Kaposi’s Sarcoma
Kaposi’s sarcoma (KS) has remained a subject of extensive research for over 20 years, yet its cell of origin remains elusive. KS exhibits a wide range of clinicopathological variations depending on:
- Location of lesions (lymph node, internal, or cutaneous).
- Clinical stage (patch, plaque, or nodular).
- Epidemiological classification, which includes:
- Classic KS in older men.
- African (endemic) KS in younger African men and children from Central Africa.
- Iatrogenic KS, primarily in transplant patients or due to chemotherapy and other immunosuppressive therapies.
- Epidemic HIV/AIDS-associated KS.
Endemic KS features variations, such as indolent nodular forms, aggressive variants with invasive cutaneous tumors, and a pediatric variant presenting as lymphadenopathy in young children.
The majority of HIV-associated KS cases occur in men who have sex with men, but it also affects women, children, intravenous drug users, and organ transplant recipients. Additional subgroups include HIV-associated KS on combined antiretroviral therapy (cART), KS with no or failing cART (end-stage AIDS), HIV-associated pediatric KS, and KS associated with immune reconstitution inflammatory syndrome (IRIS).
Causes and Transmission
Kaposi’s sarcoma is caused by infection with the human herpesvirus 8 (HHV8), also known as Kaposi sarcoma-associated herpesvirus (KSHV). The virus infects endothelial cells lining blood vessels and lymphatic vessels, introducing genes that:
- Promote cell division.
- Prolong cell survival.
- Induce inflammatory chemicals.
These changes may eventually lead to cancer. KSHV infection is necessary for KS development, but not all infected individuals will develop the disease. KS is most common in individuals with weakened immune systems due to HIV infection, organ transplantation, aging, or other factors.
Types of Kaposi’s Sarcoma
There are four major types of Kaposi’s sarcoma:
- Classic Kaposi’s Sarcoma: A rare, slow-growing skin tumor typically affecting men of Eastern European Jewish ancestry or Italians.
- African Kaposi’s Sarcoma: Occurs in young men in African countries. It may grow slowly or invade bone and tissues aggressively.
- Immunosuppressive-Treatment-Related Kaposi’s Sarcoma: Seen in organ transplant recipients on immune-suppressing medications, which may improve if the medication is adjusted.
- AIDS-Related Kaposi’s Sarcoma: The most common type, rapidly progressing in individuals with weakened immune systems due to HIV/AIDS.
Symptoms and Signs
Kaposi’s sarcoma commonly presents with:
- Skin lesions: Slightly elevated purple, brown, pink, black, blue, or red blotches or bumps.
- Lymphedema: Swelling caused by lymphatic blockages.
- Chest pain or cough: Indicative of pulmonary involvement.
- Gastrointestinal symptoms: Pain, diarrhea, or digestive blockages caused by internal lesions.
- Other symptoms: Difficulty eating, shortness of breath, nausea, pain, anemia, weight loss, and fatigue.
Treatment and Prevention
Kaposi’s sarcoma is incurable but manageable with the following therapies:
- Radiation therapy: Effective for most patients.
- Chemotherapy: Can shrink tumors but may weaken the immune system.
- Biological therapy: Includes treatments like interferon and interleukin-2.
Prevention strategies include:
- Avoiding HIV infection.
- Adhering to HAART (highly active antiretroviral therapy) for HIV-positive individuals, reducing the risk of KS.
- Avoiding direct contact with KS lesions.
Epidemiology and Global Spread
The prevalence of KSHV varies worldwide. In the U.S., less than 12% of individuals are infected with KSHV, with higher rates among men who have sex with men and those with HIV. In some parts of Africa, up to 80% of the population shows signs of KSHV infection. Transmission may occur through saliva, semen, vaginal fluids, and from mother to child.
Advancements in Treatment
- Doxil and Paclitaxel: Effective but with significant toxicity.
- New therapies: Sirolimus, VEGF/VEGF receptor inhibitors, and immune-modulatory agents show promise but require further research.
The histopathological diagnosis of KS has improved with the detection of LANA in biopsies of KS lesions, although KSHV DNA or RNA detection lacks standard accuracy. Localized KS lesions in HIV+ patients with suppressed viral loads may be treated with intralesional therapy or newer agents with less toxicity than chemotherapy.
Conclusion
Kaposi’s sarcoma remains a significant health challenge, particularly in regions with high HIV and KSHV co-infection rates. Continued advancements in treatment and prevention will improve outcomes for affected individuals.