January 17, 2007

Kaposi Sarcoma

Synonyms and related keywords: Kaposi's sarcoma, KS, Kaposi tumor, Kaposi's tumor, Kaposi malignancy, Kaposi's malignancy, epidemic AIDS-related Kaposi sarcoma, immunocompromised Kaposi sarcoma, classic Kaposi sarcoma, endemic African Kaposi sarcoma


Background: Kaposi sarcoma (KS) was described initially in 1872 by a Hungarian dermatologist, Moritz Kaposi. KS is a spindle-cell tumor thought to be derived from endothelial cell lineage. This condition carries a variable clinical course ranging from minimal mucocutaneous disease to extensive organ involvement. KS can occur in several different clinical settings.

Epidemic AIDS-related KS: This entity occurs in patients with advanced HIV infection, and is the most common presentation of KS. In the United States, KS serves as an AIDS-defining illness in 10-15% of HIV-infected homosexual men. In Africa and developing regions, epidemic AIDS-related KS is common in heterosexual adults and occurs less often in children. Visceral involvement is common. AIDS-related KS is the most clinically aggressive form of KS.

Immunocompromised KS: This entity can occur following solid-organ transplantation or in patients receiving immunosuppressive therapy. However, individuals with congenital immunodeficient states are not at increased risk for developing KS. The average time to development of KS following transplantation is 30 months. Visceral involvement is common.

Classic KS: This entity typically occurs in elderly men of Mediterranean and Eastern European background. Classic KS usually carries a protracted and indolent course. Common complications include venous stasis and lymphedema. As many as 30% of patients with classic KS subsequently may develop a second malignancy. Visceral involvement is uncommon.

Endemic African KS: This entity occurs in men who are HIV seronegative in Africa and may carry an indolent or aggressive course.

Pathophysiology: KS is caused by an excessive proliferation of spindle cells thought to have an endothelial cell origin. Molecular studies suggest that KS originates from a single cell clone rather than a multifocal origin. Human herpes virus 8 (HHV-8) genomic sequences have been identified by polymerase chain reaction in more than 90% of all types of KS lesions (including epidemic and endemic forms), suggesting a causative role. These sequences additionally have been associated with body cavity–based lymphomas, Castleman disease, and leiomyosarcomas that occur in individuals infected with HIV. Factors that are thought to contribute to the development of KS in individuals infected with HHV-8 and HIV include an abnormal cytokine milieu associated with HIV infection (interleukin [IL]-6, IL-1, granulocyte-macrophage colony-stimulating factor [GM-CSF], basic fibroblast growth factor [bFGF], oncostatin M, tumor necrosis factor [TNF]) and the HIV-tat protein, which acts as a mitogen for KS cells.


Mortality/Morbidity: AIDS-related KS, unlike other forms of KS, tends to have an aggressive clinical course. Morbidity may occur from extensive cutaneous, mucosal, or visceral involvement. In patients receiving highly active antiretroviral therapy (HAART), the disease often has a more indolent clinical course or may regress spontaneously. The most common causes of morbidity include cosmetically disfiguring cutaneous lesions, lymphedema, gastrointestinal involvement, or pulmonary involvement (see History and Physical). Pulmonary involvement is the most common cause of mortality.


  • In Africa and developing regions, epidemic AIDS-related KS is common in heterosexual adults and occurs less often in children.
  • Classic KS typically occurs in elderly men of Mediterranean and Eastern European background.
  • Endemic African KS occurs in HIV seronegative men in Africa.


  • AIDS-related KS: In the United States, this condition occurs primarily in homosexual males, bisexual men, and in the female sexual partners of bisexual men.
  • African KS occurs in heterosexual men and women with equal frequency.
  • Classic KS occurs primarily in males, with a male-to-female ratio of 10:1.


  • AIDS-related KS generally occurs in adults.
  • Classic KS typically occurs in patients aged 50-70 years.
  • African KS occurs in people of a younger age (35-40 y).


History: AIDS-related KS carries a variable clinical course ranging from minimal mucocutaneous disease to widespread organ involvement. The lesions may involve the skin, oral mucosa, lymph nodes, and visceral organs. Most patients present with cutaneous disease. Visceral disease occasionally may precede cutaneous manifestations. Lesions have been reported in autopsy series involving virtually every organ.

    • Tumor-associated lymphedema - Typically manifested by lower extremity or facial involvement, thought to occur secondary to obstruction of lymphatic channels
    • Pain associated with ambulation - Due to lesions involving the soles of the feet
  • Gastrointestinal - Lesions can occur anywhere within gastrointestinal tract
    • Often asymptomatic and clinically indolent
    • Odynophagia, dysphagia
    • Nausea, vomiting, abdominal pain
    • Hematemesis, hematochezia, melena
    • Bowel obstruction
  • Pulmonary - May be difficult to distinguish from opportunistic infections
    • Cough
    • Dyspnea
    • Hemoptysis
    • Chest pain
    • Asymptomatic radiographic finding




Bacillary Angiomatosis

Other Problems to be Considered:

Bacillary angiomatosis: This entity often is difficult to distinguish clinically from KS. It is caused by Rochalimaea species, a slow-growing, fastidious gram-negative bacillus that is readily treated with antibiotics. Bacillary angiomatosis lesions typically possess capillary proliferation and neutrophilic inflammation. In contrast, KS lesions display slitlike vascular spaces containing lymphoplasmacytic infiltrates. A skin biopsy is required to establish diagnosis.

Pyogenic granuloma


Lab Studies:

Imaging Studies:


Histologic Findings: Typical histologic findings include proliferation of spindle cells, prominent slitlike vascular spaces, and extravasated red blood cells.

Staging: KS does not lend itself to conventional tumor, node, metastases (TNM) classification. Although no staging system has been accepted, several have been proposed. The AIDS Clinical Trials Group (ACTG) has proposed a system based on immune status, extent of tumor involvement, and presence of systemic illnesses. The staging system has not been evaluated prospectively; however, some evidence suggests that it may have prognostic significance.


Medical Care:

Consultations: Obtain a radiation oncology consultation when considering the use of radiation as definitive therapy for palliation of locally advanced symptomatic disease or a cosmetically disturbing cutaneous


The goals of pharmacotherapy are to eradicate the sarcoma, reduce morbidity, and prevent complications.

Drug Category: Taxanes -- Inhibit cell growth and differentiation by preventing depolymerization of microtubules.
Drug Name
Paclitaxel (Taxol) -- Promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. FDA-approved for the treatment of patients with AIDS-related KS.
Adult Dose100 mg/m2 IV q2wk
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; documented hypersensitivity to polyoxyethylated castor oil; peripheral neuropathy; bone marrow suppression; liver failure; severe cardiac disease
InteractionsCoadministration with cisplatin may further increase myelosuppression
Pregnancy D - Unsafe in pregnancy
PrecautionsPremedicate with steroids, H1 blockers, and H2 blockers to decrease risk of hypersensitivity reactions; myelosuppression, alopecia, arthralgia/myalgias, and cardiac arrhythmia may occur
Drug Category: Anthracyclines -- Inhibit cell growth and differentiation by inhibiting topoisomerase II and producing free radicals, which may cause the destruction of DNA.
Drug Name
Doxorubicin HCL liposome (Doxil) -- Binds to DNA and impairs nucleic acid synthesis. Doxil is doxorubicin encapsulated in a pegylated liposome. This technology allows for longer area under the time-concentration curve than with free doxorubicin. Additionally allows for increased selective drug delivery to tumor tissues. Doxorubicin and daunorubicin currently serve as first-line treatment for individuals with advanced KS. An ongoing clinical trial being conducted by the Eastern Cooperative Oncology Group (ECOG) is comparing paclitaxel to Doxil in chemo-naïve patients with advanced symptomatic KS.
Adult Dose20 mg/m2 IV q3wk
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; severe CHF; cardiomyopathy; preexisting myelosuppression; impaired cardiac function
InteractionsToxicity increases with cyclophosphamide, cyclosporine, mercaptopurine, verapamil, streptozocin, paclitaxel, and progesterone; phenobarbital decreases effect; decreased toxicity with digoxin; phenytoin levels are decreased
Pregnancy D - Unsafe in pregnancy
PrecautionsMay produce severe local toxicity in irradiated tissues, even when the 2 therapies are not administered concomitantly; caution in patients who have received radiotherapy; cardiomyopathy is a well-known characteristic of doxorubicin; monitor for drug-induced cardiomyopathy; mortality rate is >50% once cardiomyopathy has developed
Drug Name
Daunorubicin citrate liposome (DaunoXome) -- Liposomal preparation of daunorubicin. Inhibits DNA and RNA synthesis by intercalating between DNA base pairs.
Adult Dose40 mg/m2 IV q2wk
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; CHF; arrhythmias; cardiopathy
InteractionsNone reported
Pregnancy D - Unsafe in pregnancy
PrecautionsExtravasation may occur, resulting in severe tissue necrosis; caution with impaired hepatic, renal, or biliary function
Drug Category: Interferons -- Naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alpha, beta, and gamma interferons may be administered topically, systemically, and intralesionally.
Drug Name
Interferon-alfa 2b (Intron) -- Thought to exert activity in KS through antiproliferative tumor effect and antiviral properties. Protein product manufactured by recombinant DNA technology. Mechanism of antitumor activity is not understood clearly; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles.
Adult Dose30 million U/m2 SC 3 times per wk
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; anaphylactic sensitivity to mouse immunoglobulin (IgG), egg protein, or neomycin
InteractionsPotential risk of renal failure when administered concurrently with IL-2; theophylline may increase INF-alfa toxicity by reducing its clearance
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsDepression and suicidal ideation may be adverse effects of treatment; infrequently, severe or fatal GI hemorrhage has been reported in association with INF-alfa therapy; prior to therapy initiation, perform tests to quantitate peripheral blood hemoglobin, platelets, granulocytes, hairy cell, and bone marrow hairy cells; monitor periodically (eg, monthly) during treatment to determine treatment response; if a patient does not respond within 6 mo, discontinue treatment; if a response occurs, continue treatment until no further improvement is observed (whether continued treatment after that time is beneficial is not known)
Drug Category: Retinoids -- May reduce potential for malignant degeneration.
Drug Name
Alitretinoin gel 0.1% (Panretin) -- Naturally occurring endogenous retinoid. Inhibits growth of KS by binding to retinoid receptors.
Adult Dose0.1% gel, apply topically bid/qid to affected cutaneous lesions
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsIncreases toxicity of DEET if used concurrently
Pregnancy D - Unsafe in pregnancy
PrecautionsPreexisting cutaneous T cell lymphoma; do not use occlusive dressing; avoid UV light exposure of treated areas
Drug Category: Vinca alkaloids -- Inhibit microtubule formation, which in turn disrupts the formation of mitotic spindle, causing cell proliferation to arrest at metaphase.
Drug Name
Vinblastine sulfate (Velban) -- Vinca alkaloid derived from the periwinkle plant. Induces arrest of cell division by inhibiting microtubule formation.
Adult Dose0.1 mL/cm2 (at a concentration of 0.2 mg/mL) administered intralesionally
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; preexisting severe granulocytopenia
InteractionsPhenytoin plasma levels may be reduced when administered concomitantly with vinblastine; with mitomycin, the toxicity of vinblastine may increase significantly
Pregnancy D - Unsafe in pregnancy
PrecautionsCaution in patients diagnosed with impaired liver function and neurotoxicity; when patient is receiving mitomycin C, monitor closely for shortness of breath and bronchospasm


In/Out Patient Meds:




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