Kaposi sarcoma

Synonyms

6

Overview

Kaposi sarcoma (KS) is a cancer that develops from the cells that line lymph or blood vessels. It usually appears as tumors on the skin or on mucosal surfaces such as inside the mouth, but tumors can also develop in other parts of the body (including the lymph nodes, lungs, or digestive tract). The abnormal cells of Kaposi sarcoma cause purplish, reddish blue, or dark brown/black skin lesions (macules, nodules, plaques) on the legs and the face. These lesions may look bad, but they usually cause no symptoms. However, when the lesions are in the lungs, liver, or digestive tract, they may cause serious problems like gastrointestinal bleeding or trouble breathing. 
Kaposi sarcoma is caused by infection with a virus called the Kaposi sarcoma associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8). Kaposi sarcoma is classified into four types based upon the different populations in which it develops: classic (which presents in middle or old age), endemic (described in sub-Saharan indigenous Africans), iatrogenic (associated with immunosuppressive drug therapy) and AIDS-associated (epidemic KS). Options for treatment may include local therapy, radiation therapy, chemotherapy and biologic therapy (immunotherapy). The main aim is to restore immunity.

Symptoms

KS lesions are nodules or blotches that may be red, purple, brown, or black, and are usually papular (in other words, palpable or raised).

They are typically found on the skin, but spread elsewhere is common, especially the mouth, gastrointestinal tract and respiratory tract. Growth can range from very slow to explosively fast, and is associated with significant mortality and morbidity.

Skin:

Commonly affected areas include the lower limbs, back, face, mouth, and genitalia. The lesions are usually as described above, but may occasionally be plaque-like (often on the soles of the feet) or even involved in skin breakdown with resulting fungating lesions. Associated swelling may be from either local inflammation or lymphoedema (obstruction of local lymphatic vessels by the lesion). Skin lesions may be quite disfiguring for the sufferer, and a cause of much psychosocial pathology.

Mouth:

The mouth is involved in about 30% of cases, and is the initial site in 15% of AIDS-related KS. In the mouth, the hard palate is most frequently affected, followed by the gums. Lesions in the mouth may be easily damaged by chewing and bleed or suffer secondary infection, and even interfere with eating or speaking.

Gastrointestinal tract:

Involvement can be common in those with transplant-related or AIDS-related KS, and it may occur in the absence of skin involvement. The gastrointestinal lesions may be silent or cause weight loss, pain, nausea/vomiting, diarrhea, bleeding (either vomiting blood or passing it with bowel motions), malabsorption, or intestinal obstruction.

Respiratory tract:

Involvement of the airway can present with shortness of breath, fever, cough, hemoptysis (coughing up blood), or chest pain, or as an incidental finding on chest x-ray. The diagnosis is usually confirmed by bronchoscopy when the lesions are directly seen, and often biopsied.

Causes

Human herpesvirus-8 (HHV-8) is found in the lesions of all patients with Kaposi sarcoma. This virus is also called Kaposi sarcoma herpesvirus (KSHV). Most people infected with HHV-8 do not get Kaposi sarcoma. Those infected with HHV-8 who are most likely to develop Kaposi sarcoma have immune systems weakened by disease or by drugs given after an organ transplant.

Prevention

Blood tests to detect antibodies against KSHV have been developed and can be used to determine whether a person is at risk for transmitting infection to their sexual partner, or whether an organ is infected prior to transplantation. However, these tests are not available except as research tools, and, thus, there is little screening for persons at risk for becoming infected with KSHV, such as people following a transplant.

Diagnosis

Despite its name, in general it is not considered a true sarcoma, which is a tumor arising from mesenchymal tissue. The histogenesis of KS remains controversial. According to some, KS arises as a cancer of lymphatic endothelium and forms vascular channels that fill with blood cells, giving the tumor its characteristic bruise-like appearance. KSHV proteins are uniformly detected in KS cancer cells.

KS lesions contain tumor cells with a characteristic abnormal elongated shape, called spindle cells. The most typical feature of Kaposi sarcoma is the presence of spindle cells forming slits containing red blood cells. Mitotic activity is only moderate and pleomorphism is usually absent. The tumor is highly vascular, containing abnormally dense and irregular blood vessels, which leak red blood cells into the surrounding tissue and give the tumor its dark color. Inflammation around the tumor may produce swelling and pain. Variously sized PAS positive hyaline bodies are often seen in the cytoplasm or sometimes extracellularly.

The spindle cells of Kaposi sarcoma differentiate toward endothelial cells, probably of lymph vessel rather than blood vessel nature. The consistent immunoreactivity for podoplanin supports the lymphatic nature of the lesion.

HHV8 is present in almost 100% of Kaposi sarcoma lesions, whether HIV-related, classic, endemic, or iatrogenic.

Although KS may be suspected from the appearance of lesions and the patient's risk factors, definite diagnosis can be made only by biopsy and microscopic examination. Detection of the KSHV protein LANA in tumor cells confirms the diagnosis.

In differential diagnosis, arteriovenous malformations, pyogenic granuloma and other vascular proliferations can be microscopically confused with KS.

The following tests and procedures may be used:

  • Physical exam and history: An exam of the body to check general signs of health, including checking skin and lymph nodes for signs of disease, such as lumps or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken.
  • Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer.
  • Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body. This is used to find Kaposi sarcoma in the lungs.
  • Endoscopy: A procedure to look at organs and tissues inside the body to check for abnormal areas. An endoscope is inserted through an incision (cut) in the skin or opening in the body, such as the mouth. An endoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of disease. This is used to find Kaposi sarcoma lesions in the gastrointestinal tract.
  • Bronchoscopy: A procedure to look inside the trachea and large airways in the lung for abnormal areas. A bronchoscope is inserted through the nose or mouth into the trachea and lungs. A bronchoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue samples, which are checked under a microscope for signs of cancer.

Prognosis

The prognosis and treatment options depend on the following:

  • The type of Kaposi sarcoma.
  • The general health of the patient, especially the immune system.
  • Whether the cancer has spread.
  • Whether the cancer has just been diagnosed or has recurred.

Treatment

Kaposi sarcoma is not curable but it can often be treatable for many years. In KS associated with immunodeficiency or immunosuppression, treating the cause of the immune system dysfunction can slow or stop the progression of KS. In 40% or more of peoples with AIDS-associated Kaposi sarcoma, the Kaposi lesions will shrink upon first starting highly active antiretroviral therapy (HAART). However, in a certain percentage of such people, Kaposi sarcoma may again grow after a number of years on HAART, especially if HIV is not completely suppressed.

People with a few local lesions can often be treated with local measures such as radiation therapy or cryosurgery. Weak evidence suggests that antiretroviral therapy in combination with chemotherapy is more effective than either of those two therapies individually. In general, surgery is not recommended, as Kaposi sarcoma can appear in wound edges. 

Approved therapies:

  • Daunorubicin citrate liposome injection (DaunoXome) - FDA-approved indication: First line cytotoxic therapy for advanced, HIV related Kaposi's sarcoma. 
  • Interferon alfa-2b (recombinant) (Intron A) - FDA-approved indication: Treatment of selected patients with AIDS-related Kaposi's sarcoma. 
  • Alitretinoin (Panretin(topical)) - FDA-approved indication: Topical treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma. 
  • Paclitaxel (Taxol) - FDA-approved indication: For the second line treatment of AIDS-related Kaposi's sarcoma. 
  • Pazopanib (Votrient) - FDA-approved indication: Advanced soft tissue sarcoma (STS) who have received prior chemotherapy. 

Resources

Refer to Research Publications.