ovarian Sertoli-Leydig tumor
Definition: Sertoli-Leydig cell tumour is a group of tumors composed of variable proportions of Sertoli cells, Leydig cells, and in the case of intermediate and poorly differentiated neoplasms, primitive gonadal stroma and sometimes heterologous elements. (WHO, 2003)
Sertoli-Leydig cell tumors (SLCT) comprise less than 1% of ovarian tumors.
Synopsis
usually unilateral ovarian tumor
may release male sex steroid hormones and produce defeminization (breast atrophy, amenorrhea, loss of hair and sterility) to masculinization (hirsutism, voice change and hypertrophy of the clitoris).
Macroscopy
solid tumors with a white-grey cut surface
Microscopy
Sertoli cells and Leydig cells.
cellular lobules separated by stroma
Leydig cells may be absent.
Types
well-differentiated Sertoli-Leydig tumor: cells are arranged as tubules within a fibroconnenctive stroma.
moderately-differentiated Sertoli-Leydig tumor: poorly formed tubules and Leydig cells.
poorly-differentiated Sertoli-Leydig tumor: disorderly arranged epithelial cells scattered in a sarcomatous stroma.
Differential diagnosis
Leydig cell tumor
- Some tumors are made purely of the Leydig cells. These so-called Hilus cell tumors, are rare and micoscopically consist of large lipid-laden cells. These cells exhibit the Reinke cystals, ultrastructural structures characteristic of the Leydig cells.
- The true Leydig cell tumors are benign. These tumors may occur at the non-hilar region of the ovary (non-hilar Leydig cell tumors).
Prognosis
recurrence or metastasis: less than 5%.
Immunochemistry
inhibin +
+/- BCL2 + (#14734221#)
Cytogenetics
t(5;18)(p13;q12)
der(18)r(5;18)(p15.3p13;p11.3q12)
+6,+12
Molecular biology
DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors. (#21205968#)
- DICER1 mutations are associated with both familial multinodular goiter and multinodular goiter with ovarian Sertoli-Leydig cell tumor of the ovary (OSLCT), independent of pleuropulmonary blastoma (PPB). (#21205968#)
- These germline DICER1 mutations are associated with dysregulation of miRNA expression patterns.
Histogenesis
The nature of the Leydig cells has been a subject of controversy and it is unclear whether they are clonally related to the neoplasm or instead proliferate as a non-neoplastic response to the Sertoli-cell component. (#17885485#)
At least in some cases, the Leydig cell component of SLCT is neoplastic rather than reactive in nature, and shares a common clonal origin with the coexisting Sertoli cell component. Similarly, the heterologous components, when present, appear to share clonal origin with the Sertoli cell components. (#17885485#)
See also
ovarian tumors
- ovarian sex cord-stromal tumors
References
DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors. Rio Frio T, Bahubeshi A, Kanellopoulou C, Hamel N, Niedziela M, Sabbaghian N, Pouchet C, Gilbert L, O’Brien PK, Serfas K, Broderick P, Houlston RS, Lesueur F, Bonora E, Muljo S, Schimke RN, Bouron-Dal Soglio D, Arseneau J, Schultz KA, Priest JR, Nguyen VH, Harach HR, Livingston DM, Foulkes WD, Tischkowitz M. JAMA. 2011 Jan 5;305(1):68-77. PMID: #21205968#
Molecular genetic evidence supporting the neoplastic nature of the Leydig cell component of ovarian Sertoli-Leydig cell tumors. Emerson RE, Wang M, Roth LM, Zheng W, Abdul-Karim FW, Liu F, Ulbright TM, Eble JN, Cheng L. Int J Gynecol Pathol. 2007 Oct;26(4):368-74. PMID: #17885485#
Second and third malignant solid tumor in a girl with ovarian Sertoli-Leydig tumor. Panagiotou JP, Polychronopoulou S, Sofou K, Vanvliet-Constantinidou C, Papandreou E, Haidas S. Pediatr Blood Cancer. 2006 May 1;46(5):654-6. PMID: #16411221#
Overexpression of the BCL2 gene in a Sertoli-Leydig cell tumor of the ovary: a pathologic and cytogenetic study. Truss L, Dobin SM, Rao A, Donner LR. Cancer Genet Cytogenet. 2004 Jan 15;148(2):118-22. PMID: #14734221#
Trisomy 8 as sole karyotypic aberration in an ovarian metastasizing Sertoli-Leydig cell tumor. Manegold E, Tietze L, Günther K, Fleischer A, Amo-Takyi BK, Schröder W, Handt S. Hum Pathol. 2001 May;32(5):559-62. PMID: #11381376#