Discussion:

Sertoli-Leydig cell tumors (SLCTs) are rare neoplasms that make up less than 0.5% of ovarian tumors. They most commonly occur in females in the second and third decades of life. SLCTs may cause virilization due to androgen production by the tumor in around one third of patients. These patients often present with oligomenorrhea that progresses to amenorrhea over a course of months (1). Other patients may have estrogenic syndromes, and approximately one half of the patients do not exhibit any endocrine problems at al (2).

The tumors have a nonspecific macroscopic appearance, and may be solid, cystic, or a combination of the two. Histologically, the tumors are composed of Sertoli and Leydig cells with varying levels of differentiation. In better differentiated tumors, the Sertoli cells form tubules. With decreasing differentiation, the Sertoli cells are present in cords with less tubular differentiation, along with hyperchromatic primitive gonadal stroma. Leydig cells may surround the periphery of the Sertoli lobules and tubules and uncommonly contain Reinke crystals. In intermediate and poorly differentiated tumors, the Sertoli cells exhibit increased mitotic activity; mitoses are rare in the Leydig cell component. It is not clear whether the Leydig cell component of SLCT is truly neoplastic. Mooney, et al. suggest that the Leydig cells are polyclonal reactive ovarian stromal cells (3), while Emerson, et al. showed that, in at least some cases, the Leydig cells were clonal and shared a common origin with the Sertoli cell component (4).

SLCTs can have a histologic appearance similar to other ovarian neoplasms, particularly variants of endometrioid carcinoma. Immunohistochemistry is helpful in this regard. The Sertoli component of SLCT is cytokeratin positive and EMA negative. The stroma and Leydig cells do not stain for either of these markers. Inhibin is typically positive in the Leydig and Sertoli cell components. If heterologous tissues are present in the SLCT, as can occur in 20% of the cases, immunohistochemistry may be useful in their recognition and classification (5).

Generally, SLCTs have a favorable prognosis, however with decreasing differentiation, the tumors may behave malignantly. Malignant behavior was observed in 11% of intermediately differentiated and 59% of poorly differentiated SLCTs in one study (2).

References:

1. Kurman, R. J. (ed.) Blaustein's Pathology of the Female Genital Tract (Springer-Verlag, New York, 2002).

2. Tavassoli, F. D., Peter (ed.) Pathology and Genetics of Tumours of the Breast and Female Genital Organs (IARC Press, Lyon, 2003).

3. Mooney, E. E., Man, Y. G., Bratthauer, G. L. & Tavassoli, F. A. Evidence that Leydig cells in Sertoli-Leydig cell tumors have a reactive rather than a neoplastic profile. Cancer 86, 2312-9 (1999).

4. Emerson, R. E. et al. Molecular Genetic Evidence Supporting the Neoplastic Nature of the Leydig Cell Component of Ovarian Sertoli-Leydig Cell Tumors. Int J Gynecol Pathol 26, 368-374 (2007).

5. Dabbs, D. J. (ed.) Diagnostic Immunohistochemistry (Churchill Livingstone, Philadelphia, 2006).