THE DIAGNOSTIC CHALLENGE OF PULMONARY KAPOSI’S SARCOMA WITH PULMONARY TUBERCULOSIS IN A RENAL TRANSPLANT RECIPIENT: A CASEREPORT

Abstract

Wereport a case of a 39-year-old, HIV-negative, post renal transplant patientwho developed mucocutaneous Kaposi’s sarcoma with lung parenchymalinvolvement and concurrently culture proven pulmonary tuberculosis. To thebest of our knowledge, this is the first case report of this combination,which presented with cavitating lung nodules and responded well to withdrawalof immunosuppressive drugs beside antituberculoustreatment.

INTRODUCTION

MorizKaposi in 1872 first described five patients presenting with “sarcomaidiopathicum multiple hemorrhagicum”⁽¹⁾. Kaposi’s sarcoma (KS) is a multicentric, low-grade tumor that usuallybegins with the development of violaceous skin lesions and is associated withthe presence of human herpesvirus 8 ⁽²⁾. KS is the most common malignancy associated with human immunodeficiency virus(HIV) infection and occurs in approximately 6–20% of HIV-infectedpatients ⁽³⁾. It has also been described in immunocompromised patients, particularly afterrenal transplantation, in which cutaneous involvement is the most salientfinding ^{(4, 5)}. In patients with known KS who present with a respiratory problem, up to 50%are due to parenchymal involvement with KS ⁽⁶⁾. Infectious and noninfectious pulmonary disorders in immunocompromised patientscan simulate the radiological manifestations of pulmonary KS. We report anHIV-negative, immunosuppressed patient with pulmonary KS as well as pulmonarytuberculosis, presenting with minimal respiratory symptoms but remarkableradiological abnormalities. This report highlights the dilemma in diagnosingsuch unique pulmonary complications and reviews the management ofimmunosuppression-relatedKS.

CASEREPORT

A 39-year-old Saudi male, 20 packs/year smoker, whois a renal transplant recipient for 14 years, presented with a 3-month historyof fever, night sweats, poor appetite, weight loss, and dry cough. The patienthad occasional high-grade fever associated with night sweat. His appetite waspoor, and he developed significant weight loss. There was no history ofshortness of breath, hemoptysis, or chest pain. He was maintained on 150 mg ofcyclosporin and 20 mg of prednisolone daily, since his renal transplant. Hehad been hypertensive for the last 10 years, taking 10 mg of amlodipine daily.He had no history of diabetes mellitus, tuberculosis, alcohol intake, or riskfactors for HIV infection. He denied any contact with patients withtuberculosis or recent travel. The systemic review was otherwiseunremarkable.

Physical examination revealed Cushingoidfeatures. He was ill looking, febrile, and pale. Multiple skin lesions werepresent over his left shoulder, trunk, and lower limbs. The largest was on hisright lower abdomen: 10×6 cm, dark red, raised, and nontender, withwell-defined irregular margins. A cherry-red, 3×2-cm, fungating,painless mass was present on the right side of the hard palate. There were nopalpable lymph nodes. Chest examination revealed normal vesicular breathsounds and abdominal examination showed no organomegaly. His proximal musclesshowed mild wasting with slightly reducedpower.

Investigations revealed normochromic, normocyticanemia with hemoglobin of 10.9 g/dl and an erythrocyte sedimentation rate(ESR) of 98 mm/1 hr. Urea was normal but creatinine was raised to 189μmol/l. Serum electrolytes were normal, apart from low bicarbonate of 18mmol/l. Herpes simplex IgG antibody titer was 1:21,000 with a negative IgMantibody titer. HIV serology was negative. Chest x-ray showed multipleill-defined nodular opacities, predominantly distributed peripherally in themiddle zone. Computerized tomography (CT) of the chest confirmed the nodularshadows, which had a tendency toward peripheral distribution. The nodules were0.5–2 cm in size, with irregular but well-defined margins mostly alongthe bronchovascular bundles. No pleural effusion or intrathoraciclymphadenopathy was found (Fig. 1).

Figure. 1: CT scan of the chest showingbilateral peripheral nodular shadows of variable sizes mostly along thebronchovascularbundles.

Thehistopathology of a skin biopsy from the abdominal wall lesion was consistentwith KS. In view of the close association between KS and immunosuppressiveagents, the dose of cyclosporin was reduced to 100 mg daily. One week laterthe patient’s fever disappeared; his appetite improved and he hadstarted to gain weight. Flexible bronchoscopy was performed and there was noevidence of endobronchial KS. The bronchoalveolar lavage (BAL) deposit waspositive for acid-fast bacilli by Ziehl-Neelsen stain and Mycobacterium tuberculosis-DNA(MTB-DNA) using a polymerase chain reaction. Special stains for Pneumocystis carinii and fungi werenegative. The patient was started on four antituberculous medications,including rifampicin, isoniazid, ethambutol, and pyrazinamide. Because hisradiological picture was atypical of pulmonary tuberculosis, a fine needleaspiration biopsy of a pulmonary nodule was performed under CT guidance.Cytological preparations showed hypocellular smears with two loose aggregatesof spindle cells with elongated, slightly hyper-chromatic nuclei. Nogranulomas were identified. The findings were highly suggestive ofKS.

Three weeks after starting antituberculous therapy,the patient restarted to have low-grade fever, weakness, poor appetite, and aweight loss of 2 kg. However, his skin lesions continued to show regression.Renal function was stable and the ESR was still elevated. A repeat chest x-raydemonstrated mild regression in the nodular infiltrate. Repeated highresolution CT (HRCT) of the chest showed development of new nodular shadowsand regression of some of the previously existing nodules. However, some ofthe nodules showed clear cavitation(Fig. 2). Accordingly, the patient underwent video-assisted thoracoscopic wedge biopsyof the lung. The histopathological examination revealed multiple caseatinggranulomas with acid-fast bacilli. In addition, spindle cell proliferationsseparated by slit like spaces, concentrated mostly around the bronchovascularbundles, and stained positive for endothelial markers, including CD34 wasdiagnostic for KS; hence, pulmonary Kaposi’s sarcoma with tuberculosiswas confirmed.

Figure. 2: HRCT of the chest showingcavitating lungnodules.

Thepatient was subsequently managed with 50 mg of cyclosporine a day andcontinued on antituberculous medications for a period of 6 months. Eight weeksafter commencing antituberculous therapy, BAL culture became positive for MTB,which was sensitive to first line antituberculous agents; hence, ethambutoland pyrazinamide were stopped. After 11 months, the patient showed significantimprovement in appetite and energy; he gained 7 kg in body weight and remainedafebrile. His skin and oral lesions remarkably regressed and his renalfunction remained stable. Repeat chest radiograph was normal, and HRCT scan ofthe chest showed remarkable regression of the multinodular pattern anddisappearance of the cavitations (Fig. 3).

Figure. 3: HRCT of the chest showingremarkable regression of the cavitatingnodules.

DISCUSSION

Amarked increased incidence of malignancy in transplant recipients is wellrecognized. The incidence of posttransplantation KS has varied among differentreports and ranged from 1.3–6%^{(4, 5)}. In a review of 8724 de novo malignancies that occurred in 8191 organtransplant recipients, Kaposi’s sarcoma accounted for 5.7% and was mostcommon in Arab, African, Italian, Jewish, and Greek patients ⁽⁷⁾. Qunibi et al. ⁽⁸⁾ from Saudi Arabia reported a similar incidence of 5.3%, making KS the mostcommon tumor in post renal transplantation. In another local study, among 350recipients of renal transplants, 12 (3.4%) developed Kaposi’s sarcomaand 2 (16.6%) presented primarily with lung involvement ⁽⁹⁾.

Cyclosporine-treatedpatients were noted to have a higher incidence of KS compared with patientstreated with conventional immunosuppressive agents ⁽⁴⁾. This, together with the high incidence of tuberculosis after renal transplantin Saudi Arabia ⁽¹⁰⁾, might have exposed our patient to a greater risk of developing both diseasessimultaneously. In a nation-wide study in Saudi Arabia based on Mantoux test,al-Kassimi et al. ⁽¹¹⁾ placed the Jeddah region (where our patient is from) as a region of highprevalence of tuberculosis (20%), compared with 6% for the national average.The incidence, however, of tuberculosis in the Jeddah region was reported tobe 63.4 per 100,000 ⁽¹²⁾, which is higher than that reported for the whole country for the same year(18.6 per 100,000) ⁽¹²⁾.

Approximatelyone-third of KS patients has clinically evident pulmonary disease, and 50%have pulmonary involvement at autopsy ^{(4, 13)}. Most of the affected patients present with shortness of breath, fever, cough,chest pain, and hemoptysis, whereas others may be asymptomatic but have anabnormal chest x-ray ^{(6, 13)}. The radiographic findings can vary from a normal chest radiograph to nodularopacities associated with hilar adenopathy, interstitial or alveolar opacity,and pleural effusion ⁽¹⁴⁾. These findings are nonspecific and may be confused with findings related topulmonary infections ⁽⁶⁾. In a patient with known KS who develops either changing symptoms or newroentgenographic findings, an attempt must be made to rule out an associatedinfectious process.

The role of the CT scan indiagnosing intrathoracic KS has been evaluated in several studies and found tobe more specific than routine roentgenograms for identifying pulmonary KS ⁽¹⁴⁾. In the absence of concomitant pulmonary infections, the main signs forintrathoracic KS were numerous nodules, bronchovascular thickening, tumoralmasses, and pleural effusion ⁽¹⁵⁾. The nodular pattern observed in the initial CT scan of our patient was inkeeping with the most common radiological manifestations of this malignancy ^{(14, 15)}. Pulmonary KS does not usually cavitate, however, there has been one report inthe literature of cavitating pulmonary KS associated with non-Hodgkin’slymphoma affecting the lung in a patient with acquired immune deficiencysyndrome ⁽¹⁶⁾. Therefore, searching for concomitant infectious or tumoral pathology isessential whenever there is a cavitary lung lesion as in our patient. Invasiveprocedures are usually required to diagnose such pulmonary complicationswhenever the diagnosis is in doubt.

The management ofposttransplantation KS has been based on the reduction or cessation ofimmunosuppression, because disease progression has been observed whenimmunosuppression was continued ^{(4, 5)}. Interestingly, the cessation of immunosuppression does not always result ingraft loss ⁽⁴⁾. This has been postulated to be related to the depletion of CD4 T lymphocytes,which results in immune tolerance to the allograft even with minimalimmunosuppression ⁽¹⁷⁾. Montagnino et al. ⁽⁴⁾ reported complete remission in nine patients and partial remission in twoafter reduction or withdrawal of immunosuppressive therapy. In his report, 69%of the patients remained dialysis-free after a mean follow-up period of 35months. Using this approach for our patient, we have achieved a remarkableclinical and radiological regression of the cutaneous and pulmonary KS lesionsand remained dialysis-free after 12 months of follow up, despite being onlow-dose cyclosporine (50 mg perday).

CONCLUSION

Thecase that we are reporting highlights the dilemma in reaching an accuratediagnosis in patients presenting with pulmonary complications ofimmunosuppression, where the coexistence of more than one pathology is wellrecognized. To our knowledge, this is the first case report of coexistence ofpulmonary Kaposi’s sarcoma and pulmonary tuberculosis in anHIV-negative, renal transplant recipient who presented with cavitary lunglesions and responded well to reduction of immunosuppression and institutionof antituberculous medications. We recommend that in an immunosuppressedpatient with an atypical presentation of a specific complication, furtherwork-up is warranted to rule out a co-existingpathology.