Kaposi sarcoma (KS) is a low-grade vascular tumor associated with Kaposi sarcoma herpes virus (KSHV)/Human gammaherpes virus 8 (HHV-8) infection and is an AIDS-defining illness. Kaposi sarcoma lesions present predominantly at mucocutaneous sites but may involve all organs and anatomic locations.

KS

• In the U.S., epidemic or acquired immunodeficiency syndrome (AIDS)-associated KS is the most common presentation; however, transplant or iatrogenic immunosuppression-related KS is on the increase. In clinical practice, classic and endemic KSs are also encountered.
• AIDS-related KS affects about 47 per 100,000 person-yr with HIV.
• Highest incidence is in homosexual men.

• KS lesions evolve from early (patch stage) macules into plaques (plaque stage) that may subsequently develop into larger nodules (tumor stage).¹ These tumors may ulcerate, cause marked lymphedema, present as exophytic growths (e.g., cutaneous horns), or invade subjacent tissues (e.g., underlying bone). Different stages can coexist in the same individual at the same time.
• Although KS commonly presents at mucocutaneous sites, tumors may involve lymph nodes as well as visceral organs, most notably the respiratory and gastrointestinal tracts.
• Extracutaneous KS has been described in unusual anatomic locations, including the musculoskeletal system, nervous system, heart, wounds, within pemphigus lesions, and in blood clots.
• AIDS-related KS: Multifocal and widespread red-purple (Fig. E1) or dark plaques and/or nodules on cutaneous or mucosal surfaces. This is a more aggressive illness with early dissemination.²
• Generalized lymphadenopathy at the time of diagnosis is present in >50% of patients with AIDS-related KS; the initial lesions have a rust-colored appearance; subsequent progression to red or purple nodules or plaques occurs (Fig. E2).
• Most frequently affected areas are the face, trunk, oral cavity, and upper and lower extremities.
• The GI tract is the most frequent site of internal involvement in classic KS.
• In AIDS-associated KS, 25% of patients have cutaneous involvement alone, whereas 29% have visceral lesions only (lymph nodes 50%, GI tract 50%, lungs 37%).
• In most patients with HIV-associated KS who initiate highly active antiretroviral therapy (HAART), the KS lesions stabilize with decreasing HIV plasma viremia and immune reconstitution, or even resolve completely without any specific treatment.

• KSHV/HHV-8 is thought to be the causative agent and can be transmitted through sexual (homosexual or heterosexual activities) or nonsexual contact such as maternal-infant transmission (common in African countries).³ KSHV establishes lifelong infection in the host, and its DNA is found in all KS lesions. In most cases fulminant KS is accompanied and preceded by a rise in KSHV viral load. KS is primarily the consequence of systemic viral reactivation from a latent reservoir, most likely a lymph node resident B cell. KS develops in response to severe T-cell depletion or inactivation. Infant immunodeficiency or aging-, chemical-, or HIV-induced immune deficiency is an essential cofactor for the development of KS.
• It can be divided into the following four subsets:^1,4
  1. Classic KS: Occurs mostly in elderly Eastern European and Mediterranean males. It consists initially of violaceous macules and papules with subsequent development of plaques and red-purple nodules. Growth is slow, and most patients die of unrelated causes.
  2. Epidemic (AIDS-related) KS: Most frequently occurs in HIV-infected persons. Lesions are generally multifocal and widespread (see Fig. E1). Lymphadenopathy may be associated.
  3. Endemic KS: Usually affects sub-Saharan African children and adults. An aggressive lymphadenopathic form affects African children in particular.
  4. Organ transplant-associated, KS: Usually associated with immunosuppressive therapy. Transplant can transmit HHV-8.

• Stasis dermatitis
• Pyogenic granuloma
• Capillary hemangiomas
• Granulation tissue
• Postinflammatory hyperpigmentation
• Cutaneous lymphoma
• Melanoma
• Dermatofibroma
• Hematoma
• Prurigo nodularis

Diagnosis can generally be made on clinical appearance in a patient with one of the earlier clinical categories; a tissue biopsy is required to confirm the diagnosis. Chest x-ray can be done to look for pulmonary lesions. Stool occult blood rules out gastrointestinal tract involvement.

• Serology for human immunodeficiency virus (HIV), CD4+ T-lymphocyte counts, viral load (if HIV positive)
• Complete blood count, renal and hepatic function

Therapy goals include cosmetic improvement, palliation, or cessation of progression. Observation is a reasonable option in patients with slowly progressive disease. At present, there is no cure for KS.

• Treatment goals of KS include symptom palliation, prevention of progression and organ compromise, improvement of cosmesis, and relieving psychologic stress. Treatment options include cryotherapy, intralesional vinblastine, radiotherapy, and alitretinoin gel. Because treatment is essentially for cosmesis, side effects such as pigmentary changes and pain become important in therapeutic decisions.
• For patients with resistant limited disease, extensive cutaneous involvement, systemic KS, or tumor-associated lymphedema, treatment modalities include liposomal anthracyclines (pegylated liposomal doxorubicin or liposomal daunorubicin), taxanes (paclitaxel), and interferon-α. An algorithm for management of AIDS-associated Kaposi sarcoma is illustrated in Fig. E3.
• A significant proportion of HIV-related KS cases can regress following the start of ART alone, indicating the role of immune reconstitution in the management of this disease.
• All types of KS are radiosensitive. Radiation therapy is effective in non-AIDS KS and for large tumor masses that interfere with normal function.
• Surgical excision is restricted for cosmetically disturbing KS lesions, to alleviate discomfort, or to control local tumor growth. It often provides adequate treatment for single lesions and resected recurrences in classic KS.
• Liquid nitrogen cryotherapy can result in complete response in 80% of lesions.
• Interlesional chemotherapy with vinblastine is useful for nodular lesions >1 cm in diameter. Intralesional injection of interferon alfa-2b has also been reported as effective and well tolerated.
• Other local therapies used include laser therapy, cryotherapy, photodynamic therapy, and topical alitretinoin gel.
• Indications for systemic chemotherapy include widespread skin involvement, extensive oral KS, rapidly progressive disease, symptomatic visceral disease, and disease flare.
• Liposomal anthracyclines and paclitaxel are FDA-approved as first-line and second-line monotherapy for advanced KS. Other chemotherapy regimens like bleomycin plus vincristine or oral etoposide have proven to be inferior to paclitaxel in HIV patients with advanced KS.⁵ Interferon-α has been used with clinical responses dependent upon the underlying immune status of the patient; the best responses are seen in patients with CD4 counts >400/μL.
• Pomalidomide is presently approved for AIDS-related KS following failure of combined ART.
• Sirolimus is effective in inhibiting the progression of dermal KS in kidney transplant recipients.

Figure E3 Algorithms for management of AIDS-associated Kaposi sarcoma (KS).

cART, Combination antiretroviral therapy; CXR, chest radiograph; HIV, human immunodeficiency virus.

From Niederhuber JE: Abeloff’s clinical oncology, ed 6, Philadelphia, 2020, Elsevier.

• An increasing number of investigational therapeutics have been explored for the treatment and prevention of KS, including antiangiogenic agents, antiviral agents, matrix metalloproteinase inhibitors, tyrosine kinase inhibitors, laser therapy, PD-1 inhibitors, and agents targeting interleukin (IL)-12.
• Immunosuppression-associated KS usually regresses with the cessation, reduction, or modification of immunosuppression therapy in most patients. Similarly, in HIV patients KS responds concurrently with the decrease in serum HIV RNA and increase in the CD4 count.
• KS is associated with an increased risk of developing secondary malignancies (lymphomas, leukemia, myeloma).

Kaposi Sarcoma (Patient Information)

Acquired Immunodeficiency Syndrome (Related Key Topic)