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Mutations in DICER1 and Sertoli–Leydig Cell Tumors

• DICER1: Encodes an endoribonuclease involved in miRNA processing.

• Mutations: Commonly found in Sertoli–Leydig cell tumors and associated with:

  • Young age at diagnosis.

  • Higher-grade tumors.

  • Use of heterologous elements or retiform patterns.

• Germline Mutations: Imply hereditary predisposition not only to Sertoli–Leydig tumors but also to pleuropulmonary blastoma and embryonal rhabdomyosarcoma.

• Somatic FOXL2 Mutation: Found in few low-grade Sertoli or Sertoli–Leydig tumors, linked to older (postmenopausal) patients.

Patient Demographics and Symptoms

• Incidence: Mostly in young patients (average age 25).

  • Rare after menopause; some diagnosed during pregnancy.

  • Presentation can include significant intercellular edema.

• Bilateral Involvement: Seen in less than 2% of cases.

• Associated Symptoms: Around 50% exhibit signs of androgen excess such as:

  • Defeminization: Amenorrhea, breast atrophy, loss of subcutaneous tissue.

  • Masculinization: Excessive body hair, voice changes.

• Heterologous Elements: May present with tissues similar to mucinous epithelium, liver, skeletal muscle, or cartilage.

Types of Sertoli-Leydig Cell Tumors

• Classification:

  • Typical Components: Includes a variety of endocrine cells; can lead to carcinoid tumors.

  • Retiform Variant (15%): Comprises features resembling ovarian/testicular rete structures.

    • Microscopic findings: Irregular cleft-like spaces with cuboidal cells; prominent blunt papillae.

• Staining Characteristics:

  • Immune-staining may reveal testosterone and estradiol in Sertoli and Leydig cells; positive in primitive stromal cells.

  • Areas of Sertoli differentiation stain for keratin and Sox-9; positivity for inhibin, calretinin, WT1 is common.

Hormonal Influence and Clinical Features

• Endocrine Effects: Not all Sertoli–Leydig tumors show endocrine manifestations; some (especially pure Sertoli cell tumors) may secrete estrogen or progesterone.

• Prognosis:

  • Generally favorable but correlates with tumor differentiation and stage.

  • Overall malignancy rates vary:

    • Well-differentiated = benign;

    • Intermediate differentiation: 11% malignant;

    • Poor differentiation: 59% malignant.

• Management: Conservative surgery advised for young women with tumors confined to the ovary.

Steroid Cell Tumors

• Characteristics: Ovarian tumors composed of steroid hormone-secreting cells; exhibit eosinophilic or vacuolated cytoplasm.

• Hormonal Activity: Often associated with virilizing syndromes; some silent in terms of observable hormonal activity.

• Clinical Outcomes: Approx. 25% malignancy risk; larger tumors tend to present necrosis and atypia features.

Tumors in Ovary: Non-Specific Tumors and Metastases

• Differentiating Factors: Important to distinguish between primary tumors and metastatic involvement. Metastatic tumors often bilaterally involved, commonly from sources like:

  • Stomach, large bowel, appendix, breast, uterus, lung, skin (melanoma).

• Diagnostic Challenges: Overlap between ovarian and metastatic signs; immunohistochemical staining essential for differential diagnosis.