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

• Malignant Abrikossoff Tumour of Vulva
• Malignant Granular Cell Myoblastoma of Vulva
• Vulvar Malignant GCT

What is Malignant Granular Cell Tumor of Vulva? (Definition/Background Information)

• Malignant granular cell tumor is very rare variant of granular cell tumor (GCT); less than 1 in 50 GCTs has a tendency of becoming malignant. Generally, a malignant GCT would have higher amounts of abnormal cells (called cellular atypia) and increased proliferation/growth
• Malignant Granular Cell Tumor of Vulva is an uncommon malignancy of the soft tissue that occurs in the vulva (area around the external opening of the vagina), typically of middle-aged women
• It is important to note that a granular cell tumor can either be benign or malignant. Benign GCTs are more common than malignant GCTs. Malignant granular cell tumors, by definition, are granular cell tumors that have metastasized from the site of origin
• Malignant Granular Cell Tumor of Vulva forms as a rapidly-growing solitary mass on the vulva; an ulceration of the overlying skin may be noticed. Advanced stage tumors may metastasize to the lungs and liver
• A combination of chemotherapy (drugs), radiation therapy, and surgical procedures, are used to treat these soft tissue tumors. The prognosis of Vulvar Malignant Granular Cell Tumor depends on the cancer stage and overall health of the individual

Who gets Malignant Granular Cell Tumor of Vulva? (Age and Sex Distribution)

• Malignant Granular Cell Tumor of Vulva is a rare tumor that may be observed both in adult women and in young girls (to a much lesser extent)
• Generally, most vulvar granular cell tumors are observed in middle-aged women. Also, about 15% of all GCTs are found to arise in the vulva
• Generally, no preference for any race or ethnic group is noted

What are the Risk Factors for Malignant Granular Cell Tumor of Vulva? (Predisposing Factors)

• No documented risk factors have been reported for Malignant Granular Cell Tumor of Vulva
• Even though GCTs do not usually run in families, rare cases of increased incidence within families, have been reported

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 Malignant Granular Cell Tumor of Vulva? (Etiology)

• The exact cause of Malignant Granular Cell Tumor of Vulva is unknown
• Researchers have documented certain genetic changes within the tumor. However, cases where these specific genetic mutations have been observed are rare. Thus, studies regarding genetic changes are limited
• Even though rare cases of familial granular cell tumors have been noted, malignant GCTs are not associated with any known congenital syndromes

What are the Signs and Symptoms of Malignant Granular Cell Tumor of Vulva?

The signs and symptoms of Malignant Granular Cell Tumor of Vulva may include:

• The tumors are usually fast-growing (unlike benign GCTs)
• Initially, it may be present as a subcutaneous mass in the vulva (commonly in the labium majus)
• The tumor may present the following features:
  • Size greater than 3 cm (along the larger dimension)
  • Ulceration of overlying skin
  • A rapid increase in size
• The tumor is locally infiltrative and poorly-circumscribed
• The tumors may be itchy and painful to touch
• Enlarged lymph nodes
• Pelvic pain
• Frequent urination or urination difficulties
• Lower back pain

In general, with granular cell tumor, about 1 in 10 individuals may simultaneously have multiple tumors in the body. However, having multiple benign GCTs do not indicate that the individual has a malignant GCT.

How is Malignant Granular Cell Tumor of Vulva Diagnosed?

A Malignant Granular Cell Tumor of Vulva is diagnosed using the following tools and methods:

• 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
• 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 cervix
  • 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

Although the above modalities can be used to make an initial diagnosis, a tissue biopsy of the tumor is necessary to make a definitive diagnosis to begin treatment. The tissue for diagnosis can be procured in multiple different ways which include:

• Fine needle aspiration (FNA) biopsy of the tumor: A FNA biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the tumor. Hence, a FNA biopsy as a diagnostic tool has certain limitations, and an open surgical biopsy is preferred
• Core biopsy of the tumor
• Open biopsy of the tumor

Tissue biopsy:

• A tissue biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
• Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
• Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely, electron microscopic studies to assist in the diagnosis

Note:

• A tissue biopsy cannot help definitively diagnose a benign GCT from a malignant GCT. A tissue biopsy may show overlapping features between a malignant granular cell tumor and a benign granular cell tumor, when examined under a microscope by a pathologist. Clinical correlation as regards the behavior of the tumor is often necessary for a definitive diagnosis of malignancy. A malignant GCT is diagnosed when the tumor metastasizes to structures away from the primary site of tumor origin
• Clinical correlation is very important to arrive at a diagnosis of malignant granular cell tumor. A malignant GCT may show the following features: Size greater than 3 cm (along the larger dimension), ulceration of overlying skin, and a rapid increase in size
• Benign granular cell tumors are also found within the muscles, tendons, ligaments, soft tissues, and rarely within lymph nodes. Presence of GCT within the lymph nodes is a difficult problem for the doctors. This is because it is difficult to tell whether the presence of such tumors in the lymph nodes are due to a metastasis from a different body site, or if the GCT originated within the lymph nodes itself (primary site)
• The granular cell tumors should be clinically and histologically distinguished from other tumors. These tumors include rhabdomyoma, hibernoma, fibroxanthoma, neurofibroma and schwannoma.  A pathologist will help eliminate other tumor types
• Sometimes, the pathologist may perform special studies, which include immunohistochemical stains and histochemical stains. The common immuno stains used are S100 protein, neuron specific enolase (NSE), calretinin, peripheral myelin protein, myelin basic protein (MBP), alpha 1 antitrypsin protein, CD68, and vimentin. These immuno stains are usually positive in granular cell tumors. The GCTs are negative for neural filaments and GFAP immunostains
• The tumors are positive for PAS histochemical stains when examined by the pathologist under a microscope. Even though the tumors are positive for PAS stain, the tumors do not contain glycogen

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 Malignant Granular Cell Tumor of Vulva?

The possible complications of a Malignant Granular Cell Tumor of Vulva include:

• Metastasis to other regions of the body, especially to the lung, liver, bones, and regional lymph nodes; extensive metastasis may result in fatalities
• 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 Malignant Granular Cell Tumor of Vulva Treated?

The treatment of Malignant Granular Cell Tumor of Vulva may depend upon a consideration of the following set of factors:

• Size of the tumor
• Stage of the tumor
• Age of the individual
• Whether the women is pregnant or not,
• And the women’s desire to have children in future

The treatment measures for Malignant GCT of Vulva include:

• Pain medications, in case of tumors causing pain
• Surgical intervention (complete excision of the tumor) with chemotherapy and radiation therapy may be employed. However, poorly-circumscribed tumors with infiltrative margins make complete surgical tumor removal more difficult
• Surgery may include the following procedures:
  • 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
• 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: Minimum activity level is to be ensured until the surgical wound heals
• Follow-up care with regular screening and check-ups are important

How can Malignant Granular Cell Tumor of Vulva be Prevented?

• The cause of Malignant Granular Cell Tumor of Vulva is unknown; hence, there are no known methods to prevent the tumor occurrence
• 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 Malignant Granular Cell Tumor of Vulva? (Outcomes/Resolutions)

• Malignant Granular Cell Tumor of Vulva is a rare, aggressive, and highly-malignant tumor. The long-term prognosis depends on a combination of factors, such as:
  • 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
• Studies indicate that malignant GCTs are known to metastasize rapidly. The same study indicates that individuals with malignant GCTs have a survival rate of 35% over a period of 2.5 years (following its diagnosis)
• 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 Malignant Granular Cell Tumor of Vulva:

There are two variants of granular cell tumor (GCT) and these include:

Granular cell epulis of infancy:

• Granular cell epulis of infancy. This is a rare tumor that occurs on the gums of the newborn. It is more common in females. A pathologist would be able to arrive at a diagnosis of granular cell epulis of infancy after examination under microscope and also after performing a variety of special studies called immunostains. This tumor is negative for S100 protein, neuron specific enoloase (NSE), laminin and, myelin basic protein (MBP), CD-57 and alpha-1 antitrypsin protein. The above stains show a pattern that is different from the staining pattern of a classical granular cell tumor. This difference in staining pattern helps in the correct diagnosis
• This tumor is usually slow-growing. The tumor does not grow after birth and there is no tendency for local recurrence. In majority of cases a congenital granular cell tumor would either stop to grow or completely disappear without treatment
• This type of tumor tend to be smaller size compared to traditional soft tissue tumor (about 1 cm along the larger dimension)
• There are no documented cases of a congenital granular cell tumor undergoing a malignant transformation to develop into a malignant granular cell tumor

Malignant granular cell tumor:

• Malignant granular cell tumor is a very rare variant of the granular cell tumor. Less than 1 in 50 GCTs would have tendency to become malignant. Malignant granular cell tumor can occur at any age, but is more commonly seen in ages between 30-50 years. It is also more common in females, than males. Unlike benign granular cell tumor, which is more common in head and neck region; the malignant variant of GCT is more common in the arms and legs (particularly common in the thigh region). Unlike benign granular cell tumors, the malignant tumors grow more rapidly
• The skin over the malignant granular cell tumor could often break, causing ulceration. The tumor can spread to the surrounding areas through infiltration, and spread to other distant regions of the body too (metastasis)
• When examining a biopsy of the tumor, a pathologist and would be able to distinguish benign GCT from a malignant one, after examination under a microscope. Normally, a malignant granular cell tumor would have a higher amount of abnormal cells and increased proliferation (growth). Clinical correlation is very important to arrive at a diagnosis of malignant granular cell tumor. A malignant granular cell tumor may show the following features: Size greater than 3 cm (along the larger dimension), ulceration of overlying skin, and a rapid increase in size