Ovary tumor
Sex cord stromal tumors
Sertoli-Leydig cell tumor

Author: Natalia Buza, M.D.
Editor-in-Chief: Debra Zynger, M.D.

Revised: 26 November 2018, last major update September 2018

Copyright: (c) 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: Sertoli-Leydig cell tumor[title] ovary
Cite this page: Buza, N. Sertoli-Leydig cell tumor. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/ovarytumorsertolileydig.html. Accessed December 11th, 2018.
Definition / general
  • Rare ovarian tumor composed of sex cord (Sertoli cells) and stromal (Leydig cells) elements, accounting for less than 0.5% of all ovarian neoplasms
Essential features
  • Rare ovarian tumor composed of sex cord (Sertoli cells) and stromal (Leydig cells) elements
  • May occur sporadically or in patients with DICER1 syndrome
  • Often harbors DICER1 (germline or sporadic) mutations
  • Express general sex cord markers (inhibin, calretinin, SF1, FOXL2 and CD56), CK7 and EMA immunostains are negative
  • Behavior correlates with tumor grade and histologic subtype
    • Well differentiated Sertoli-Leydig cell tumors are essentially benign
    • Approximately 10% of moderately differentiated and 13 - 59% of poorly differentiated tumors have malignant behavior, heterologous elements, retiform pattern, tumor rupture and spread outside the ovary (stage II or higher tumor stage) are adverse prognostic factors
Terminology
  • Sertoli-Leydig cell tumor
    • Well differentiated
    • Moderately differentiated / intermediate grade
    • Poorly differentiated
  • Sertoli-Leydig cell tumor with heterologous elements
  • Sertoli-Leydig cell tumor, retiform variant
  • Histologic grade and subtype correlates with clinical behavior (see below)
Epidemiology
Etiology
Clinical features
  • Clinical presentation may include pelvic pain or a pelvic mass, rarely with ascites and tumor rupture
  • Androgenic hormonal symptoms (virilization) are common and present in approximately 50% of patients; they include hirsutism, clitoromegaly, breast atrophy and menstrual irregularity or amenorrhea (Am J Surg Pathol 1985;9:543)
  • Estrogenic hormonal manifestations are rare
Diagnosis
  • May be suspected clinically in a young patient presenting with a combination of virilization, elevated testosterone levels and ovarian / pelvic mass on imaging studies
  • Clinical presentation often overlaps with other, more common entities, as nearly half of patients with Sertoli-Leydig cell tumors lack the characteristic androgenic symptoms and may be older (peri or postmenopausal, expanding the clinical differential diagnosis) (Eur J Gynaecol Oncol 2017;38:214)
  • Intraoperative frozen section evaluation is helpful to confirm the clinical suspicion and guide the surgical management
Laboratory
Radiology description
  • Ultrasound, pelvic CT or MRI can show a solid or solid and cystic adnexal mass
Radiology images

Images hosted on other servers:

Large tumor

Prognostic factors
Case reports
Treatment
Gross description
  • Almost always unilateral (Am J Surg Pathol 1985;9:543)
  • Tumor size ranges widely from < 1 cm to 35 cm (mean 12 - 14 cm) (Am J Surg Pathol 1985;9:543)
  • Cut surface is typically solid, tan-yellow
  • Cystic component may also be seen, especially in tumors with heterologous elements or with a retiform morphologic pattern
  • Poorly differentiated tumor may show grossly identifiable foci of necrosis
Gross images

Images hosted on PathOut server:

Contributed by Natalia Buza, M.D.

Sertoli-Leydig cell tumor, intermediate grade


 Contributed by AFIP

Solid yellow lobulated mass

Cystic tumor

Retiform pattern

Heterologous elements


Frozen section description
Frozen section images

Images hosted on PathOut server:

Contributed by Natalia Buza, M.D.

Well differentiated tumor

Moderately differentiated tumor

Poorly differentiated tumor

Heterologous elements

Microscopic (histologic) description
  • 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
Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Natalia Buza, M.D.

Well differentiated tumor

Moderately differentiated tumor


Poorly differentiated tumor

Retiform pattern

Heterologous elements



AFIP

Heterologous elements


Positive stains
Negative stains
Molecular / cytogenetics description
  • Up to 60% harbor hotspot missense mutation affecting the RNase IIIb domain of DICER1 (Mod Pathol 2015;28:1603)
  • More recent study identified DICER1 mutations in all of their moderately and poorly differentiated tumors, whereas none of the well differentiated tumors had DICER1 mutations, raising the possibility that well differentiated Sertoli-Leydig cell tumors may represent a different pathogenetic entity (Am J Surg Pathol 2017;41:1178)
  • FOXL2 mutation, a common molecular event in adult granulosa cell tumors of the ovary, is typically absent in Sertoli-Leydig cell tumors and has only been reported in a small number of cases (Histopathology 2016;68:279, J Pathol 2010;221:147, Int J Gynecol Pathol 2018;37:305)
Differential diagnosis
Board review question #1
Sertoli-Leydig cell tumors of the ovary commonly harbor mutations in which gene?

  1. ARID1A
  2. DICER1
  3. FOXL2
  4. SMARCA4
  5. STK11
Board review answer #1
B. Somatic hotspot 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.
Board review question #2
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-
Board review answer #2
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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