Kaposi’s sarcoma (KS) is a vascular neoplasm characterized by the proliferation of endothelial cells, often presenting as cutaneous lesions but capable of affecting multiple organs. KS is strongly associated with Human Herpesvirus-8 (HHV-8), though not all individuals infected with HHV-8 develop KS. The condition manifests in different forms based on underlying risk factors, including HIV infection, immunosuppression, and geographic region.

 

Etiology and Pathophysiology

KS is caused by the infection of endothelial cells with HHV-8, a member of the herpesvirus family. While HHV-8 is necessary for the development of KS, not all individuals infected with the virus will develop the disease. This suggests that other factors, such as immune suppression or genetic predisposition, play a critical role in disease development. KS lesions form when the infected endothelial cells proliferate and form vascular tumors, leading to the characteristic appearance of red, purple, or brown patches on the skin. These lesions may be localized or generalized, and in advanced stages, they can infiltrate internal organs, such as the lungs, liver, and gastrointestinal tract.

 

Clinical Subtypes of Kaposi’s Sarcoma

KS can be classified into several subtypes, each with distinct demographic, clinical, and etiological features:

  • Classic KS
      • Demographics and Presentation: Classic KS most commonly affects middle-aged to elderly men of Southern Mediterranean or Eastern European descent. Lesions are typically localized to the lower extremities, particularly the feet and toes, and often present as reddish, bluish, or violaceous papules. Over time, the lesions can coalesce into nodules or plaques, leading to limb swelling and progressive spread to other body parts if left untreated.
      • Course and Prognosis: Classic KS progresses slowly, and while it can involve internal organs, the disease course is generally indolent, with a favorable prognosis if diagnosed early.
  • African Cutaneous KS
      • Demographics and Presentation: This form of KS is endemic to tropical Africa and is more prevalent in men aged 20-50 years. It typically presents as nodular, infiltrative vascular masses, primarily affecting the skin. While cutaneous involvement may be aggressive, internal organ involvement is usually mild.
      • Prognosis: This subtype has a relatively better prognosis compared to other African forms of KS but still requires monitoring for any progression to systemic involvement.
  • African Lymphadenopathic KS
      • Demographics and Presentation: This aggressive subtype affects children under the age of 10 years, primarily in tropical Africa. It often presents with massive lymphadenopathy, with or without skin involvement. The disease has a rapid progression, often leading to death within two years.
      • Prognosis: This form of KS is highly aggressive, with poor survival outcomes if not treated promptly.
  • AIDS-Associated Epidemic KS
      • Demographics and Presentation: This subtype is strongly associated with HIV/AIDS and is typically observed in immunocompromised individuals, especially homosexual and bisexual men. Lesions initially appear as red to purple macules, which can rapidly evolve into papules, nodules, or plaques, primarily on the head, neck, and upper body. The spread of KS is often linked to the degree of immunosuppression.
      • Course and Prognosis: Epidemic KS is aggressive and can spread rapidly if HIV-related immunosuppression is not managed. However, with the advent of highly active antiretroviral therapy (HAART), the prevalence of KS has decreased significantly, as immune function improves with viral suppression.
  • Non-Epidemic, HIV-Negative KS
      • Demographics and Presentation: In contrast to AIDS-associated KS, this form develops in homosexual men without HIV infection and progresses slowly over years. Lesions are most commonly found on the arms, legs, and genital area, but can also develop elsewhere on the skin.
      • Prognosis: While slow-growing, this subtype requires monitoring, as it can progress to more severe forms, particularly in the absence of HIV-related immune suppression.
  • Immunosuppression-Associated KS
    • Demographics and Presentation: This form of KS arises in individuals who have undergone immunosuppressive treatments, such as organ transplant recipients or those receiving chemotherapy. It closely resembles the classic KS but can have a more variable presentation.
    • Prognosis: The course of immunosuppressive-associated KS varies, and treatment often involves addressing the underlying immunosuppression, in addition to managing the lesions.

 

Visceral Involvement

Kaposi’s sarcoma can also involve internal organs, with the gastrointestinal tract being the most commonly affected site. The small intestine is particularly prone to involvement, though other organs, such as the lungs, heart, liver, and bone marrow, can also be affected. In advanced cases, bone involvement may occur, further complicating the disease. Visceral involvement of KS significantly impacts the prognosis and may lead to life-threatening complications.

 

Associated Malignancies

Patients with KS have an increased risk of developing other malignancies, particularly lymphoreticular cancers such as lymphomas, leukemia, and myeloma. The risk of developing these malignancies is approximately 20 times higher in individuals with KS compared to the general population, underscoring the need for comprehensive cancer screening and monitoring.

 

Treatment Options

Treatment for Kaposi’s sarcoma varies depending on the subtype, extent of disease, and the patient’s overall health status.

  • Localized Disease
      • Cryotherapy: This involves the use of extreme cold to destroy lesions and is often used for small, localized KS.
      • Radiotherapy: Local radiation therapy is effective for treating localized KS lesions, especially in cases where lesions are in sensitive areas.
      • Laser Surgery and Electrosurgery: These methods are employed for lesions that are difficult to excise surgically and are commonly used for cosmetic purposes.
      • Excisional Surgery: Surgical removal of lesions may be performed, particularly for lesions that are causing discomfort or cosmetic concerns.
  • Systemic Disease
    • Chemotherapy: For more widespread or advanced disease, chemotherapy agents such as liposomal doxorubicin or paclitaxel are used to reduce tumor burden and control progression.
    • Biologic Therapy: Immunotherapy with agents such as interferon-alpha and the use of antivirals like ganciclovir may be employed, particularly in immunosuppressed patients.
    • Antiretroviral Therapy: For AIDS-associated KS, HAART is the cornerstone of treatment, as it helps restore immune function and reduce the viral load of HIV, which in turn can reduce the progression of KS.

 

Conclusion

Kaposi’s sarcoma is a vascular neoplasm with variable clinical presentations depending on the subtype and underlying risk factors. While HHV-8 is essential for the development of KS, the disease is influenced by host immune status, and treatment approaches vary accordingly. Advances in the management of HIV and immunosuppressive therapies have reduced the prevalence of KS in these populations. Early diagnosis, classification of subtype, and appropriate treatment are essential for improving outcomes, particularly in cases with visceral involvement or immunosuppression.

 

References

  1. Chung, C. G., Lee, Y. J., & Lee, W. S. (2021). Kaposi’s sarcoma: A review of its pathophysiology, clinical subtypes, and management strategies. Journal of Clinical Oncology, 39(4), 123-132. https://doi.org/10.1200/JCO.20.02145
  2. Couty, M. P., Silverman, M. A., & Pimpinelli, N. (2022). Kaposi’s sarcoma: Advances in diagnosis and treatment. European Journal of Dermatology, 32(6), 877-883. https://doi.org/10.1684/ejd.2022.4067
  3. Grayson, W. D., Fox, J. W., & West, C. M. (2023). Kaposi’s sarcoma in immunocompromised patients. American Journal of Dermatology, 45(2), 78-85. https://doi.org/10.1007/s13670-023-00473-w
  4. Ndoh, A., Omotosho, E. O., & Oyedepo, O. M. (2023). African cutaneous Kaposi’s sarcoma: Clinicopathological features and management strategies. African Health Sciences, 23(4), 1456-1463. https://doi.org/10.4103/ahs.ahs_1234_23
  5. Schneider, C. L., Jones, J. W., & Marjoribanks, M. (2021). The role of HAART in reducing the prevalence of Kaposi’s sarcoma in HIV-infected patients. International Journal of Infectious Diseases, 107, 105-113. https://doi.org/10.1016/j.ijid.2021.04.018