AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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.

Frequency

United States

KS currently is the most common AIDS-associated malignancy. KS serves as the presenting manifestation of AIDS in approximately 15% of homosexual men and in approximately 2% of patients with HIV infection in other risk groups.

International

In Europe, the highest rates of classic KS are in Sicily (Ragusa, 30.1 cases per million in men/5.4 cases per million in women) and Sardinia (24.3 cases per million in men/7.7 cases per million in women).

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.

Race

• 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.

Sex

• 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.

Age

• 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).

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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.

• Cutaneous lesions - Occur in virtually all patients
• • Multiple skin lesions - See Physical for description
  • 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

Physical

• Cutaneous lesions may occur at any location but typically are concentrated on the lower extremities and the head and neck region.
• Lesions may have macular, papular, nodular, or plaquelike appearances.
• Nearly all lesions are palpable and nonpruritic.
• Lesions may range in size from several millimeters to several centimeters in diameter
• Lesions may assume a brown, pink, red, or violaceous color and may be difficult to distinguish in dark-skinned individuals.
• Lesions may be discrete or confluent and typically appear in a linear, symmetric distribution, following Langer lines.
• Mucous membrane involvement is common (palate, gingiva, conjunctiva). Ulcerated or bulky tumor involvement may interfere with speech or mastication.

Causes

• Coinfection with HIV and HHV-8 (Kaposi sarcoma-associated herpesvirus [KSHV])
• Iatrogenic immunosuppression (including corticosteroids)
• Elevated degree of expression of numerous cytokines and angiogenic growth factors, including TNF-alpha, IL-6, bFGF, and oncostatin M

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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.

Hematoma
Hemangioma
Dermatofibroma
Pyogenic granuloma
Purpura

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• CD4 lymphocyte counts and plasma HIV viral-load studies should be performed for patients with HIV infection.

Imaging Studies

• Chest radiographs: Radiographic findings are variable and nonspecific. They may include diffuse reticulonodular infiltrates, interstitial infiltrates, pleural effusions, hilar or mediastinal lymphadenopathy, or an isolated pulmonary nodule.
• Thallium or gallium scans: These studies may help to differentiate pulmonary KS from infection. Pulmonary KS lesions typically demonstrate intense thallium uptake and no gallium uptake, whereas infection often is gallium avid and thallium negative.

Procedures

• A punch biopsy of the skin or an endoscopic, pleural, or transbronchial biopsy is necessary to establish a definitive diagnosis.
• Bronchoscopy: Pulmonary involvement typically is characterized by a slightly raised (submucosal) cherry-red lesion. Biopsy generally is avoided due to the risk of bleeding.
• Esophagogastroduodenoscopy (EGD) or colonoscopy: Gastrointestinal lesions frequently are observed. The yield of endoscopic biopsy may be low secondary to the submucosal location of many lesions.

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.

• ACTG KS staging classification
• • Good risk
    • Tumor (T) - Confined to skin and/or lymph nodes and/or minimal oral disease
    • Immune system (I) - CD4 greater than 200/mm³
    • Systemic illness (S) - No history of opportunistic infection, more than 10% involuntary weight loss, or diarrhea persisting more than 2 weeks
    • Karnofsky performance status greater than 70
  • Poor risk
    • Tumor (T) - Tumor-associated edema or ulceration, extensive oral KS, gastrointestinal KS, KS in other non-nodal viscera
    • Immune system (I) - CD4 less than 200/mm³
    • Systemic illness (S) - History of opportunistic infection, unexplained fever, night sweats, more than 10% involuntary weight loss, or other HIV-related illness (ie, lymphoma, neurologic disease)
    • Karnofsky performance status less than 70
• An accurate assessment of response to treatment for KS often is difficult because the lesions may not be subject to conventional bidimensional tumor measurements.
• New KS response criteria, using an assessment of the impact of treatment on tumor-related symptoms, currently are being evaluated prospectively.
• ACTG response criteria establish a cutaneous lesion response as a 50% decrease in total body lesion count and a flattening of 50% of previously raised lesions. Evaluation of visceral and oral KS is more difficult because it does not lend itself to measurement.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

• Antiretroviral therapy: Optimal control of HIV infection using HAART is an integral part of successful KS therapy. The choice of therapy beyond HAART must be individualized and depends on the extent of disease, the presence and nature of the symptoms, the rate of disease progression, and the overall therapeutic goals.
• Local therapy: Local therapy is best suited for individuals who require palliation of locally advanced symptomatic disease (eg, radiation) or for individuals who have cosmetically unacceptable lesions. This therapy also is well suited for individuals with significant comorbidities and refractory or resistant disease. Local therapy fails to halt the development of new KS lesions.
• • Radiation therapy: This is the most widely used and effective local therapy. Responses occur in 80-90% of patients. A higher cumulative dose (40 Gy) results in better local control than lower doses (8 Gy or 20 Gy). Electron beam therapy is reserved for treatment of superficial lesions. Patients with HIV are more prone to develop radiation-induced mucositis.
  • Intralesional vinblastine commonly is used and generally is well tolerated. Adverse effects include skin discoloration and superficial erythema. The lesion is injected with 0.1 mL/cm² (at a concentration of 0.2 mg/mL).
  • Cryotherapy entails liquid nitrogen applied topically and may be useful for small facial lesions. Cryotherapy may cause skin hypopigmentation.
  • Topical retinoids: IL-6 is a cytokine implicated in the pathogenesis of KS. In vitro, retinoic acid down-regulates IL-6 receptor expression. A 0.1% (alitretinoin [Panretin]) gel is available commercially and may be applied topically 2-4 times daily. This agent generally is well tolerated but may cause local erythema and irritation.
• Systemic therapy is indicated for extensive or symptomatic visceral disease, rapidly progressive mucocutaneous disease, and symptomatic lymphedema.
• • Interferon-alfa: Clinical activity in KS may be mediated by its antiangiogenic, antiviral, and immunomodulatory properties. Time to clinical response is long (ie, 4 mo). Interferon-alfa is most effective when the CD4 count is greater than 150-200/µL or when administered in conjunction with antiretroviral therapy. This therapy entails subcutaneous administration daily or 3 times weekly. Response may occur with low (1 million U/m²), intermediate (30 million U/m²), or high doses (50 million U/m²). Toxicity is more common and severe with higher doses; symptoms may include fatigue, flulike symptoms, myalgia, arthralgia, fever, myelosuppression, and hepatotoxicity.
  • Chemotherapy is not used with curative intent. It is capable of achieving rapid tumor regression and palliation of tumor-related symptoms. Chemotherapy is indicated for symptomatic visceral or rapidly progressive mucocutaneous disease. Several cytotoxic agents are approved by the Food and Drug Administration (FDA) for AIDS-related KS and include liposomal doxorubicin (Doxil), liposomal daunorubicin (DaunoXome), and paclitaxel (Taxol).

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 lesion.

MEDICATION

Section 7 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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 Category: Anthracyclines

Inhibit cell growth and differentiation by inhibiting topoisomerase II and producing free radicals, which may cause the destruction of DNA.

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 Category: Retinoids

May reduce potential for malignant degeneration.

Drug Category: Vinca alkaloids

Inhibit microtubule formation, which in turn disrupts the formation of mitotic spindle, causing cell proliferation to arrest at metaphase.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

In/Out Patient Meds:

• Emerging investigational therapies
• • Signal transduction inhibitors
  • Anti–HHV-8 agents
  • Cytokine inhibitors
  • Antiangiogenesis agents: Vascular endothelium growth factor (VEGF) inhibitor, eg, SU-5416 (a recent trial using an intranasal VEGF inhibitor [IM862] reported an overall response rate of 36%, with an acceptable toxicity profile); TNP-470; thalidomide

Complications:

• Cutaneous KS lesions may be cosmetically disfiguring and often generate significant psychologic distress for individuals infected with AIDS

Prognosis:

• Patients with pulmonary KS lesions often are symptomatic and may present emergently with respiratory failure

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Biopsy of pulmonary lesions generally is avoided due to an increased risk of bleeding

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Kaposi sarcoma (KS), antrum. Endoscopic view of a KS lesion situated in the gastric antrum.
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Media file 2:  Epidemic Kaposi sarcoma (KS). Large violaceous truncal nodules with typical linear and symmetric distribution pattern.
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Media file 3:  Kaposi sarcoma (KS), facial. Confluent, violaceous nodules involving the chest wall; extensive facial involvement with accompanied edema.
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Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Antman K, Chang Y. Kaposi''s sarcoma. N Engl J Med. Apr 6 2000;342(14):1027-38. [Medline].
• Centers for disease control. Surveillance for AIDS-defining opportunistic illnesses, 1992-1997. MMWR. 1999;48:SS2:1-22.
• DeVita V. AIDS-related malignancies. In: DeVita V, Vincent T Jr, eds. Cancer,: Principles and practice of clinical oncology. 5th ed. Philadelphia, Pa:. Lippincott, Williams, & Wilkins;1997:2445-9.
• Dezube BJ. Clinical presentation and natural history of AIDS-related Kaposi''s sarcoma. Hematol Oncol Clin North Am. Oct 1996;10(5):1023-9. [Medline].
• Dezube BJ. Acquired immunodeficiency syndrome-related Kaposi''s sarcoma: clinical features, staging, and treatment. Semin Oncol. Aug 2000;27(4):424-30. [Medline].
• Gill PS, Tulpule A, Espina BM. Paclitaxel is safe and effective in the treatment of advanced AIDS-related Kaposi''s sarcoma. J Clin Oncol. Jun 1999;17(6):1876-83. [Medline].
• Iscovich J, Boffetta P, Franceschi S. Classic Kaposi sarcoma: epidemiology and risk factors. Cancer. Feb 1 2000;88(3):500-17. [Medline].
• Krown SE, Metroka C, Wernz JC. Kaposi''s sarcoma in the acquired immune deficiency syndrome: a proposal for uniform evaluation, response, and staging criteria. AIDS Clinical Trials Group Oncology Committee. J Clin Oncol. Sep 1989;7(9):1201-7. [Medline].
• Lee FC, Mitsuyasu RT. Chemotherapy of AIDS-related Kaposi''s sarcoma. Hematol Oncol Clin North Am. Oct 1996;10(5):1051-68. [Medline].
• Tulpule A, Scadden DT, Espina BM. Results of a randomized study of IM862 nasal solution in the treatment of AIDS-related Kaposi''s sarcoma. J Clin Oncol. Feb 2000;18(4):716-23. [Medline].
• Von Roenn J. Kaposi's sarcoma evaluation and treatment. In: American Society of Clinical Oncology (ASCO) Educational book. 1998: 76-85.

Article Last Updated: Nov 15, 2004