What are the other Names for this Condition? (Also known as/Synonyms)

• Cervical Embryonal Rhabdomyosarcoma
• Embryonal RMS of Cervix
• ERMS of Uterine Cervix

What is Embryonal Rhabdomyosarcoma of Uterine Cervix? (Definition/Background Information)

• Rhabdomyosarcoma of uterine cervix is a very uncommon, high-grade malignant tumor of the cervix. The rhabdomyosarcoma (RMS) is an infrequent, but malignant ‘skeletal muscle’ tumor of the soft tissues. RMS tumors are poorly-defined, fleshy, expanding masses that form deep within the body tissues, or below the skin surface
• There are 3 types of rhabdomyosarcomas including the embryonal, alveolar, and pleomorphic subtypes. Embryonal Rhabdomyosarcoma (ERMS) of Uterine Cervix is the most common histological subtype of rhabdomyosarcoma of cervix
• Currently, there are no specific risk factors identified for Embryonal Rhabdomyosarcoma of Uterine Cervix. However, RMS may be associated with certain genetic disorders including Beckwith-Wiedemann syndrome, Costello syndrome, and neurofibromatosis type 1, among others
• The cause of formation of Embryonal Rhabdomyosarcoma of Uterine Cervix is not well-established. It is believed to occur due to certain genetic mutations
• The signs and symptoms of Cervical Embryonal Rhabdomyosarcoma include abnormal vaginal discharge and vaginal bleeding, which is seen during the initial stages of the cancer. Due to this, an early detection of the tumor is mostly enabled
• The treatment of Embryonal Rhabdomyosarcoma of Uterine Cervix is undertaken through surgery and/or chemotherapy. The prognosis of ERMS depends on many factors including age of the individual, the stage of the cancer, and response to therapy

Who gets Embryonal Rhabdomyosarcoma of Uterine Cervix? (Age and Sex Distribution)

• Embryonal Rhabdomyosarcoma of Uterine Cervix is a rare and invasive tumor seen in adolescent girls and young adult women (between 10-30 years)
• However, a wide age range of 20-90 years have been observed for RMS affecting the female genital tract
• No racial or ethnic preference is generally noted

What are the Risk Factors for Embryonal Rhabdomyosarcoma of Uterine Cervix? (Predisposing Factors)

Currently, no specific risk factors are noted for the development of Embryonal Rhabdomyosarcoma of Uterine Cervix. But, in general, rhabdomyosarcomas may be associated with the following factors:

• Family history of the condition has been observed, though very rarely
• Use of drugs, such as cocaine or marijuana, by the parent mother
• Carcinogens (some have been found on mice and certain types of fish)
• Beckwith-Wiedemann syndrome
• Costello syndrome
• Li-Fraumeni syndrome
• Neurofibromatosis (type) 1
• Noonan syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Embryonal Rhabdomyosarcoma of Uterine Cervix? (Etiology)

The exact cause and mechanism of formation of Embryonal Rhabdomyosarcoma of Uterine Cervix is unknown.

• Approximately 70-75% of cervical rhabdomyosarcomas are of the embryonal variant, which are thought to arise from embryonic connective tissues responsible for skeletal muscle development
• It is suspected that either inherited genetic defects or de novo (sporadic and spontaneous) genetic mutations may be the causative factors
• Chromosomes 2, 8, and 11 have been found to be altered, indicating complex mutations with gain/loss of genetic material. Also, an absence or modification of tumor suppressor gene has been observed. These changes are said to be responsible for ERMS; but the exact process how the tumor develops, is not clearly understood

What are the Signs and Symptoms of Embryonal Rhabdomyosarcoma of Uterine Cervix?

The signs and symptoms of Embryonal Rhabdomyosarcoma of Cervix may include:

• Abnormal vaginal bleeding and/or vaginal discharge may be noted in early stage of the cancer development
• Presence of a fleshy polyp or infiltrative mass in the cervix
• The size of the tumor can range from 1 cm to over 20 cm (mean size of 4 cm)
• Some tumors may grow to large sizes and may cause a feeling of fullness in the abdomen; enlargement of lower abdomen
• Pain in the pelvic region
• Frequent urination due to compression/pressure of the tumor
• Lower back pain
• Pain during sexual intercourse
• Functional impairment of organs are not observed until advanced stages of the tumor development takes place

How is Embryonal Rhabdomyosarcoma of Uterine Cervix Diagnosed?

The following tools may be used towards establishing a diagnosis of Embryonal Rhabdomyosarcoma of Uterine Cervix:

• Evaluation of the individual’s medical history and a thorough physical (pelvic) examination
• Ultrasound scan of the abdomen
• CT or CAT scan with contrast of the abdomen and pelvis may show a well-defined mass. This radiological procedure creates detailed 3-dimensional images of structures inside the body
• MRI scans of the abdomen and pelvis: Magnetic resonance imaging (MRI) uses a magnetic field to create high-quality pictures of certain parts of the body, such as tissues, muscles, nerves, and bones. These high-quality pictures may reveal the presence of the tumor
• A Pap smear may be ordered as a screening procedure. An abnormal Pap smear warrants further testing
• Colposcopy: The cervix is examined with an instrument, called a colposcope. This helps the physician get a magnified view of the cervix

Cervical biopsy: Biopsy is the process of removing tissue for examination. A pathologist looks at the tissue sample under a microscope, to detect any evidence of cancer. Types of cervical biopsies include:

• Colposcopic biopsy: The abnormal areas of the cervix are visualized with a colposcope. After numbing the cervix with a local anesthetic, an instrument, called a biopsy forceps, is used to get a tissue sample.  Mild cramps, pain, and some light bleeding, may occur following the procedure
• Endocervical curettage (endocervical scraping): The curette is an instrument that can be used to scrape out tissue. Using a curette, cells are scraped out from the endocervix (the inner part of the cervix, close to the uterus/womb) and examined under a microscope. Mild pain and bleeding maybe present following the procedure.

Cone biopsy or conization: This procedure is only helpful if the tumors are small enough to be completely excised by conization surgical procedure. In a majority of cases of cervical rhabdomyosarcoma, the tumor is diagnosed in the advanced stages, and hence, conization is rarely helpful.

• A cone-shaped piece of tissue is removed from the cervix during conization
• The exocervix (the outer part) forms the base of this cone, while the endocervix (the inner part) forms the apex

Two methods can be used to obtain a cone biopsy specimen:

• Loop electrosurgical procedure (LEEP, LLETZ): After numbing the area with a local anesthetic, a wire loop heated with electricity is used to remove a tissue specimen. This procedure, lasting about 10 minutes, may cause some cramping and mild-to-moderate bleeding, for a few weeks
• Cold knife cone biopsy: This procedure is performed, either under general anesthesia or under spinal anesthesia. The tissue sample is removed using a surgical scalpel or through laser

If tumor has metastasized (into the lungs or other regions) then PET scan, bone scan, and chest X-rays may be taken.

Note: In general, Pap smear is not a good screening tool for cervical RMS.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Embryonal Rhabdomyosarcoma of Uterine Cervix?

Complications due to Embryonal Rhabdomyosarcoma of Uterine Cervix could include:

• Metastasis of the tumor to other sites in the body
• Recurrence of the tumor after surgery, when the entire tumor is not removed
• Blood loss during invasive treatment methods may be heavy
• Damage of vital nerves, blood vessels, and surrounding structures during surgery
• Side effects from chemotherapy (toxicity), radiation therapy (radiation fibrosis)
• Sexual dysfunction can take place as a side effect of surgery, chemotherapy, or radiation therapy

How is Embryonal Rhabdomyosarcoma of Uterine Cervix Treated?

Once a diagnosis of cervical cancer has been made, the extent to which the tumor has spread is assessed. This is called staging.

Following is the staging protocol for cervical cancer, according to the American Joint Committee on Cancer (AJCC), updated July 2016:

Stage 0 cervical cancer (carcinoma in situ):

• In this stage, abnormal cells are found in the innermost lining of the cervix
• These abnormal cells may become cancer and spread into nearby normal tissue

Stage I cervical cancer: The cancer is found only in the cervix. Stage I is divided into stages IA and IB, based on the amount of cancer that is found.

• Stage IA: A very small amount of cancer that can only be seen with a microscope is found in the tissues of the cervix
  • In stage IA1, the cancer is not more than 3 mm deep and not more than 7 mm wide
  • In stage IA2, the cancer is more than 3 mm, but not more than 5 mm deep; it is not more than 7 mm wide
• Stage IB: It is divided into stages IB1 and IB2, based on the size of the tumor
  • In stage IB1, the cancer can only be seen with a microscope and is more than 5 mm deep and more than 7 mm wide; or the cancer can be seen without a microscope and is not more than 4 cm
  • In stage IB2, the cancer can be seen without a microscope and is more than 4 cm

Stage II cervical cancer: The cancer has spread beyond the uterus, but not onto the pelvic wall (the tissues that line the part of the body between the hips), or to the lower third of the vagina. Stage II is divided into stages IIA and IIB, based on how far the cancer has spread.

• Stage IIA: The cancer has spread beyond the cervix to the upper two-thirds of the vagina, but not to tissues around the uterus
• Stage IIA is divided into stages IIA1 and IIA2, based on the size of the tumor
  • In stage IIA1, the tumor can be seen without a microscope and is not more than 4 cm in size
  • In stage IIA2, the tumor can be seen without a microscope and is more than 4 cm in size
• Stage IIB: The cancer has spread beyond the cervix to the tissues around the uterus, but not onto the pelvic wall

Stage III cervical cancer: The cancer has spread to the lower third of the vagina, and/or onto the pelvic wall, and/or has caused kidney problems. Stage III is divided into stages IIIA and IIIB, based on how far the cancer has spread.

• Stage IIIA: The cancer has spread to the lower third of the vagina, but not onto the pelvic wall
• Stage IIIB: The cancer has spread to the pelvic wall; and/or the tumor has become large enough to block the ureters (the tubes that connect the kidneys to the urinary bladder). This blockage can cause the kidney to enlarge or stop working

Stage IV cervical cancer: In stage IV, the cancer has spread beyond the pelvis, or can be seen in the lining of the bladder and/or rectum, or has spread to other parts of the body. Stage IV is divided into stages IVA and IVB, based on where the cancer has spread.

• Stage IVA: The cancer has spread to the nearby organs, such as the urinary bladder or rectum
• Stage IVB: The cancer has spread to other parts of the body, such as to the lymph nodes, lung, liver, intestine, or bone

(Source: Stages of Cervical Cancer, July 2016, provided by the National Cancer Institute at the National Institutes of Health; U.S. Department of Health and Human Services)

The treatment of Embryonal Rhabdomyosarcoma of Uterine Cervix may be undertaken as:

• Any combination of chemotherapy, radiation therapy, and invasive surgical procedures may be used to treat RMS of uterine cervix. A combination of surgery and chemotherapy is found to be generally effective in treating the tumor
• Surgery may include the following procedures:
  • Conization procedure, besides helping with the biopsy, can also help in treating very early-stage cervical cancers in women, who want to preserve their childbearing ability
  • Radical trachelectomy: The surgeon removes the cervix, upper part of the vagina, and nearby lymph nodes, while preserving the ability to have children
  • Hysterectomy: In this procedure, the uterus and cervix are removed. This is done by making an incision on the abdomen (termed abdominal hysterectomy), or through the vagina (termed vaginal hysterectomy), or by using a laparoscope (termed laparoscopic hysterectomy). Surgery is performed under general or epidural anesthesia, though the ability to have children is lost. Complications, such as bleeding, infection, or damage to the urinary tract, or the intestinal system may occur in rare cases
  • Radical hysterectomy: The uterus, cervix, the upper part of the vagina and tissues, next to the uterus are removed. Additionally, some pelvic lymph nodes may also be surgically taken out. The surgery is performed under anesthesia and may be carried out, via an incision made on the abdomen or by using laparoscopy. With this invasive procedure, the ability to have children is lost. Rarely, complications such as bleeding, infection, or damage to the urinary tract or the intestinal system, may occur. Removal of lymph nodes may lead to swelling of legs (lymphedema)
  • Pelvic exenteration: The uterus, tissues surrounding the uterus, cervix, pelvic lymph nodes, and the upper part of the vagina, are removed. In addition, depending on the tumor spread, the remainder of the vagina, the bladder, rectum, and a part of the colon, may also be removed. Recovery from this surgery takes a long period
• Arterial embolization may be used to provide temporary relief from the symptoms, and reduce blood loss during a surgical procedure
• Chemotherapy:
  • Medications are used to kill the tumor cells, which may be given as oral pills or injected into veins
  • A combination of chemotherapy medications may be used
• Radiation therapy:
  • This procedure uses high-energy beams to kill the cancer cells
  • These beams may be delivered from outside the body (external beam radiation therapy) or the radioactive material maybe placed inside the vagina or the uterus (internal radiation therapy or brachytherapy)
• Post-operative care is important: One must maintain minimum activity levels, until the surgical wound heals
• Follow-up care with regular screening and check-ups are important and encouraged

How can Embryonal Rhabdomyosarcoma of Uterine Cervix be Prevented?

• Current medical research has not established a way of preventing the formation of Embryonal Rhabdomyosarcoma of Uterine Cervix
• Genetic counseling and testing: If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Due to its high metastasizing potential and recurrence rate, regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory for those who have already been treated for this tumor

What is the Prognosis of Embryonal Rhabdomyosarcoma of Uterine Cervix? (Outcomes/Resolutions)

• The prognosis of Embryonal Rhabdomyosarcoma of Uterine Cervix depends on a combination of factors that include:
  • The size of the tumor and the extent of its invasion: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Stage of cancer: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Cell growth rate of the cancer
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • Individuals with bulky disease have a poorer prognosis
  • Involvement of the regional lymph nodes, which can adversely affect the prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical respectability of the tumor (meaning, if the tumor can be removed completely)
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
  • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
  • Progression of the condition makes the outcome worse
• In general, Cervical Embryonal Rhabdomyosarcomas are found to have a better prognosis than vaginal embryonal rhabdomyosarcomas. Individuals have been known to respond well to treatment that includes surgery (removal of the tumor) and chemotherapy
• Also, the embryonal variant of RMS has a better outcome than the alveolar variant of RMS. However, in almost all cases, early detection and prompt treatment is the key to a favorable outcome
• The combination chemotherapy drugs used, may have some severe side effects (like cardio-toxicity). This chiefly impacts the elderly adults, or those who are already affected by other medical conditions. Individuals, who tolerate chemotherapy sessions better, generally have better outcomes

Additional and Relevant Useful Information for Embryonal Rhabdomyosarcoma of Uterine Cervix:

Amongst pediatric soft tissue sarcomas (affecting children less than 15 years), rhabdomyosarcomas form the largest category of malignant tumors.