Kaposi's sarcoma
Encyclopedia
Kaposi's sarcoma is a tumor caused by Human herpesvirus 8
(HHV8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV). It was originally described by Moritz Kaposi (KA-po-she), a Hungarian dermatologist practicing at the University of Vienna
in 1872. It became more widely known as one of the AIDS defining illnesses
in the 1980s. The viral cause for this cancer was discovered in 1994. Although KS is now well-established to be caused by a virus infection, there is widespread lack of awareness of this even among persons at risk for KSHV/HHV-8 infection.
Restated, Kaposi’s sarcoma (KS) is a systemic disease which can present with cutaneous lesions with or without internal involvement. Four subtypes have been described: Classic KS, affecting middle aged men of Mediterranean and Jewish descent, African endemic KS, KS in iatrogenically immunosuppressed patients, and AIDS-related KS. The erythematous to violaceous cutaneous lesions seen in KS have several morphologies: macular, patch, plaque, nodular, and exophytic. The cutaneous lesions can be solitary, localized or disseminated. KS can involve the oral cavity, lymph nodes, and viscera. Classic KS tends to be indolent, presenting with erythematous or violaceous patches on the lower extremities. African endemic KS and AIDS-related KS tend to be more aggressive. The AIDS-related KS lesions often rapidly progress to plaques and nodules affecting the upper trunk, face, and oral mucosa. The diagnosis can be made with a tissue biopsy and, if clinically indicated, internal imaging should be done.
Once the diagnosis of KS has been made, treatment is based on the subtype and the presence of localized versus systemic disease. Localized cutaneous disease can be treated with cryotherapy, intralesional injections of vinblastine, alitretinoin gel, radiotherapy, topical immunotherapy (imiquimod), or surgical excision. Extensive cutaneous disease and/or internal disease may require IV chemotherapy and immunotherapy. Discontinuation or reduction of immunosuppressive therapy is recommended when KS arises in the setting of iatrogenic immunosuppression. However, with AIDS-related KS, HAART has been shown to prevent or induce regression of KS. Some AIDS patients have complete resolution of the lesions and prolonged remission while continuing the therapy. Therefore, HAART should be considered first-line treatment for these patients, though they may require other concomitant treatments.
Classic KS
as originally described was a relatively indolent disease affecting elderly men from the Mediterranean region, or of Eastern European descent. Countries bordering the Mediterranean basin have higher rates of KSHV/HHV-8 infection than the remainder of Europe
Endemic KS
was described later in young African people, mainly from sub-Saharan Africa
, as a more aggressive disease which infiltrated the skin extensively, especially on the lower limbs. This, it should be noted, is not related to HIV
infection. KS is prevalent worldwide.
Transplant Related KS
had been described, but only rarely until the advent of calcineurin inhibitors (such as ciclosporin
es, which are inhibitors of T-cell function) for transplant
patients in the 1980s, when its incidence grew rapidly. The tumor arises either when an HHV 8-infected organ is transplanted into someone who has not been exposed to the virus or when the transplant recipient already harbors pre-existing HHV 8 infection.
Epidemic KS
was described during the 1980s as an aggressive disease in AIDS
patients (HIV also causes a defect in T-cell immunity). It is over 300 times more common in AIDS patients than in renal transplant recipients. In this case, HHV 8 is sexually transmitted among people who are also at risk for sexually transmitted HIV infection.
s are nodules or blotches that may be red, purple, brown, or black, and are usually papular (i.e. 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.
-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.
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.
, bleeding (either vomiting blood or passing it with bowel motions), malabsorption
, or intestinal obstruction.
, 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.
, which is a tumor arising from mesenchymal tissue
. KS actually 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 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.
Although KS may be suspected from the appearance of lesions and the patient's risk factors, definite diagnosis can only be made by biopsy
and microscopic examination, which will show the presence of spindle cells. Detection of the KSHV protein LANA
in tumor cells confirms the diagnosis.
KSHV is transmissible during organ transplantation
and to a lesser extent through blood transfusion. Testing for the virus before these procedures is likely to effectively limit iatrogenic transmission.
Kaposi's sarcoma is not curable (in the usual sense of the word) but it can often be effectively palliated for many years and this is the aim of treatment. 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 patients with AIDS-associated Kaposi's sarcoma, the Kaposi lesions will shrink upon first starting highly active antiretroviral therapy (HAART). However, in a certain percentage of such patients, Kaposi's sarcoma may again grow after a number of years on HAART, especially if HIV is not completely suppressed. Patients with a few local lesions can often be treated with local measures such as radiation therapy or cryosurgery
. Surgery is generally not recommended as Kaposi's sarcoma can appear in wound edges. More widespread disease, or disease affecting internal organs, is generally treated with systemic therapy with interferon
alpha, liposomal anthracyclines (such as Doxil) or paclitaxel
.
With the decrease in the death rate among AIDS patients receiving new treatments in the 1990s, the incidence and severity of epidemic KS also decreased. However, the number of patients living with AIDS is increasing substantially in the United States, and it is possible that the number of patients with AIDS-associated Kaposi's sarcoma will again rise as these patients live longer with HIV infection.
dermatologist who first described the symptoms in 1872. Research over the next century suggested that KS, like some other forms of cancer, might be caused by a virus or genetic factors, but no definite cause was found.
In 2007, San Francisco doctors reported a Kaposi's sarcoma cluster among gay men. All 15 patients undergoing treatment were long-term HIV patients whose HIV infections were firmly controlled with antiviral drugs. None appeared to be in any danger. The new cases were not aggressive, invasive or lethal as was typical with uncontrolled HIV during the 1980s. The unsightly, difficult-to-treat lesions raised questions about the immune response of ageing HIV patients.
, Patrick S. Moore
, and Ethel Cesarman at Columbia University
in New York
isolated genetic pieces of a virus from a KS lesion. They used representational difference analysis
(a method to subtract out all of the human DNA from a sample) to isolate the viral genes. They then used these small DNA fragments as starting points to sequence the rest of the viral genome in 1996. This, the eighth human herpesvirus (HHV-8)—now known as Kaposi's sarcoma-associated herpesvirus (KSHV)
—has since been found in all KS lesions tested, and is considered the cause of the disease. KSHV is a unique human tumor virus that has incorporated into its genome cellular genes that cause tumors ("molecular piracy"); the stolen cellular genes may help the virus escape from the immune system, but in doing so it also causes cells to proliferate. It is related to Epstein-Barr virus
, a very common herpesvirus that can also cause human cancers. KSHV is readily found in all forms of KS. The virus is sexually transmitted and can be transmitted through organ donation. In Africa, high rates of KSHV infection has led to KS becoming the most common cancer in sub-Saharan Africa. KSHV infection is thought to be life-long so that persons infected with KSHV may develop KS years later if they develop AIDS or other immunosuppression.
In AIDS patients, Kaposi's sarcoma is considered an opportunistic infection
, a disease that is able to gain a foothold in the body because the immune system
has been weakened. With the rise of HIV/AIDS in Africa
, where KSHV is widespread, KS has become the most frequently reported cancer in some countries.
Nigerian bandleader Fela Kuti
succumbed to the disease in 1997.
Because of their highly visible nature, external lesions are sometimes the presenting symptom of AIDS. Kaposi's sarcoma entered the awareness of the general public with the release of the film Philadelphia
, in which the main character was fired after his employers found out he was HIV-positive due to visible lesions. Unfortunately, by the time KS lesions appear, it is likely that the immune system has already been severely weakened.
Kaposi's sarcoma-associated herpesvirus
Kaposi's sarcoma-associated herpesvirus is one of seven currently known human cancer viruses, or oncoviruses. It is also the eighth human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses is HHV-8. Like other herpesviruses, its informal name is used...
(HHV8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV). It was originally described by Moritz Kaposi (KA-po-she), a Hungarian dermatologist practicing at the University of Vienna
University of Vienna
The University of Vienna is a public university located in Vienna, Austria. It was founded by Duke Rudolph IV in 1365 and is the oldest university in the German-speaking world...
in 1872. It became more widely known as one of the AIDS defining illnesses
AIDS defining clinical condition
AIDS defining clinical conditions is the terminology given to a list of diseases published by the United States government run Centers for Disease Control and Prevention . This list governs the U.S. government classification of HIV disease...
in the 1980s. The viral cause for this cancer was discovered in 1994. Although KS is now well-established to be caused by a virus infection, there is widespread lack of awareness of this even among persons at risk for KSHV/HHV-8 infection.
Restated, Kaposi’s sarcoma (KS) is a systemic disease which can present with cutaneous lesions with or without internal involvement. Four subtypes have been described: Classic KS, affecting middle aged men of Mediterranean and Jewish descent, African endemic KS, KS in iatrogenically immunosuppressed patients, and AIDS-related KS. The erythematous to violaceous cutaneous lesions seen in KS have several morphologies: macular, patch, plaque, nodular, and exophytic. The cutaneous lesions can be solitary, localized or disseminated. KS can involve the oral cavity, lymph nodes, and viscera. Classic KS tends to be indolent, presenting with erythematous or violaceous patches on the lower extremities. African endemic KS and AIDS-related KS tend to be more aggressive. The AIDS-related KS lesions often rapidly progress to plaques and nodules affecting the upper trunk, face, and oral mucosa. The diagnosis can be made with a tissue biopsy and, if clinically indicated, internal imaging should be done.
Once the diagnosis of KS has been made, treatment is based on the subtype and the presence of localized versus systemic disease. Localized cutaneous disease can be treated with cryotherapy, intralesional injections of vinblastine, alitretinoin gel, radiotherapy, topical immunotherapy (imiquimod), or surgical excision. Extensive cutaneous disease and/or internal disease may require IV chemotherapy and immunotherapy. Discontinuation or reduction of immunosuppressive therapy is recommended when KS arises in the setting of iatrogenic immunosuppression. However, with AIDS-related KS, HAART has been shown to prevent or induce regression of KS. Some AIDS patients have complete resolution of the lesions and prolonged remission while continuing the therapy. Therefore, HAART should be considered first-line treatment for these patients, though they may require other concomitant treatments.
Classification
HHV-8 is responsible for all varieties of KS.Classic KS
as originally described was a relatively indolent disease affecting elderly men from the Mediterranean region, or of Eastern European descent. Countries bordering the Mediterranean basin have higher rates of KSHV/HHV-8 infection than the remainder of Europe
Endemic KS
was described later in young African people, mainly from sub-Saharan Africa
Sub-Saharan Africa
Sub-Saharan Africa as a geographical term refers to the area of the African continent which lies south of the Sahara. A political definition of Sub-Saharan Africa, instead, covers all African countries which are fully or partially located south of the Sahara...
, as a more aggressive disease which infiltrated the skin extensively, especially on the lower limbs. This, it should be noted, is not related to HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
infection. KS is prevalent worldwide.
Transplant Related KS
had been described, but only rarely until the advent of calcineurin inhibitors (such as ciclosporin
Ciclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...
es, which are inhibitors of T-cell function) for transplant
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
patients in the 1980s, when its incidence grew rapidly. The tumor arises either when an HHV 8-infected organ is transplanted into someone who has not been exposed to the virus or when the transplant recipient already harbors pre-existing HHV 8 infection.
Epidemic KS
was described during the 1980s as an aggressive disease in AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
patients (HIV also causes a defect in T-cell immunity). It is over 300 times more common in AIDS patients than in renal transplant recipients. In this case, HHV 8 is sexually transmitted among people who are also at risk for sexually transmitted HIV infection.
Types
Since Moritz Kaposi first described this malignant neoplasm, the disease has been reported in five separate clinical settings, with different presentations, epidemiology, and prognoses:- Classic Kaposi sarcomaClassic Kaposi sarcomaClassic Kaposi sarcoma most commonly appears early on the toes and soles as reddish, violaceous, or bluish-black macules and patches that spread and coalesce to form nodules or plaques....
- African cutaneous Kaposi sarcomaAfrican cutaneous Kaposi sarcomaAfrican cutaneous Kaposi sarcoma presents with nodular, infiltrative, vascular masses on the extremities, mostly in men between the ages of 20 and 50, and is endemic in tropical Africa....
- African lymphadenopathic Kaposi sarcomaAfrican lymphadenopathic Kaposi sarcomaAfrican lymphadenopathic Kaposi sarcoma is aggressive, occurring in children under 10 years of age, presenting with lymph node involvement, with or without skin lesions....
- AIDS-associated Kaposi sarcomaAIDS-associated Kaposi sarcomaAIDS-associated Kaposi sarcoma or KS-AIDS presents with cutaneous lesions that begin as one or several red to purple-red macules, rapidly progressing to papules, nodules, and plaques, with a predilection for the head, neck, trunk, and mucous membranes. KS-AIDS simulated the greatest interest as one...
- Immunosuppression-associated Kaposi sarcomaImmunosuppression-associated Kaposi sarcomaImmunosuppression-associated Kaposi sarcoma resembles that of classic Kaposi sarcoma; however, the site of presentation is more variable.-References:...
Signs and symptoms
KS lesionLesion
A lesion is any abnormality in the tissue of an organism , usually caused by disease or trauma. Lesion is derived from the Latin word laesio which means injury.- Types :...
s are nodules or blotches that may be red, purple, brown, or black, and are usually papular (i.e. palpable or raised).
They are typically found on the skin, but spread elsewhere is common, especially the mouth, gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
and respiratory tract
Respiratory tract
In humans the respiratory tract is the part of the anatomy involved with the process of respiration.The respiratory tract is divided into 3 segments:*Upper respiratory tract: nose and nasal passages, paranasal sinuses, and throat or pharynx...
. Growth can range from very slow to explosively fast, and is associated with significant mortality
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
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 plaqueRash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
-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
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
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
Is involved in about 30%, and is the initial site in 15% of AIDS related KS. In the mouth, the hard palateHard palate
The hard palate is a thin horizontal bony plate of the skull, located in the roof of the mouth. It spans the arch formed by the upper teeth.It is formed by the palatine process of the maxilla and horizontal plate of palatine bone....
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, diarrheaDiarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, bleeding (either vomiting blood or passing it with bowel motions), malabsorption
Malabsorption
Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
, or intestinal obstruction.
Respiratory tract
Involvement of the airway can present with shortness of breath, feverFever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, cough
Cough
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
, hemoptysis
Hemoptysis
Hemoptysis or haemoptysis is the expectoration of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis is the expectoration (coughing up) of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis ...
(coughing up blood), or chest pain, or as an incidental finding on chest x-ray
Chest X-ray
In medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...
. The diagnosis is usually confirmed by bronchoscopy
Bronchoscopy
Bronchoscopy is a technique of visualizing the inside of the airways for diagnostic and therapeutic purposes. An instrument is inserted into the airways, usually through the nose or mouth, or occasionally through a tracheostomy. This allows the practitioner to examine the patient's airways for...
when the lesions are directly seen, and often biopsied.
Pathophysiology and diagnosis
Despite its name, it is generally not considered a true sarcomaSarcoma
A sarcoma is a cancer that arises from transformed cells in one of a number of tissues that develop from embryonic mesoderm. Thus, sarcomas include tumors of bone, cartilage, fat, muscle, vascular, and hematopoietic tissues...
, which is a tumor arising from mesenchymal tissue
Mesenchyme
Mesenchyme, or mesenchymal connective tissue, is a type of undifferentiated loose connective tissue that is derived mostly from mesoderm, although some are derived from other germ layers; e.g. some mesenchyme is derived from neural crest cells and thus originates from the ectoderm...
. KS actually arises as a cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
of lymphatic endothelium
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
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
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
with a characteristic abnormal elongated shape, called spindle cells. The tumor is highly vascular
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
, containing abnormally dense and irregular blood vessels, which leak red blood cells into the surrounding tissue and give the tumor its dark color. Inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
around the tumor may produce swelling and pain.
Although KS may be suspected from the appearance of lesions and the patient's risk factors, definite diagnosis can only be made by biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
and microscopic examination, which will show the presence of spindle cells. Detection of the KSHV protein LANA
LANA
The latency-associated nuclear antigen or LANA-1, is a Kaposi's sarcoma-associated herpesvirus latent protein which has been suspected of playing a crucial role in modulating viral and cellular gene expression.. LANA was found by Moore and colleagues as a speckled nuclear antigen present in...
in tumor cells confirms the diagnosis.
Transmission
In Europe and North America KSHV is transmitted through saliva. Thus, kissing is a theoretical risk factor for transmission although transmission between heterosexuals appears to be rare. Higher rates of transmission among gay and bisexual men has been attributed to "deep kissing" sexual partners with KSHV. Another alternative theory suggests that use of saliva as a sexual lubricant might be a major mode for transmission. Prudent advice is to use commercial lubricants when needed and avoid deep kissing with partners who have KSHV infection or have unknown status.KSHV is transmissible during organ transplantation
and to a lesser extent through blood transfusion. Testing for the virus before these procedures is likely to effectively limit iatrogenic transmission.
Treatment and prevention
Blood tests to detect antibodies against KSHV have been developed and can be used to determine if a patient is at risk for transmitting infection to their sexual partner, or if an organ is infected prior to transplantation. Unfortunately, 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 transplant patients.Kaposi's sarcoma is not curable (in the usual sense of the word) but it can often be effectively palliated for many years and this is the aim of treatment. In KS associated with immunodeficiency
Immunodeficiency
Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...
or immunosuppression, treating the cause of the immune system dysfunction can slow or stop the progression of KS. In 40% or more of patients with AIDS-associated Kaposi's sarcoma, the Kaposi lesions will shrink upon first starting highly active antiretroviral therapy (HAART). However, in a certain percentage of such patients, Kaposi's sarcoma may again grow after a number of years on HAART, especially if HIV is not completely suppressed. Patients with a few local lesions can often be treated with local measures such as radiation therapy or cryosurgery
Cryosurgery
Cryosurgery is the application of extreme cold to destroy abnormal or diseased tissue. The term comes from the Greek words cryo and surgery meaning "hand work" or "handiwork"....
. Surgery is generally not recommended as Kaposi's sarcoma can appear in wound edges. More widespread disease, or disease affecting internal organs, is generally treated with systemic therapy with interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
alpha, liposomal anthracyclines (such as Doxil) or paclitaxel
Paclitaxel
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a U.S. National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol...
.
With the decrease in the death rate among AIDS patients receiving new treatments in the 1990s, the incidence and severity of epidemic KS also decreased. However, the number of patients living with AIDS is increasing substantially in the United States, and it is possible that the number of patients with AIDS-associated Kaposi's sarcoma will again rise as these patients live longer with HIV infection.
Discovery
The disease is named after Moritz Kaposi (1837–1902), a HungarianHungary
Hungary , officially the Republic of Hungary , is a landlocked country in Central Europe. It is situated in the Carpathian Basin and is bordered by Slovakia to the north, Ukraine and Romania to the east, Serbia and Croatia to the south, Slovenia to the southwest and Austria to the west. The...
dermatologist who first described the symptoms in 1872. Research over the next century suggested that KS, like some other forms of cancer, might be caused by a virus or genetic factors, but no definite cause was found.
Relationship to AIDS
With the rise of the AIDS epidemic, KS, as initially one of the most common AIDS symptoms, was researched more intensively in hopes that it might reveal the cause of AIDS. The disease was erroneously referred to as the "AIDS rash".In 2007, San Francisco doctors reported a Kaposi's sarcoma cluster among gay men. All 15 patients undergoing treatment were long-term HIV patients whose HIV infections were firmly controlled with antiviral drugs. None appeared to be in any danger. The new cases were not aggressive, invasive or lethal as was typical with uncontrolled HIV during the 1980s. The unsightly, difficult-to-treat lesions raised questions about the immune response of ageing HIV patients.
Viral cause isolated
In 1994, Yuan ChangYuan Chang
Yuan Chang is an American virologist and pathologist who co-discovered Kaposi's sarcoma-associated herpesvirus and Merkel cell polyomavirus, two of the seven known human cancer viruses....
, Patrick S. Moore
Patrick S. Moore
Patrick S. Moore is an American virologist and epidemiologist who co-discovered together with his wife, Yuan Chang, two different human viruses causing the AIDS-related cancer Kaposi's sarcoma and the skin cancer Merkel cell carcinoma...
, and Ethel Cesarman at Columbia University
Columbia University
Columbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...
in New York
New York
New York is a state in the Northeastern region of the United States. It is the nation's third most populous state. New York is bordered by New Jersey and Pennsylvania to the south, and by Connecticut, Massachusetts and Vermont to the east...
isolated genetic pieces of a virus from a KS lesion. They used representational difference analysis
Representational Difference Analysis
Representational Difference Analysis is a technique used in biological research to find sequence differences in two genomic or cDNA samples. Genomes or cDNA sequences from two samples are PCR amplified and differences analyzed using subtractive DNA hybridization...
(a method to subtract out all of the human DNA from a sample) to isolate the viral genes. They then used these small DNA fragments as starting points to sequence the rest of the viral genome in 1996. This, the eighth human herpesvirus (HHV-8)—now known as Kaposi's sarcoma-associated herpesvirus (KSHV)
Kaposi's sarcoma-associated herpesvirus
Kaposi's sarcoma-associated herpesvirus is one of seven currently known human cancer viruses, or oncoviruses. It is also the eighth human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses is HHV-8. Like other herpesviruses, its informal name is used...
—has since been found in all KS lesions tested, and is considered the cause of the disease. KSHV is a unique human tumor virus that has incorporated into its genome cellular genes that cause tumors ("molecular piracy"); the stolen cellular genes may help the virus escape from the immune system, but in doing so it also causes cells to proliferate. It is related to Epstein-Barr virus
Epstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
, a very common herpesvirus that can also cause human cancers. KSHV is readily found in all forms of KS. The virus is sexually transmitted and can be transmitted through organ donation. In Africa, high rates of KSHV infection has led to KS becoming the most common cancer in sub-Saharan Africa. KSHV infection is thought to be life-long so that persons infected with KSHV may develop KS years later if they develop AIDS or other immunosuppression.
Awareness
Only 6% of homosexual men are aware that KS is caused by a virus different from HIV. Thus, there is little community effort to prevent KSHV infection. Similarly, no systematic screening of organ donations is in place.In AIDS patients, Kaposi's sarcoma is considered an opportunistic infection
Opportunistic infection
An opportunistic infection is an infection caused by pathogens, particularly opportunistic pathogens—those that take advantage of certain situations—such as bacterial, viral, fungal or protozoan infections that usually do not cause disease in a healthy host, one with a healthy immune system...
, a disease that is able to gain a foothold in the body because the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
has been weakened. With the rise of HIV/AIDS in Africa
HIV/AIDS in Africa
HIV/AIDS is a major public health concern and cause of death in Africa. Although Africa is home to about 14.5% of the world's population, it is estimated to be home to 67% of all people living with HIV and to 72% of all AIDS deaths in 2009.-Overview:...
, where KSHV is widespread, KS has become the most frequently reported cancer in some countries.
Nigerian bandleader Fela Kuti
Fela Kuti
Fela Anikulapo Kuti , or simply Fela , was a Nigerian multi-instrumentalist musician and composer, pioneer of Afrobeat music, human rights activist, and political maverick.-Biography:...
succumbed to the disease in 1997.
Because of their highly visible nature, external lesions are sometimes the presenting symptom of AIDS. Kaposi's sarcoma entered the awareness of the general public with the release of the film Philadelphia
Philadelphia (film)
Philadelphia is a 1993 American drama film that was one of the first mainstream Hollywood films to acknowledge HIV/AIDS, homosexuality and homophobia. It was written by Ron Nyswaner and directed by Jonathan Demme. The film stars Tom Hanks and Denzel Washington...
, in which the main character was fired after his employers found out he was HIV-positive due to visible lesions. Unfortunately, by the time KS lesions appear, it is likely that the immune system has already been severely weakened.
External links
- http://hivinsite.ucsf.edu/InSite?page=kb-authors&doc=kb-06-02-01
- Kaposi's sarcoma photo library at Dermnet
- Kaposi Sarcoma information
- Office of HIV and AIDS Malignancy in the National Cancer Institute