Uterine Leiomyosarcoma

NORD gratefully acknowledges Dennis S. Chi, MD, Deputy Chief, Gynecology Service,
Department of Surgery, Memorial Sloan Kettering Cancer Center, for assistance in the
preparation of this report.

Synonyms of Uterine Leiomyosarcoma

leiomyosarcoma of the uterus

General Discussion
A uterine leiomyosarcoma is a rare malignant (cancerous) tumor that arises from
the smooth muscle lining the walls of the uterus (myometrium). There are
essentially two types of muscles in the body: voluntary and involuntary. Smooth
muscles are involuntary muscles; the brain has no conscious control over them.
Smooth muscles react involuntarily in response to various stimuli. For example,
the myometrium stretches during pregnancy to help accommodate the fetus and
contracts during labor to help push out a baby during childbirth.
Leiomyosarcoma is a form of cancer. The term "cancer" refers to a group of
diseases characterized by abnormal, uncontrolled cellular growth that invades
surrounding tissues and may spread (metastasize) to distant bodily tissues or
organs via the bloodstream, the lymphatic system, or other means. Different
forms of cancer, including leiomyosarcomas, may be classified based upon the
cell type involved, the specific nature of the malignancy, and the disease's clinical
course.
Leiomyosarcoma is classified as a soft tissue sarcoma. Sarcomas are malignant
tumors that arise from the connective tissue, which connects, supports and
surrounds various structures and organs in the body. Soft tissue includes fat,
muscle, never, tendons, tissue surrounding the joints (synovial tissue), and blood
and lymph vessels. The exact cause of leiomyosarcoma, including uterine
leiomyosarcoma, is unknown.

Signs & Symptoms

Symptoms of uterine leiomyosarcoma may vary from case to case depending
upon the exact location, size and progression of the tumor. Many women will not
have any apparent symptoms (asymptomatic). The most common symptom is
abnormal bleeding from the vagina and the uterus. Postmenopausal bleeding is
an important factor that may indicate a uterine leiomyosarcoma.
Additional symptoms may occur including pressure or pain affecting the pelvis or
stomach, abnormal vaginal discharge, and a change in bladder or bowel habits.
General symptoms often associated with cancer include fatigue, fever, weight
loss, and a general feeling of ill health (malaise).

Uterine leiomyosarcomas are malignant and may spread (metastasize) locally

and to other areas of the body, especially the lungs and liver often causing lifethreatening complications. Leiomyosarcomas recur in more than half of the cases
sometimes within eight to 16 months of the initial diagnosis and treatment.

Causes
The exact cause of uterine leiomyosarcoma is unknown. They often occur
spontaneously, for no apparent reason. In extremely rare cases, some
researchers believe they may signify a malignant change (transformation) of a
benign (noncancerous) fibroid. However, other researchers argue that malignant
transformation of fibroids is unproven. Fibroids are the most common tumors
affecting women and often appear during childbearing years. Fibroids may also
be known as leiomyomas or myomas. Most fibroids do not cause any symptoms
or complications.
Researchers speculate that genetic and immunologic abnormalities,
environmental factors (e.g., exposure to ultraviolet rays, certain chemicals,
ionizing radiation), diet, stress, and/or other factors may play contributing roles in
causing specific types of cancer. Investigators are conducting ongoing basic
research to learn more about the many factors that may result in cancer.
In individuals with cancer, including leiomyosarcoma, malignancies may develop
due to abnormal changes in the structure and orientation of certain cells known
as oncogenes or tumor suppressor genes. Oncogenes control cell growth; tumor
suppressor genes control cell division and ensure that cells die at the proper
time. The specific cause of changes to these genes is unknown. However,
current research suggests that abnormalities of DNA (deoxyribonucleic acid),
which is the carrier of the bodys genetic code, are the underlying basis of cellular
malignant transformation. These abnormal genetic changes may occur
spontaneously for unknown reasons or, more rarely, may be inherited.
Leiomyosarcomas are associated with specific genetic and environmental risk
factors. Certain inherited conditions that run in families may increase the risk of
developing a leiomyosarcoma. These disorders include Gardner syndrome, LiFraumeni syndrome, Werner syndrome, neurofibromatosis and several immune
deficiency syndromes. The exact association between leiomyosarcoma and
these disorders is not understood. (For more information on these disorders,
choose the specific disorder name as your search term in the Rare Disease
Database.)
Researchers have speculated that exposure to high dose radiation and certain
chemicals (e.g., herbicides) may be linked to an increased risk of developing
leiomyosarcoma but no definitive link has been established.

Affected Populations
Uterine leiomyosarcoma is an extremely rare form of cancer, estimated to occur
in 6 out of every 1,000,000 women in the United States each year. The average

age at diagnosis is 51. Uterine leiomyosarcomas account for 1-2 percent of all
malignant tumors of the uterus.
Leiomyosarcoma is a form of soft tissue sarcoma. According to the American
Cancer Society, 9,530 new cases of soft tissue sarcoma will occur in the United
States in 2006. Soft tissue sarcomas affect men slightly more often than women
and occur more often in adults than children and adolescents.

Related Disorders
Symptoms of the following disorders can be similar to those of uterine
leiomyosarcoma. Comparisons may be useful for a differential diagnosis.
Endometrial carcinoma refers to cancer of the inner membrane lining the uterus
(endometrium). It is the most common type of gynecologic cancer in the United
States and most cases occur after menopause. Endometrial carcinoma may
cause postmenopausal bleeding. In women during their reproductive years, it
may cause abnormalities with the menstrual cycle. The exact cause of
endometrial carcinoma is unknown but factors known to increase risk are obesity,
ingestion of unopposed estrogen, and certain hereditary cancer syndromes..
Uterine fibroids, also known as leiomyomas, are benign smooth muscle tumors of
the uterus. These common tumors affect approximately 20 percent of women by
the age of 40. Most cases of uterine fibroids do not cause symptoms
(asymptomatic) and do not require treatment. These tumors can grow in size to
eventually cause heavy menstrual bleeding, prolonged menstrual bleeding,
pressure or pain of the pelvis, and abnormalities of the urinary and
gastrointestinal tracts. The exact cause of uterine fibroids is unknown.

Diagnosis
The diagnosis of a uterine leiomyosarcoma is most commonly made incidentally
when affected individuals are operated on for benign smooth muscle tumors of
the uterus (leiomyomas or fibroids). The pathologic review of the fibroid surgery
specimens may reveal certain characteristics under the microscope that are
more characteristic of a leiomyosarcoma than a benign myoma. Thus, pathologic
review is key diagnostic aspect is distinguishing malignant leiomyosarcoma from
its benign counterpart, the leiomyoma.
Specialized imaging techniques may be used to help evaluate the size,
placement, and extension of the tumor and to serve as an aid for future surgical
procedures, among individuals with uterine leiomyosarcomas. Such imaging
techniques may include computerized tomography (CT) scanning, magnetic
resonance imaging (MRI) and ultrasound. During CT scanning, a computer and
x-rays are used to create a film showing cross-sectional images of certain tissue
structures. An MRI uses a magnetic field and radio waves to produce crosssectional images of particular organs and bodily tissues. During an ultrasound
reflected sound waves create an image of the uterus. Laboratory tests and
specialized imaging tests may also be conducted to determine possible
infiltration of regional lymph nodes and the presence of distant metastases.

To confirm the diagnosis of metastatic leiomyosarcoma a fine-needle aspiration

may be performed. Fine-need aspiration (FNA) is a diagnostic technique in which
a thin, hollow needle is passed though the skin and inserted into the nodule or
mass to withdraw small samples of tissue. The collected tissue is then studied
under a microscope. In some cases, FNA may prove inconclusive and physicians
may perform an incisional biopsy. During an incisional biopsy, a small sample
tissue is surgically removed and sent to a pathology laboratory where it is
processed and studied to determine its microscopic structure and makeup
(histopathology).

Standard Therapies
Treatment
The therapeutic management of individuals with a uterine leiomyosarcoma may
require the coordinated efforts of a team of medical professionals, such as
physicians who specialize in the diagnosis and treatment of gynecologic cancers
(gynecologic oncologists), specialists in the use of radiation to treat cancer
(radiation oncologists), specialists in the use of chemotherapy to treat cancer
(medical oncologists), oncology nurses, and other specialists.
Specific therapeutic procedures and interventions may vary, depending upon
numerous factors, such as primary tumor location, extent of the primary tumor
(stage), and degree of malignancy (grade); whether the tumor has spread to
lymph nodes or distant sites; an individual's age and general health; and/or other
elements. Decisions concerning the use of particular interventions should be
made by physicians and other members of the health care team in careful
consultation with the patient, based upon the specifics of his or her case; a
thorough discussion of the potential benefits and risks; patient preference; and
other appropriate factors.
The primary form of treatment for a uterine leiomyosarcoma is surgical removal
of the entire tumor and any affected tissue. Total surgical removal of the uterus
(hysterectomy) is usually performed. Usually, surgical removal of the fallopian
tubes and ovaries (bilateral salpingo-oophorectomy) may also be recommended,
especially for women who are menopausal or have metastases.
Anti-cancer drugs used alone or combination (chemotherapy) and radiation
therapy have been used to treat individuals with leiomyosarcoma following
surgery (adjuvant therapy) with limited benefit. Investigational therapies are
underway to develop new chemotherapeutic combinations that may prove
beneficial in treating leiomyosarcomas. In some cases, radiation therapy may be
used before surgery to reduce the size of a tumor.
Because leiomyosarcomas have a high risk of recurrence, individuals should be
examined routinely after surgery.