Carcinosarcoma of Uterine Cervix

Carcinosarcoma of Uterine Cervix

Article
Sexual Health
Women's Health
+3
Contributed byKrish Tangella MD, MBAAug 12, 2018

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

  • Cervical Carcinosarcoma
  • Malignant Mixed Müllerian Tumor of Cervix
  • Metaplastic Carcinoma of Uterine Cervix

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

  • Cervical cancer is a malignancy of the uterine cervix, which is the lower part of the uterus/womb. It is the 2nd or 3rd most common cancer in women worldwide, and over half a million cases are diagnosed each year
  • Carcinosarcoma of Uterine Cervix is a rare malignancy arising in the cervix. It is generally observed in women following menopause. This cancer type is also known as Malignant Mixed Müllerian Tumor (MMMT) of Uterine Cervix
  • Almost all cervical cancers are believed to originate from a premalignant lesion. The most common type of human papilloma virus (HPV) associated with Cervical Carcinosarcoma is HPV-16
  • The development of cervical cancer occurs slowly and the process of pre-cancerous changes (dysplasia) leading onto invasive cancer, generally takes place over years and decades. Hence, periodic screening of women with Pap smears helps in early detection and management of any pre-cancerous change, before a full-blown malignancy develops
  • Screening with Pap smear helps in early detection of pre-cancers and cancers. Any abnormality found on a Pap smear is further scrutinized with an instrument, called a colposcope, and a biopsy of the abnormal areas performed to make a diagnosis
  • If the biopsy shows Carcinosarcoma of Uterine Cervix; then, the tumor is staged (growth and spread of cancer is examined) and treatment options chosen, based on the staging. The treatment may involve a combination of surgery, chemotherapy, and radiation therapy
  • The prognosis depends upon a set of several factors including the stage of the tumor, age of the individual, the size of the tumor, and many other factors. In general, early detection and adequate treatment of Carcinosarcoma of Uterine Cervix, can help achieve a better outcome

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

  • Carcinosarcoma of Uterine Cervix is a rare form of cervical cancer. Most cases are seen in adult women over 48-50 years (post-menopause); although, a wider age range may be presented
  • Generally, all racial and ethnic groups are at risk and the cancer is observed worldwide
  • Carcinosarcomas, arising in the cervix, is much rarer compared to other locations within the female reproductive system, such as the ovary or uterus

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

The following factors increase the risk for Carcinosarcoma of Uterine Cervix:

  • Infection with human papilloma virus (HPV) types:
    • HPV infection is the most important risk factor predisposing one to cervical cancer
    • The virus is transmitted sexually
    • The most common type associated with Cervical Carcinosarcoma is HPV-16 (high-risk HPV)
  • Sexual promiscuity (multiple sexual partners) and high-risk sexual behavior
  • Poor immune system: HIV infection or AIDS, organ transplantation, immunosuppressant medications, greatly increase risk for chronic infection
  • Lack of periodic/regular Pap smear tests
  • Smoking
  • Use of oral contraceptives for long time duration
  • Having the first child at a young age (before 17 years) and having had multiple pregnancies
  • Presence of other sexually transmitted infections (such as chlamydia)
  • Chronic inflammation, in some cases
  • A diet lacking fruits and vegetables
  • Poverty or poor socio-economic status

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 Carcinosarcoma of Uterine Cervix? (Etiology)

  • Carcinosarcoma of Uterine Cervix is believed to be of Müllerian origin (abnormal embryological tissue remnants during the fetal growth and development stage)
  • The human papilloma virus (HPV-16) infection is associated with the development of Carcinosarcoma of Cervix

What are the Signs and Symptoms of Carcinosarcoma of Uterine Cervix?

Signs and symptoms of Carcinosarcoma of Cervix may include:

  • The presence of a large fleshy mass that is shaped like a polyp; this may grow in the cervix and protrude into the cervical canal
  • Abnormal vaginal bleeding
  • Pain during and bleeding after intercourse
  • Menstrual cycle disturbances
  • Abnormal vaginal discharge
  • Anemia (due to bleeding)
  • Often, the tumor is associated with bleeding and necrosis

Advanced cancer signs and symptoms may include:

  • Persistent feeling of abdominal bloating with nausea or vomiting
  • Changes in bowel movements, such as constipation
  • Feeling full soon, after eating less
  • Loss of appetite with weight loss
  • Fatigue, feeling tired easily
  • Frequent urination (polyuria)

How is Carcinosarcoma of Uterine Cervix Diagnosed?

In order to make a diagnosis of Carcinosarcoma of Uterine Cervix, a detailed medical history followed by a physical and pelvic exam is undertaken. This is followed by additional tests and procedures.

  • Pelvic examination:
    • During a pelvic examination, the healthcare provider will exam the uterus, cervix, vagina, ovaries, fallopian tubes, bladder, and rectum to check for any abnormal changes in these organs
    • Also, during the exam, the tumor may appear as a polyp (exhibiting exophytic growth), or it may appear as a firm, non-polyp area (exhibiting endophytic growth pattern)
    • Small tumors that may arise in the cervical canal area may be difficult to visualize. Hence, a careful exam in a high-risk individual is recommended
    • A Pap smear, if not performed already, may be ordered as a screening procedure. An abnormal Pap smear warrants further testing
    • HPV DNA testing can be used as a tool to help screen for infections and administer vaccines

Blood tests to aid in the diagnostic process may include:

  • Complete blood count (CBC) with differential of white blood cells
  • Liver function test and kidney function test
  • Blood tests called serum tumor markers that include:
    • CA-125 test
    • Human chorionic gonadotropin (hCG)
    • Alpha-fetoprotein (AFP)
    • Lactate dehydrogenase (LDH)
    • Inhibin (hormone)
    • Estrogen and testosterone levels

Some of the definitive tests that help in diagnosing the cancer include:

Colposcopy:

  • The cervix is examined with an instrument, called a colposcope. This helps the physician get a magnified view of the cervix
  • In order for this procedure to be performed, the female individual has to lie on a table, as for a pelvic exam. An instrument, called the speculum, is placed in the vagina to keep the opening apart, in order to help the physician visualize the cervix. The colposcope is then used to get a magnified view of the inside
  • To make the abnormal areas more visible, a weak acetic acid (like vinegar) solution is applied to the cervical surface. The abnormal (suspicious) areas appear whiter than the surrounding regions. A solution of Lugol’s iodine may also be used for this purpose
  • The procedure is usually not performed, when a woman has menstrual bleeds
  • It is generally not painful, but in some women it may cause discomfort or cramping

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 may be present following the procedure
  • Cone biopsy or conization:
    • 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
    • The cone biopsy has the added advantage that it also serves as a treatment for pre-cancers and some early cancers

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 a diagnosis of cancer is made on biopsy, further imaging (or other) studies may be conducted. These include:

  • X-ray of the abdomen and pelvic region
  • Chest X-ray: Chest X-rays are used to detect if the cancer has spread to the lung
  • Barium enema X-ray
  • CT (computed tomography) or MRI (magnetic resonance imaging) scan of the abdomen/pelvis, or other suspected areas of spread
  • Transvaginal ultrasound: Transvaginal ultrasound inserts an ultrasound probe into the vagina designed to take pictures of the insides of the uterus
  • Vascular radiological studies of abdomen and pelvic region
  • Positron emission tomography (PET scan): A PET scan is a nuclear medicine imaging technique that uses three-dimensional images to show how tissue and organs are functioning. A small amount of radioactive material is required with this test. The radioactive material may be injected into a vein, inhaled, or swallowed. It may be performed to see if the cancer has metastasized/spread to other regions
  • Cystoscopy (to look at the inside of the bladder)
  • Proctoscopy (to look at the inside of the rectum)
  • Sometimes, an intravenous pyelogram (to find any abnormality/blockage in the urinary tract) may be conducted
  • Whole body bone scan

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 Carcinosarcoma of Uterine Cervix?

The complications of Carcinosarcoma of Uterine Cervix could include:

  • As the cancer progresses, it may invade into the surrounding tissues
  • Over time, the pelvic lymph nodes and other pelvic organs may be affected
  • The cancer can also spread to distant organs, such as the liver and lungs
  • Side effects of chemotherapy (such as toxicity) and radiation
  • Sexual dysfunction can take place as a side effect of surgery, chemotherapy, or radiation therapy
  • Recurrence of the cancer following incomplete surgical removal

How is Carcinosarcoma 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.

  • The FIGO (International Federation of Gynecology and Obstetrics) and the AJCC (American Joint Committee on Cancer) TNM staging systems - are two similar, commonly used staging systems
  • A tumor that remains confined only to the superficial layers of the cervix is said to be carcinoma in situ (Stage 0 according to AJCC system)
  • Depending on how far the tumor has spread beyond the cervix, stages I through IV are defined
  • Stage I cancer is confined wholly to the cervix (the cancer has spread to involve even the deeper layers of the cervix unlike stage 0)
  • Stage IV cancer involves the nearby organs, such as the bladder, rectum, or even other distant organs

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 modality is chosen, depending on the type and stage of the tumor, age of the individual, and the need to preserve the ability to bear children. Sometimes, more than one type of treatment modalities may be necessary.

In general, Cervical Carcinosarcoma is a highly-aggressive cancer and the treatment can be challenging. A multidisciplinary approach with a team of healthcare specialists and experts from various medical fields may be necessary to treat the cancer at a healthcare institution that has the experience and expertise in dealing with such high-grade cancers.

Treatment options for Carcinosarcoma of Uterine Cervix may include:

Surgery:

  • Stage 0 tumors, confined to the superficial layers of cervix can be treated with cryosurgery (the cells are killed using extreme cold temperatures) or by using laser therapy
  • 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

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
  • Chemotherapy may be used in addition to radiation and/or surgery, to treat cancers that have spread or recurred. When chemotherapy and radiation therapy are used together, it is called concurrent chemoradiation
  • Side effects of chemotherapy may include nausea, vomiting, hair loss, loss of appetite, diarrhea, fatigue, increased risk of infection, mouth sores, and easy bruising, depending on the drugs 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)
  • Possible side effects may include:
    • Fatigue, nausea, vomiting, and diarrhea
    • Bladder irritation, leading to inflammation (cystitis)
    • Ovaries may be affected resulting in menstrual changes, or premature menopause
    • The vulva and vagina may be affected, causing soreness, or even scar tissue formation

Once treatment is complete, it is recommended that the individual schedule regular check-ups, based on the recommendation of the specialist treating them. 

How can Carcinosarcoma of Uterine Cervix be Prevented?

Some steps for the prevention of Carcinosarcoma of Uterine Cervix include:

  • Use of measures to prevent sexually-transmitted infections, such as usage of condoms, avoiding multiple sexual partners, and circumcision in men
  • Avoidance of smoking
  • Regular screening to detect pre-cancers:
    • The American Cancer Society recommends screening of women from age 21 years
    • A Pap smear is recommended every 3 years, from ages 21-29 years
    • From age 30-65 years, a Pap smear and HPV testing is recommended, once every 5 years
    • More frequent screenings are advised for women having a high-risk for cervical cancer
  • Vaccination against human papilloma virus (HPV):
    • Two vaccines have been studied and approved for use in the United States - Gardasil (against HPV types 6, 11, 16, and 18) and Cervarix (against HPV types 16 and 18)
    • Cervarix has been approved for use in females aged 10-25 years, while Gardasil may be used in the 9-26 years age group
    • The American Cancer Society recommends routine vaccination of girls at 11-12 years of age
    • HPV vaccines are not successful against women who are already infected though

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

  • The prognosis of Carcinosarcoma of Uterine Cervix is better than uterine carcinosarcoma, because in many cases the cancer is contained within the cervix or uterus
  • Nevertheless, the prognosis depends upon a set of several 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
    • FIGO grade of the tumor: Tumors that are graded 1 and 2 have better prognoses than grade 3 tumors
    • 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
  • An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment
  • 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 Carcinosarcoma of Uterine Cervix:

  • Cervical cancer is a very common cancer in women worldwide. It affects the uterine cervix, which is the lower part of the uterus/womb

The following link can help provide some useful information of cervical cancer:

https://www.dovemed.com/diseases-conditions/cervical-cancer/

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Krish Tangella MD, MBA

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