MfA - Kaposi's Sarcoma

Medicine for Africa - Medical Information Service

APOSI'S ARCOMA

Definition:

Kaposi’s sarcoma (KS) is named after Dr. Moritz Kaposi, a Hungarian dermatologist who first described the sarcoma in 1872. This form of classic KS was a relatively indolent (harmless) skin disease that primarily affected elderly men from the Mediterranean region or of Eastern European origin.

Kaposi’s sarcoma is not, as its name may imply, a true sarcoma, arising from mesenchymal tissue, but rather a tumor of lymphatic endothelium that forms vascular channels which fill with blood and blood cells, thus giving this tumor its characteristic bluish, bruise-like appearance.

Prior to the surfacing of the AIDS epidemic, KS was a slowly developing skin disease, primarily occurring in elderly men (> 60 years of age) in the Mediterranean region. The immunosuppressed status of HIV/AIDS infected people in the 1980s and beyond, has made this rare sarcoma a wide-spread and now commonly seen form of vascular sarcoma in predominantly men of any age and race.

All forms of Kaposi’s sarcoma are considered to be the direct result of an infection with the human herpes virus type eight ( HHV-8), also known as the Kaposi’s sarcoma associated herpes virus - KSHV. The viral cause of this sarcoma was proven only in 1994; since the virus can be transmitted via sexual intercourse, this potentially malignant tumor can be added to the group of sexually transmitted diseases.

The various origins of Kaposi’s sarcoma include:

Epidemic KS was first described in the 1980s as an aggressive “associated” disease in patients with HIV/AIDS. In AIDS patients, the occurrence of KS is more than 300 times more likely than even in transplant related KS (see below), especially in view of the fact that HHV-8 is sexually transmitted by gay and bisexual men who are also at an increased risk for sexually transmitted HIV infection.

Endemic KS was later described in young African (mostly) men, primarily from sub-Saharan Africa (SSA). This type of KS proved to be more aggressive and to infiltrate the skin more extensively, especially on the lower leg(s). It is believed that the herpes virus is generally very prevalent and wide-spread in Africa which is the reason of the more aggressive form of KS in SSA.

Transplant related KS – used to be a rare cause of the development of KS until the usage of so-called calcineurin inhibitors, such as cyclosporine, when used in (especially renal) transplant patients in order to inhibit body-own T-cell functions. The sarcoma arises as a result of transmitting HHV-8 via the transplant or by causing a re-surfacing of the virus in the transplant recipient, subsequent to the physiological stress or general immuno-suppressive condition (probably THE most important single cause for KS), following the surgery and subsequent therapy.

Kaposi’s sarcoma represents itself as characteristic flat or raised purple plaque-like vascular nodules in the skin and other organs. KS consists of an extensive network of small blood vessels and red blood cells (RBCs) that are moving through these channels and, at times, into perivascular tissue (so-called ecchymotic KS); or resemble ‘cavernous’ hemangiomas in a rare but locally aggressive form of KS. Other rare forms of KS include the teleangiectatic KS, presenting with translucent skin nodules; the keloidal KS consisting of keloid containing brown-violaceous colored skin nodules; or the lymphangioma-like KS in which dilated vascular spaces produce a bullous-appearing eruption, usually on the lower legs.

Risk factors for the development of Kaposi’s sarcoma include:

KS develops only in people who are positive for HHV-8, the Kaposi sarcoma herpes virus (KSHV) – a variant of the herpes virus that is part of the sexually transmitted disease complex – however, not everyone who is infected with KSHV actually gets KS;
Decreased efficiency and/or effectiveness of the body-own immune system can increase the likelihood of developing KS, such as in AIDS patients prior to receiving antiretroviral therapy, or in patients, who received an organ transplant, followed by an immunosuppressive therapy to prevent organ rejection;
Ethnicity: people, mostly men, of Mediterranean, Eastern European and Middle Eastern descent have a higher rate of classic KS, probably due to an inborn or inherited variation in their immune system, which makes them more susceptible;
Men appear to have a larger likelihood of becoming infected with KS, although, in Africa, men, women and even children are at an increased risk of developing KS;
Promiscuity, especially among homosexual men, harbors an increased risk of developing KS – the reasons for this fact are not quite understood (but see point above); women who have sex with these men, appear to be less likely to develop KS than their male sexual counterparts;
KSHV appears to be transmitted via saliva, but also among drug users by way of shared injection needles.

Kaposi’s sarcoma typically presents as a focal cancer, but can also produce distant metastases; KS can be limited to skin lesions, or manifest itself in a fulminant fashion, involving multiple organs and lymph node regions throughout the body. Thus, there are three different types of Kaposi’s sarcoma, based on their appearance:

Nodular lesion – is of varying size and thickness; purple in color with, at times, brown or yellow pigmentation around the primary lesion;
Infiltrating KS – may become quite large, locally aggressive in its growth pattern, rising above skin level, or growing deep downward into lower skin levels;
Lymphatic KS lesions – can mimic other disease processes that are associated with swollen lymph nodes; they often require a diagnostic biopsy in order to rule out an infectious process.

Histologically – under the pathologist’s microscope – the three KS types look rather similar, as they are also treated in much the same way. While the spindle cell variant has the slowest growth rate, the anaplastic type of KS is the most aggressive one, and the mixed cell variation displays an intermediate growth rate.

Symptoms:

Sarcoma growth can be very slow or explosively fast, then, it is associated with significant morbidity and mortality.

Lesions of Kaposi’s sarcoma usually appear as red, purple, brown or black nodules or blotches in a ‘papular’ (palpable or raised) shape, anywhere on the skin. However, especially in connection with AIDS, KS can occur anywhere else within the body, such as the mouth and lips, genitalia, gastrointestinal tract (GI-tract) and respiratory tract. Associated symptoms may range from local inflammation to wider spread lymphedema.

The mouth may be involved in up to 30% of cases, and has been identified as initial site in 15% of AIDS related KS cases. The hard palate and gums are the most frequently affected areas.

KS within the gastrointestinal (GI) tract is often subsequent to organ transplantation and/or AIDS, due to a suppressed immune system of the body in either case. These lesions can present without any symptoms, or cause non-specific symptoms such as nausea and vomiting, diarrhea, bleeding, malabsorption, weight loss and/or intestinal obstruction. Persistent blood loss via the GI-tract can lead to a more or less pronounced state of anemia and subsequent feeling of weakness, tiredness and feebleness.

KS affecting the respiratory tract can result in shortness of breath, cough, hemoptysis (coughing up blood), fever and chest pain, and is often found incidentally on a (routine) chest X-ray.

Diagnosis:

Kaposi’s sarcoma associated herpes virus (KSHV) specific proteins are uniformly detected in the tumor cells of Kaposi’s sarcoma. KS cells have a typical abnormally elongated shape, called spindle cells. The tumor is highly vascular, consisting of very dense and irregular blood vessels, which leak red blood cells (RBCs) into the surrounding connective tissue, thus giving the tumor its characteristic dark blue-brown color. Subsequent inflammation around these areas may produce additional swelling and local pain.

While KS can be suspected during a thorough physical examination, definite diagnosis requires the taking of a punch biopsy (removing a small round piece of tissue) or an excisional biopsy (in which the entire lesion is removed) of the suspected area, which has to be submitted to a pathologist for microscopic examination. The characteristic appearance with the presence of spindle cells and the detection of the KSHV-associated protein, called LANA-1 (latency-associated nuclear antigen) confirm the suspected diagnosis.

An X-ray of the lungs (chest x-ray) may often be the first test to identify whether KS has spread to the lungs; a subsequent bronchoscopy with sampling of cells (‘washing’) or tissue (biopsies) will then be required to confirm the suspected diagnosis.

When KS appears to have spread to the gastrointestinal tract (GI-tract), including the stomach and/or intestines, the diagnostic approach requires an endoscopy, esophagogastroendoscopy (EGD) for the upper GI-tract, or a colonoscopy for the lower GI-tract, in order to confirm suspected KS involvement.

Other organs that can become affected by KS include liver, spleen, heart or bone marrow. If KS has already been diagnosed from biopsies of other tissues, it may not be necessary to take an additional biopsy from these organs, to confirm the tumor’s spread.

There are also blood tests which can detect antibodies against KSHV and its associated protein. These tests are useful to determine, if a patient can potentially transmit the infection to his/her sexual partner (sexually transmitted disease, STD), or whether a transplant organ may be infected with the virus. However, at this point in time, these tests are only available for research purposes, and thus not available for screening procedures or general clinical usage.

Treatment:

Kaposi’s sarcoma is not curable! While neither surgical removal of single or multiple lesions, nor a complete remission of multiple sites via chemotherapy or other therapeutic techniques, such as radiation therapy, results in a permanent cure, long-term survival can occur both with and without treatment.

If KS is associated with immunodeficiency (AIDS) or immunosuppression (e.g. following organ transplantation), treating the cause of the immune system dysfunction can slow the progression of the tumor. In AIDS-associated KS, the lesions will shrink considerably upon the beginning of HAART (highly active antiretroviral therapy), but may start to grow again after years of treatment, especially if the human immunodeficiency virus, HIV, has not been suppressed completely.

Disseminated (wide-spread) KS, affecting multiple organs and organ systems can be treated with interferon alpha, liposomal anthracyclines (e.g. Doxil), or paclitaxel, an inhibitor if cell mitosis used in chemotherapy for lung, breast and ovarian cancer, as well as for advanced KS therapy.

Radiation therapy is useful for cosmetically disturbing, painful lesions, especially involving the mouth – response rates are quite high, since all forms of KS are sensitive to radiation therapy, and the procedures are usually well tolerated.

Prevention:

Currently, there is no vaccine available against the Kaposi’s sarcoma associated herpes virus, KSHV. Thus, preventing KS depends on reducing potential chances of becoming infected with the virus.

Since most KSHV cases are associated with a concurrent HIV infection, safe sex procedures are adamant, including using a male or female condom and other protective measurement to prevent sexually transmitted diseases, STDs. These include abstinence, faithfulness to your partner, not sharing needles or other dug paraphernalia for injecting recreational drugs, and testing yourself for the presence of the HI virus, if your life style may have exposed you to the infection. Detecting an HIV infection early, and starting an effective HAART as soon as possible after infection, can reduce the risk of developing KS. Furthermore, antiviral drugs that block the herpes virus, such as ganciclovir or foscamet, can also block KSHV and thus the development of Kaposi’s sarcoma.

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