• Rare, accounting for less than 0.5% of all ovarian neoplasms
• Most common in young patients with a mean age of 25 years (Am J Surg Pathol 1985;9:543)
• May also present after menopause (Eur J Gynaecol Oncol 2017;38:214)

• May occur sporadically or in patients with DICER1 syndrome (601200: Pleuropulmonary Blastoma; PPB [Accessed 21 September 2018])
  • Rare tumor predisposition syndrome caused by germline mutations in DICER1, a gene encoding the RNase III enzyme in the microRNA maturation pathway (N Engl J Med 2012;366:234, Br J Cancer 2013;109:2744)
  • Other tumors and disorders associated with DICER1 syndrome include pleuropulmonary blastoma, cystic nephroma, multinodular goiter and botryoid embryonal rhabdomyosarcoma, among others (Nat Rev Cancer 2014;14:662)
  • Germline mutation is generally a truncating mutation; may occur anywhere in the gene
  • Second hit somatic mutation is a focused hot spot missense mutation affecting the RNase IIIb domain of DICER1 (Histopathology 2016;69:903)
  • Sporadic Sertoli-Leydig cell tumors (moderately and poorly differentiated) harbor somatic mutations at the same hot spot of DICER1 gene (Am J Surg Pathol 2017;41:1178)
  • Prevalence of germline DICER1 mutations among unselected Sertoli-Leydig cell tumor patients is currently unknown because not all patients undergo genetic counseling and testing

• Ultrasound, pelvic CT or MRI can show a solid or solid and cystic adnexal mass

Images hosted on other servers:

• 9 year old girl with retiform tumor (Int J Clin Oncol 2011;16:705)
• 17 year old girl with heterologus elements masquerading as mucinous tumor on frozen section (J Clin Diagn Res 2015;9:ED01)
• 19 year old woman with heterologous element (Int J Clin Exp Pathol 2014;7:1176)
• 21 year old woman with mucinous adenocarcinoma as heterologous element in moderately differentiated tumor (Pathol Res Pract 2010;206:489)
• Familial multinodular goiter and Sertoli-Leydig cell tumors associated with a large intragenic in frame DICER1 deletion (Eur J Endocrinol 2018;178:K11)

• Conservative fertility sparing surgery (unilateral salpingo-oophorectomy) and staging procedure (with or without lymphadenectomy) is usually performed in young patients with stage I tumors (Gynecol Oncol 2012;125:673, Gynecol Oncol 2012;127:384, J Obstet Gynaecol Res 2013;39:305)
• Older patients who do not wish to preserve fertility typically undergo bilateral salpingo-oophorectomy, total hysterectomy and complete surgical staging
• Platinum based adjuvant chemotherapy has also been reported in patients with moderately and poorly differentiated tumors, heterologous mesenchymal elements, advanced stage or rupture (J Obstet Gynaecol Res 2013;39:305, Eur J Gynaecol Oncol 2017;38:214)
• Genetic counseling and germline DICER1 mutation testing is recommended (Am J Surg Pathol 2017;41:1178)

 

Contributed by Natalia Buza, M.D.

• Difficulty of histologic diagnosis increases with tumor grade
• While Sertoli and Leydig components can be readily identified in well differentiated tumors, less differentiated tumors lack well formed Sertoli cell tubules and have fewer Leydig cells
• Well differentiated
  • Open or compressed Sertoli cell tubules, admixed with clusters of Leydig cells in the intervening stroma
  • Sertoli cells are low columnar to cuboidal with oval to round nuclei, which often show nuclear grooves and small nucleoli
  • Leydig cells can be recognized by their round nuclei and abundant eosinophilic cytoplasm with characteristic Reinke crystals and lipofuscin pigment
  • No significant atypia or mitotic activity
• Moderately differentiated
  • Typically has a diffuse or lobulated architectural pattern and may show alternating hypo and hypercellularity on low magnification
  • Sertoli cells form compressed tubules, cords or diffuse sheets and have hyperchromatic, oval or spindled nuclei with mild to moderate atypia and occasional mitotic figures (average 5 per 10 high powered fields)
  • Rare small clusters of Leydig cells are admixed with the Sertoli cell component
• Poorly differentiated
  • Diffuse sheets of immature, sarcomatoid Sertoli cells with moderate to marked nuclear atypia and only rare foci of vague cord formation
  • Increased mitotic activity, up to 20 mitoses per 10 high powered fields
  • Leydig cells are difficult to find; a few small clusters are typically located at the periphery of tumor nodules
• Sertoli-Leydig cell tumor with heterologous elements
  • Heterologous (epithelial or mesenchymal) elements may be seen in approximately 20% of moderately or poorly differentiated tumors and in retiform Sertoli-Leydig cell tumor (Am J Surg Pathol 1985;9:543)
  • Most common heterologous element is mucinous (intestinal or gastric type) epithelium, which may be benign, borderline or malignant (Cancer 1982;50:2448)
  • Carcinoid tumor (trabecular or goblet cell) has also been described arising from heterologous mucinous epithelial elements (Cancer 1982;50:2448)
  • Heterologous mesenchymal (cartilage or skeletal muscle) elements are less common (Cancer 1982;50:2465)
  • Rare focal hepatocyte differentiation has also been reported and may be associated with increased serum AFP (Hum Pathol 1999;30:611)
• Sertoli-Leydig cell tumor, retiform variant
  • Approximately 15% of Sertoli-Leydig cell tumors demonstrate focal or diffuse retiform pattern, forming anastomosing, slit-like, irregular spaces or multicystic, sieve-like or papillary architecture (Am J Surg Pathol 1985;9:543, Am J Surg Pathol 1983;7:755)

Contributed by Natalia Buza, M.D.



AFIP images

Sertoli-Leydig cell tumors of the ovary commonly harbor mutations in which gene?

1. ARID1A
2. DICER1
3. FOXL2
4. SMARCA4
5. STK11

B. Somatic hot spot missense mutation affecting the RNase IIIb domain of DICER 1 gene are common in Sertoli-Leydig cell tumors. In a recent large case series all moderately and poorly differentiated Sertoli-Leydig cell tumors harbored DICER 1 mutations.

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Reference: Sertoli-Leydig cell tumor

Sertoli-Leydig cell tumors of the ovary typically show which of the following immunoprofiles?

1. CK7+ / EMA+ / inhibin- / calretinin+
2. CK7- / EMA+ / inhibin+ / calretinin-
3. CK7- / EMA- / inhibin+ / calretinin+
4. CK7- / EMA- / inhibin+ / calretinin-

C. Sertoli-Leydig cell tumors express general sex cord immunohistochemical markers, such as inhibin and calretinin. CK7 and EMA immunostains are negative and can help differentiating Sertoli-Leydig cell tumors from sertoliform endometrioid adenocarcinoma of the ovary, which is typically positive for both CK7 and EMA.

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Reference: Sertoli-Leydig cell tumor