ovary chapter aca

Granulosa Cell Tumors

• Adult Granulosa Cell Tumors

  • Often positive for CD99, a marker for Ewing sarcoma.

  • Almost all cases show somatic mutation in FOXL2 gene (402C→G), useful for diagnosis.

  • FOXL2 mutation is specific for adult granulosa cell tumor except in rare Sertoli–Leydig tumors.

  • Testing for FOXL2 mutations may be helpful in complex cases.

• Juvenile Granulosa Cell Tumors

  • Typically diagnosed during the first two decades of life (80% of cases).

  • Presents with isosexual precocity.

  • Morphological features include:

    • Diffuse or macrofollicular growth patterns

    • Mucin-positive intrafollicular secretion

    • Larger cells, extensive luteinization

    • Lack of nuclear grooves and nuclear atypia

    • Variable mitotic activity, often high.

  • May show pseudopapillary features and consistent trisomy for chromosome 12.

• Differential Diagnosis:

  • Includes poorly differentiated tumors with scant cytoplasm.

  • Keratin expression (CK8, CK18) seen in one-third to half of cases.

  • Approximately 50% reactive for S-100 protein; none reactive for EMA.

  • Estrogen and progesterone receptors commonly expressed.

  • Elevated levels of inhibin and follicle regulatory proteins in serum.

Thecoma

• Most common after menopause (65% of patients).

• Usually unilateral with a well-defined capsule, solid cut surface, but may have cysts.

• Yellow color differentiates from fibromas.

• Microscopic Features:

  • Composed of spindle cells with pale grayish-pink cytoplasm and centrally located nuclei.

  • Intervening tissue may show collagen deposition and focal hyaline plaques.

  • Tumors may be heavily calcified in young women.

  • Cells exhibit abundant neutral fat staining with oil red O, and reticulin fibers surround individual cells.

Differential Diagnosis for Thecoma

• Luteinized adult granulosa cell tumor; FOXL2 mutation analysis can resolve diagnosis.

• Other differential considerations include epithelial-origin carcinomas, carcinoid tumors, and endometrial stromal tumors.

Prognosis of Granulosa Cell Tumors

• Adult granulosa cell tumors are generally indolent, with a prognosis similar to age-matched controls.

• Recurrences or metastases may occur many years post-surgery (10-20 years).

• Juvenile granulosa cell tumors also have a favorable prognosis when confined to ovary at diagnosis.

Fibromas and Related Tumors

• Fibromas:

  • Commonly unilateral, occur post-puberty, typically solid and lobulated.

  • Appear white and lack adhesions.

• Microscopic Features:

  • Composed of tightly packed spindle cells in a storiform pattern.

  • Variability in cellularity, hyaline bands, edema present.

  • Associated with specific syndromes (e.g., Gorlin syndrome).

Ovarian Edema and Fibromatosis

• Massive Edema:

  • Presents with abdominal pain and menstrual irregularities, potentially mistaken for neoplasm.

  • Characterized by stroma edema surrounding normal structures microscopically.

Sclerosing Stromal Tumor

• A benign ovarian neoplasm found in younger individuals, characterized by lobular growth pattern and dual cell population.

• Rarely presents with endocrine manifestations.

Small Cell Carcinoma of Hypercalcemic Type

• High-grade malignancy, often mistaken for granulosa cell tumor.

• Associated with hypercalcemia, large solid tumor appearance with necrosis.

• Poor prognosis, associated with mutations in SMARCA4.

Sertoli–Leydig Cell Tumors

• Composed of Sertoli and Leydig cells in varying proportions; predominance of Sertoli cell elements.

• Rare, comprising less than 0.1% of ovarian neoplasms, grossly solid with possible cystic areas.

Classification of Sertoli–Leydig Cell Tumors

1. Well Differentiated: Tubules lined by Sertoli-like cells.

2. Moderately Differentiated: Cords and sheets of Sertoli-like cells.

3. Poorly Differentiated: Sarcomatoid appearance with spindle-shaped cells.

Important Diagnostic Features

• Hermorrhagic and necrotic foci are indicative of high-grade malignancies and must be distinguished from other tumors.

• Proper immunohistochemical evaluation is crucial for accurate diagnosis and differentiation between tumor types.