Ovarian Serous Carcinoma
~Introduction
Ovarian serous carcinoma is the most common and most aggressive malignant tumor of the ovary, accounting for nearly 70% of all epithelial ovarian cancers and the majority of ovarian cancer–related deaths worldwide. It arises from the serous epithelium, which closely resembles the epithelium of the fallopian tube, supporting the modern concept that many high-grade serous carcinomas originate from the fimbrial end of the fallopian tube rather than the ovary itself.
Ovarian serous carcinoma is characterized by silent progression, late presentation, rapid spread within the peritoneal cavity, and high recurrence rates, making it one of the deadliest gynecologic malignancies.
~Epidemiology
Most commonly affects women aged 50–70 years
High-grade serous carcinoma occurs predominantly in postmenopausal women
Low-grade serous carcinoma occurs in younger women
Lifetime risk of ovarian cancer: ~1 in 70 women
Risk Factors
Increasing age
Family history of ovarian or breast cancer
BRCA1 and BRCA2 gene mutations
Lynch syndrome
Nulliparity
Early menarche and late menopause
Hormone replacement therapy
Protective Factors
Oral contraceptive use
Multiparity
Breastfeeding
Tubal ligation and salpingectomy
~Classification of Ovarian Serous Carcinoma
Ovarian serous carcinoma is classified into two distinct entities based on morphology, molecular genetics, and clinical behavior:
1. High-Grade Serous Carcinoma (HGSC)
Most common subtype (~90%)
Highly aggressive
Usually diagnosed at advanced stage
Associated with TP53 mutations and BRCA mutations
2. Low-Grade Serous Carcinoma (LGSC)
Rare
Indolent course
Develops from serous borderline tumors
Associated with KRAS and BRAF mutations
~Pathogenesis
High-Grade Serous Carcinoma
Originates from serous tubal intraepithelial carcinoma (STIC) in the fallopian tube
TP53 mutation is nearly universal
BRCA1/2 mutations impair DNA repair mechanisms
Rapid progression and genomic instability
Low-Grade Serous Carcinoma
Arises through a stepwise progression:
Benign serous tumor → Borderline tumor → LGSC
Less genetic instability
Hormone receptor positive
~Gross Pathology
Bilateral ovarian involvement (common in HGSC)
Large, solid-cystic masses
Irregular surface with papillary excrescences
Ascites frequently present
Peritoneal implants common
~Microscopic Features
High-Grade Serous Carcinoma
Complex papillary structures
Marked nuclear atypia
High mitotic activity
Tumor necrosis
Psammoma bodies may be present
Low-Grade Serous Carcinoma
Uniform small cells
Mild to moderate atypia
Low mitotic rate
Psammoma bodies common
~Clinical Features
Ovarian serous carcinoma often presents late due to nonspecific symptoms.
Common Symptoms
Abdominal distension
Bloating
Pelvic or abdominal pain
Early satiety
Weight loss
Urinary frequency
Menstrual irregularities (less common)
Signs
Ascites
Palpable adnexal mass
Pleural effusion (advanced disease)
~Diagnostic Evaluation
1. Tumor Markers
CA-125: Elevated in most cases
HE4 (Human Epididymis Protein 4)
Used for monitoring treatment response and recurrence
2. Imaging
Ultrasound: Complex ovarian mass
CT scan: Peritoneal spread and staging
MRI: Soft tissue characterization
3. Histopathology
Confirmatory diagnosis
Immunohistochemistry:
WT-1 positive
PAX8 positive
p53 mutation pattern (HGSC)
~Staging (FIGO Staging for Ovarian Cancer)
Stage I
Tumor limited to ovaries
Stage II
Extension to pelvis
Stage III
Peritoneal metastasis outside pelvis or lymph node involvement
Stage IV
Distant metastasis (liver parenchyma, lung, pleural effusion)
~Management
1. Surgical Treatment
Primary debulking surgery is the cornerstone
Total abdominal hysterectomy
Bilateral salpingo-oophorectomy
Omentectomy
Removal of all visible tumor
2. Chemotherapy
Platinum-based chemotherapy:
Carboplatin
Paclitaxel
Neoadjuvant chemotherapy in advanced disease
3. Targeted Therapy
PARP inhibitors (olaparib, niraparib)
Anti-angiogenic therapy (bevacizumab)
4. Hormonal Therapy
Useful in low-grade serous carcinoma
Aromatase inhibitors
~Prognosis
Prognosis depends on:
Stage at diagnosis
Completeness of cytoreduction
Tumor grade
BRCA mutation status
5-Year Survival Rates
Stage I: ~90%
Stage II: ~70%
Stage III: ~30–40%
Stage IV: ~15–20%
Low-grade tumors have better survival but frequent recurrences.
~Recurrence and Follow-Up
High recurrence rate, especially in HGSC
Monitoring with CA-125 and imaging
Long-term follow-up required
~Prevention and Screening
No effective screening for general population
Genetic testing for high-risk women
Risk-reducing salpingo-oophorectomy in BRCA mutation carriers
~Recent Advances
Liquid biopsy
Immunotherapy trials
Molecular subclassification
Personalized medicine approaches
~Conclusion
Ovarian serous carcinoma remains a major challenge in gynecologic oncology due to its aggressive nature and late presentation. Advances in molecular biology have transformed understanding of its origin and treatment, particularly with the introduction of targeted therapies. Early detection, optimal cytoreduction, and personalized therapy remain key to improving survival outcomes.
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