Japanese Journal of Clinical Oncology 31:333-336 (2001)
© 2001 Foundation for Promotion of Cancer Research
Pulmonary Intravascular Lymphoma Complicated with Pneumocystis Carinii Pneumonia: a Case Report
1Second Department of Internal Medicine, Gunma University, School of Medicine, Maebashi, Gunma and 2Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
|---|
We report a case of intravascular lymphoma (IVL) complicated with Pneumocystis carinii pneumonia (PCP). A 65-year-old male complaining of dyspnea and dementia was diagnosed to have pulmonary IVL by transbronchial lung biopsy. Concomitantly, deoxyribonucleic acid sequence specific to Pneumocystis carinii was detected in bronchoalveolar lavage fluid by polymerase chain reaction. Differential responses to the sequential treatments for PCP and IVL implied that increased serum lactate dehydrogenase (LDH) was due to PCP, whereas hypoxemia and dementia were due to IVL. Although pulmonary IVL and PCP share many clinical presentations, exact diagnosis is essential for their successful treatment.
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
|---|
Intravascular lymphoma (IVL) is an uncommon neoplastic disorder characterized by proliferation of malignant lymphoid cells within small arterioles, capillaries and venules, which presents various clinical manifestations (1). Pneumocystis carinii pneumonia (PCP) mainly affects immunocompromised hosts, including patients with acquired immunodeficiency syndrome or hematological diseases. When IVL and PCP coincide in a patient, the diagnostic process might be confused because these two disorders share many clinical features such as fever, dyspnea and high serum lactate dehydrogenase (LDH) levels (2,3). We report here a case of pulmonary IVL complicated with Pneumocystis carinii pneumonia.
|
CASE REPORT |
|---|
|
TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
|---|
A 65-year old-male was admitted to our hospital on 20 April 1999 because of dyspnea at rest. He had been taking medicine for hypertension for 17 years, but was in good health until September 1996, when he felt dizziness and unsteady gait. Computed tomography (CT) and magnetic resonance imaging of the brain revealed a tumor in left thalamus sized 3 cm accompanied by peripheral edema. Malignant lymphoma B cell type was confirmed by stereotactic brain biopsy. The chest and abdominal CT was unremarkable, depicting no lymphadenopathy. Whole-body scan of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) revealed a solitary abnormal accumulation in the brain. Therefore, the lymphoma was considered to be originating from the central nervous system. He was treated with brain irradiation (50 Gy), followed by three courses of systemic chemotherapy (carboplatin 300 mg/m2 day 1, mitoxantrone 4 mg/m2 day 1, etoposide 60 mg/m2 days 1–5, prednisolone 40 mg/m2 days 1–5), which induced complete remission. However, he again felt dizziness and malaise in December 1998. Since leukoencephalopathy after irradiation therapy was suspected, bethamethazone was prescribed, but without symptomatic improvement. In March 1999 he suffered from shortness of breath when walking. Because his dyspnea deteriorated, he was admitted to our hospital.
His past medical history was unremarkable except for hypertension. He consumed no alcohol, but had smoked 40 cigarettes per day for 37 years since he was 20 years old. His father had gastric cancer and his mother had cerebral vascular disease.
On admission, he appeared ill with dyspnea. He was 162 cm tall and weighed 70.7 kg. His vital signs were as follows: body temperature, 36.7°C; blood pressure, 100/60 mmHg; pulse, 90/min; respiration, 24/min. His physical findings were unremarkable. There was neither swelling of superficial lymph nodes nor skin eruption. In spite of the lack of focal neurological signs, he was moderately demented.
The white blood cell count was 8200/µl with a normal differential count. Although hemoglobin was 12.2 g/dl, reticulocytes were increased to 54. In combination with increased serum bilirubin (total bilirubin 2.2 mg/dl, direct bilirubin 0.9 mg/dl), high LDH levels (2327 IU/l) and low haptoglobin (<12.3 mg/dl), a hemolytic process was expected. Examination of a peripheral blood smear, however, revealed normal morphology of the erythrocytes and absence of atypical cells. Coomb’s test and other autoantibodies were negative. The platelet count was 13.1 x 104/µl. Other abnormal laboratory data were as follows: blood sedimentation rate, 24 mm in 1 h; C-reactive protein, 3.9 mg/dl; total protein, 5.3 g/dl; aspartate aminotransferase (AST), 52 IU/l; serum soluble interleukin-2 receptor (sIL-2R), 1820 U/ml. Bone marrow aspiration revealed normocellular bone marrow without atypical cells. Urinalysis showed proteinuria of moderate degree. Arterial blood gas analyses breathing ambient air were pH 7.513, PaCO2 30.4 Torr (40.4 hPa), PaO2 51.4 Torr (68.4 hPa), HCO3– 24.2 mEq/l.
His chest radiograph was unremarkable except for a belt-shaped shadow in the right lower lobe (Fig. 1). A computed tomography scan of the whole body showed consolidation in the lower lobe of the right lung (Fig. 2A), thickening of bronchovascular bundles, swelling of bilateral hilar lymph nodes (Fig. 2B) and mild splenomegaly. Pulmonary thromboembolism was unlikely because of the lack of defects in pulmonary ventilation–perfusion scintigraphy. In gallium-67 scintigraphy and FDG-PET (Fig. 3A), abnormal accumulation of tracers was noted in bilateral lung fields and hilar regions. Brain magnetic resonance imaging depicted a diffuse T2 high lesion, but no intracranial recurrence of the lymphoma. We suspected IVL from preceding brain malignant lymphoma, dementia, hypoxia of unknown origin, high serum LDH level, hemolysis, proteinuria and abnormal accumulation of gallium-67 and FDG-PET in both lungs.
|
|
|
Pulmonary intravascular lymphoma was confirmed by transbronchial lung biopsy taken from the right upper and lower lobes, which demonstrated the invasion of many atypical lymphoid cells into capillary vessels of the alveolar septae (Fig. 4A and B). Immunohistochemical staining revealed that these atypical cells were positive for leukocyte common antigen (Fig. 4C).
|
In addition, Pneumocystis carinii infection was revealed by bronchoalveolar lavage (BAL), which was performed in the lateral segment of the right middle lobe. BAL fluid contained 2.6 x 105 cells/ml with 92.8% of macrophages. The deoxyribonucleic acid (DNA) sequence specific to Pneumocystis carinii was detected in BAL fluid by polymerase chain reaction (PCR) according to the method described by Wakefield (4), but those specific to mycobacteria were not found. Bacterial culture and cytology were negative. Antigens of cytomegarovirus, candida and aspergillus were not detected.
He started to take sulfamethoxazole (4800 mg/day) and trimethoprim (960 mg/day) on May 18. Ten days later, the serum LDH had decreased from 2327 to 571 IU/l and C-reactive protein was negative. Restudy of FDG-PET revealed that tracers were distributed mainly in the bilateral hilar regions; the lung field was no longer positive (Fig. 3B). In contrast, serum sIL-2R, a marker of malignant lymphoma, rose from 1820 to 2500 U/ml. Hypoxemia and dementia also did not improve. Thereafter, six courses of CHOP therapy (cyclophosphamide 750 mg/m2 day1, adriamycin 50 mg/m2 day 1, vincristine 2 mg/body day 1, predonisolone 60 mg/m2 days 1–5) were performed, which improved his hypoxemia and dementia.
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
|---|
In this case pulmonary intravascular lymphoma (IVL) was complicated with Pneumocystis carinii pneumonia (PCP). Because of their similar clinical presentations, these two disorders should be diagnosed with caution.
Intravascular lymphoma is a rare type of non-Hodgkin’s lymphoma characterized by intravascular proliferation of neoplastic lymphoid cells, which are usually of B-cell lineage (3). Occlusion of small vessels in the various organs probably accounts for a variety of clinical presentations of IVL, including progressive dementia, paresis, convulsion, skin rash, dyspnea, proteinuria, etc. Fever, hemolytic anemia, increased serum LDH and high soluble IL-2 receptor are also observed. Lymphadenopathy is an exceptional finding in IVL. The small number of atypical cells in blood and bone marrow often delay the diagnosis of IVL. The mechanisms for the selective intravascular growth of lymphoma cells are still unclear, but it has been suggested that expression patterns of adhesion molecules are relevant to specific disease progression (5,6). Recently, Murase and Nakamura (7) reported an Asian variant of intravascular lymphomatosis (AIVL), a peculiar variant of IVL among Asians that is characterized by hemophagocytic syndrome, bone marrow involvement at presentation and an aggressive clinical course.
In this case, the combination of preceding brain malignant lymphoma and an assortment of clinical findings led us to suspect intravascular lymphoma. Subsequently, IVL was confirmed by transbronchial lung biopsy, which showed many atypical lymphoid cells in pulmonary small vessels. The lineage of the lymphoma cell could not be determined, because these cells stained positive to leukocyte common antigen (CD45) but negative to UCHL-1 (CD45RO), MT-1 (CD43), L-26 (CD20) and MB-2.
Pneumocystis carinii DNA was detected in the BAL fluid by PCR. The patient was first treated with oral sulfamethoxazole–trimethoprim (ST), which decreased serum LDH markedly. In FDG-PET assessments, abnormal uptake into both lungs disappeared after ST therapy. Therefore, we were convinced that oral ST was effective against PCP. Because six courses of CHOP therapy improved hypoxemia and dementia, which remained even after administering ST, these clinical manifestations should be assigned to IVL.
FDG-PET has been reported as a sensitive method in detecting lung cancer. In a series, FDG-PET was 100% sensitive and 52% specific in predicting the malignant nature of a chest radiographic abnormality (8). FDG-PET is also potent in lymph node staging in non-small cell lung cancer. Vansteenkiste et al. (9) made a prospective study of 690 lymph node stations from 68 patients and reported an improvement in the detection of locally advanced disease (N2/N3) by FDG-PET; the sensitivity, specificity and accuracy of CT alone were 75, 63 and 68%, respectively, but the combination of CT with FDG-PET increased this to 93, 95 and 94%, respectively (P = 0.0004). The usefulness of FDG-PET has also been demonstrated in detecting recurrence of lung cancer (10). Because of its very high sensitivity in cancer detection, FDG-PET could reduce unnecessary surgical staging by mediastinoscope (9) and affect clinical decision-making (11).
When pulmonary IVL and PCP coincide in a patient, the correct diagnosis might be challenging, because these disorders share many clinical presentations. Both pulmonary IVL and PCP present positive gallium-67 scintigraphy in the lungs, hypoxemia and high serum LDH values. Dementia is one of the most common symptoms of IVL, but hypoxia from PCP could disturb consciousness, resembling dementia. The radiographic findings are also confusing. Chest roentgenogram findings may be acinar infiltrates, interstitial shadows or normal in PCP (2), whereas pulmonary IVL shows normal or interstitial pneumonia (12). However, correct diagnosis of IVL and PCP is essential for successful treatment. We propose bronchofiberscopy as a robust tool in diagnosing pulmonary IVL and PCP. It should be remembered that pulmonary IVL and PCP could coincide in a patient.
|
FOOTNOTES |
|---|
+ For reprints and all correspondence: Yoshichika Sando, Second Department of Internal Medicine, Gunma University, School of Medicine, 3–39–22 Showa-machi, Maebashi 371-8511, Japan. E-mail: sandouy@showa.sb.gunma-u.ac.jp
Abbreviations: IVL, intravascular lymphoma; PCP, Pneumocystis carinii pneumonia; LDH, lactate dehydrogenase; FDG-PET, [18F]fluorodeoxyglucose positron emission tomography; CT, computed tomography; AST, aspartate aminotransferase; sIL-2R, soluble interleukin-2 receptor; BAL, bronchoalveolar lavage; DNA, deoxyribonucleic acid; AIVL, Asian variant of intravascular lymphomatosis; ST, sulfamethoxazole–trimethoprim
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
|---|
1 Carroll TJ Jr, Schelper RL, Goeken JA, Kemp JD. Neoplastic angioendotheliomatosis: immunopathologic and morphologic evidence for intravascular malignant lymphomatosis. Am J Clin Pathol 1986;85:169–75.[ISI][Medline]
2 Opravil M, Marincek B, Fuchs WA, Weber R, Speich R, Battegay M, et al. Shortcomings of chest radiography in detecting Pneumocystis carinii pneumonia. J Acquired Immune Defic Syndr 1994;7:39–45.
3 DiGiuseppe JA, Nelson WG, Seifter EJ, Boitnott JK, Mann RB. Intravascular lymphomatosis: a clinicopathologic study of 10 cases and assessment of response to chemotherapy. J Clin Oncol 1994;12:2573–9.
4 Wakefield AE, Pixley FJ, Banerji S, Sinclair K, Miller RF, Moxon ER, et al. Detection of Pneumocystis carinii with DNA amplification. Lancet 1990;336:451–3.[ISI][Medline]
5 Ponzoni M, Arrigoni G, Gould VE, Del Curto B, Maggioni M, Scapinello A, et al. Lack of CD 29 (beta1 integrin) and CD 54 (ICAM-1) adhesion molecules in intravascular lymphomatosis. Hum Pathol 2000;31:220–6.[ISI][Medline]
6 Kanda M, Suzumiya J, Ohshima K, Tamura K, Kikuchi M. Intravascular large cell lymphoma: clinicopathological, immuno-histochemical and molecular genetic studies. Leuk Lymphoma 1999;34:569–80.[ISI][Medline]
7 Murase T, Nakamura S. An Asian variant of intravascular lymphomatosis: an updated review of malignant histiocytosis-like B-cell lymphoma. Leuk Lymphoma 1999;33:459–73.[ISI][Medline]
8 Sazon DA, Santiago SM, Soo Hoo GW, Khonsary A, Brown C, Mandelkern M, et al. Fluorodeoxyglucose-positron emission tomography in the detection and staging of lung cancer. Am J Respir Crit Care Med 1996;153:417–21.[Abstract]
9 Vansteenkiste JF, Stroobants SG, De Leyn PR, Dupont PJ, Bogaert J, Maes A, et al. Lymph node staging in non-small-cell lung cancer with FDG-PET scan: a prospective study on 690 lymph node stations from 68 patients. J Clin Oncol 1998;16:2142–9.[Abstract]
10 Inoue T, Kim EE, Komaki R, Wong FC, Bassa P, Wong WH, et al. Detecting recurrent or residual lung cancer with FDG-PET. J Nucl Med 1995;36:788–93.
11 Weng E, Tran L, Rege S, Safa A, Sadeghi A, Juillard G, et al. Accuracy and clinical impact of mediastinal lymph node staging with FDG-PET imaging in potentially resectable lung cancer. Am J Clin Oncol 2000;23:47–52.[ISI][Medline]
12 Yousem SA, Colby TV. Intravascular lymphomatosis presenting in the lung. Cancer 1990;65:349–53.[ISI][Medline]
Received December 29, 2000; accepted March 22, 2001.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Martusewicz-Boros, E. Wiatr, E. Radzikowska, K. Roszkowski-Sliz, and R. Langfort Pulmonary Intravascular Large B-Cell Lymphoma As a Cause of Severe Hypoxemia J. Clin. Oncol., May 20, 2007; 25(15): 2137 - 2139. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||