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

• Ewing’s Sarcoma of Vulva
• Peripheral Primitive Neuroectodermal Tumor (PNET) of Vulva
• Primary Vulvar Ewing Sarcoma

What is Ewing Sarcoma of Vulva? (Definition/Background Information)

• Ewing Sarcoma of Vulva is a rare, but highly-malignant tumor that is mostly observed in young adult women. Ewing’s sarcoma frequently affect the bones; cancers occurring outside the bone (known as extraosseous Ewing’s sarcoma) are very uncommon
• It is believed that the tumor is caused by genetic defects on chromosome 11 and chromosome 22. Some cases of Ewing’s sarcoma are known to be seen in the background of prior radiation therapy to the pelvic region
• The signs and symptoms of Ewing Sarcoma of Vulva include pain during sex and abnormal bleeding from the tumor due to ulceration of the overlying skin. The complications are dependent upon the stage of the cancer and may also include treatment complications
• Treatment for Ewing Sarcoma of Vulva is mainly through surgery and other supplementary treatment measures. The prognosis of Vulva Ewing Sarcoma depends on the cancer stage and overall health of the individual. In general, the prognosis for individuals with the malignancy is poor

Who gets Ewing Sarcoma of Vulva? (Age and Sex Distribution)

• Ewing Sarcoma of Vulva are extremely rare primary cancers affecting the vulva
• The tumor may be seen in a wide age range of women. However, women of reproductive age (in the 20s and 30s) are affected the most
• Some cases have been reported in children too
• There is no known ethnic or racial preference observed

What are the Risk Factors for Ewing Sarcoma of Vulva? (Predisposing Factors)

• The risk factors for Ewing Sarcoma of Vulva are not clearly evident or identified
• In general, Ewing Sarcoma may develop in individuals who have a past history of radiation therapy undertaken for other medical conditions. The cancer often forms at the site of the radiation (in this case, in the pelvic region)

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 Ewing Sarcoma of Vulva? (Etiology)

Currently, the cause of Ewing Sarcoma of Vulva is not clearly known. However, tumor studies have revealed the following:

• The cell of origin of Vulvar Ewing’s Sarcoma is debated. Some researchers believe that the tumors arise from post-ganglionic cholinergic neurons or neural crest
• In 9 out of 10 cases, abnormal chromosomal translocations have been noted (chromosomes 11 and 22 are involved)
• Also, fusion of the EWS and FL11 gene is noted in some cases

Vulvar Ewing’s Sarcoma is not a sexually-transmitted disease/condition.

What are the Signs and Symptoms of Ewing Sarcoma of Vulva?

The signs and symptoms of Ewing Sarcoma of Vulva may include:

• Presence of a slowly-growing tumor mass on the vulva; the tumor is well-defined and soft to touch
• Initially, the tumor is small and localized to the lips of the vulva (the labia majora or labia minora)
• It may be seen below the vulvar skin surface or as a polyp (that may present like Bartholin cyst)
• Ulceration of overlying skin may be seen due to which, non-menstrual related bleeding may occur
• In some cases, the tumor may be as large as 20 cm
• Large-sized tumors can be bulky expanding masses; they may project into the vagina and cervix
• Pain during sex
• Pain in the pelvic or abdominal region
• Urinary tract associated signs and symptoms such as frequent urination, painful urination, blood in urine (hematuria), etc.
• If the urinary bladder is involved, then it may obstruct the bladder and lead to retention of urine

How is Ewing Sarcoma of Vulva Diagnosed?

A diagnosis of Ewing Sarcoma of Vulva may be made by using the following resources:

• Preliminary examination composed of:
  • Complete physical examination including pelvic exam
  • Evaluation  of medical (and family) history
• Initial diagnosis that is made by:
  • Transvaginal ultrasound of the uterus can provide an image of the vagina and surrounding pelvic organs
  • MRI scans can be used to observe if a vulvar tumor has the characteristics of cancer, along with visualizing the cancer spread (if it has spread to other areas)
• Plain radiographs of the chest can provide evidence if the tumor has spread to the lungs
• CT scans are rarely used in diagnosing vulvar cancer, but can be used to determine if metastasis has occurred
• Colposcopy:
  • The cervix (including the vagina and vulva) is examined with an instrument, called a colposcope. This helps the physician get a magnified view of the region
  • In order for this procedure to be performed, the 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
• A tissue biopsy of the tumor mass may be necessary to determine, if the tumor present is Ewing’s sarcoma, or a different soft tissue sarcoma. In the tissue biopsy procedure, the physician removes a sample of the tissue and sends it to the laboratory for a histopathological examination. The pathologist examines the biopsy under a microscope and arrives at a definitive diagnosis after a thorough evaluation of the clinical and microscopic findings, as well as by correlating the results of special studies on the tissues (if required)

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 possible Complications of Ewing Sarcoma of Vulva?

The possible complications of Ewing Sarcoma of Vulva include:

• Ulceration of large tumor masses may get secondarily infected with bacteria or fungus
• Metastasis of the tumor to other sites such as the lungs and lymph nodes
• The tumor may also adversely impact adjoining/surrounding structures, such as the nerves, leading to a loss of feeling
• Topical therapy for initial stage cancers can result in side effects such as severe vaginal and vulvar irritations
• Side effects of chemotherapy (such as toxicity) and radiation
• Sexual dysfunction can take place as a side effect of surgery, chemotherapy, or radiation therapy, after a long duration of time
• Recurrence of the cancer following incomplete surgical removal is known to take place

How is Ewing Sarcoma of Vulva Treated?

Once a diagnosis of vulvar cancer has been made, the extent to which the tumor has spread is assessed, known as staging. The staging for vulvar cancer is based upon the FIGO (International Federation of Gynecology and Obstetrics) and the AJCC (American Joint Committee on Cancer) TNM staging systems.

The TNM classification for vulvar cancer is given below:

Tumor extent (T):

• Tis: The cancer is not growing into the underlying tissues. This stage, also known as carcinoma in situ, is not included in the FIGO system
• T1: The cancer is growing only in the vulva or perineum
  • T1a: The cancer has grown no more than 1 mm into underlying tissue (stroma) and is 2 cm or smaller in size (about 0.8 inches)
  • T1b: The cancer is either more than 2 cm or it has grown more than 1 mm into underlying tissue (stroma)
• T2: The tumor can be any size. The cancer is growing into the anus or the lower third of the vagina or urethra (the tube that drains urine from the bladder). This is called stage 2/3 in the FIGO system
• T3: The tumor can be any size. The cancer is growing into the upper urethra, bladder or rectum or into the pubic bone. This is called stage 4 in the FIGO system

Lymph node spread of cancer (N):

• N0: No lymph node spread
• N1: The cancer has spread to 1 or 2 lymph nodes in the groin with the following features:
  • N1a: The cancer has spread to 1 or 2 lymph nodes and the areas of cancer spread are both less than 5 mm (about 1/5th of an inch) in size
  • N1b: The cancer has spread to one lymph node and the area of cancer spread is 5 mm or greater
• N2: The cancer has spread to groin lymph nodes with the following features:
  • N2a: The cancer has spread to 3 or more lymph nodes, but each area of spread is less than 5 mm
  • N2b: The cancer has spread to 2 or more lymph nodes with each area of spread 5 mm or greater
  • N2c: The cancer has spread to lymph nodes and has started growing through the outer covering of at least one of the lymph nodes (called extracapsular spread)
• N3: The cancer has spread to the lymph nodes causing open sores (ulceration) or causing the lymph node to be stuck (fixed) to the tissue below it

Distant spread of cancer (M)

• M0: No distant spread
• M1: The cancer has spread to distant sites (includes spread to pelvic lymph nodes)

Stage grouping: Once the T, N, and M categories have been assigned, this information is combined to assign an overall stage in a process called stage grouping. The stages identify tumors that have a similar outlook and are treated in a similar way.

Stage 0 (Tis, N0, M0):

• This is a very early cancer found on the surface of the skin of the vulva only. It is also known as carcinoma in situ and as Bowen disease
• This stage is not included in the FIGO system

Stage I (T1, N0, M0):

• The cancer is in the vulva or the perineum (the space between the rectum and the vagina) or both
• The tumor has not spread to lymph nodes or distant sites
• Stage IA (T1a, N0, M0):
  • These are stage I cancers with tumors that are 2 cm or less that have grown into the underlying tissue no deeper than 1 mm (about 1/25 inch)
• Stage IB (T1b, N0, M0):
  • These are stage I cancers that have invaded deeper than 1 mm and/or are larger than 2 cm

Stage II (T2, N0, M0):

• The cancer has grown outside the vulva or perineum to the anus or lower third of the vagina or urethra (T2)
• It has not spread to lymph nodes (N0) or distant sites (M0)
• In FIGO, this grouping is T2/T3, N0, M0, but it is still stage II

Stage III is subdivided into 3 stages that are termed as Stage IIIA, Stage IIIB, and Stage IIIC.

Stage IIIA (T1 or T2, N1a or N1b, M0):

• Cancer is in the vulva or perineum or both (T1) and may be growing into the anus, lower vagina, or lower urethra (T2)
• Either it has spread to a single nearby lymph node with the area of cancer spread 5 mm or greater in size (N1a);
• OR it has spread to 1 or 2 nearby lymph nodes with both areas of cancer spread less than 5 mm in size (N1b). It has not spread to distant sites (M0)

In FIGO, this stage is also IIIA, but it is split into IIIAi and IIIAii.

• Stage IIIAi (T1 or T2, N1a, M0):
  • The cancer is in the vulva or perineum and may be any size and growing into the anus, lower vagina, or lower urethra (T1 or T2)
  • It has spread to a single lymph node with the area of spread 5 mm or greater in size (N1a)
  • It has not spread to distant sites (M0)
• Stage IIIAii (T1 or T2, N1b, M0):
  • The cancer is in the vulva or perineum and may be any size and growing into the anus, lower vagina, or lower urethra (T1 or T2)
  • It has spread to 1 or 2 lymph nodes with the areas of cancer spread less than 5 mm in size (N1b)
  • It has not spread to distant sites (M0)

Stage IIIB (T1 or T2, N2a or N2b, M0):

• Cancer is in the vulva or perineum or both (T1) and may be growing into the anus, vagina, or lower urethra (T2)
• Either, the cancer has spread to 3 or more nearby lymph nodes, with all areas of cancer spread less than 5 mm in size (N2a)
• OR the cancer has spread to 2 or more lymph nodes with each area of spread 5 mm or greater in size (N2b)
• The cancer has not spread to distant sites (M0)

In FIGO, this stage is also IIIB, but it is split into IIIBi and IIIBii.

• Stage IIIBi (T1 or T2, N2a, M0):
  • The cancer is in the vulva or perineum and may be any size and growing into the anus, lower vagina, or lower urethra (T1 or T2)
  • The cancer has spread to 3 or more nearby lymph nodes, with all areas of cancer spread less than 5 mm in size (N2a)
  • It has not spread to distant sites (M0)
• Stage IIIBii (T1 or T2, N2b, M0):
  • The cancer is in the vulva or perineum and may be any size and growing into the anus, lower vagina, or lower urethra (T1 or T2)
  • The cancer has spread to 2 or more lymph nodes with each area of spread 5 mm or greater in size (N2b)
  • It has not spread to distant sites (M0)

Stage IIIC (T1 or T2, N2c, M0):

• Cancer is in the vulva or perineum or both (T1) and may be growing into the anus, lower vagina, or lower urethra (T2)
• The cancer has spread to nearby lymph nodes and has started growing through the outer covering of at least one of the lymph nodes (called extracapsular spread; N2c)
• The cancer has not spread to distant sites (M0)

In FIGO, this stage is also called IIIC.

Stage IV is subdivided into 2 stages that are termed as Stage IVA and Stage IVB.

• Stage IVA: Either of the following -
• T1 or T2, N3, M0:
  • Cancer is in the vulva or perineum or both (T1) and may be growing into the anus, vagina, or lower urethra (T2)
  • Cancer spread to nearby lymph nodes has caused them to be stuck (fixed) to the underlying tissue or caused open sores (ulceration) (N3)
  • It has not spread to distant sites

In FIGO, this stage is also called IVA.

OR

• T3, any N, M0:
  • The cancer has spread beyond nearby tissues to the bladder, rectum, pelvic bone, or upper part of the urethra (T3)
  • It may or may not have spread to nearby lymph nodes (any N). It has not spread to distant sites (M0)

In FIGO, this stage is also IVA.

• Stage IVB (any T, any N, M1):
• Cancer has spread to distant organs or lymph nodes (M1)
• This is the most advanced stage of cancer

In FIGO, this stage is also IVB.

(Source: “The FIGO/AJCC system for staging vulvar cancer”; information provided by the American Cancer Society, February 2016)

Vulvar cancers are treated using several methods depending on the stage of the cancer:

In situ and initial stage cancers: Stage I

• The vulvar cancer may be treated using topical applications, laser surgery, or local excisional surgery
• A lesser-invasive procedure, called ultrasound surgical aspiration, may be used to break the tumor into smaller segments and destroy them using ultrasound vibrations
• In some cases, a minor procedure known as skinning vulvectomy may be undertaken, which is followed through by surgical skin grafts to cover the surgery site
• Stage I cancers are removed either through wide local excisional surgery or radical local excisional surgery. In case lymph node involvement is noted, then the local lymph nodes are also removed
• Radiation therapy may be an option for individuals in whom surgical intervention is not possible

Higher stage cancers: Stage II to Stage IV

• Large-sized tumors may be removed through radical vulvectomy, modified radical vulvectomy, or by performing a radical local excisional surgery. In case the lymph nodes are involved, then they are also removed
• Radiation therapy may be an option for individuals in whom surgical intervention is not possible, or following surgery to destroy the remaining cancer cells
• Chemotherapy may be considered before or following surgery, either independently, or in combination with radiation therapy
• Advanced stage cancers (stage IV) are treated through a combination of radical vulvectomy, pelvic exenteration (if necessary), and radation therapy and/or chemotherapy
• Individuals who cannot withstand radical surgical procedures may be treated by a combination of radation therapy and chemotherapy. They may also be recommended for clinical trials

Recurrent cancers are treated on a case-by-case basis based on their stage and site of recurrence. They are treated through radical vulvectomy and/or pelvic exenteration invasive techniques. Often, a combination of treatment measures may be used by the healthcare providers (including recommendation for clinical trials, when recurrence is associated with higher stage cancers). Advanced stage tumors with metastasis may be treated on a case-by-case basis; often symptomatic treatment with radiation and/or chemotherapy is attempted.

In general, Ewing Sarcoma of Vulva 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.

The treatment of Ewing Sarcoma of Vulva involves surgery, which is the most common treatment option considered.

Surgery:

• Vulvectomy: It is a surgical intervention technique to remove a part or the entire vulva. It may be of the following types:
  • If only the top layer of the skin over the vulva is removed, it is known as skinning vulvectomy. This procedure also involves the use of skin grafts (taken from other body sites) to cover surgical site
  • If only a portion of the vulva is removed, which may or may not be accompanied by removal of the affected lymph nodes; then, it is known as modified radical vulvectomy
  • If the entire vulva that is affected by cancer is removed, then it is called a radical vulvectomy. In such cases, the local lymph nodes are also removed. The entire vulva may include the clitoris and the inner and outer lips of the vagina
• Pelvic exenteration: It is an extensive surgical procedure wherein the entire vulva, the vagina, the surrounding tissues, and the pelvic lymph nodes are removed. In addition, depending on the extent of tumor spread, parts affected around the region (such as the cervix, urinary bladder, rectum, colon, etc.) may be removed. Recovery from this surgery usually 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
• In general, chemotherapy (either oral drugs or intravenous administration) is usually not found to be very effective

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 (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

Currently, clinical trials on adjuvant chemotherapy and combinational chemotherapy, as secondary treatment, are showing promising results on reducing the risk of relapse.

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 Ewing Sarcoma of Vulva be Prevented?

• There are currently no known methods of preventing Ewing Sarcoma of Vulva
• 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 Ewing Sarcoma of Vulva? (Outcomes/Resolutions)

• According to the US National Cancer Institute (NCI) database, the 5-year survival rate for vulvar cancers range from 86% for local cancers that do not show nearby lymph node involvement, to 16% for cancers that have spread to other organs and body sites (say stage IV)
• The prognosis for Ewing Sarcoma of Vulva 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
  • 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
• However, in general, the prognosis of Vulvar Ewing’s Sarcoma is poor; lung metastasis is frequently known to occur. Appropriate treatment through complete surgical excision followed by radiation therapy/chemotherapy may prolong survival to over 3 years
• 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
• It is important to schedule and attend follow-up appointments with the healthcare provider. Many patients with metastatic or locally advanced tumors may be referred for clinical trials for experimental treatment options

Additional and Relevant Useful Information for Ewing Sarcoma of Vulva:

Please visit our Cancer & Benign Tumor Health Center for more physician-approved health information:

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