Low Grade Serous Carcinoma (LGSC) is a distinct and rare subtype of epithelial ovarian cancer, accounting for less than 10% of all serous ovarian malignancies. This disease is characterized by its relatively slow-growing nature, setting it apart from the more common and aggressive high-grade serous carcinoma (HGSOC). Unlike HGSOC, LGSC often affects women at a younger age and follows a protracted clinical course. Its unique biological and molecular profile requires a specialized approach to diagnosis and treatment.
Understanding the Pathology of Low Grade Serous Carcinoma
The designation “low grade” refers to specific cellular characteristics observed under a microscope. LGSC cells exhibit low mitotic activity and a lack of significant nuclear atypia. These features indicate a less aggressive cellular behavior compared to high-grade tumors.
LGSC is genetically distinct, with a characteristic profile involving the Mitogen-Activated Protein Kinase (MAPK) signaling pathway. A significant portion of these tumors harbor activating mutations in genes like KRAS, BRAF, or NRAS, found in approximately 33%, 6%, and 8% of cases, respectively. These mutations drive tumor growth by constantly activating the cell signaling pathway.
The molecular profile of LGSC is also notable for the near-absence of TP53 tumor suppressor gene mutations. This is in stark contrast to HGSOC, where TP53 mutations are almost universally present. This difference in genetic makeup explains why LGSC is often less responsive to conventional platinum-based chemotherapy regimens.
Symptoms and Diagnostic Procedures
The symptoms associated with LGSC are often vague and nonspecific, making early detection challenging. Patients commonly report persistent abdominal bloating, pelvic discomfort, or a feeling of being full quickly when eating. Other symptoms may include changes in bowel habits, such as constipation, or an increased frequency or urgency in urination, as the tumor mass presses on surrounding organs.
Diagnostic workup begins with imaging studies, including transvaginal ultrasound and cross-sectional imaging like CT or MRI scans. These tests help visualize the tumor’s size and extent and detect potential spread to the pelvis or abdomen. The tumor marker CA-125 is also measured in the blood.
Although an elevated CA-125 level can support suspicion, its utility in LGSC is limited, as levels may not be as high as with HGSOC, and the marker can be elevated due to benign conditions. Definitive diagnosis and grading rely on a biopsy or surgical sample examined by a pathologist. This tissue analysis confirms the low-grade nature and distinguishes it from other ovarian cancer subtypes.
Specialized Treatment Strategies
The initial step in managing LGSC is maximal cytoreductive surgery. The goal of this procedure is to remove all visible evidence of the tumor, as the amount of residual disease strongly influences the long-term outcome. Achieving no visible residual disease is a primary objective for patients with advanced-stage LGSC.
Following surgery, systemic therapy is often considered, but the approach differs significantly from HGSOC due to the disease’s inherent chemoresistance. Traditional platinum and taxane-based chemotherapy regimens show low response rates, and their benefit is frequently questioned. This has shifted the focus toward molecularly driven treatments.
Hormonal therapy is a preferred systemic option because LGSC tumors frequently express high levels of estrogen and progesterone receptors. Treatments such as aromatase inhibitors (e.g., letrozole or anastrozole) or the anti-estrogen drug tamoxifen are commonly used, particularly in the adjuvant or maintenance setting. Hormonal therapy can offer prolonged disease stabilization with relatively few side effects.
Targeted therapies represent a significant advancement, leveraging the MAPK pathway mutations. Mitogen-activated protein kinase kinase (MEK) inhibitors, such as trametinib, directly target this hyperactive signaling cascade. These agents have demonstrated objective response rates around 15% to 26% in clinical trials, providing a valuable option for patients, especially those with recurrent disease.
Prognosis and Long Term Management
LGSC is characterized by a more favorable long-term outlook compared to HGSOC, with median overall survival often reported in the range of 81 to 97 months. Despite this slower growth, LGSC has a high tendency to recur, even after many years, with historical recurrence rates estimated as high as 70-80%.
The extended timeline necessitates a long-term, structured approach to management and surveillance. Follow-up typically involves regular physical examinations, monitoring of tumor markers like CA-125, and periodic imaging studies to detect any recurrence early.
For patients who experience recurrence, treatment options are guided by the patient’s prior therapies and the location of the disease. Secondary cytoreductive surgery may be considered if a complete resection is possible. If surgery is not feasible, systemic options revolve around hormonal therapy, targeted MEK inhibitors, or participation in clinical trials exploring new drug combinations.