Leiomyosarcomas

RELATED CONDITIONS: Gastrointestinal stromal tumors (GISTs), leiomyomas

DEFINITION: Leiomyosarcomas are rare malignant tumors arising from smooth muscle, most commonly in between the muscular and mucosal layers of the digestive tract and the uterus's myometrium (muscular layer). The stomach and small intestine are the most commonly involved organs. The ileum is the most common region of small bowel affected.

Risk factors: Shared factors implicated in endometrial cancer and leiomyosarcoma include nulliparity (no births), obesity, and diabetes. Some studies associated pelvic irradiation and chlorophenol exposure with extrauterine leiomyosarcoma. Another study found Concomitant Crohn's disease in 6 percent of patients.

Etiology and the disease process: The malignant cells are clones of a single, spindle-shaped cell transformed by an external mutagen. Biological etiologies such as Epstein-Barr virus (EBV), as seen in leiomyosarcomas with EBV deoxyribonucleic acid (DNA) from immunosuppressed patients such as transplant recipients and patients infected with the human immunodeficiency virus (HIV), are possible mutagens. One characteristic of a leiomyosarcoma’s growth that differentiates it from other tumors is its propensity to grow outward into the abdominal cavity instead of inward, causing obstructive symptoms relatively late in the disease. Malignant transformation of a preexisting uterine leiomyoma is possible but has been estimated to occur in only 0.2 percent of cases.

Incidence: Leiomyosarcomas are comparatively rare, accounting for around 2 to 9 percent of all soft-tissue sarcomas. About 30 percent of leiomyosarcomas are found in the small intestine. Uterine leiomyosarcomas make up 1 to 4 percent of all uterine cancers and about 30 percent of all uterine sarcomas. In the United States, extrauterine leiomyosarcomas are estimated at 1.4 cases per 100,000, while uterine leiomyosarcomas have an annual incidence rate of 0.64 per 100,000.

Symptoms: Most symptoms of a leiomyosarcoma mimic those of other, more common digestive tract cancers, such as colorectal cancer. These include overt symptoms such as bleeding or obstruction (constipation) in large tumors. Bleeding may be acute and severe enough to require blood transfusions if a tumor has eroded a blood vessel. Patients may complain of vague symptoms such as fatigue, weight loss, malaise (from long-term blood loss), and abdominal pain. Some patients may have no symptoms, delaying diagnosis. In uterine leiomyosarcomas, a mass may be felt through the abdominal wall and mistaken for pregnancy. However, a pregnancy test would be negative. Other symptoms may include menometrorrhagia (increased, frequent, and irregular bleeding from the vagina), infertility and pressure symptoms causing difficulty in swallowing, and compression or invasion of the bladder and ureter (urine duct from the kidney to the bladder).

Screening and diagnosis: An ultrasound-guided biopsy may confirm an extrauterine leiomyosarcoma diagnosis. Ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) are less helpful. A pathologist diagnoses the tumor type and can determine cancerous changes in cells and the histologic grades (number of cell divisions, defined as five or more in ten microscopic field samples). Immunohistochemical identification may help differentiate leiomyosarcoma from gastrointestinal stromal tumors (GISTs) by identifying GIST protein markers such as hematopoietic progenitor cell antigen CD34 and mast or stem cell growth factor receptor kit (SCFR). Differentiating the two is essential to determining the proper treatment. Specific screening tests other than regular pelvic examinations are not available for leiomyosarcoma of the uterus. A pelvic ultrasound may reveal a vague mass darker than the surrounding normal tissue within the myometrium. An endometrial biopsy also helps rule out endometrial cancer in bleeding women.

The American Joint Committee on Cancer (AJCC) uses the TNM (tumor/lymph node/metastasis) classification for tumor staging of intestinal tumors:

• Stage I: The tumor is less than 5 centimeters (cm), low grade, with no sign of lymph node spread or spread to other parts of the body.
• Stage II: The tumor is greater than 5 cm, localized, low grade, and has not spread to or other parts of the body.
• Stage III: The tumor is either high grade of any size or has spread to regional lymph nodes or the peritoneum.
• Stage IVA: The tumor has metastasized or is deemed unresectable.
• Stage IVB: Tumor rupture has occurred despite resection.

For uterine leiomyosarcomas, the staging criteria for uterine cancers developed by the International Federation of Gynecology and Obstetrics (FIGO) is used:

• Stage I: Tumor is limited to the endometrium and myometrium.
• Stage II: Endocervical and cervical stroma are involved.
• Stage III: Invasion of serosa or adjacent reproductive organs has taken place, or malignant cells are found in peritoneal, vaginal, pelvic, or para-aortic lymph nodes.
• Stage IVA: Bladder or bowel mucosa invasion or distant metastases have occurred.

Note that cell grade is not as significant in staging of uterine leiomyosarcomas as in staging intestinal leiomyosarcomas.

Treatment and therapy: Irrespective of location, radical surgical resection of the leiomyosarcoma through abdominal surgery (bowel resection or hysterectomy) is warranted. Although lymph node spread is an ominous sign, it rarely occurs. In such cases, removing lymph nodes draining the immediate area of the tumor is sufficient. In unresectable tumors, palliative therapy is appropriate, including intestinal bypass of the tumor followed by radiotherapy. In cases of metastases, palliative resection, radiotherapy, and chemotherapy are carried out.

Prognosis, prevention, and outcomes: Prognosis is based on the cellular grade and size of the tumor upon diagnosis and surgical staging. The five-year survival rate for operable extrauterine leiomyosarcoma is approximately 63 percent. Liver metastasis may occur in as many as 55 percent of patients with recurrence. In individuals whose cancer spreads to only nearby organs, five-year survival rates are about 36 percent, but for those whose cancer spreads to distant organs, the rate is 14 percent.

Prevention is impossible, but avoiding radiation and some infections, as well as the drug Tamoxifen, improves one's chances of preventing the disease.

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