Available online at www.annclinlabsci.org 348 Annals of Clinical & Laboratory Science, vol. 45, no. 3, 2015 Ovarian Sertoli-Leydig Cell Tumor with Predominant Heterologous Mucinous Differentiation and Foci of Hepatocytic Differentiation: Case Report and Review of The Literature Li Liang1,3, Andrew Menzin2, John Louis Lovecchio2, and Maria D. Navarro1 1Department of Pathology and Laboratory Medicine, NSLIJHS/ Hofstra North Shore-LIJ School of Medicine Program, New Hyde Park, NY, 2Department of OBS-GYN-Oncology, NSLIJHS/ Hofstra North Shore-LIJ School of Medicine Program, New Hyde Park, NY, and 3Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract. Sertoli-Leydig cell tumor is a rare ovarian neoplasm and belongs to the group of sex cord stromal tumors. We present a case of a 15-year old girl diagnosed with Sertoli-Leydig cell tumor with heterologous elements consisting predominantly of mucinous epithelium and a sparse Sertoli-Leydig cell component, mimicking mucinous neoplasm. Furthermore, foci of hepatocytic differentiation were also identified. Im- munohistochemical stains showed the component of Sertoli cell differentiation was positive for cytokera- tin 18 and inhibin. The component of Leydig cell differentiation was strongly positive for inhibin. The component of hepatocytic differentiation was positive for low molecular weight keratin, HepPar1, alpha- fetoprotein and weakly positive for inhibin. Thus, this was a very rare case which created a challenge for pathologists, especially on frozen sections. Key words: Sertoli-Leydig cell tumor, sex cord stromal tumor, heterologous elements. Introduction challenging case of SLCT with predominant muci- nous differentiation but also with foci of hepato- Ovarian Sertoli-Leydig cell tumors (SLCTs) are cytic differentiation, while Sertoli and Leydig cells rare sex cord stromal neoplasms and account for were only a small component of the tumor. less than 1% of ovarian neoplasms [1-6]. The aver- age age of presentation is 25-years-old. The well- Case Report differentiated SLCTs usually present at an older age, while the retiform variant usually presents at a A 15-year-old girl presented with constipation for 8 younger age [2]. Sertoli-Leydig cell tumors can be months. Physical examination revealed a distended ab- classified into well-differentiated, intermediate-dif- domen. Lab test showed elevated alpha-fetoprotein (AFP). Computerized Tomography (CT scan) showed a ferentiated, poorly-differentiated, retiform variant 26x24x14 cm abdominal/pelvic mass displacing the and SLCTs with heterologous elements. Sertoli stomach, pancreas, splenic vessels, and small intestine. cells, Leydig cells, and gonadal stroma are cell types Clinically, the differential diagnosis of complex cystic native to the ovary. Other cell types not native to ovarian epithelial neoplasm and/or germ cell neoplasm, the ovary are called heterologous elements, which such as yolk sac tumor, had been considered. have been reported in approximately 20% of SLCTs [1]. Mucinous epithelium is the most common het- The patient underwent exploratory laparotomy, left sal- erologous elements, but carcinoid, rarely hepato- pingo-oophorectomy, and omentectomy. According to cyte-like cells, and mesenchymal heterologous ele- the operation report, a smooth-walled mass replacing the ments such as immature cartilage and skeletal left ovary was removed intact. Grossly, the tumor was mostly cystic with focal solid areas. The cysts were filled muscles have also been reported. We report a very with straw-colored mucinous material. The solid areas were gray-white to yellow-tan and partially translucent. Address correspondence to Maria D. Navarro, MD, Department of Pathology and Laboratory Medicine, NSLIJHS/Hofstra North Shore- Intraoperative consultation was performed, and the di- LIJ School of Medicine Program, 6 Ohio Drive, New Hyde Park, agnosis was benign seromucinous cystadenoma, defer- NY 11042, USA; phone: 516 304 7235; fax: 516 224 8586; e mail: [email protected] ring the final diagnosis until permanent sections could 0091-7370/15/0300-348. © 2015 by the Association of Clinical Scientists, Inc. Ovarian Sertoli-Leydig Cell Tumor 349 be examined. Final pathology findings showed a varied histologic appearance (Figure 1). Bland mucinous epithe- lial cells lined the numerous small and large cysts. The underlying stroma was fi- brotic with scat- tered small foci of cells forming ir- regular, slightly lobulated clusters and cords, and in some places form- ing nests, trabec- ulae, and open tubules compati- ble with Sertoli cell differentia- tion (positive for cytokeratin 18 and inhibin). Intermixed with these cells were small aggregates of Leydig cells (strongly positive for inhibin) and non-differentiat- ed hyperchromat- ic stromal cells. A Figure 1. A Sertoli-Leydig cell tumor composed of mucinous epithelium (asterisk), Sertoli cell dif- particularly inter- ferentiation (arrowhead), Leydig cell differentiation (blue arrow), and hepatocytic differentiation esting feature of (red arrow). A and B. H&E stain (original magnification ×200). C and D. Immunohistochemical this tumor was stains for inhibin (original magnification ×200). E. Immunohistochemical stain for alpha-fetopro- the presence of tein (original magnification ×200). F. Immunohistochemical stain for HepPar1 (original magnifi- cation ×200). heterologous he- patocyte-like cells within these aggregates, which were epithelium, foci of hepatocytic differentiation, and large polygonal cells with abundant eosinophilic cyto- a sparse Sertoli-Leydig cell component, is extremely plasm (positive for low molecular weight keratin, rare and diagnostically challenging. The differential HepPar1, and alpha-fetoprotein and weakly positive for diagnoses of SLCTs include epithelial tumors of the inhibin). This findingov pr ided an explanation for the ovary (e.g., mucinous neoplasm and endometrioid patient’s elevated alpha-fetoprotein. carcinoma with sex cord-like differentiation), germ cell tumors (e.g., yolk sac tumor), other sex cord Discussion stromal tumors, and metastatic carcinoma [1,2]. The abundant heterologous mucinous cystic com- SLCTs account for less than 1% of ovarian neo- ponent in our case mimicked a mucinous neoplasm plasm [1,2]. Our case, with heterologous elements of the ovary, especially on frozen section. It may be consisting of a predominance of mucinous helpful to take multiple sections for intraoperative Table 1. Cases of Sertoli-Leydig Cell Tumor with Hepatocytic Differentiation: Review of the Literature. 35 0 Case Reference Age Hepatocytic Differentiation Leydig Cell Differentiation Other Heterologous Follow-uP Status (year) Keratin Inhibin AFP HeP Keratin Inhibin AFP HeP Elements++ Part1 Part1 Ann 1 Young et al.11+ 13 NA NA + NA NA NA - NA Mucinous epithelium, DOD, 9 months al s rhabdomyosarcoma of 2 Chadha et al.12 11 NA NA + NA NA NA - NA No Recurrent Cl -month in 14* ic 3 Hammad et al. 17 + NA + NA - NA - NA Carcinoid tumor NED, 8 months al 7# 4 Mooney et al. 44 No NED, 6 years & 7# 5 Mooney et al. 74 Sarcoma DOD, 6 months La 7# 6 Mooney et al. 18 + Weak to + NA - Strong+ - NA Cartilage NED, 6 months bora moderate+ 7 Mooney et al.7# 23 No NA to 8 Mooney et al.7# 15 Sarcoma Recurrent ry 9 Present case 15 + Weak+ + + - Strong+ - - Mucinous epithelium NA Sc ie nc Abbreviations: AFP: Alpha-fetoprotein; DOD: died of disease; NED: No evidence of disease; NA: not available. e, +SLCT in this article was also reported to be weakly positive for anti-trypsin. vo *SLCT in this article was also reported to be positive for anti-chymotrypsin and negative for vimentin. l. # 45 SLCTs in this article were also reported to be positive for albumin, ferritin, anti-trypsin and carcinoembryonic antigen (canalicular pattern), negative for vimentin. , ++All the cases above have components of Sertoli cell, Leydig cell and hepatocyte differentiation. The other components were listed here. no . 3, 20 15 we negative for vimentin.to The moderately Leydig positive cells onic for antigen inhibin, (canalicular and albumin, pattern), anti-trypsin and carcinoembry- (AE1/AE3 and CAM5.2),that AFP, hepatocytes ferritin, hepatocytic differentiationnohistochemical profile and of found Mo the munohistochemistry has been and detailed clinicalSLCTs history with and/or hepatocytic im- we differentiation, always present. bile or bile plugs withinity canaliculi are to not Leydig cells,cases the and hepatocytes intracytoplasmic are inby close pr tion is rarer and may need toum be confirmed [7-14]. or heterologous gastrointestinal epitheli- been detected in with elevated alpha-fetoprotein, AFP had viously El nent wassuspected. not identifiedespecially in pha-fetoprotein.our case. Thus, germIn cell tumor, diagnosis. essentialthe for stroma underneath theatypical making epithelium features. is Careful examinationconsultation, the of especially in correct tumors with [8]. tive for vimentin, and negative for keratin tocellular carcinoma has been is still unclear. The developmentmucinous and ofhepa- hepatocytic differentiation The clinical significance heterologous of cells with hepatocyte differentiation. also performed and was positivenohistochemical in tumor stain of tochemical features. evated alpha-fetoprotein has been pr re re addition, the patient had elevated al- immunohistochemistry since in some oney et al. (1999) studied the immu- En Ou strongly positive for inhibin, posi- only appr glish language literature r case sho re ported in SLCTs. yo Ho Tr lk sac tumor,