Version May 2024
INTRODUCTION — AIDS-related Kaposi sarcoma (KS) is a low-grade vascular tumor associated with human herpesvirus 8 (HHV-8), which is also known as the Kaposi sarcoma-associated herpesvirus (KSHV). HHV-8 is also causally linked to primary effusion lymphoma and multicentric Castleman’s disease. The widespread application of potent combination antiretroviral therapy (ART) has led to a striking decrease in the incidence of KS and has changed its natural history [1].
The clinical manifestations, diagnosis, and complications of pulmonary AIDS-associated KS are discussed here. Other aspects of AIDS-related KS are reviewed separately. (See "AIDS-related Kaposi sarcoma: Clinical manifestations and diagnosis" and "AIDS-related Kaposi sarcoma: Staging and treatment" and "Human herpesvirus-8 infection".)
CLINICAL MANIFESTATIONS — In 80 to 90 percent of cases, pulmonary involvement with KS occurs in conjunction with more extensive mucocutaneous disease [2,3]. However, pulmonary involvement can be the initial manifestation of KS and occurs in the absence of mucocutaneous disease in 15 percent [4].
Pulmonary KS can involve the lung parenchyma, airways, pleura, and/or intrathoracic lymph nodes. There are no unique manifestations that distinguish KS from other pathologic processes in the lungs.
●Parenchymal lung involvement is usually manifest clinically by dyspnea, hypoxemia, and dry cough developing over a few weeks [5]. Hemoptysis, fever, fatigue and occasionally respiratory failure can also occur.
●Endobronchial KS may be asymptomatic; however, intractable cough, hemoptysis, wheezing, upper airway obstruction, and atelectasis may occur.
●Pleural effusions are radiographically visualized in up to two-thirds of patients with parenchymal KS and occasionally may occur as an isolated manifestation of KS. However, large, difficult to manage pleural effusions are much less common since the introduction of antiretroviral therapy (ART). (See "Pleural effusions in HIV-infected patients", section on 'Kaposi sarcoma'.)
●Enlarged mediastinal nodes are frequent in patients with pulmonary KS although the cause of the lymphadenopathy is often unclear. Adenopathy in patients suspected to have pulmonary KS is important because of the need to identify other diseases that can cause adenopathy, including opportunistic infections and other tumors.
Rapid progression of pulmonary KS can be precipitated by systemic glucocorticoids, which are often used to treat other conditions in HIV infected patients. Thus, the possibility of pulmonary KS should be considered when pulmonary symptoms develop following the initiation of glucocorticoid therapy.
When evaluating a patient for possible pulmonary KS, a careful skin and mucous membrane exam is essential [2,3]. Cutaneous KS lesions are typically found on the lower extremities, tip of the nose, and genitalia, but may be widespread (picture 1 and picture 2 and picture 3 and picture 4). (See "AIDS-related Kaposi sarcoma: Clinical manifestations and diagnosis", section on 'Cutaneous KS'.)
EVALUATION — Patients with known mucocutaneous KS have a higher likelihood of lung involvement with KS, but still need a careful evaluation of any new pulmonary symptoms or findings to identify other infections or malignancies. The evaluation of pulmonary symptoms in patients with HIV infection typically involves a combination of assessing the degree of immune compromise, imaging to ascertain the pattern and extent of lung, pleural, and mediastinal disease, thoracentesis if a pleural effusion is present, and often performing flexible bronchoscopy to obtain samples for immunoassay, stains, culture, and cytology. (See "Evaluation of pulmonary symptoms in persons with HIV".)
Laboratory — When a new diagnosis of KS is suspected in a patient with HIV infection, the degree of HIV-related immunosuppression is assessed by measuring the CD4 count and HIV viral load. Patients with KS typically have a low CD4 cell count (<150 cells per cubic millimeter) and a high HIV viral load (>10,000 copies per milliliter). (See "AIDS-related Kaposi sarcoma: Staging and treatment", section on 'Staging and evaluation'.)
Imaging — A conventional chest radiograph is part of the initial evaluation of respiratory symptoms in patients with HIV/AIDS. KS typically involves the lung parenchyma in one of two patterns on chest radiographs:
●Tumor infiltrating the septae presents radiographically as patchy reticular opacities that frequently occur in a peribronchovascular distribution. This pattern is seen in approximately 60 percent of cases [6-9].
●Ill-defined nodular densities are also common, occurring in approximately 25 percent of chest radiographs [8-11].
Overlap radiographic patterns, areas of focal consolidation, a solitary nodule, coalescence of nodules, and normal radiographs can also be seen in some patients [6,7,12,13].
Computed tomography (CT) of the chest is typically obtained to evaluate abnormalities noted on chest radiograph or pulmonary function tests. In addition, CT is useful to evaluate hemoptysis in patients with a normal chest radiograph.
Two findings on chest CT are highly suggestive of parenchymal KS: hilar densities extending into the parenchyma along perivascular or peribronchial pathways and a characteristic septal or nodular pattern with concomitant pleural effusions [8,14-16]. Correlation between pathology and imaging has shown that central peribronchovascular opacities represent tumor growth involving the bronchovascular bundles, while nodules correspond to proliferations of neoplastic cells in the lung parenchyma [17].
Bronchoscopy — Bronchoscopy and bronchoalveolar lavage (BAL) are often performed in HIV-infected patients with pulmonary symptoms and parenchymal abnormalities on chest radiograph or chest CT scan. The main purposes are to examine the airways for endobronchial KS lesions and to obtain BAL samples for microbiologic stains and culture, immunoassays for infectious agents, and cytologic examination for viral inclusions or tumors other than KS. The diagnosis of KS cannot be made from cytologic specimens, as biopsy specimen is needed to see the characteristic architecture of spindle cells surrounding thin vascular channels. (See "Evaluation of pulmonary symptoms in persons with HIV".)
Endobronchial KS lesions typically appear violaceous or bright red and are macular or papular (picture 5). Common sites include the mucosa of the lower airways, especially at branching points, or, less commonly, in the trachea (picture 6 and picture 7A-B) [12,18]. Bacillary angiomatosis can also cause violaceous endobronchial mucosal lesions, but these lesions are typically raised or polypoid, while those of KS are typically flat.
Endobronchial and transbronchial biopsies have a low diagnostic yield for KS [10,12,19], although the occasional biopsy is positive (picture 8 and picture 9 and picture 7B). We avoid performing transbronchial biopsies when KS is thought to be likely, as significant hemorrhage has occurred following biopsy of KS lesions in up to 30 percent of patients [12,20].
Thoracentesis and pleural biopsy — The main roles for thoracentesis and pleural biopsy in evaluating pleural KS are to exclude infection or other causes of malignant effusions (eg, multicentric Castleman’s disease, non-Hodgkin lymphoma, primary effusion lymphoma, lung cancer) (table 1 and table 2). Thoracentesis may also be useful to relieve dyspnea when an effusion is large. (See "Pleural effusions in HIV-infected patients".)
KS lesions are found on the visceral but not parietal pleura, so closed pleural biopsy is not useful for detecting pleural KS. On the other hand, closed pleural biopsy is often helpful in the diagnosis of pleural infections such as mycobacterial disease. Biopsy samples are sent for special stains, routine and mycobacterial culture, and pathology.
Video-assisted thoracoscopy is sometimes performed to evaluate an undiagnosed pleural effusion. During thoracoscopy, violaceous patchy lesions of KS may be seen on the visceral pleural surface.
Pathology — The microscopic features of KS lesions include angiogenesis, inflammation, and spindle cell proliferation (picture 8 and picture 9 and picture 7B and picture 7A). Spindle cells consistently stain for CD34 and commonly CD31 but are factor VIII negative. Polymerase chain reaction to detect amplified human herpesvirus 8 (HHV-8) DNA sequences and immunohistochemical staining for HHV-8 antigen can be performed on biopsy specimens to confirm the diagnosis. (See "Classic Kaposi sarcoma: Epidemiology, risk factors, pathology, and molecular pathogenesis", section on 'Pathology'.)
DIAGNOSIS — The presumptive diagnosis of AIDS-related pulmonary KS is often clinical, based on features such as the epidemiology (eg, geographic location, people who engage in unprotected anal intercourse), presence of mucocutaneous KS lesions, degree of immunodeficiency, radiographic appearance, appearance of endobronchial lesions, and exclusion of other infectious or neoplastic processes.
Pulmonary parenchymal and endobronchial disease — The diagnostic evaluation of suspected parenchymal pulmonary KS requires bronchoscopy to look for endobronchial lesions typical of KS and to exclude intercurrent infection. The diagnosis is confirmed when:
●Endobronchial lesions characteristic of KS are identified by bronchoscopy
●The clinical and radiographic findings are suggestive of parenchymal pulmonary KS and an infectious etiology has been excluded
Although a tissue diagnosis is not required to establish the diagnosis of pulmonary KS, open lung biopsy may be necessary if the clinical, radiographic, and/or bronchoscopic picture is atypical. When tissue is obtained, the diagnosis is confirmed by finding the typical pathologic features of angiogenesis, inflammation, and spindle cell proliferation, in addition to positive polymerase chain reaction or immunoassay for human herpesvirus 8 (HHV-8). (See 'Pathology' above.)
Pleural disease — Establishing the diagnosis of pleural KS in the absence of lung or airway KS is difficult. Pleural fluid cytology and pleural biopsies are not helpful in documenting KS, but they may be useful for excluding other processes (eg, infection, lymphoma). In cases of rapidly recurrent pleural effusion accumulation, alternative diagnoses (eg, pleural effusion lymphoma) should be entertained. The diagnosis and differential diagnosis of pleural KS are described separately. (See "Pleural effusions in HIV-infected patients", section on 'Kaposi sarcoma'.)
DIFFERENTIAL DIAGNOSIS — Patients with AIDS may have pulmonary symptoms due to parenchymal or pleural disease to a wide range of infectious and neoplastic processes. Given the time course of onset of symptoms in pulmonary KS, infections due to atypical bacteria (eg, Bartonella), mycobacteria, and fungi are particularly important in the differential diagnosis. The differential diagnosis and an approach to their evaluation are discussed separately. (See "Evaluation of pulmonary symptoms in persons with HIV" and "Pleural effusions in HIV-infected patients".)
Neoplastic diseases in the differential of KS lung and pleural involvement include pulmonary lymphoma, primary effusion lymphoma, multicentric Castleman’s disease (also associated with HHV-8), and lung cancer, which is significantly more common in those with HIV infection compared with the general population. (See "Primary effusion lymphoma" and "HHV-8/KSHV-associated multicentric Castleman disease" and "Pleural effusions in HIV-infected patients", section on 'Malignant effusions' and "HIV infection and malignancy: Management considerations", section on 'Lung cancer' and "HIV-related lymphomas: Clinical manifestations and diagnosis", section on 'Lung and pleura'.)
TREATMENT
Systemic treatment — The mainstay of treatment of pulmonary KS is antiretroviral therapy (ART). Prior to the introduction of potent ART, pulmonary AIDS-related KS was associated with a very poor prognosis, with median survivals of 2 to 10 months in various reports [12,21,22]. However, the use of ART in this patient population has significantly altered the natural history of KS as well as decreasing the incidence of this disease. (See 'Prognosis' below.)
For patients with asymptomatic pulmonary KS, we typically initiate ART without concomitant chemotherapy. In some cases, however, treatment of KS with ART alone may be associated with a flare of the KS. For patients with symptomatic pulmonary KS or those with disease progression of pulmonary KS after initiation of ART, the addition of systemic chemotherapy to ART is indicated [23-25]. (See "AIDS-related Kaposi sarcoma: Staging and treatment", section on 'Immune reconstitution inflammatory syndrome' and "AIDS-related Kaposi sarcoma: Staging and treatment", section on 'Treatment'.)
For patients being treated with systemic glucocorticoids for another process (eg, Pneumocystis jirovecii pneumonia), discontinuation of glucocorticoids has been associated with regression of KS. (See "AIDS-related Kaposi sarcoma: Staging and treatment", section on 'Steroid reduction or withdrawal'.)
Airway obstruction and bleeding — Obstructive KS lesions of the upper airway are rare. Initial therapy is aimed at securing patency of the airway to achieve adequate ventilation and oxygenation. This may include endoscopic laser resection via rigid bronchoscopy, stent placement, and/or radiation therapy [26-28]. After establishing airway patency, systemic therapy with ART and chemotherapy is necessary to provide long term control of the KS. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Follow-up' and "AIDS-related Kaposi sarcoma: Staging and treatment", section on 'Local symptomatic therapy'.)
Hemoptysis due to tracheobronchial KS has been described only rarely; the optimal management is not known. Massive hemoptysis may require local therapy (eg, laser therapy, cryotherapy, balloon tamponade, topical epinephrine) to control bleeding and protect the airway. (See "Evaluation and management of life-threatening hemoptysis".)
Pleural effusions — The management of large pleural effusions due to KS can be difficult. We favor the use of repeated thoracentesis in combination with ART and chemotherapy rather than more upfront invasive procedures in this setting. If a pleural effusion recurs quickly (eg, in less than three weeks) despite repeated thoracentesis, an indwelling pleural catheter can be placed or talc pleurodesis can be performed, although experience with these therapies for pleural KS is limited [29,30]. (See "Management of malignant pleural effusions" and "Chemical pleurodesis for the prevention of recurrent pleural effusion".)
PROGNOSIS — Prior to the widespread introduction of ART, the presence of pulmonary KS was associated with a particularly poor prognosis, and the presence of visceral disease was incorporated into the AIDS Clinical Trials Group (ACTG) staging system [31]. Pulmonary KS is no longer associated with the same poor prognosis that it once had.
SUMMARY AND RECOMMENDATIONS
●Pathogenesis and epidemiology – Kaposi sarcoma (KS) is a low-grade vascular tumor associated with human herpesvirus 8 (HHV-8). The incidence of KS has decreased markedly since the use of potent combination antiretroviral therapy (ART) became widespread. (See "AIDS-related Kaposi sarcoma: Clinical manifestations and diagnosis", section on 'Epidemiology and risk factors'.)
●Clinical manifestations – Patients with pulmonary KS can present with shortness of breath, fever, cough, hemoptysis, or chest pain. In some cases, asymptomatic patients will have abnormalities on imaging as the only findings suggestive of pulmonary involvement.
•Imaging findings – Two findings on chest computed tomography (CT) are highly suggestive of parenchymal KS: hilar densities extending into the parenchyma along peribronchovascular pathways and a characteristic septal or nodular pattern with concomitant pleural effusions. (See 'Clinical manifestations' above and 'Imaging' above.)
●Diagnostic evaluation – The diagnosis of AIDS-related pulmonary KS is often clinical, typically based on the presence of mucocutaneous disease, compatible features on chest computed tomography, and endobronchial lesions characteristic of KS (when present) (picture 5). However, a detailed evaluation should exclude an infectious etiology or other tumors if any atypical features are present. (See 'Diagnosis' above.)
●Differential diagnosis – The differential diagnosis of pulmonary KS is broad and includes the full range of AIDS-associated infections and neoplasms that cause pulmonary symptoms developing over a few weeks. (See 'Differential diagnosis' above and "Evaluation of pulmonary symptoms in persons with HIV".)
●Systemic treatment – Patients living with HIV and pulmonary KS should receive treatment that includes antiretroviral therapy (ART). (See "AIDS-related Kaposi sarcoma: Staging and treatment", section on 'Treatment'.)
•Asymptomatic pulmonary KS – For patients with asymptomatic pulmonary KS, we typically initiate ART without concomitant chemotherapy. In some cases, however, treatment of KS with ART alone may be associated with a flare of the KS. (See 'Systemic treatment' above and "AIDS-related Kaposi sarcoma: Staging and treatment", section on 'Combined antiretroviral therapy'.)
•Symptomatic pulmonary KS or progression on ART – For patients with symptomatic pulmonary KS or those with disease progression after initiation of ART, the addition of systemic chemotherapy to ART is indicated. Further details on the chemotherapy regimens used to treat AIDS-related KS are discussed separately. (See "AIDS-related Kaposi sarcoma: Staging and treatment", section on 'Systemic therapy'.)
●Treatment of endobronchial obstruction – In patients with symptomatic endobronchial obstruction due to KS, therapy is aimed at securing patency of the airway to achieve adequate ventilation and oxygenation. This may include endoscopic laser resection, stent placement, and/or radiation therapy. (See 'Airway obstruction and bleeding' above.)
●Treatment of pleural effusions – For patients with pleural effusions due to KS, we favor the use of repeated thoracentesis in combination with ART and chemotherapy rather than more upfront invasive procedures. If a pleural effusion recurs quickly (eg, in less than three weeks) despite repeated thoracentesis, an indwelling pleural catheter can be placed or talc pleurodesis performed, although experience in pleural KS is limited. (See 'Pleural effusions' above and "Management of malignant pleural effusions", section on 'Expandable lung with rapid reaccumulation'.)
ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Talmadge King, Jr, MD, and Bruce J Dezube, MD, who contributed to earlier versions of this topic review.
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