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J, Pendame R, et al. Effects of HIV-1 serostatus, HIV-1 RNA concentration and CD4 cell count on the incidence of malaria infection in a cohort of adults in rural Malawi. J Infect Dis 2005;192:984-91. Chandramohan D, Greenwood BM. Is there an interaction between human immunodeficiency virus and Plasmodium falciparum? Int J Epidemiol 1998;27:296-301. Kublin JG, Patnaik P, Jere CS, Miller WC, Hoffman IF, Chimbiya N, et al. Effect of Plasmodium falciparum malaria on concentration of HIV-1-RNA in the blood of adults in rural Malawi: A prospective cohort study. Lancet 2005;365:233-40. Khasnis AA, Karnad DR. Human immunodeficiency virus type 1 infection in patients with severe falciparum malaria in urban India. J Postgrad Med 2003;49:114-7. Taylor-Robinson AW, Phillips RS, Severn A, Moncada S, Liew FY.The role of TH1 and TH2 cells in a rodent malaria infection. Science 1993;260:1931-4. Whitworth J, Morgan D, Quigley M, Smith A, Mayanja B, Eotu H, et al. Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: A cohort study. Lancet 2000;356:1051-6.

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8. French N, Nakiyingi J, Lugada E, Watera C, Whitworth JA, Gilks CF. Increasing rates of malarial fever with deteriorating immune status in HIV-1infected Ugandan adults. AIDS 2001;15:899-906. 9. ter Kuile FO, Parise ME, Verhoeff FH, Udhayakumar V, Newman RD, van Eijk AM, et al. The burden of co-infection with human immunodeficiency virus type 1 and malaria in pregnant women in sub-saharan Africa. Am J Trop Med Hyg 2004;71:41-54. 10. Cohen C, Karstaedt A, Frean J, Thomas J, Govender N, Prentice E, et al . Increased prevalence of severe malaria in HIV-infected adults in South Africa. Clin Infect Dis 2005;41:1631-7. 11. Kamya MR, Gasasira AF, Yeka A, Bakyaita N, Nsobya SL, Francis D, et al. Effect of HIV-1 infection on antimalarial treatment outcomes in Uganda: A population-based study. J Infect Dis 2006;193:9-15. 12. Peters RP, Zijlstra EE, Schijffelen MJ, Walsh AL, Joaki G, Kumwenda JJ, et al. A prospective study of bloodstream infections as cause of fever in Malawi: Clinical predictors and implications for management. Trop Med Int Health 2004;9:928-34. Source of Support: Nil, Conflict of Interest: None declared.

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Indian J Med Sci, Vol. 60, No. 9, September 2006

380

FATAL SECONDARY PULMONARY HYPERTENSION DUE TO

CARDIAC INVOLVEMENT IN AIDS-ASSOCIATED BURKITT’S

LYMPHOMA

ASHUTOSH S. SINGH, DHIREN J. DAVE*, SUNIL THANVI*, DHANASHRI A. ATRE**,

PRASHANT PARIKH*, NEHAL H. PATEL*

ABSTRACT Primary cardiac lymphomas are rare lesions in children with acquired immunodeficiency syndrome (AIDS). Most of them are high-grade Burkitt’s or Burkitt-like lymphomas. They usually present with congestive cardiac failure, pericardial effusion or tamponade, arrhythmias, with predominant systemic ‘B’ symptoms and often with widespread extranodal involvement. The clinical profile and operative and pathological findings of a 4-year-old boy with AIDS-associated Burkitt’s lymphoma of the heart presenting with acute right heart failure and fatal secondary pulmonary hypertension is reported. Key words: AIDS-associated Burkitt’s lymphoma, cardiac lymphoma, pulmonary hypertension

INTRODUCTION Though the prevalence of malignant lymphomas in acquired immunodeficiency syndrome (AIDS) is 20-60 times more than in general population, involvement of the hear t is infrequent, repor ted mostly as individual cases.[1,2] Majority of these AIDSassociated lymphomas are high-grade Burkitt’s or Burkitt-like lymphomas. [3] The unusual clinical presentation of AIDSassociated Burkitt’s lymphoma in a 4-year-old boy seropositive for human immunodeficiency International Centre of Cardiothoracic and Vascular Diseases, Frontier Lifeline Hospital, Chennai, *U. N. Mehta Cardiology Institute, Ahmedabad, Gujarat, **Department of Internal Medicine, Seth GS Medical College and KEM Hospital, Mumbai, India Correspondence Dhiren J. Dave, International Centre of Cardiothoracic and Vascular Diseases, Frontier Lifeline Hospital, Chennai - 600 101, India. E-mail: [email protected]


virus (HIV) as acute right heart failure due to right ventricular inflow obstruction followed by fatal secondary pulmonary hypertension due to chronic embolisation is reported here.

CASE REPORT A 4-year-old boy presented to us with worsening acute onset dyspnea, NYHA class IV or thopnea, oligur ia, pedal edema and abdominal distension. There was no history suggesting rheumatic fever or other preceding illnesses. The clinical, radiological and investigation profile is summarized in Table 1. The child was taken up for an emergency surgical excision of the right atrial mass. The pericardium was not involved and there was no pericardial effusion. The surgery was performed via a median sternotomy and standard cardiopulmonary bypass was instituted by aorto-bicaval canulation on moderate


Table 1: Salient clinical, radiological and laboratory investigations of the patient Clinical features � Acute onset class iv dyspnoea. � Ascites, pedal edema, oliguria. � Tachycardia, hypotension (80/50 mm Hg) � Pallor and icterus � Prominent ‘a’ and ‘c’ waves in the JVP � Parasternal heave and diatolic shock � Mid-diastolic murmur at tricuspid and ejection systolic murmurs at the pulmonary areas � Hepatomegaly and ascites Chest radiograph ECG � Cardiothoracic ratio 65%. � Sinus tachycardia. � Right atrial enlargement. � Right atrial enlargement prominant branch pulmonary. arteries Right ventricular hypertrophy with strain. Echocardiography [Figure 1] � Lobulated mass on right atrial free wall prolapsing into the right ventricle � 12 mm Hg gradient across the Tricuspid valve � Right ventricle systolic pressure 50 mm Hg � No right ventricular outflow tract obstruction Laboratory � Seropositive for human immunodeficiency virus � Hemoglobin: 8.6 g% � Leucocyte count: 10800, lymphocytosis: 52% � Bilirubin: 4 mg%, indirect bilirubin: 3.1 mg%· � Serum proteins: 5.2 g%

hypothermia. Myocardial protection was achieved by electromechanical arrest with antegrade cold blood potassium cardioplegia after clamping the ascending aor ta. The pulmonary arter y was vented. After caval snaring, the right atrium was opened longitudinally parallel to the atrioventricular groove. There was a single lobulated friable mass attached to the free wall of the right atrium. The tricuspid valve was free of the tumor. The mass was excised with a rim of right atrial wall. There was no other tumor in the heart. The atriotomy was closed and the patient was weaned of cardiopulmonary bypass. A pulmonary arterial catheter was placed for monitoring. There was no involvement of the mediastinal lymph nodes. The lungs were unremarkable on gross appearance. The child was shifted to the ICU with stable

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hemodynamics on inotropic suppor ts. Postoperatively, the patient persistently had high pulmonary artery pressures. His arterial blood gases showed a gradual development of hypoxia, hypercarbia and acidosis. He deteriorated on the third postoperative day and expired. Grossly, the tumor has a lobulated grayish white appearance [Figure 2]. There were areas

Figure 1: Echocardiographic appearance of the right atrial mass in a two-chamber view

Figure 2: Gross morphology of the excised right atrial tumor tissue


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AIDS-ASSOCIATED BURKITT’S LYMPHOMA OF HEART

of necrosis and hemorrhage on cross section. On histopathology [Figure 3], the tumor was found to be composed of monomorphic, medium-sized cell-large round nuclei; multiple nucleoli; and abundant basophilic cytoplasm. There were numerous benign macrophages scattered throughout the section, giving a ‘starry-sky’ appearance typical of Burkitt’s lymphoma. Cross section of lung specimen showed diffuse distribution of tumor emboli throughout the parenchyma. Lung biopsy confirmed presence of Burkitt’s tumor in the pulmonary vasculature [Figure 4].

grade, with Burkitt-like cells, reticular cell sarcomas or large cell immunoblastic sarcomas, collectively termed as AIDSassociated Burkitt’s lymphomas. The majority originate from B cells.[1,2]

DISCUSSION

Cardiac lymphomas usually demonstrate pallor of the hear t secondar y to diffuse lymphomatous infiltration or patchy involvement of the epicardium, myocardium and endocardium in the form of focal circumscribed nodules, most frequently affecting the right atrium.[5] The tumor in this case was a right atrial mass lesion attached to its free wall, an uncommon finding.

Malignant lymphomas constitute the primary manifestation of AIDS only in 3-4% of the population.[1] Primary cardiac lymphoma is a very rare malignancy, accounting for about 1% of the primary cardiac tumors and 0.5% of the extranodal lymphomas. However, disseminated lymphoma with cardiac involvement can occur in up to 20% of patients.[4] Most non-Hodgkin’s lymphomas affecting the heart in HIV infection are high

AIDS-associated cardiac lymphomas present clinically as congestive cardiac failure, pericardial effusion or tamponade, arrhythmias.[6] Predominance of systemic ‘B’ symptoms like fever, drenching night sweats and weight loss in excess of 10% of normal body weight are described in as many as 82% of patients with systemic AIDS-associated lymphomas. These patients often present with widespread extranodal involvement; it was

Figure 3: Histopathological appearance of the tumor characterized by a ‘starry-sky’ appearance suggestive of Burkitt’s lymphoma (H/E, 200x)

Figure 4: Histopathology of the lung showing presence of embolic tumor mass in pulmonary vasculature



found to be occurring in 88 of 90 (98%) patients included in a large, multi-center retrospective report.[7,8] The patient mentioned here had neither of these and had presented initially as acute right heart failure due to right ventricular inflow obstruction by right atrial mass lesion. The excision of the tumor however did not restore the hemodynamics to normal. The pulmonary artery pressures remained high postoperatively and the child succumbed to right heart failure. Autopsy findings suggested chronic embolisation of the lung vasculature by lymphomatous tissue. The involvement of any extracardiopulmonary system was remarkably absent. Primary pulmonary hypertension affects about 0.5% of hospitalized adults with AIDS and is a cause of severe cardiac impairment with associated cor pulmonale and death.[9] Right heart tumors are known to embolise to lungs and lead to secondary pulmonary hypertension.[10] Fatal secondary pulmonary hyper tension caused by AIDS-associated Burkitt’s lymphoma in a child with AIDS has not been described previously to the best of our knowledge. Detailed histopathological and immunohistochemical studies were not done in view of its normal gross features. This remains a major limitation of this report. Outcome is usually poor in these patients and the optimal approach to treatment has yet to be determined. Clinical remission has been obtained with combination chemotherapy with highly active antiretroviral therapy. Ratner et al.[11] in their series of 65 patients have shown that both modified and full-dose regimens of cyclophosphamide and doxorubicin, combined with vincristine and prednisone, with highly active antiretroviral therapy are

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effective and well tolerated in patients with HIV-associated non-Hodgkin’s lymphomas. Though chemotherapy has been the mainstay of treatment in these patients, the case discussed here had to undergo emergency cardiac surgery in view of his worsening hemodynamics. Secondary pulmonary hypertension leading to fatal r ight hear t failure can be a clinical presentation of AIDS-associated Burkitt’s lymphoma in children with AIDS. A high index of suspicion and optimum chemotherapy regimen with highly active antiretroviral therapy may help in improving the outcome of this potentially lethal condition.

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AIDS-ASSOCIATED BURKITT’S LYMPHOMA OF HEART

heart: Case report and literature review. Pathol Int 2004;54:187-95. 7. Levine AM, Sullivan-Halley J, Pike MC, Rarick MU, Loureiro C, Bernstein-Singer M, et al. HIV-related lymphoma: Prognostic factors predictive of survival. Cancer 1991;68:2466-72. 8. Ziegler JL, Beckstead JA, Volberding PA, Abrams DI, Levine AM, Lukes RJ, et al. Non-Hodgkin’s lymphoma in 90 homosexual men: Relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome. N Engl J Med 1984;311:565-70. 9. Rerkpattanapipat P, Wongpraparut N, Jacobs LE,

Kotler MN. Cardiac manifestations of acquired

immunodeficiency syndrome. Arch Intern Med 2000;160:602-8. 10. Stern MJ, Cohen MV, Fish B, Rosenthal R. Clinical presentation and non-invasive diagnosis of right heart masses. Br Heart J 1981;145:552-8. 11. Ratner L, Lee J, Tang S, Redden D, Hamzeh F, Herndier B, et al. Chemotherapy for human immunodeficiency virus-associated nonHodgkin’s lymphoma in combination with highly active antiretroviral therapy. J Clin Oncol 2001;19:2171-8.

Source of Support: Nil, Conflict of Interest: None declared.

REFERENCES 1. Duong M, Dubois C, Buisson M, Eicher JC, Grappin M, Chavanet P, et al. Non-Hodgkin’s lymphoma of the heart in patients infected with human immunodeficiency virus. Clin Cardiol 1997;20:497-502. 2. Barbaro G, Di Lorenzo G, Grisorio B, Barbarini G. Cardiac involvement in the acquired immunodeficiency syndrome: A multicenter clinical pathological study. AIDS Res Hum Retroviruses 1998;14:1071-7. 3. Ioachim HL, Dorsett B, Crmin W, Maya M, Wahl S. Acquired immunodeficiency syndrome associated lymphomas: Clinical, pathological, immunologic and viral characteristics of 111 cases. Hum Pathol 1991;22:659-73. 4. Gowda RM, Khan IA. Clinical perspectives of primary cardiac lymphoma. Angiology 2003;54:599-604. 5. D’Amati G, Di Gioia CR, Gallo P. Pathological findings of HIV-associated cardiovascular disease. Ann NY Acad Sci 2001;946:23-45. 6. Ikeda H, Nakamura S, Nishimaki H, Masuda K, Takeo T, Kasai K, et al. Primary lymphoma of the


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