Endometrial stromal sarcoma is a rare form of uterine cancer that originates in the supportive connective tissue, or stroma, of the uterine lining (endometrium). This cancer is distinct from the more frequently diagnosed endometrial carcinomas, which arise from the glands of the endometrium. These sarcomas grow within the wall of the uterus and can sometimes extend to other parts of the body, and their behavior is a defining feature of the disease.
Causes and Symptoms
While the precise cause of endometrial stromal sarcoma remains unknown, research has identified several risk factors. Prolonged exposure to estrogen without the balancing effects of progesterone, a state known as unopposed estrogen, is a primary risk factor. This hormonal imbalance is associated with conditions like obesity, polycystic ovary syndrome (PCOS), and endometrial hyperplasia. The use of tamoxifen, a drug used in breast cancer treatment, has also been linked to an increased risk.
The most common sign is abnormal uterine bleeding, which can manifest as bleeding between periods, heavy menstrual flow, or any postmenopausal bleeding. Some individuals may experience pelvic pain or a feeling of pressure in the abdomen. In some cases, a noticeable lump or mass in the pelvic area may be present, though it is possible for the tumor to cause no symptoms in its early stages.
Diagnosis and Staging Process
The diagnostic process begins with a pelvic exam to assess the uterus. If an abnormality is suspected, imaging tests like a transvaginal ultrasound or a more detailed magnetic resonance imaging (MRI) scan are used. While imaging can suggest a sarcoma, a definitive diagnosis requires a tissue sample for examination by a pathologist.
This tissue can be obtained through an endometrial biopsy, which takes a small sample, or a dilation and curettage (D&C) for more extensive sampling. In many instances, the final diagnosis is made after a hysterectomy is performed for a presumed benign condition.
Once the diagnosis is confirmed, the cancer is staged using the FIGO system to determine if it has spread. Stage I indicates the cancer is confined to the uterus. Stage II means it has spread to the cervix, while Stage III involves nearby pelvic tissues, the vagina, or lymph nodes. Stage IV signifies that the cancer has metastasized to distant organs like the bladder, rectum, or lungs.
Classification of Endometrial Stromal Sarcomas
Endometrial stromal sarcomas are classified into subtypes based on their microscopic appearance and genetic features, which has implications for their behavior and treatment. The World Health Organization (WHO) system distinguishes between tumors that are slow-growing and those that are more aggressive.
Low-Grade Endometrial Stromal Sarcoma (LG-ESS) is the most common type. These tumors are composed of cells that resemble the normal stroma and are slow-growing. LG-ESS often expresses estrogen and progesterone receptors, making it responsive to hormonal therapies, but it has a tendency for late recurrence.
High-Grade Endometrial Stromal Sarcoma (HG-ESS) is a more aggressive form. Its cells appear more abnormal, and the tumor is characterized by rapid growth and a higher likelihood of spreading. HG-ESS often lacks hormone receptors, making it less responsive to hormonal treatments.
Undifferentiated Uterine Sarcoma (UUS) is the rarest and most aggressive type. These tumors do not resemble endometrial stroma and are characterized by very rapid growth and spread, with a generally poorer prognosis. The specific classification is a determining factor in planning treatment.
Primary Treatment Modalities
The primary treatment for all stages and types of endometrial stromal sarcoma is surgery. The standard procedure is a total hysterectomy, removing the uterus and cervix, combined with a bilateral salpingo-oophorectomy, the removal of both fallopian tubes and ovaries. Removing the ovaries is an important step for low-grade tumors, as it eliminates the body’s main source of estrogen. In some cases, pelvic lymph nodes are also removed to check for cancer spread.
Following surgery, additional treatments may be recommended based on the sarcoma’s classification and stage. For LG-ESS, which is often hormone-receptor-positive, hormonal therapy is a common adjuvant treatment. Aromatase inhibitors or progestins are used to block estrogen’s effects and reduce the risk of recurrence.
For HG-ESS and UUS, chemotherapy is the primary adjuvant therapy. These aggressive tumors are less likely to respond to hormonal treatments, so drugs like doxorubicin are used to kill remaining cancer cells. Radiation therapy may be used in specific situations to control tumor growth in the pelvis, but its role in improving survival is more limited.
Prognosis and Long-Term Monitoring
The long-term outlook varies depending on the tumor’s grade and stage at diagnosis. Low-grade endometrial stromal sarcoma (LG-ESS), especially when diagnosed early, has a favorable prognosis. However, a defining characteristic of LG-ESS is its potential for late recurrence, which can occur many years after the initial treatment. High-grade (HG-ESS) and undifferentiated uterine sarcoma (UUS) are more aggressive, with recurrences happening sooner and a more challenging prognosis.
Given the risk of recurrence, long-term monitoring is a standard part of post-treatment care. This involves regular follow-up appointments with a physician, including pelvic exams. Imaging studies, such as CT or MRI scans, are also used to monitor for any signs of the cancer returning in the pelvis, abdomen, or lungs.
Because LG-ESS can recur a decade or more after diagnosis, lifelong vigilance is often recommended. This allows for the early detection of any recurrent disease, which can be managed with further treatment.