner tumour. Gynecol Endocrinol 27:345–350 23. Böttcher B, Hinney B, Keyser J et al (2011) Sertoli–Leydig cell tumour in a 13-year-old girl. Gynecol Endocrinol 27:107–1099 24. Heintz APM et al (2006) Carcinoma of the ovary. Int J Gynaecol Obstet 95:S161–S192
Review
Sertoli–Leydig cell tumor in a 12‑year‑old girl: a review article and case report Fernanda Cabrera‑Cantú · Marta Urrutia‑Osorio · Fernando Valdez‑Arellano · Liliana Rivadeneyra‑Espinoza · Alejandro Papaqui · Elena Soto‑Vega
Received: 7 April 2014 / Accepted: 21 May 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract Background The Sertoli and Leydig cell tumor is an unusual neoplasm that belongs to the sex cord-stromal tumors. Generally these tumors are associated with good prognosis. These tumors usually present virilizing symptoms such as oligomenorrhea or amenorrhea, hirsutism, voice raucity, laryngeal protuberance and clitoromegaly. Case presentation A 12 year old girl referred acute abdominal pain with no other clinical manifestations. An abdominal ultrasound showed a semisolid mass suggestive of ovarian tumor. The diagnosis was confirmed by a computed tomography. A unilateral salpingo oophorectomy was performed and the pathologist reported a Sertoli-Leydig tumor with intermediate differentiation. The outcome was excellent. Conclusions These tumors represent a rare condition in children. However, they can occur at any age, therefore it is important to acknowledge the clinical manifestations, diagnostic approach and therapeutic options. In this case the patient presented unusual symptoms which makes it more interesting.
F. Cabrera‑Cantú · M. Urrutia‑Osorio · F. Valdez‑Arellano Facultad de Medicina, Universidad Popular Autónoma del Estado de Puebla, Puebla, Puebla, Mexico L. Rivadeneyra‑Espinoza · E. Soto‑Vega (*) Research Department, Facultad de Medicina, Universidad Popular Autónoma del Estado de Puebla, 21 sur 1103, Col. Barrio de Santiago, 72410 Puebla, Puebla, Mexico e-mail: [email protected] A. Papaqui Pediatrics Department, Hospital Ángeles de Puebla, Puebla, Puebla, Mexico
Keywords Sertoli–Leydig cell tumor · Ovarian tumor · Virilizing symptoms · Ovarian cancer · Sex cord-stromal tumors
Introduction The National Cancer Institute estimated in 2012 that there were 22,280 new cases of ovarian cancer in the United States [1]. The most common ovarian tumors are surface epithelial-stromal tumors that account for 60 % of the ovarian tumors [2], followed by germ cells tumors that constitute 30 % of primary ovarian tumors and finally the sex cord-stromal tumors, accounting for about 8 % of ovarian neoplasms [3]. Sertoli and Leydig cell tumors (SLCTs) constitute 0.5 % of ovarian tumors and they represent about 1 % of sex cordstromal tumors [4]. Intermediate and poorly differentiated SLCTs are the most common histological forms [3]. These tumors can occur in women of all ages but they are most commonly presented in young women, with an average age of 25. However, it is rare to find these neoplasms before menarche or after menopause [5]. Sertoli–Leydig cell tumor has the same stage classification of all ovarian tumors. Based on FIGO classification (Table 1), over 97 % of these tumors are unilateral and only 2–3 % of tumors can metastasize [3]. Origin of the cells Sertoli cells Evidence suggests that Sertoli cells are derived from the coelomic epithelium or from mesonephros, which are potential contributors of sex cord elements in the ovary.
13
Arch Gynecol Obstet
Table 1 FIGO stage classification for ovarian cancer Stage 1 The tumor is confined to the ovary or ovaries IA IB Ovarian capsule intact Both ovaries affected by tumor Only one ovary affected No ascites
Ovary capsule intact No tumor on the external surfaces
IC Tumor stage IA or IB on the surface of one or both ovaries Ovary capsule ruptured Ascites or peritoneal washings contain malignant cells
No tumor on the external surfaces No ascites Stage 2 The tumor involves one or both ovaries and has extended into the pelvis 2A 2B The tumor has extended and/or metastasized The tumor has extended to another pelvic into the uterus and/or the fallopian tubes tissue
2C Tumor stage 2A or 2B and malignant cells are detected in the ascites or peritoneal washings Capsule ruptured Stage 3 The tumor involves one or both ovaries with microscopically confirmed peritoneal metastases outside the pelvis and/or regional lymph node metastasis. Includes liver capsule metastases 3A 3B 3C Microscopic peritoneal metastasis beyond Microscopic peritoneal metastasis beyond the Microscopic peritoneal metastasis beyond the the pelvis pelvis 2 cm Negative nodes Negative nodes Positive retroperitoneal or inguinal nodes Stage 4 The tumor involves one or two ovaries with distant metastasis beyond the peritoneal cavity. And liver parenchymal metastasis Consulted in: Heintz et al. [24]
However, there are some similarities with testicular Sertoli cells, such as the presence of anti-müllerian hormone and inhibin. Testicular Sertoli cells have three subunits of inhibin one A and two B subunits, whereas SLCTs only express two subunits: bA and bB [6]. Leydig cells The origin of Leydig cells in the SLCT is due to the formation of neoplastic cells from Leydig cells found in the normal ovary, which have a mesonephric origin. Interstitial cells in the hilar region are analogs to the testicular Leydig cells. Both cell types produce androgens, insulin growth factor family called relaxin-like factor and also a calciumbinding protein called calretinin [6]. The main theories about the histogenesis of SLCTs propose that they arise either from the gonadal mesenchyme of the ovary or from remnants in the hilum [7]. Imaging According to imaging, this tumor can be a solid, cystic, or solid/cystic mass or even papillary on ultrasound, magnetic resonance imaging (MRI), or computed tomography (CT) [3]. The best imaging test for ovarian tumors is ultrasound, and color Doppler is used to characterize SLCTs because these tumors tend to be well vascularized [8]. CT scans of SLCTs show a well-defined mass with an intratumoral cyst. This study also helps to detect distant
13
metastases; despite the fact that metastases are a rare phenomena in these tumors and are only seen in a 2–3 % of the cases. MRI images demonstrate a hypointense area with multiple variables and cystic areas. In T2 the tumor has low signal intensity and the fibrous stroma is seen as weighted imaging. Signal and intensity at MRI reflect the extent of fibrous stroma. In SLCTs with heterologous elements, multicystic areas are observed [9]. In SLCTs patients with virilizing symptoms, the tumors tend to be smaller and are difficult to detect, even by transvaginal ultrasound [10]. Histology Sertoli and Leydig cell tumors originate from the sex cordstroma and are composed by Sertoli and Leydig cells. Sertoli cells are small cells that form a tubular structure with a central lumen. Leydig cells are numerous and they are usually located in the stroma in the tubular structure of the Sertoli cells, which are polygonal with distinct cytoplasmic borders and eosinophilic cytoplasm that may be solid or feathery, with a dense central nucleus with nuclear membrane and sometimes with prominent nucleoli. Reinke crystalloids found only rarely in SCLTs of the ovary are pathognomonic of testicular Leydig cells. These crystalloids are large, bright, eosinophilic, intracytoplasmatic and best seen with PAS stain or trichrome [6]. Histologically these tumors show uniform, rounded cells arranged in nests, cords, and trabeculae. The cytoplasm is clear in these cells and it is vacuolated.
Arch Gynecol Obstet
It is important to define the histological type in SLCTs; therefore it has been classified into six categories: well-differentiated, intermediate differentiated, poorly differentiated, retiform, heterologous, and mixed forms [11]. Well-differentiated SLCTs (Meyer type I) present Sertoli cells in tubules, which are opened or closed with a lack of nuclear atypia or mitotic activity. There is a delicate fibrous stroma, in which Leydig cells are forming small clusters (this is a very helpful characteristic of these tumors) [12]. In intermediate differentiated SLCTs (Meyer type II), the cellular lobules are compounded of hyperchromatic gonadal spindle-shaped stroma, separated by indistinct cytoplasm of edematous stroma. Leydig cells are found in clusters at the periphery of the lobules or mixed with other elements; these cells may have Reinke crystals, lipofuscin or can be vacuolated. Mitoses are rare in Leydig cells; there may be a range of 5–10 fields. The poorly differentiated tumors (Meyer type III) are typically larger than the two forms listed above. It is common to find necrosis and/or hemorrhages in some areas, mainly in the center of the tumor. Histologically, they are much like fibrosarcoma [11]. SLCTs with heterologous elements are present in 20 % of the SLCTs. They are present in some intermediate or poorly differentiated SLCTs, presenting predominantly as cystic tumors [12]. These tumors contain tissue that does not belong to sex cord-like elements and they are mostly mucinous epithelial, usually bland intestinal-type gastric epithelium or sometimes with malignant changes. Retiform SLCTs are present in 10–15 % of all SLCTs and tend to be larger tumors [12]. They are composed by 90 % of slit-shaped spaces similar to the rete testis. Tumors with more than 10 % but I [17].
A 12-year-old girl presented with acute abdominal pain in the right lower abdomen. On examination the patient had no findings of hormonal clinical manifestations. Abdominal ultrasound was indicated; a semisolid mass with defined
13
Fig. 1 Macroscopic view of the tumor
Arch Gynecol Obstet
measures 8.0 × 6.0 × 6.4 cm with cystic areas was seen. Contrast-enhanced computed tomography of the abdomen reported a well-defined 7.4 × 9.5 cm cystic-solid tumor with small irregular areas of necrosis. Lactic dehydrogenase, alpha-fetoprotein, chorionic gonadotropin and carcinoembryonic antigen were normal. A unilateral salpingo oophorectomy was practiced trough laparoscopy. Macroscopic examination revealed an encapsulated smooth, graybrown, shiny tumor of 10 × 7 × 6 cm weighing 256 g 8 (Fig. 1). Cut-section was solid with soft myxoid material with a well-defined yellow area. Microscopic examination showed a tumor with neoplastic cells forming sheets of small to medium cells which were forming cords. Some tumor cells have eosinophilic cytoplasm. Immunohistochemical stains showed reactive for androgen receptors and weak and multifocal to inhibin and calretinin. The cytoplasmic CD99 was intensely positive neoplastic cells, while EMA and cytokeratin 7 were negative. The final diagnosis was a Sertoli–Leydig tumor with intermediate differentiation (Meyer type 2) without vascular or capsular invasion (stage 1 FIGO classification). The patient was evaluated by the oncologist who did not recommend chemotherapy. The first follow-up was 2 months after surgery and the patient did not present any pain or other symptoms suggestive of surgical complications or recurrence. There was no evidence of recurrence in the first year of follow-up. It was recommended to continue with regular pediatric evaluations according to her age.
Discussion Sertoli and Leydig cell tumor is a rare neoplasm that constitutes 0.5 % of ovarian tumors and only about 1 % of sex cord-stromal tumors [3]. SLCT represents up to 4 % of ovarian tumors in female subjects under 20 years of age [21]. SLCT is rare in children. In 75 % of cases, age at diagnosis is 30 years [22]. This is the first report in Mexico of a Sertoli and Leydig Cell tumor on a 12-year-old girl, and one of the few cases reported worldwide at this age. The presentation of SLCT is rare in the first decade of life, so it is usually not initially suspected at the time of clinical diagnosis. In our case there was no suspicion of an ovarian tumor due to the age of the patient and the absence of typically androgen manifestations. The girl did not presented amenorrhea, hirsutism, voice raucity, laryngeal protuberance, or clitoromegaly even the patients did not has the estrogen excess manifestations as nearly 50 % of the patients. She only had abdominal pain. This was the reason for performing imaging studies like TC, which reported a cystic-solid tumor with small irregular areas of necrosis. Pain, commonly chronic and dull, is probably due to compression of visceral structures in the vicinity, in this case pain was acute, but no
torsion or bleeding was found. Because the cornerstone of the treatment is surgery, the age of the patient, the unilateral tumor with the capsule intact (stage 1 according to the FIGO), and the desire of the parents to preserve fertility, the recommended treatment was unilateral salpingo oophorectomy. The chemotherapy was not indicated because the stage IA has good prognosis and the Meyer type 2 of our patient usually are benign because only 11 % of intermediately differentiations are malignant [23]. The immunohistochemical stains showed reactive inhibin and calretinin, as are most of the SLCTs, however, given it was positive to inhibin we can exclude an epithelial tumor. The cytoplasmic CD99 was intensely positive neoplastic cells, while EMA and cytokeratin 7 were negative. These two last ones suggest the tumor had no mucinous elements, otherwise it should have stained positive. The highlight of this case is the age of presentation. It is important that clinicians take into account the possibility of the presence of SLCTs in young patients. Due to the low incidence of SLCTs, the diagnosis can pass unnoticed, making a late diagnosis and therefore making the treatment less effective. If those tumors are diagnosed in the early stages, treatment merely requires conservative surgery and monitoring after surgery. The overall survival rate is up to 92.3 % for stage one and the recurrence rate is low, so a very good prognosis will be highly probable in this patient. Acknowledgments Vania Smith-Oka and Amy Klopfenstein form Notre-Dame University for their valuable collaboration. Conflict of interest We have no conflict of interest to declare.
References 1. National Cancer Institute (2012) Available at: http://www.cancer. gov/cancertopics/types/ovarian. Accessed 4 Aug 2013 2. Chen VW, Ruiz B, Killeen JL et al (2003) Pathology and classification of ovarian tumors. Cancer 97:2631–2642 3. Tavassoli FA, Devilee P (2003) Tumors of the ovary and peritoneum. In: Kleihues P, Sobin L (eds) Tumors of the brest and female genital organs. IARC Press, Lyon, pp 113–120 4. Chakrabarti I, De A, Gangopadhyay M, Bera P (2010) Sertoli– Leydig cell tumour of ovary with heterologous elements: a case report. Internet J Gynecol Obstet 13(1) 5. Bhat RA, Lim YK, Chia YN, Yam KL (2013) Sertoli–Leydig cell tumor of the ovary: analysis of a single institution database. J Obstet Gynaecol Res 39:305–310 6. Nouriani M, Felix JC, Dubeau L (2002) Histogenesis and histopathological characteristics of Sertoli–Leydig cell tumors. CME. 7:114–120 7. Roth LM, Anderson MC, Chir B et al (1981) Sertoli–Leydig cell tumors: a clinicopathologic study of 34 cases. Cancer 48:187–197 8. Zanotti KM (2002) The clinical manifestations and diagnosis of Sertoli–Leydig cell tumors of the ovary. CME 7:129–133 9. Jung SE, Rha SE, Lee JM et al (2005) CT and MRI findings of sex cord-stromal tumor of the ovary. Am J Roentgenol 185:207–215
13
10. Tanaka YO, Tsunoda H, Kitagawa Y et al (2004) Functioning ovarian tumors: direct and indirect findings at MR imaging. Radiographics 1:S147–S166 11. Soleimanpour H, Shirian S, Oryan A et al (2011) Cytologic, immunocytologic, histopathologic and immunohistologic diagnosis of the poorly differentiated Sertoli–Leydig cell tumor. Acta Cytol 55:382–386 12. Young RH (2005) Sex cord-stromal tumors of the ovary and testis: their similarities and differences with consideration of selected problems. Mod Pathol 18:S81–S98 13. Demidov VN, Lipatenkova J, Vikhareva O et al (2008) Imaging of gynecological disease (2): clinical and ultrasound characteristics of sertoli cell tumors, Sertoli–Leydig cell tumors and Leydig cell tumors. Ultrasound Obstet Gynecol 31:85–91 14. Zhao C, Vinh TN, McManus K et al (2009) Identification of the most sensitive and robust immunohistochemical markers in different categories of ovarian sex cord-stromal tumors. Am J Surg Pathol 33:354–366 15. Al-Agha OM, Huwait HF, Chow C et al (2011) FOXL2 is a sensitive and specific marker for sex cord-stromal tumors of the ovary. Am J Surg Pathol 35:484–494 16. Gui T, Cao D, Shen K et al (2012) A clinicopathological analysis of 40 cases of ovarian Sertoli–Leydig cell tumors. Gynecol Oncol 127:384–389
13
Arch Gynecol Obstet 17. Sigismondi C, Gadducci A, Lorusso D et al (2012) Ovarian Sertoli–Leydig cell tumors. A retrospective MITO study. Gynecol Oncol 3:673–676 18. Weng CS, Chen MY, Wang TY et al (2013) Sertoli Leydig cell tumors of the ovary: a Taiwanese gynecologic oncology group study. Taiwan J Obstet Gynecol 52:66–70 19. Abu-Zaid A, Azzam A, Abdulhamid L et al (2013) Poorly differentiated ovarian Sertoli–Leydig cell tumor in a 16-year-old single woman: a case report and literature review. Case Rep Obstet Gynecol 2013:1–6 20. Thrall MM, Paley P, Pizer E et al (2011) Patterns of spread and recurrence of sex cord-stromal tumors of the ovary. Gynecol Oncol 122:242–455 21. Kawatra V, Mandal S, Khurana N, Aggarwal SK (2009) Retiform pattern of Sertoli–Leydig cell tumor of the ovary in a 4-year-old girl. J Obstet Gynaecol Res 35:176–179 22. Persechini ML, Motton S, Lequevaque P et al (2011) Virilising ovarian tumour: a case associating a Sertoli–Leydig cell tumour and a brenner tumour. Gynecol Endocrinol 27:345–350 23. Böttcher B, Hinney B, Keyser J et al (2011) Sertoli–Leydig cell tumour in a 13-year-old girl. Gynecol Endocrinol 27:107–1099 24. Heintz APM et al (2006) Carcinoma of the ovary. Int J Gynaecol Obstet 95:S161–S192
