Hepatocytic differentiation in retiform Sertoli-Leydig cell Tumors: Distinguishing a heterologous element from Leydig cells

University of Granada, Granata, Andalusia, Spain
Human Pathlogy (Impact Factor: 2.77). 07/1999; 30(6):611-7. DOI: 10.1016/S0046-8177(99)90083-7
Source: PubMed


Sertoli-Leydig cell tumors (SLCT) of the ovary are rare sex cord-stromal neoplasms. A minority of SLCT are characterized by a pattern resembling that of the rete ovarii and frequently have a range of homologous and heterologous tissues. Approximately 20 cases of SLCT have been reported to have elevation of serum alpha-fetoprotein (AFP) levels, or tissue immunoreactivity for AFP, a protein usually associated with germ cell neoplasms, especially yolk sac tumor. We identified hepatocytic differentiation in five cases of retiform SLCT (RSLCT), and confirmed immunohistochemically that these cells are hepatocytes rather than Leydig cells. Hepatocytes are positive for keratins (AE1/3 and Cam 5.2), AFP, and ferritin, negative for vimentin, and show weak to moderate staining for inhibin. Leydig cells are negative for keratins, positive for vimentin, and intensely positive for inhibin. Immunohistochemistry is needed to distinguish hepatocytic differentiation from Leydig cells with certainty. Including the cases in this report, hepatocytic differentiation has been associated with a retiform pattern in SLCT in 14 of 25 cases (56%). The association of these two patterns appears to be characteristic of a relatively primitive sex cord-stromal neoplasm.

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    ABSTRACT: BACKGROUND Leydig cells are a variable and an inconstant feature of Sertoli-Leydig cell tumors (SLCT). Controversy exists regarding their neoplastic versus reactive nature, and their molecular biologic profile is unknown.METHODS Six SLCT and one pure Leydig cell tumor were studied. Mitotic counts and immunohistochemistry for Ki-67 were performed in all cases. Leydig cells, neoplastic tissues, and normal nonneoplastic tissues were microdissected. DNA extracts of these samples were assessed for loss of heterozygosity (LOH) by polymerase chain reaction amplification with ten polymorphic DNA markers that have shown high rates of LOH in a variety of human tumors. Three SLCT and the Leydig cell tumor were assessed for clonality by examining the DNA methylation pattern at a polymorphic site on the androgen receptor gene.RESULTSLeydig cells in SLCT had a low mitotic count (0–1/50 high-power fields [HPF]) compared with the neoplastic stroma (median, 40/50 HPF). Ki-67 was positive in < 2% of Leydig cells in all SLCT, compared with a median of 7% in the neoplastic stroma. Clonality analysis confirmed the monoclonality of the neoplastic cells in the Leydig cell tumor. However, the Leydig cells from three SLCT were polyclonal, whereas the monoclonal nature of the neoplastic Sertoli tubules was confirmed in one of these cases and that of mucinous heterologous elements in another case. The Leydig cell tumor showed LOH at four of the eight loci evaluated. Leydig cells from five SLCT were evaluated: one showed LOH at one locus, two showed LOH at two loci, and the remaining two showed no LOH.CONCLUSIONS The demonstration that Leydig cells from SLCT are polyclonal strongly suggests that they are nonneoplastic in nature. This is supported by a low proliferation fraction and a lower fraction of LOH compared with the truly neoplastic Leydig cells. Cancer 1999;86:2312–19. © 1999 American Cancer Society.
    Cancer 12/1999; 86(11):2312 - 2319. DOI:10.1002/(SICI)1097-0142(19991201)86:11<2312::AID-CNCR19>3.0.CO;2-6 · 4.89 Impact Factor
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    ABSTRACT: This leader reviews recent advances in immunohistochemistry that are useful in the diagnosis of ovarian neoplasms. These include the value of different anticytokeratin antibodies in the distinction between a primary ovarian adenocarcinoma and a metastatic adenocarcinoma, especially of colorectal origin. These antibodies have also helped to clarify the origin of the peritoneal disease in most cases of pseudomyxoma peritonei. The value of antibodies against so called tumour specific antigens, such as CA125 and HAM56, in determining the ovarian origin of an adenocarcinoma is also reviewed. In recent years, several studies have investigated the value of a variety of monoclonal antibodies in the diagnosis of ovarian sex cord stromal tumours and in the distinction between these neoplasms and their histological mimics. These antibodies include those directed against inhibin, CD99, Mullerian inhibiting substance, relaxin like factor, melan A, and calretinin. Of these, anti-alpha inhibin appears to be of most diagnostic value. It is stressed that these antibodies should always be used as part of a larger panel and not in isolation.
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    ABSTRACT: A case is reported of yolk sac tumor occurring in the left ovary and complicated by pregnancy. The 22-year-old patient presented at 28 weeks gestation with virilization and elevated serum levels of testosterone and alpha-fetoprotein. The tumor showed the typical features of yolk sac tumor with a mixture of islands of Leydig cells. The accumulations of Leydig cells were well demarcated from the cellular components of the yolk sac tumor and were distributed throughout the tumor, although with predominant localization at the periphery. By immunohistochemistry the Leydig cells were intensely positive for vimentin and negative for cytokeratins, allowing clear distinction from the cell components of the yolk sac tumor, which were positive for cytokeratins and negative for vimentin. Testosterone was also identified in the cytoplasm of the Leydig cells. After tumor resection the testosterone and alpha-fetoprotein levels declined simultaneously; this, together with the immunohistochemical demonstration of testosterone, indicates that the Leydig cells were responsible for the endocrine manifestations. Furthermore, antibodies against inhibin alpha-subunit and calretinin could be used to detect the Leydig cells. The present case, a combination of yolk sac tumor and Leydig cells acting as a functioning stroma and causing virilization during pregnancy, is very rare.
    Pathology International 07/2000; 50(6):520-5. DOI:10.1046/j.1440-1827.2000.01073.x · 1.69 Impact Factor
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