Leydig Cell Tumors
Steven S. Shen, MD, PhD
Mahul B. Amin, MD
Jae Y. Ro, MD, PhD
Key Facts
Terminology
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Pure testicular stromal tumor composed of cells that recapitulate normal interstitial Leydig cells
Clinical Issues
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Most common type of sex cord stromal tumor (1-3% of testicular neoplasms)
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Majority have benign behavior; 10% malignant
Macroscopic Features
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Well-circumscribed, intraparenchymal nodule with golden-brown to yellow, or gray-white homogeneous cut surface
Microscopic Pathology
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Growth patterns: Solid (most common), insular, tubular, ribbon-like, and pseudofollicular
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Large, round or polygonal cells with well-defined cell borders, eosinophilic or vacuolated cytoplasm
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Relatively uniform round or ovoid nuclei, prominent nucleoli; focal nuclear pleomorphism, binucleated or multinucleated cells may be seen
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Cytoplasmic vacuoles or foamy cytoplasm (lipid content), lipofuscin (15%), and Reinke crystals (30-40%) may be seen
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Other uncommon features: Fatty metaplasia; spindle, clear cell, or microcystic changes; myxoid degeneration; calcification or ossification; and rhabdoid features
Ancillary Tests
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Positive for inhibin-α, calretinin, Melan-A(MART-1), and vimentin (strong and diffuse)
TERMINOLOGY
Abbreviations
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Leydig cell tumor (LCT)
Synonyms
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Interstitial cell tumor
Definitions
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Pure testicular stromal tumor composed of cells that recapitulate normal interstitial Leydig cells
CLINICAL ISSUES
Epidemiology
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Incidence
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Most common type of sex cord stromal tumor (1-3% of testicular neoplasms)
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Age
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Occurs in any age with 2 peaks: 5-10 & 30-35 years
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Presentation
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Testicular enlargement, usually painless, decreased libido (20%), gynecomastia (15%), undescended testis (10%), or precocious puberty
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May produce testosterone, androstenedione, and dehydroepiandrosterone
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May be associated with cryptorchidism, testicular atrophy, infertility
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Bilaterality in 3% of cases
Treatment
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Surgical approaches
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Orchiectomy is curative in majority of tumors; baseline staging work-up is required
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Retroperitoneal lymph node dissection may be required in older patients and those with tumors with unfavorable histology
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Testis-sparing surgery possible for young men
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Prognosis
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Majority have benign behavior
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Approximately 10% malignant and may metastasize
MACROSCOPIC FEATURES
General Features
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Well-circumscribed, intraparenchymal mass with golden-brown to yellow, or gray-white homogeneous cut surface
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Focal hemorrhage or necrosis may be seen (25%)
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Most confined within testis; extratesticular extension possible (10%)
Size
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Range: 1-10 cm (average: 3 cm)
MICROSCOPIC PATHOLOGY
Histologic Features
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Growth patterns: Solid (most common), insular, tubular, ribbon-like, and pseudofollicular
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Large, round or polygonal cells with well-defined cell borders, eosinophilic or vacuolated cytoplasm
-
Relatively uniform round or ovoid nuclei, prominent nucleoli; focal nuclear pleomorphism (including endocrine-type), binucleated, or multinucleated cells may be seen
-
Cytoplasmic vacuoles or foamy cytoplasm (lipid content), lipofuscin (15%), and Reinke crystals (30-40%) may be seen
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Frequent fibrous, hyalinized, edematous or myxoid stroma
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Other uncommon features: Fatty metaplasia; spindle, clear cell, or microcystic changes; myxoid degeneration; calcification or ossification; and rhabdoid features
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Features that tend to be seen more often in malignant tumors: Large tumor size (> 5 cm), infiltrative margins, vascular invasion, nuclear atypia, necrosis, high mitotic rate (> 3/10 high-power fields)
Cytologic Features
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Large, round or polygonal cells with prominent nucleoli, abundant eosinophilic cytoplasm, and well-defined cell borders
Predominant Pattern/Injury Type
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Diffuse and solid neoplastic growth
Predominant Cell/Compartment Type

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