Leydig Cell Tumors

Steven S. Shen, MD, PhD

Mahul B. Amin, MD

Jae Y. Ro, MD, PhD

Key Facts

Terminology

Pure testicular stromal tumor composed of cells that recapitulate normal interstitial Leydig cells

Clinical Issues

Most common type of sex cord stromal tumor (1-3% of testicular neoplasms)
Majority have benign behavior; 10% malignant

Macroscopic Features

Well-circumscribed, intraparenchymal nodule with golden-brown to yellow, or gray-white homogeneous cut surface

Microscopic Pathology

Growth patterns: Solid (most common), insular, tubular, ribbon-like, and pseudofollicular
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, binucleated or multinucleated cells may be seen
Cytoplasmic vacuoles or foamy cytoplasm (lipid content), lipofuscin (15%), and Reinke crystals (30-40%) may be seen
Other uncommon features: Fatty metaplasia; spindle, clear cell, or microcystic changes; myxoid degeneration; calcification or ossification; and rhabdoid features

Ancillary Tests

Positive for inhibin-α, calretinin, Melan-A(MART-1), and vimentin (strong and diffuse)

LCT is often a well-circumscribed mass with a homogeneous yellow-tan cut surface. Focal cystic change

is present. Hemorrhage or necrosis is lacking. LCT often do not replace the entire testis.

LCT is composed of broad cords of tumor cells separated by paucicellular and edematous fibrous stroma. The tumor cells have uniform, round to ovoid nuclei and abundant eosinophilic cytoplasm.

TERMINOLOGY

Abbreviations

Leydig cell tumor (LCT)

Synonyms

Interstitial cell tumor

Definitions

Pure testicular stromal tumor composed of cells that recapitulate normal interstitial Leydig cells

CLINICAL ISSUES

Epidemiology

Incidence
- Most common type of sex cord stromal tumor (1-3% of testicular neoplasms)
Age
- Occurs in any age with 2 peaks: 5-10 & 30-35 years

Presentation

Testicular enlargement, usually painless, decreased libido (20%), gynecomastia (15%), undescended testis (10%), or precocious puberty
May produce testosterone, androstenedione, and dehydroepiandrosterone
May be associated with cryptorchidism, testicular atrophy, infertility
Bilaterality in 3% of cases

Treatment

Surgical approaches
- Orchiectomy is curative in majority of tumors; baseline staging work-up is required
- Retroperitoneal lymph node dissection may be required in older patients and those with tumors with unfavorable histology
- Testis-sparing surgery possible for young men

Prognosis

Majority have benign behavior
Approximately 10% malignant and may metastasize

MACROSCOPIC FEATURES

General Features

Well-circumscribed, intraparenchymal mass with golden-brown to yellow, or gray-white homogeneous cut surface
Focal hemorrhage or necrosis may be seen (25%)
Most confined within testis; extratesticular extension possible (10%)

Size

Range: 1-10 cm (average: 3 cm)

MICROSCOPIC PATHOLOGY

Histologic Features

Growth patterns: Solid (most common), insular, tubular, ribbon-like, and pseudofollicular
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
Frequent fibrous, hyalinized, edematous or myxoid stroma
Other uncommon features: Fatty metaplasia; spindle, clear cell, or microcystic changes; myxoid degeneration; calcification or ossification; and rhabdoid features
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)