Can ovarian tumors other than germ cell tumors, such as epithelial and sex cord-stromal (SCS) tumors, also present as mixed types?

Mixed Ovarian Tumors: Not Limited to Germ Cell Types

All three major categories of ovarian tumors—germ cell, epithelial, and sex cord-stromal—can present as mixed types, though the frequency and clinical significance vary substantially among these categories. 1

Epithelial Ovarian Tumors Can Be Mixed

Mixed epithelial carcinomas are recognized entities but are now considered uncommon. 1 The 2014 WHO classification does not include a dedicated category for mixed epithelial carcinoma, though the prior classification specified that mixed carcinoma should only be diagnosed when the minor component represents at least 10% of the neoplasm. 1

Key Points About Mixed Epithelial Tumors:

• Mixed epithelial carcinomas combine different epithelial subtypes (e.g., serous with endometrioid, or mucinous with clear cell). 1
• The rarity of this diagnosis reflects improved understanding that most apparent "mixed" tumors are actually pure high-grade serous carcinomas with morphologic heterogeneity. 1
• When diagnosed, the 10% threshold for the minor component must be met to justify the mixed designation. 1

Mixed Epithelial-Mesenchymal Tumors

Carcinosarcomas (malignant mixed Müllerian tumors) represent a distinct category combining epithelial and mesenchymal elements. 1 These are classified separately as mixed epithelial-mesenchymal tumors in the WHO classification and are included among less common ovarian histopathologies requiring specialized management. 1

Sex Cord-Stromal Tumors Can Be Mixed

Sex cord-stromal tumors are classified into three main categories: pure stromal tumors, pure sex cord tumors, and mixed sex cord-stromal tumors. 2 This demonstrates that mixing within this tumor category is well-recognized.

Specific Mixed Sex Cord-Stromal Entities:

• Gynandroblastoma is a recognized mixed sex cord-stromal tumor. 1
• Ovarian stromal tumors with sex cord elements represent another mixed category. 1
• Stromal-Leydig cell tumors combine stromal and sex cord elements. 1

The overlapping histomorphology and immunoprofile of various sex cord-stromal tumors often contributes to diagnostic difficulties, but mixed forms are established entities. 2

Germ Cell Tumors Are Most Commonly Mixed

Mixed malignant germ cell tumors are the most frequent mixed ovarian tumor type, with yolk sac tumor (91%), dysgerminoma (61%), and immature teratoma (58%) being the most common components. 3 The most common combination is dysgerminoma with yolk sac tumor (25% of mixed germ cell tumors), often with sharply demarcated components. 3

Classification of Mixed Germ Cell Tumors:

• "Mixed GCTs (specify components)" is an explicit category in the WHO classification of germ cell tumors. 1
• These tumors frequently show haphazard arrangement of two or more subtypes resulting in complex morphology. 3
• Embryoid bodies play an apparent role in giving rise to yolk sac tumor and embryonal carcinoma components in mixed tumors. 3

Rare Mixed Germ Cell-Sex Cord-Stromal Tumors

Extremely rare tumors can combine germ cell and sex cord-stromal elements, though these are exceptional cases reported in young children with specific histologic features including retiform tubular structures. 4 This represents crossing between major tumor categories rather than mixing within a single category.

Clinical Implications

Accurate tumor typing is increasingly important for targeted therapies and identifying genetic predispositions (e.g., BRCA1/2 mutations with high-grade serous carcinoma, Lynch syndrome with endometrioid and clear cell carcinomas). 1 The correct pathological diagnosis is essential because different tumor types require completely different treatment approaches, particularly for fertility-sparing surgery in young patients. 1