Introduction
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.1,2,3
Peribronchial thickening, nodularity, and septal lines in a patient with AIDS and pulmonary involvement of Kaposi sarcoma.
Marked peribronchovascular thickening on high-resolution CT in a patient with AIDS and pulmonary Kaposi sarcoma (same patient as in Image 1 in Multimedia). Parenchymal nodularity and a unilateral pleural effusion are present.
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 of 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 confined to the visceral pleura are seen. 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.4,5,6
Frequency
United States
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: because of the use of safe sex practices, there has been a decrease in the number of patients within specific high-risk categories; there has been a relative increase in heterosexual and vertical transmission; and there has been a relative increase in the transmission of HIV via contaminated needles.
The use of antiretroviral therapy is associated with a reduction in the risk of the development of KS, ranging from a 13% reduction with monotherapy or dual therapy to a 59% reduction with triple therapy. Although 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 of cases may not be clinically evident. In 2000, pulmonary KS was reported in 20,000 cases in the United States.
International
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. In Africa, endemic KS affects young people of either sex and of any sexual orientation.7
Mortality/Morbidity
Studies of KS by the AIDS Clinical Trial Group (ACTG) 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+ T cell count of less than 100/µL
- Leukopenia and anemia
- Large pleural effusions.
Patients with KS and a CD4+ T cell count of more than 150 cells/µL had a median survival of 39 months, whereas patients with fewer than 150 cells/µL 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 the prognosis remains generally poor.
The course of pulmonary KS 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; the highest incidence is seen in Africa. Endemic Kaposi sarcoma affects young people in Africa of either sex and of 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 KS 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 of adults.
Presentation
Usually, mucocutaneous lesions are the first clinical sign of KS. Lesions usually measure 1-2 cm in diameter and are 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+ T cell counts of less than 100 cells/µL. The tumor tends to run an aggressive course, becoming more aggressive with increasing immunocompromise. Healthy patients who demonstrate positive results with HIV/KSHV serologic testing have been shown to develop clinical manifestations when the CD4+ T cell count falls. To define the natural history of AIDS-related KS, various staging systems have been proposed.8
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+ T cell count
- Evidence of HIV-associated systemic illness (S)
A change in the CD4+ T cell count from 200 to 150 cells/µL 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*
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Table
| 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+ T cell count >150/µL | CD4+ T 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) |
| 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+ T cell count >150/µL | CD4+ T 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.9
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; 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; it is not always possible to differentiate KS from opportunistic infections by using anatomic imaging.10,11,12,13,14
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 may have similar radiographic appearances (see Differentials, below).
Differential Diagnoses
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 jiroveci pneumonia (PCP)
Malignancy — AIDS-related lymphoma, KS, and lung carcinoma
More on Kaposi Sarcoma, Thoracic |
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| References |
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References
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Further Reading
Keywords
KS, Kaposi's sarcoma, thoracic Kaposi's sarcoma, acquired immunodeficiency syndrome, AIDS, human immunodeficiency virus, HIV, human herpesvirus 8, HHV-8, Kaposi sarcoma herpesvirus, KSHV
