Chest
Volume 117, Issue 4, April 2000, Pages 1128-1145
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Review
The Epidemiologic, Pathologic, and Clinical Features of AIDS-Associated Pulmonary Kaposi's Sarcoma

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AIDS-related Kaposi's sarcoma (KS) occurs principally in homosexual or bisexual men infected with the newly identified human herpes virus-8, also called KS-associated herpes virus. Unlike classical forms of the disease, AIDS-associated KS is a multicentric entity that frequently involves lymph nodes and the GI tract. KS may also occur in the lung, commonly in the setting of extensive mucocutaneous disease and very rarely as an isolated event. The exact incidence of intrathoracic KS in patients with AIDS is unknown. Before the advent of highly active antiretroviral therapy (HAART), pulmonary KS had been reported in approximately 10% of patients with AIDS, 25% of patients with cutaneous KS, and in roughly 50% of postmortem examinations of patients with AIDS, KS, and respiratory infections. In the HAART era, the incidence of KS has declined precipitously in North America and Europe but not in third world countries where HAART is largely unavailable. Pulmonary KS may cause radiographic infiltrates and respiratory symptoms that mimic a variety of other infectious and neoplastic processes. An aggressive diagnostic evaluation of patients who have this condition is essential because chemotherapy and radiation therapy may provide significant palliation, particularly if used in conjunction with HAART. This review briefly explores the changing epidemiology of KS. The pathology and pathogenesis of KS is also reviewed, along with the clinical and radiographic presentation, diagnosis, and management of pulmonary KS.

Section snippets

Epidemiology

The first cases of KS were described by Moritz Kaposi in 1872.10 Classical KS, as it is now called, was characterized as a slowly progressive disease involving the cutaneous surfaces of the lower extremity; particularly, the condition was found to be more common among elderly men from Eastern Europe (Jewish) or Mediterranean countries. KS is also common in equatorial Africa. As early as 1971, KS accounted for roughly 3 to 9% of all reported malignancies in Uganda.11 The African (endemic) form

Incidence

Even before the introduction of HAART, the prevalence of pulmonary KS in patients with AIDS was uncertain because radiographic changes due to the tumor were often attributed to pulmonary infection.8, 3435, 36 Definitive antemortem diagnosis requires lung biopsy, but this must be counterbalanced by other factors such as the clinician's differential diagnosis and the patient's willingness to undergo an invasive procedure that may be associated with such iatrogenic complications as pain,

Pathology

KS is an angioproliferative tumor. It is characterized by slit-like neovascular processes and the presence of proliferating endothelial cells, fibroblasts, infiltrating leukocytes, and a population of spindle-shaped tumor cells.48 Although the clinical expression of disease may vary, KS histopathology does not differ among the various HIV risk groups.49 In the very early stages, cutaneous KS is characterized by inflammatory cell infiltration, extravasation of RBCs, endothelial cell activation,

Pathogenesis

Important advances in our understanding of the factors that contribute to KS development and growth occurred when investigators perfected laboratory techniques to sustain the growth of a large number of KS cells in culture.57 Subsequent studies demonstrated that cultured spindle cells from KS lesions were abnormally responsive to a variety of growth factors and that transformed culture media promoted normal endothelial cells to acquire the features of the KS phenotype.58 These factors, which

Natural History

Patients with pulmonary KS face an uncertain future. It has long been assumed they have a shorter life expectancy than other AIDS patients, yet important factors such as comorbid illness and immune profile have not consistently been taken into account.75, 7677 Gill and colleagues7 reported a median CD4+ cell count of 94 cells/μL in 20 patients with pulmonary KS. Gruden and associates78 reported the median CD4+ count was 34 cells/μL; 84% of patients had counts < 100 cells/μL, and 96% had counts

Clinical Features

As with most pulmonary processes in patients with AIDS, the clinical presentation of intrathoracic KS is nonspecific and may be indistinguishable from pneumonia (Table 3). Dyspnea and cough are the most common presenting symptoms.6, 78, 940, 4142, 4344, 4585, 8687, 8889 Fever and night sweats may be present and usually suggest a concomitant infection. Hemoptysis may also occur, although its rate varies from series to series. Among 30 AIDS patients with symptomatic pulmonary KS, 100% had

Radiologic Findings

The radiologic findings of pulmonary KS were recently summarized and are outlined in Table 4.99, 100 Usually, plain chest roentgenograms reveal thickening along bronchovascular bundles, often emanating from a perihilar origin. As the tumor grows, a reticulonodular infiltrate appears, mainly in the lower lobes (Fig 6, top left, A and bottom, left, C).78, 101 With continued growth, nodules become irregular and confluent, and this, along with interstitial infiltrates, leads to dense airspace

Diagnosis

Pulmonary KS can involve the tracheobronchial tree, the pulmonary parenchyma, and the pleura. It is the most common endobronchial lesion associated with HIV and has a characteristic red or purple macular or papular appearance often located at airway bifurcations.111 It is very rare to identify KS lesions at bronchoscopic examination below the level of the carina and not detect parenchymal lesions on chest radiography.112 In a retrospective analysis of 76 patients with bronchoscopically proven

Chemotherapy

Active cytotoxic agents for patients with advanced KS with the longest track records include vinca alkaloids, anthracyclines, bleomycin, and etoposide.120 The highest response rates have been achieved when these agents are used in combination. Using a variety of chemotherapy regimens incorporating these agents, Garay and colleagues6 and Meduri and associates8 achieved median survivals ranging between 3.8 and 6.0 months in patients with pulmonary KS. A recurring theme in these and other early

Conclusion

Pulmonary KS may cause significant morbidity and mortality in the setting of HIV infection. Fortunately, AIDS-defining illnesses that have previously been deemed progressive and poorly responsive to conventional therapies may be controlled with HAART. Pulmonary KS can now be added to this list. Additional studies will continue to investigate the effect of various combinations of anti-HIV medications on the development and progression of KS. New treatment strategies and staging schemas must

ACKNOWLEDGMENT

I am grateful for the assistance of David Dail, MD, whose insights and comments helped shape this article and who generously provided the photomicrographs of pulmonary KS and the accompanying legends for this text. I am also indebted to Ms. Arleen Sierra for her assistance in manuscript preparation.

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