KAPOSI SARCOMA

KAPOSI SARCOMA - Felix B. Chang, MD; Aaron W. Way, DO
BASICS
DESCRIPTION
• A malignant multifocal neoplasm characterized by vascular tumors of skin and viscera in several different forms
- Indolent (classic) Kaposi sarcoma (KS)
 Older men of Mediterranean and Jewish descent
- African (endemic) KS
 Equatorial, sub-Saharan Africa
- AIDS-related (epidemic) KS
 HIV-infected patients and with AIDS
- Form associated with immunosuppressive medications
 Organ transplant-associated
• Human herpes virus 8 (HHV-8) has been identified by PCR in all 4 types of Kaposi sarcoma
• System(s) Affected: Hemolytic/Lymphatic/Immunologic; Skin/Exocrine
• Synonym(s): Endotheliosarcoma; Multiple idiopathic hemorrhagic sarcoma; Human herpes virus 8
ALERT
Geriatric Considerations
The indolent form is most likely to occur in men.
Pediatric Considerations
In eastern and southern Africa, KS represents 25-50% of all the soft-tissue sarcomas.
Pregnancy Considerations
Maternal-infant HIV transmission may occur.
GENERAL PREVENTION
• Safe sex practices
• Possible prophylaxis with antiviral medications
• Avoid needle sharing
• Avoid deep kissing
• Careful screening of organs transplant
EPIDEMIOLOGY
• Predominant age: 16-75
• Predominant sex: Classic and AIDS-related forms Male > Female (15:1)
• KS Endemic: Children = Adults
• AIDS-related or epidemic KS (1)
- KS is the most common tumor arising in HIV-infected persons and is an AIDS-defining illness
- Most common in homosexual or bisexual men
- >20,000 times more common in AIDS patients than in the general population
- 300 times more common in AIDS than in other immunosuppressed host
- Homosexual men: 20-30%
- Heterosexual injection drug users: 3%
- Transfusion recipients: 3%
- Women or children: 3%
- Hemophiliacs: 1%
Incidence
• Indolent/lymphadenopathy: Rare
• In AIDS patients: Common
• Male homosexual with AIDS most affected
• The incidence of KS after transplantation is estimated to be 0.4 % in the US.
• KS represent 5.7% of malignancies after transplantation (excluding skin cancer)
RISK FACTORS
• HIV infection
• Living in endemic area (especially Zaire or Uganda)
• Immunosuppressant medications
• Transplantation and chemotherapy
• Sexual activity
• Maternal-fetal transmission
• Maternal-child transmission
• Injection drug use
• Exposure to infectious saliva
• Possible association with trauma in susceptible host
• An unknown route transmits many cases.
• A herpes virus designated "KS herpes virus" (KSHV) or human herpes virus type 8 (HHV8) is required for the development of KS.
• Samples from KS lesions have been found to contain DNA sequences identical with HHV8, and HHV8 can be propagated from skin lesions of patients with KS.
• Immunosuppression of the host is an important cofactor in development of KS.
• HHV-8 may be transmitted by blood transfusion.
• High risk for KS
- Increasing anti-HHV-8 antibody titers
- The presence of HHV-8 viremia
- HIV seropositivity
- Reduced levels of neutralizing antibodies
ETIOLOGY
Kaposi sarcoma is a low-grade vascular tumor associated with HHV-8, also know as the KS-associated herpesvirus (KSHV)
ASSOCIATED CONDITIONS
• AIDS
• HIV infection
• Lymphoma


DIAGNOSIS
SIGNS AND SYMPTOMS
• Indolent Kaposi
- Multicentric red-blue violaceous tumors on the skin
- Tender skin tumors
- Pruritic skin tumors
- In older men, lesions appear 1st on toes or legs.
• African (endemic) Kaposi
- Usually involves skin, viscera, lymph nodes and bones
- It is not typically associated with immunodeficiency.
- More aggressive than classical KS
• KS associated with HIV infection (epidemic)
- Skin lesions widely disseminated on the face, arms, and trunk
- Lesions on mucous membranes
- Lesions in lymph nodes
- Lesions in viscera
• Immunosuppression-associated Kaposi
- Tends to be aggressive
- High amount of lymph node involvement
- Visceral organs involved in 1/2
TESTS
Special tests: Tissue examination
Lab
• Specific HHV8 antibodies present in 70-90%
• Southern blot hybridization assay of KS lesions for HHV8
• Polymerase chain reaction (PCR) assay
Imaging
CT or MRI scan (chest, abdomen) may assess visceral involvement.
Diagnostic Procedures/Surgery
• Biopsy of skin or lymph node
• Bronchoscopy with biopsy
• Liver biopsy
Pathological Findings
• Neovascularization with aberrant proliferation of small vessels
• Spindle-shaped cell with leukocytic infiltration
• Angiogenesis
• Proliferation of atypical spindle cells
• Proliferation of vascular channels
• Large hyperchromic nuclei
• Spindle-shaped perivascular cells
• Hemosiderin laden macrophages
DIFFERENTIAL DIAGNOSIS
• Bacillary angiomatosis
• Granuloma faciale
• Vascular proliferation
• Purpuric lesions
• Dermatofibrosarcoma protuberans
TREATMENT
GENERAL MEASURES
• Appropriate health care
- Outpatient
- Outpatient surgery
• If KS is due to immunosuppressant medications, eliminate or reduce medication dosage.
• If KS is HIV-related, optimize anti-HIV therapy to reduce HIV viral load.
• Treatment is otherwise determined by the extent and location of the disease.
• Observation
• Radiotherapy (electron beam) or x-ray therapy 1,000-2,000 rads
• Systemic chemotherapy, immunotherapy, or antiviral therapy
Activity
Remain active as long as possible.
MEDICATION (DRUGS)
First Line
• Chemotherapy
- Doxorubicin
- Bleomycin
- Vinblastine
- Vincristine: Parenteral or intralesional
- Daunorubicin
- Paclitaxel
- Interleukins
- Thalidomide
- Interferon: Parenteral or intralesional
- Alitretinoin gel
• Note: Both doxorubicin and daunorubicin are available and approved for use in liposomal forms. These liposomal formulations offer improved outcome with less toxicity.
• Contraindications: Refer to manufacturer's literature.
• Precautions: Refer to manufacturer's literature. Myelosuppression with chemotherapy
• Significant possible interactions: Refer to manufacturer's literature.
Second Line
• Several studies have reported that some individuals have responded to antiviral medications such as foscarnet (Foscavir), ganciclovir (Cytovene), and cidofovir (Vistide).
• Photodynamic therapy
SURGERY
• Cryotherapy
• Intralesional chemotherapy or immunotherapy
• Surgical excision
• CO2 laser
FOLLOW-UP
PROGNOSIS
• Improved HIV treatments and antiviral drugs may result in improved HIV-related KS survival.
• Indolent form: 10-year survival
COMPLICATIONS
• Extensive pulmonary involvement may lead to hypoxemia.
• Extensive lymphatic involvement may lead to severe edema.
PATIENT MONITORING
In HIV patients with KS, other opportunistic infections must be aggressively treated.
REFERENCES
1. Beral V, Peterman TA, Berkelman RL, et al. KS among persons with AIDS: A sexually transmitted infection? Lancet. 1990;335:123.
2. Dedicoat M, Vaithilingum M, Newton R. Treatment of Kaposi's sarcoma in HIV-1 infected individuals with emphasis on resource-poor settings. Cochrane Database Sys Rev. 2003;3:CD003256,DOI, 1002/14651858.CD003256.
3. Litte RF, Wyvill KM, Pluda JM, et al. Activity of thalidomide in AIDS-related Kaposi's sarcoma. J Clin Oncol. 2000;18:2593.
4. Webster-Cyriaque J. Development of Kaposi's sarcoma in surgical wound. N Engl J Med. 2002;346:1207-1212.