A 48-year-old African Americanwoman with HIV infection who hadbeen hospitalized several days earlierfor presumed Pneumocystis cariniipneumonia (PCP) is readmittedbecause of worsening dyspnea and atemperature of 38.8oC (102oF).She also complains of painful swellingand erythema on her right arm.Her symptoms have worseneddespite treatment with trimethoprimsulfamethoxazole.
A 48-year-old African Americanwoman with HIV infection who hadbeen hospitalized several days earlierfor presumed Pneumocystis cariniipneumonia (PCP) is readmittedbecause of worsening dyspnea and atemperature of 38.8oC (102oF).She also complains of painful swellingand erythema on her right arm.Her symptoms have worseneddespite treatment with trimethoprimsulfamethoxazole. The patient's history includesthrush, hepatitis C, and asthma. HerCD4+ cell count is 45/µL.A chest film reveals bilateraldiffuse interstitial opacities consistentwith PCP; a left pleural effusion isalso noted. Cephazolin is started forpresumed phlebitis of the right antecubitalfossa secondary to intravenousline placement during her previoushospitalization. An ultrasonogram ofthe right upper arm shows no deep venousthrombosis. However, the armbecomes more edematous and painful.A CT scan of the right upperarm reveals infiltrative changes of thesubcutaneous fat-particularly alongthe medial aspect-and a very thinlayer of fluid within and around themedial muscle fascia. Compartmentsyndrome is ruled out, and the antibioticis switched to vancomycin.On the third hospital day, nontender,macular, purplish, dark maroonlesions develop on the rightupper arm (Figure 1). Results of abiopsy of the lesions suggest Kaposisarcoma (KS).The following day, the patient hassevere dyspnea on minimal exertion.A chest CT scan reveals axillary andmediastinal lymphadenopathy anda left pleural effusion, consistent withKS of the lungs (Figure 2). Bronchoalveolarlavage verifies these findingsand rules out PCP, which obviates theneed for an open lung biopsy.The patient is given liposomaldoxorubicin and is advised to startHAART. Her respiratory symptoms resolve within 6 days, and she isdischarged.PULMONARYKAPOSI SARCOMA:AN OVERVIEW
KS typically involves the skinand lymph nodes; viscera are lessfrequently affected. Tumors thatdevelop in the lungs or GI tract aremore life-threatening than cutaneousKS lesions.Pulmonary KS has been diagnosedin approximately one thirdof AIDS patients with respiratorysymptoms and cutaneous KS.1 Thefrequency of isolated pulmonaryKS ranges from 0% to 15.3%.2-6Pulmonary KS can be difficultto distinguish from other infectiousand neoplastic conditions. Radiographicchanges associated withthe tumor are often attributed topulmonary infection. The chest filmcharacteristically shows bilaterallower lobe infiltrates that obscurethe margins of the mediastinumand diaphragm. Pleural effusions,which are seen in 70% of cases ofpulmonary KS, are often useful inthe differential diagnosis.2,7-9Before HAART became available,the rate of KS was 100,000-foldgreater among HIV-infected patientsthan among the general population.KS is more frequent in homosexualmen who acquired HIV through unprotectedsex; it is 20 times moreprevalent in homosexual HIV-infectedmen than in heterosexual HIVinfectedmen.1Men are affected more oftenthan women. Cutaneous KS is rarelydiagnosed in women, and a diagnosisof cutaneous and pulmonary KS isvery rare. There is a male-to-femaleratio of greater than 20:1 among HIVtransmissiongroups.1 The reason forthe higher incidence of KS amongcertain groups remains unknown.Particular sexual practices, hormonalmilieu, and exposure to variousviruses may promote KSgrowth.10,11PATHOLOGY
KS tissues contain human herpesvirus8, also known as KS-associated herpesvirus.12 This virus hasconsistently been detected in allforms of KS, unlike other associatedviruses, such as the Epstein-Barrvirus and human papillomavirus.13-15The angioproliferative tumorsof KS are characterized by neovascularprocesses with proliferatingendothelial cells, fibroblasts, spindleshapedtumor cells, and infiltratingleukocytes.6 Although the histopathologyremains the same amongHIV-risk groups, the clinical expressionof the disease may vary.16The pathogenesis of cutaneousKS involves angiogenesis, extravasationof red blood cells, inflammatorycell infiltration, and endothelial cellactivation. In the latter stages ofcutaneous disease, spindle-shapedcells (a heterogeneous mixture ofactivated endothelial cells, macrophages,and dendritic cells) becomethe prominent cell type.In pulmonary KS, there may betelangiectatic lesions as well as inflammation.1,17 On microscopic examination,pulmonary KS lesionsmay be subtle; the histopathologicdifferential diagnosis includes bothinflammatory conditions and othervascular proliferations.18,19 Bright todark red, violaceous lesions in themucous membranes of the transbronchialtree may be visible onbronchoscopy.20,21 Abundant spindlecells and small vascular clefts areevident in the nodular forms of pulmonaryKS. The spindle tumor cellshave small slitlike spaces that containextravasated red blood cells, whichinfiltrate and ultimately replace thesmooth muscle of bronchioles andpulmonary arteries. Extensive intraalveolarhemorrhage may also be detected,particularly at the time ofdeath.1CLINICAL FEATURES
The clinical presentation of intrathoracic KS in AIDS patients isnonspecific and is difficult to distinguishfrom pneumonia. The mostcommon symptoms are dyspnea andcough. Fever and night sweats maybe present, although these symptomsusually indicate a concomitant infection.Hemoptysis also may occur,although the incidence varies. In astudy of 30 AIDS patients with pulmonaryKS, 100% had dyspnea, 80%had cough, 47% had chest pain, 30%had hemoptysis, and 13% had a temperatureabove 38.5oC (101.2oF).22DIAGNOSTICTESTSImaging studies.
In patientswith pulmonary KS, chest radiographyoften reveals thickening alongbronchovascular bundles. Chest CTscans frequently show bronchialwall thickening and spiculated lesions.1 CT is preferable to conventionalradiography because it providesgreater detail.9The studies used most often todiagnose KS are CT and bronchoscopy.1 Direct inspection of lesionsby bronchoscopy is the most sensitivetechnique for establishing a diagnosis;however, using this procedure,only 45% to 73% of patientshave readily identifiable endobronchiallesions.23,24In the evaluation of dyspneicpatients, spiral CT is extremelyuseful because of its shorter imagingtime and higher-resolution images.25 High-resolution CT is alsouseful, because it can help guide themethod of biopsy and help directthe bronchoscopist to the diseasedlung segment.26 Although not widelyused in the United States-possiblybecause of its expense-galliumthalliumradionuclide imaging hasbeen used in AIDS patients to ruleout other diseases. KS takes up thalliumbut does not take up gallium,unlike other infectious or neoplastic AIDS-related complications.27 Therole of MRI has not been extensivelydetailed; further analyses areneeded to better define its use indiagnosing pulmonary KS.Biopsy. Because of the lack ofmalignant features, biopsy findingsmay be misinterpreted as reactivefibrous tissue. Furthermore, sincethe lesions are composed of somespindle cells and blood vessels thatmay appear normal, identificationby histologic methods is difficult.Open lung biopsy has a diagnosticyield of approximately 50%; however,this procedure is rarely performedbecause of pain and other possiblecomplications.3,28-30 Polymerasechain reaction-based localizationstudies for KS-associated herpesvirusmay assist in the diagnosis ofpulmonary KS.MANAGEMENTChemotherapy.
Advanced KS istreated with a combination of activecytotoxic agents, such as Vinca alkaloids,anthracyclines, leomycin, andetoposide.31 Combination chemotherapyhas yielded the highest responserates. A chemotherapy regimenwith adriamycin, bleomycin, andvincristine or vindesine (ABV) hasbeen used, particularly in the treatmentof pulmonary KS.1Unfortunately, cytotoxic chemotherapyprovides only transient relief,and time until relapse is usuallybrief. In a study of 20 patients whowere treated with ABV or bleomycinplus vincristine or vindesine, 12 patientshad a favorable response totherapy; their median survival was12 months, whereas the mediansurvival for nonresponders was 6months.28 Common adverse effectsinclude bone marrow suppression,mucositis, GI symptoms, alopecia,cardiac dysfunction, and peripheralnerve dysesthesias.1Liposomal daunorubicin and liposomaldoxorubicin have been approvedby the FDA as the first-linetreatment of AIDS-related KS.32 Liposomalanthracycline agents areconsidered the chemotherapy drugsof choice over the nonliposomal anthracyclineagents, because they aregenerally associated with less mucositis,alopecia, and cardiactoxicity.33,34Paclitaxel (at dosages rangingbetween 100 and 175 mg/m2 IVevery 2 to 3 weeks) has shownsignificant anti-KS activity, with responserates of 53% to 65% amongpatients who had a poor prognosis.35,36 In one study, all 5 patientswith AIDS and pulmonary KS respondedto treatment with paclitaxel.35 The effects of paclitaxel in patientswith pulmonary KS, however,continue to be limited.Radiation therapy. This typicallyoffers patients short-term palliationbefore death from pulmonarycomplications or superimposed opportunisticinfections.1 In one study,9 of 11 patients with pulmonary KSwho were treated with radiotherapyhad significant relief until death.37 Itis still uncertain whether long-termpalliation can be provided if radiotherapyis given to these patients atan earlier stage of the disease. BecauseKS is a very radiosensitivetumor, patients who receive modestdoses of radiation therapy will experienceside effects. These may includealopecia, neutropenia, and peripheralneuropathy. However, radiationpneumonitis does not occur.1HAART. This therapy alonemay be an effective maintenanceregimen for patients with pulmonaryKS. Studies have shown thatthose who responded well toHAART experienced decreasedplasma HIV levels, increased circulatingCD4+ T-cell counts, reducedoccurrence of opportunistic infections,and decreased short-termmortality.38,39Various studies haveshown that HAART reduces KSassociatedherpes viral loads andtumor size.1 Although it appearsthat HAART may be effective in theregression of KS, the mechanismsby which HAART influences thegrowth of tumors and the lengthof time that HAART can effectivelysuppress viral replication are notfully understood.40
PROGNOSISIn a study of 168 AIDS patientswith pulmonary KS, a median CD4+cell count of 19/µL was reported.6 The clinical expression of KS appearsto worsen as the immune systemis further weakened.41 Withouttreatment, patients with a CD4+ cellcount of greater than 150/µL havea median survival of 39 months,whereas those with a CD4+ cellcount of less than 150/µL are likelyto survive for only 12 months.1Patients with pulmonary KSseem to respond relatively well totreatment. However, a definite prognosiscannot be ascertained becausethe paucity of documented casesof pulmonary KS limits the ability todetect survival differences, if theydo indeed exist. Furthermore, underdiagnosisof this disease and theselection bias for analyses may skewthe data.42
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