|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
© 2000 American Society for Clinical Oncology
Two Unusual LymphomasCase 2: Pulmonary Intravascular LymphomatosisArthur Skarin MD Consultant Editor
Queen Mary Hospital, The University of Hong Kong, Hong Kong A 62-year-old man presented with a 6-month history of fever of unknown origin (FUO), dyspnea, and weight loss. Physical examination showed fever, pallor, and tachypnea but no hepatosplenomegaly or peripheral lymphadenopathy. Results of extensive investigation for FUO, including tests for infection, malignancy, and autoimmune disease, were negative. The complete blood picture showed a hemoglobin level of 10 g/dL (normal range [NR], 13 to 18 g/dL), platelet count of 50 x 109/L (NR, 150 to 400 x 109/L), and leukocyte count of 2.7 x 109/L (NR, 4 to 11 x 109/L), with normal differential. The serum lactate dehydrogenase level was 1,367 u/L (NR, < 400 µm/L). Serum albumin and globulin levels were 26 g/L (NR, 42 to 54 g/L) and 41 g/L (NR, 24 to 36 g/L). Serum bilirubin and transaminase levels were normal. Serology for human immunodeficiency virus was negative. Bone marrow biopsy showed hypocellular marrow without abnormal cellular infiltration. A chest x-ray (CXR) showed a small left pleural effusion but no parenchymal abnormality. However, he became progressively tachypnoeic and hypoxemic with type 1 respiratory failure (PO2, 7.1 Kpa [NR, 10.6 to 14.0 Kpa], PCO2, 3.8 KPa [NR, 4.6 to 6.0 Kpa]). Lung function tests showed a markedly decreased diffusing capacity of 6.1 mL/min/mmHg (30% predicted). A contrast-enhanced computed tomographic (CT) scan of the thorax showed bilateral, subpleural, wedge-shaped, subsegmental opacities, some of which were ground glass, suggestive of peripheral infarction in the apical, posterior, and anterior segments of the upper lobes, including the lingula segment (Fig 1A and 1B). No thrombi were seen in the central and segmental pulmonary arteries. Small bilateral pleural effusions were also noted. A ventilation-perfusion (V/Q) scan showed a mismatched segmental defect in the posterior segment of right upper lobe, with multiple subsegmental and nonsegmental perfusion defects in the upper lobes of both lungs. A Doppler ultrasound of the legs did not reveal evidence of deep vein thrombosis. An electrocardiogram showed sinus tachycardia only. A CT scan of the abdomen did not reveal any organomegaly or intra-abdominal lymphadenopathy.
Despite treatment with multiple broad-spectrum antibiotics and antifungal therapy, the patient died 1 month after admission. Postmortem biopsies of the lung showed diffuse intravascular infiltration by medium-sized tumor cells with ovoid hyperchromatic nuclei, distending capillaries within alveolar septa, and interstitial venules (Fig 2A and 2B). Similar infiltration was seen within the portal vein branches in the liver parenchyma and focally within capillaries in the myocardium. The tumor cells were immunoreactive for leukocyte common antigen (LCA) and B-cell marker L26 (CD20) (Fig 3) but were negative for T-cell marker CD3. In situ hybridization for Epstein-Barr virus–encoded RNA was negative. Polymerase chain reaction of the DNA extracted from the lung tissue for immunoglobulin heavy-chain gene rearrangement showed a monoclonal band, which measured 118 base pairs (Fig 4). On the basis of these findings, the diagnosis of intravascular lymphomatosis (IVL) was made.
Since first described as systemisierten endotheliomatose by Pfleger and Tappeiner in 1959,1 there have been more than a hundred cases of IVL reported in the literature.2-4 Although an endothelial origin has been suspected originally, immunoreactivity for LCA (CD45) and lineage (B or T cell) markers reveals the lymphoid origin of the disease, which is further confirmed by the demonstration of monoclonality by light-chain restriction and gene rearrangement studies.2,5 IVL is characterized by neoplastic proliferation of lymphoid cells within the lumen of capillaries, small veins, and arteries.1,3,4 Clinically, the majority of patients present with FUO or pulmonary, CNS, or cutaneous manifestations.3,4 Although the lung is involved in approximately 60% of cases at autopsy regardless of the site of initial clinical presentation,6,7 primary pulmonary presentation in IVL is rare. The diagnosis of IVL in our case was based on the presence of lymphoma cells exclusively in the intravascular compartment and immunoreactivity for LCA and CD20. The diagnosis was confirmed by the demonstration of monoclonality. The major pathologic differential diagnoses included angiocentric lymphoma and intravascular carcinomatous emboli.8 The lack of prominent perivascular and vessel wall infiltration and the absence of central necrosis helped to differentiate IVL from angiocentric lymphoma. On the other hand, intravascular carcinomatous emboli can be distinguished from IVL by the cohesiveness of carcinoma and immunoreactivity with cytokeratin. Radiologically, the majority of cases with pulmonary IVL were reported to have diffuse interstitial infiltrates or opacities on CXR,4,9,10 in contrast to our case. V/Q or perfusion scans usually show multiple mismatched perfusion defects consistent with pulmonary embolism,5,7,11 similar to our case. The normal CXR seen in our patient is consistent with the early presentation of pulmonary embolism, particularly if the obstructing lesions were lodged in small, subsegmental peripheral arteries. The CT appearance of peripheral wedge-shaped opacities in our case was highly suggestive of peripheral lung infarction and concurred with the V/Q findings of occlusion of pulmonary vasculature. Clinical diagnosis of IVL, however, still remains evasive because of the nonspecific systemic symptoms, the usual lack of extravascular tissue infiltration, and thus the late tissue diagnosis. Indeed, in a recent review of 86 patients with IVL, almost half were diagnosed at postmortem,2,3 and the median survival of those diagnosed antemortem was only 5 months. However, occasional prolonged remissions of up to 9 years have been reported with combination chemotherapy.2 Therefore, a high degree of awareness of this diagnosis and early tissue diagnosis are of paramount importance. REFERENCES 1. Pfleger L, Tappeiner J: Zur kenntnis der systemisierten endotheliomatose der cutanen blutgefaße (reticuloendotheliose). Hautarzt 10: 359-363, 1959[Medline] 2. Domizio P, Hall PA, Cotter F, et al: Angiotropic large cell lymphoma (ALCL): Morphological, immunohistochemical and genotypic studies with analysis of previous reports. Hematol Oncol 7: 195-206, 1989[Medline]
3.
DiGiuseppe JA, Nelson WG, Seifter EJ, et al: Intravascular lymphomatosis: A clinicopathologic study of 10 cases and assessment of response to chemotherapy. J Clin Oncol 12: 2573-2579, 1994 4. Stroup RM, Sheibani K, Moncada A, et al: Angiotropic (intravascular) large cell lymphoma. Cancer 66: 1781-1788, 1990[Medline] 5. Kamesaki H, Matsui Y, Ohno Y, et al: Angiocentric lymphoma with histologic features of neoplastic angioendotheliomatosis presenting with predominant respiratory and hematologic manifestations. Am J Clin Pathol 94: 768-772, 1990 [Medline] 6. Wick MR, Mills SE, Scheithauer BW, et al: Reassessment of malignant angioendotheliosis: Evidence in favor of its reclassification as intravascular lymphomatosis. Am J Surg Pathol 10: 112-123, 1986[Medline]
7.
Snyder LS, Harmon KR, Estensen RD: Intravascular lymphomatosis (malignant angioendotheliomatosis) presenting as pulmonary hypertension. Chest 96: 1199-1200, 1989 8. Wick MR, Mills SE: Intravascular lymphomatosis: Clinicopathologic features and differential diagnosis. Semin Diagn Pathol 8: 91-101, 1991[Medline] 9. Yousem SA, Colby TV: Intravascular lymphomatosis in the lung. Cancer 65: 349-353, 1990[Medline]
10.
Tan TB, Spander PJ, Blaisse M, et al: Angiotropic large cell lymphoma presenting as interstitial lung disease. Thorax 43: 578-579, 1988 11. Demirer T, Dail DH, Aboulafia DM: Four varied cases of intravascular lymphomatosis and a literature review. Cancer 73: 38-45, 1994
This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2000 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
