What are the definitions and differences between borderline, benign, and malignant ovarian tumors in adult females, particularly those with a family history of ovarian cancer or previous gynecological conditions?

Definitions of Borderline, Benign, and Malignant Ovarian Tumors

Borderline ovarian tumors are primary epithelial lesions with cytologic features suggesting malignancy but critically lacking frank stromal invasion, resulting in a clinically indolent course with 5-year survival exceeding 80%. 1

Borderline Ovarian Tumors (Tumors of Low Malignant Potential)

Key Defining Characteristics:

• Borderline tumors exhibit epithelial proliferation with cytologic atypia and architectural complexity but without destructive stromal invasion. 1 This is the critical pathologic distinction separating them from malignant tumors.

• The preferred terminology is "borderline tumor" (e.g., serous borderline tumor, mucinous borderline tumor), with "atypical proliferative tumor" as an acceptable synonym. 1 The term "low malignant potential" is no longer recommended. 1

• These tumors comprise 10-15% of all ovarian tumors and do not fit into benign or malignant categories. 1

Clinical Behavior:

• Borderline tumors occur predominantly in younger women (mean age 38 years), present most commonly as stage I disease (92% in one series), and are candidates for fertility-sparing surgery. 1, 2

• The 5-year survival rate exceeds 80%, with overall survival reaching 98% in some series. 1, 3, 2

• Recurrences can occur late—70% after 5 years and 30% after 10 years—but most recurrences remain borderline rather than progressing to invasive carcinoma. 3, 4, 5

Histologic Subtypes:

• Serous and mucinous types are most common, though endometrioid, clear cell, Brenner, and seromucinous subtypes also occur. 1

• Serous borderline tumors form part of the spectrum of low-grade serous cancers and are managed primarily by surgery, responding poorly to chemotherapy. 1

Pathologic Features:

• Borderline tumors may have the visual appearance of peritoneal carcinomatosis, but microscopic evaluation fails to reveal frank invasion by tumor nodules. 1

• Microinvasion is defined as stromal invasion <5 mm according to the 2014 WHO Classification. 1

• Extra-ovarian implants occur in approximately 20% of serous borderline tumors and are classified as non-invasive (epithelial or desmoplastic type) or invasive. 1 The presence of invasive implants is the most important adverse prognostic factor. 1

Benign Ovarian Tumors

Benign ovarian tumors lack cytologic atypia, architectural complexity, and any invasive characteristics. 1

• These include cystadenomas and cystadenofibromas with simple epithelial lining and no proliferative activity. 1

• The threshold for diagnosing borderline tumor from benign tumor is epithelial stratification/complexity involving ≥10% of the epithelial volume, though some pathologists diagnose borderline tumors with <10% involvement. 1

• Benign serous cystadenomas have an 8-10% recurrence rate after cystectomy in the ipsilateral ovary. 3

Malignant Ovarian Tumors (Invasive Carcinomas)

Malignant ovarian tumors demonstrate frank stromal invasion with destructive infiltration of underlying tissue. 1

Type I vs Type II Classification:

• Type I cancers are low-grade, indolent tumors including low-grade serous, endometrioid, mucinous, clear-cell, and malignant Brenner tumors. 1 These are characterized by mutations in KRAS, BRAF, ERBB2, PTEN, PIK3CA, and ARID1A, with a stepwise progression from benign precursor lesions (including borderline tumors) to malignancy. 1

• Type II cancers are high-grade, aggressive tumors comprising high-grade serous, high-grade endometrioid, carcinosarcomas (MMMTs), and undifferentiated tumors. 1 These are associated with TP53 mutations (97% of high-grade serous cancers) and approximately 20% carry BRCA1/2 mutations. 1 There is no clear precursor lesion for Type II cancers. 1

Specific Malignant Subtypes:

• High-grade serous carcinomas account for 80-85% of ovarian carcinomas in Western countries, with 95% presenting as stage III-IV disease. 1 The majority originate in the fimbria of the fallopian tube (serous tubal intraepithelial carcinoma) and metastasize to ovaries and peritoneum. 1

• Endometrioid carcinomas account for approximately 10% of ovarian cancers, are usually early stage (stage I) and low grade, and are associated with endometriosis and ARID1A mutations. 1

• Clear-cell carcinomas account for approximately 5% of ovarian cancers, have good prognosis in stage I but worse prognosis in advanced stages due to chemotherapy resistance. 1

• Mucinous carcinomas have 5-year disease-specific survival of 80-90% overall, with excellent prognosis in early-stage disease. 6

• Carcinosarcomas (MMMTs) are the most aggressive ovarian tumors with the poorest prognosis, now considered variants of poorly differentiated epithelial ovarian cancer. 1, 7

Clinical Implications:

• In contrast to borderline tumors, frankly invasive carcinomas demonstrate peritoneal implants that microscopically and/or macroscopically invade the peritoneum. 1

• Patients with malignant tumors are typically older, present with advanced-stage disease, and require aggressive surgical debulking followed by platinum-based chemotherapy. 1, 7