Background: Moritz Kaposi first described Kaposi sarcoma (KS) in 1872. Although the disease was described initially in elderly men of Mediterranean extraction, KS is currently widely recognized as the most common malignancy associated with acquired immunodeficiency syndrome (AIDS). Originally, the disease was believed to be a form of primary skin cancer; however, a viral etiology now has been firmly established.

Pathophysiology: A virus belonging to the herpes family (human herpesvirus 8 [HHV-8], also called Kaposi sarcoma herpesvirus [KSHV]), has been identified as the probable cause of KS. This virus likely acts in conjunction with other cofactors. KSHV serology always demonstrates positive results in affected individuals, regardless of immune status, and the presence of antibodies is predictive for KS and has prognostic value. KSHV DNA is present in the lymphoid system, peripheral blood mononuclear cells, saliva, and semen of patients with KS.

In AIDS, KS is a polyclonal neoplasm with distinct pathologic features. In the very early stages, KS is characterized by inflammatory cell infiltration, extravasation of red blood cells, endothelial cell activation, and angiogenesis. After activation, endothelial cells acquire the appearance of typical spindle-shaped cells mixed with macrophages and dendritic cells. In advanced disease, spindle cells tend to become the predominant cell type, although angiogenesis remains a prominent feature.

KS affects mucocutaneous tissues, particularly involving the trunk and lower limbs, as well as the thoracic cavity and gastrointestinal (GI) system. Histologic appearances are identical irrespective of the organ of involvement. Thoracic KS may involve the upper airways, the pulmonary parenchyma, or the pleura. However, the upper airways are rarely affected in patients with pulmonary KS.

Classic violaceous endobronchial plaques may be seen bronchoscopically; typically, the lesions are located at airway bifurcations. Pleural effusions, which are frequently bloody and often large, occur in 15-89% of patients with pulmonary KS. Typically, these effusions are exudates and often contain reactive mesothelial cells without evidence of neoplasm. Macroscopically, flat or slightly raised, disk-shaped, red or violaceous plaques are seen confined to the visceral pleura. Pulmonary parenchymal changes include lymphangitic infiltration by tumor, causing nodular thickening and red-blue discoloration of interlobular septa and the peribronchovascular interstitium. The nodules may coalesce to form larger masses.

Frequency:

• In the US: By far, KS is the most common AIDS-related malignancy, affecting approximately 25% of patients with AIDS overall and 50% of cohorts of homosexual men who have HIV infection. Data collected by the US Centers for Disease Control and Prevention reveal that the incidence of KS has declined by an estimated 10% per year between 1990 and 1997. Furthermore, the number of homosexual patients with AIDS who have KS as an AIDS-defining illness has decreased from 40% in the early 1980s to 10-20%. This decline likely reflects a change in the demographics of AIDS, with a decrease in the number of patients within specific high-risk categories due to safe sex practices and relative increased heterosexual, vertical, and needle HIV transmission.

  The use of antiretroviral therapy is associated with reduced risk for development of KS, ranging from a 13% reduction with monotherapy or dual therapy to a 59% reduction with triple therapy. While the incidence of KS is falling in the United States, in impoverished countries, the incidence is likely to continue to rise.

  Postmortem studies of individuals with AIDS with cutaneous KS reveal pulmonary involvement in 47-75% of patients, although as many as two thirds may not be clinically evident. In 2000, pulmonary KS was reported in 20,000 cases in the United States.

• Internationally: Iatrogenic KS occurs in approximately 6% of male European, Jewish, or African patients after solid-organ transplantation. The incidence of KS after renal transplantation in these patients is 500-times greater than in other populations. Endemic Kaposi sarcoma affects young people in Africa of either sex or any sexual orientation.

Mortality/Morbidity: AIDS Clinical Trial Group (ACTG) KS studies show that pulmonary involvement is not associated with diminished survival among patients with extensive KS. Poor prognostic factors for survival among patients with thoracic KS in non-ACTG clinical trials have included the following:

• Absence of cutaneous KS
  
  

   

• Prior opportunistic infections
  
  

   

• CD4⁺ cell count of less than 100/mL
  
  

   

• Leukopenia and anemia

   

• Large pleural effusions.

Patients with KS and a CD4⁺ count of more than 150 cells/mL had a median survival of 39 months, whereas patients with fewer than 150 cells/mL survived a median of only 12 months (P <0.001).

Considerable progress has been made in the treatment of KS with the development of liposomal anthracycline therapy, paclitaxel-based regimens, and newer agents such as retinoids and antiangiogenic drugs, although prognosis remains generally poor.

The course of pulmonary Kaposi sarcoma is variable; it may be either slowly progressive or aggressive.

Race: AIDS-related KS does not show any racial predominance, although more patients are black than white, with the highest incidence seen in Africa. Endemic Kaposi sarcoma affects young people in Africa of either sex or any sexual orientation.

Sex: KS is seen almost exclusively in homosexual or bisexual men with HIV infection or in their partners. The male-to-female ratio is 50:1. KS is 20 times more prevalent among homosexual men with HIV infection than among heterosexual patients with hemophilia and HIV infection or among patients of either sex who abuse intravenous drugs. Endemic Kaposi sarcoma affects young people in Africa of either sex or any sexual orientation.

In the United States, the prevalence of people having serum antibodies to HHV-8 is 1% in the general blood-donor population, 35% in homosexual men with HIV infection, and 4% in women with HIV infection. Correspondingly, KS develops in 20-30% of homosexual or bisexual men with HIV infection and in only 1% of women with HIV infection.

Age: KS is usually a disease found in adults.

Clinical Details: Usually, mucocutaneous lesions are the first clinical sign of KS. Lesions are usually 1-2 cm in diameter, raised, violaceous, and plaquelike. They may appear brown or black in patients with dark skin. Lesions increase in size and number as the disease progresses. Involvement of the GI tract, lymph nodes, lungs, and other viscera is common. Pulmonary involvement occurs in one third of patients and is recognized clinically in 10-15% of patients.

Symptoms, such as breathlessness, cough, fever, and wheezing are nonspecific. Hemoptysis may occur but is unusual. Although lung involvement invariably follows mucocutaneous disease, this may not be clinically apparent.

KS usually affects patients with CD4 counts less than 100 cells/mm³. The tumor tends to run an aggressive course, becoming more aggressive with increasing immunocompromise. Healthy patients who demonstrate positive results with HIV/KSHV serologic tests have been shown to develop clinical manifestations when the CD4 count falls. To define the natural history of AIDS-related KS, various staging systems have been proposed.

In the United States, the schema originally developed by the ACTG Committee on Malignancies has been used the most. It classifies patients into good-risk or poor-risk groups on the basis of 3 main factors, as follows:

• Tumor extent (T)

   

• Immune profile status (I) as measured by CD4 lymphocyte count

   

• Evidence of HIV-associated systemic illness (S)

A change in the CD4 count from 200 to 150 cells/mL is the only modification needed to best distinguish between good-risk and poor-risk immune system categories.

Revised AIDS Clinical Trial Group Staging Classification for KS*

 

Findings	Good-Risk Group (All of the Following)	Poor-Risk Group (Any of the Following)
Clinical	Confined to skin and/or lymph nodes and/or nonnodular oral disease confined to the palate	Tumor-associated edema or ulceration, extensive oral KS; GI tract KS, or KS in other non-nodal viscera
Immune system (I)	CD4 cell count >150/µL	CD4 cell count <150/µL
Systemic illness (S)	No history of opportunistic infection or thrush, no B symptoms (unexplained fever, night sweats, involuntary weight loss >10%, diarrhea) persisting >2 weeks, and performance status >70	History of opportunistic infections and/or thrush, B symptoms present, performance status <70, or other HIV-related illness (eg, neurologic disease, lymphoma)

*Adapted from Krown et al, 1989.

Preferred Examination: A chest radiograph is usually the initial examination in patients in whom KS is suggested because radiographic appearances of pulmonary KS are among the most distinctive seen in patients with AIDS, and even subtle abnormalities should be viewed as suggestive of pulmonary involvement in a patient with known mucocutaneous disease.

An accurate diagnosis of pulmonary KS can be established by using CT scanning in 90% of patients. The role of MRI in the diagnosis of KS has not been defined. Ultrasonography of the thorax is useful in the evaluation of pleural disease and for guiding therapeutic thoracentesis. Radionuclide imaging is a useful adjunct to radiography and CT in selected patients because it is not always possible to differentiate KS from opportunistic infections by using anatomic imaging.

Limitations of Techniques: A wide variety of pulmonary complications may occur in patients who are immunocompromised, including opportunistic infections, drug-induced lung disease, malignancy, and unrelated pathologic processes such as pulmonary edema and pulmonary embolism. These disorders can have similar radiographic appearances (see Differentials below).

DIFFERENTIALS

Lung, Nontuberculous Mycobacterial Infections
Lung, Postprimary Tuberculosis
Lung, Primary Tuberculosis
Lymphangitic Carcinomatosis

Other Problems to be Considered:

Differential diagnosis of pulmonary nodules in AIDS

Infections - Bacterial infection, septic emboli, infection with Mycobacterium tuberculosis and Mycobacterium avium-intracellulare, fungal infection, viral infection, and toxoplasmosis

Malignancy - KS, AIDS-related lymphoma, and lung carcinoma

Differential diagnosis of lymphadenopathy in AIDS

Infections - Tuberculosis, infection by M avium-intracellulare, fungal infection, and Pneumocystis carinii pneumonia (PCP)

Malignancy - AIDS-related lymphoma, KS, and lung carcinoma

X-RAY

Findings:

• Radiographic findings in diffuse KS comprise 2 major patterns, ie, linear interstitial nodules and fluffy ill-defined nodules. Coexistence of the 2 patterns is not uncommon.

   

• A tendency toward a perihilar distribution has been observed. This reflects the bronchovascular-centric nature of the disease, with characteristic thickening along bronchovascular bundles. The thickening becomes more nodular with tumor progression, with eventual confluence of poorly marginated nodules leading to dense airspace consolidation.

   

• The middle and lower portions of the lungs are affected more frequently than the upper zones.

   

• Classically, nodules are described as flame shaped or spiculated. They typically measure 1-2 cm in diameter and frequently number more than 10.

   

• Septal lines may be seen as a result of lymphatic obstruction or tumor invasion.

   

• The less common focal form appears as segmental, lobar, or masslike consolidation.

   

• Airway involvement is common, occurring in as many as 75% of patients and occasionally leading to distal atelectasis.

   

• Effusions are seen commonly (30-90%) and may be unilateral or bilateral.

   

• Although hilar or mediastinal lymphadenopathy is reported in 10-16% of patients, this is rarely bulky and often not appreciated radiographically.

Degree of Confidence: Radiographic appearances of pulmonary KS are among the most distinctive seen in patients with AIDS, and even subtle abnormalities should be viewed as suggestive of pulmonary involvement in a patient with known mucocutaneous disease.

False Positives/Negatives: See Differentials.