Definition/General
Introduction:
Sertoli-Leydig cell tumor is a rare sex cord-stromal tumor of the ovary
It accounts for <1% of all ovarian tumors
It is composed of Sertoli cells and Leydig cells in varying proportions
It typically causes virilization due to testosterone production.
Origin:
Originates from the sex cord-stromal cells of the ovary
These cells normally form the testicular architecture in male development
The tumor recapitulates male gonadal development
It produces androgens, particularly testosterone and androstenedione.
Classification:
Classified by degree of differentiation: Well-differentiated (tubular pattern)
Moderately differentiated (mixed pattern)
Poorly differentiated (sarcomatoid pattern)
Retiform variant (resembles rete testis)
With heterologous elements (cartilage, skeletal muscle).
Epidemiology:
Peak incidence in 2nd-3rd decades (average age 25 years)
Rare tumor (0.5% of ovarian tumors)
Unilateral in >95% cases
Higher incidence in reproductive age group
Indian population shows similar age distribution.
Clinical Features
Presentation:
Virilization (75-85% cases) with hirsutism and deepening voice
Amenorrhea or oligomenorrhea
Male pattern baldness
Clitoral enlargement
Muscle mass increase
Abdominal mass and pain.
Symptoms:
Progressive masculinization over months
Hirsutism (facial and body hair)
Voice changes (deepening)
Acne and oily skin
Decreased breast size
Menstrual irregularities
Abdominal distension.
Risk Factors:
Young age (reproductive years)
No established genetic factors
Rare familial cases reported
No environmental associations identified
Previous ovarian disorders (unclear association)
Hormonal factors (unclear).
Screening:
Serum testosterone levels (markedly elevated)
DHEA-S levels (elevated)
LH and FSH (suppressed)
Pelvic ultrasound
MRI for tumor characterization
Regular monitoring of virilization signs.
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Gross Description
Appearance:
Solid, lobulated mass with smooth capsule
Yellow-tan to gray cut surface
Size ranges from 2-20 cm (average 8-10 cm)
Hemorrhage and necrosis may be present
Cystic areas less common.
Characteristics:
Unilateral in >95% cases
Well-encapsulated appearance
Cut surface shows solid yellow-brown areas
Lobulated architecture
Hemorrhagic foci common
Firm to soft consistency.
Size Location:
Variable size (1-30 cm diameter)
Average size 8-12 cm
Unilateral involvement (>95%)
No specific ovarian location preference
Larger tumors may show surface nodularity
Capsular integrity usually maintained.
Multifocality:
Unifocal within the affected ovary
Bilateral disease extremely rare (<2%)
Single dominant mass pattern
No multicentricity
Capsular breach indicates advanced disease.
Microscopic Description
Histological Features:
Tubular structures lined by Sertoli cells
Leydig cells in intervening stroma
Variable architectural patterns
Lipid-rich Leydig cells with eosinophilic cytoplasm
Crystalloids of Reinke may be present.
Cellular Characteristics:
Sertoli cells: Columnar to cuboidal with pale cytoplasm
Oval nuclei with prominent nucleoli
Leydig cells: Large polygonal cells
Abundant eosinophilic cytoplasm
Round nuclei with prominent nucleoli
Lipid vacuoles common.
Architectural Patterns:
Tubular pattern (well-differentiated)
Solid nests and cords (intermediate differentiation)
Sarcomatoid pattern (poorly differentiated)
Retiform pattern (rete testis-like)
Mixed patterns common.
Grading Criteria:
Well-differentiated: Tubular architecture predominant
Intermediate: Mixed tubular and solid areas
Poorly differentiated: Solid spindle cell areas
Nuclear atypia and mitotic activity increase with poor differentiation.
Immunohistochemistry
Positive Markers:
Inhibin-alpha (85-95%)
Calretinin (80-90%)
SF-1 (steroidogenic factor-1)
CD99 (variable)
Vimentin
Alpha-smooth muscle actin (Sertoli cells)
Androgen receptor (positive)
Melan-A (Leydig cells).
Negative Markers:
Cytokeratin (usually negative)
EMA (negative)
WT1 (negative)
S-100 (negative)
Alpha-fetoprotein (negative)
HCG (negative)
Chromogranin (negative)
Synaptophysin (negative).
Diagnostic Utility:
Essential for sex cord-stromal tumor confirmation
Inhibin and calretinin distinguish from epithelial tumors
Distinguish from granulosa cell tumor
SF-1 positivity confirms steroidogenic origin
Androgen receptor supports androgen production.
Molecular Subtypes:
DICER1 mutations (60-70% of cases)
FOXL2 wild-type (unlike granulosa cell tumor)
Wnt/β-catenin pathway activation
AKT pathway alterations
CTNNB1 mutations (retiform variant)
PIK3CA mutations (rare).
Molecular/Genetic
Genetic Mutations:
DICER1 mutations (60-70%)
CTNNB1 mutations (retiform variant)
APC mutations (rare)
PIK3CA mutations
FOXL2 wild-type
TP53 mutations (poorly differentiated)
Chromosomal instability (advanced cases).
Molecular Markers:
DICER1 protein loss (mutated cases)
β-catenin nuclear accumulation (retiform)
Steroidogenic enzymes overexpression
Androgen receptor expression
Inhibin-alpha overexpression
Anti-Müllerian hormone expression.
Prognostic Significance:
Degree of differentiation most important prognostic factor
Well-differentiated tumors have excellent prognosis
Poorly differentiated tumors higher recurrence risk
Retiform variant intermediate prognosis
Heterologous elements may worsen prognosis.
Therapeutic Targets:
Anti-androgens (spironolactone, cyproterone acetate)
GnRH agonists (leuprolide)
5α-reductase inhibitors (finasteride)
mTOR inhibitors (experimental)
Wnt pathway inhibitors (experimental)
Anti-angiogenic agents.
Differential Diagnosis
Similar Entities:
Granulosa cell tumor (coffee-bean nuclei, estrogenic effects)
Steroid cell tumor (pure Leydig cells)
Fibroma-thecoma (spindle cells, no tubules)
Krukenberg tumor (signet ring cells)
Hilus cell tumor (hilar location).
Distinguishing Features:
Sertoli-Leydig: Tubular architecture
Virilization
Testosterone elevation
Granulosa: Coffee-bean nuclei
Call-Exner bodies
Estrogenic effects
Steroid cell: Pure Leydig cells
No tubular pattern
Fibroma: Dense collagen
Inhibin negative
Krukenberg: Signet ring cells
Bilateral.
Diagnostic Challenges:
Distinguishing degree of differentiation
Differentiating from other sex cord tumors
Retiform variant recognition
Identifying heterologous elements
Bilateral vs unilateral disease assessment
Immunohistochemistry essential.
Rare Variants:
Retiform Sertoli-Leydig tumor (rete testis pattern)
With heterologous elements (cartilage, muscle)
Well-differentiated tubular variant
Poorly differentiated sarcomatoid variant
Sertoli cell tumor (pure form)
Leydig cell tumor (pure form).
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Ovarian mass, [side], measuring [X x Y x Z] cm, weighing [X] grams
Diagnosis
Sertoli-Leydig Cell Tumor, [Well/Moderately/Poorly] Differentiated
Classification
WHO Classification: Sex Cord-Stromal Tumor, Sertoli-Leydig Cell Tumor
Histological Features
Shows [tubular/solid/mixed] architecture with Sertoli cells and Leydig cells
Degree of Differentiation
[Well/Intermediate/Poor] differentiation with [describe pattern]
Hormonal Effects
Associated with [virilization/no virilization], testosterone [elevated/normal]
Special Studies
IHC: Inhibin [positive/negative], Calretinin [positive/negative], SF-1 [positive/negative]
Molecular: DICER1 mutation [detected/not detected]
Hormones: Testosterone [X] ng/dL (normal <50 ng/dL)
Prognostic Factors
Differentiation: [Well/Intermediate/Poor], Size: [X] cm, Stage: [I/II/III/IV]
Final Diagnosis
Ovarian Sertoli-Leydig Cell Tumor, [differentiation grade], [Side]