Asian Cardiovasc Thorac Ann 2001;9:344-346
© 2001 Asia Publishing EXchange Pte Ltd
Pseudolymphoma of the Lung: Benign or Malignant?
Rana Sandip Singh, MCh,
Rajinder Singh Dhaliwal, MCh,
Pradeep Bambery, MD1,
Nandita Kakkar, MD2
Department of Cardiovascular and Thoracic Surgery
1 Department of Internal Medicine
2 Department of Histopathology Postgraduate Institute of Medical Education and Research Chandigarh, Punjab, India
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For reprint information contact: Rana Sandip Singh, MCh Tel: 91 172 74 7585 Ext. 400 Fax: 91 172 74 4401 email: medinst{at}pgi.chd.nic.in Department of Cardiovascular and Thoracic Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, Punjab 160012, India.
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ABSTRACT
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Pseudolymphoma of the lung has been considered benign, premalignant, or frankly malignant. A case that responded to simple surgical resection is described. The patient remained well during a follow-up of more than 10 years.
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INTRODUCTION
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Pseudolymphomas of the lung are rare lesions of unknown etiology. They have been considered to be a stage in a chronic inflammatory process with lymphocytic predominance, a "pre-lymphoma," or an intermediate phase between hyperplasia and lymphoma. Saltztein1 opined that these inflammatory pseudolymphomas could be separated from true lymphomas on the basis of histologic criteria. However, subsequent reports high-lighted the difficulties in establishing the distinction between these two as clinical, radiologic, and histologic features tend to overlap. Isaacson and Spencer2 reported that extranodal lymphoid hyperplasia, previously known as pseudolymphoma, is not a reactive process but a distinct clinical entity: malignant lymphoma of mucosa-associated lymphoid tissue. This opinion was supported by molecular genetic and cytogenetic studies.3
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CASE REPORT
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A 41-year-old male nonsmoker, a known case of childhood asthma, presented with moderate fever of 10 days duration and pleuritic chest pain on the left side. The fever did not respond to antibiotics and antimalarials. He had diffuse bilateral rhonchi. Radiography showed bilateral lym-phadenopathy, blunting of the left costophrenic angle, increased radiolucency of the left lower zone, and pleural thickening. All hematological and other laboratory investigations, including sputum culture and acid-fast bacilli staining, were negative. The patient was given antituberculosis agents, but irregular low-grade fever and pain persisted. New left middle and lower zone opacity with obliteration of the left cardiac silhouette and regression of hilar lymph nodes was noted on radiography 4 months later (Figure 1
). A transbronchial lung biopsy showed nonspecific histopathology. Antitubercular treatment was continued for another 7 months but the opacity persisted and the patient, who had lost 8 kg in weight, was readmitted. His erythrocyte sedimentation rate was 75 mm in the 1st hour (versus 6 mm during the first admission); fungal serology and immunological tests including antinuclear factor and rheumatoid factor were negative. Fiberoptic bronchoscopy revealed edema of the lingular bronchus but no growth could be seen. Fine-needle aspiration cytology of the lesion showed polymorphs, macrophages, and lymphocytes with no evidence of malignancy. Because of the lack of a definitive diagnosis, surgical resection of the lingular segment was undertaken. Grossly, the lingular lobe was congested with patchy pleural thickening. The cut section showed multiple whitish foci. Histopathologically, the lesion showed extensive atelectasis, fibrosis, and hyperplasia of the submucosal lymphoid tissue, forming large follicles with well-defined germinal centers and hyalinized vessels in the center. Sheets of histiocytes, some with foamy cytoplasm, were seen mixed with lymphocytes, eosinophils, and plasma cells in the background. The bronchiolar lumen was filled with a similar exudate (Figure 2). The vessels showed fibrous intimal hyperplasia, thus a diagnosis of pseudolymphoma was made. The patient has been regularly followed up for more than 10 years, and has remained well except for his asthmatic symptoms.
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Figure 2. Photomicrograph showing replacement of the lung parenchyma by lymphoid tissue forming large follicles, some with germinal centers. A mixed inflammatory infiltrate composed of lymphocytes, plasma cells, eosinophils, and fibrosis is seen in the background (hematoxylin and eosin stain, original magnification x180).
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DISCUSSION
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Lymphocytic pulmonary infiltrates, whether or not associated with Sjögren's syndrome, are considered benign if histologically they show the presence of geminal centers and a mixed character of cellular infiltrate with many plasma cells. The lack of hilar lymph node involvement has been reported as the most reliable difference between pseudolymphoma and true malignant lymphoma.1 However, histopathologic criteria alone may fail to predict the evolution of the disease, and ultimate diagnosis may be made only by the subsequent clinical course. Lesions with features of benign pseudolymphomas of the lung occasionally do not respond to therapy and tend to relapse or are followed by malignant lymphoprolifera-tive disorders. Not infrequently, patients with primary malignant pulmonary lymphomas are cured solely by excision of the lesion.4 Marchevsky and colleagues5 proposed that patients with nodular lymphoid infiltrates be divided into 2 groups: those with features of lymphoma limited to the lung or pseudolymphoma; and those with primary malignant lymphoma of the lung, involving extrapulmonary structures. This simple classification separated 2 groups of patients with different prognoses until new diagnostic criteria were developed.
Immunoperoxidase staining has been proposed to predict the benign or malignant potential of these lesions, but results so far have been inconclusive. Immunologic determination of clonality may be diagnostically definitive, with the monoclonal pattern tending to predict malignant potential, while the benign process is considered polyclonal.6 Holland and colleagues7 radiologically followed up 4 cases of pseudolymphoma (confirmed by clonality) for a period of 4 to 9 years and found that the opacities showed gradual expansion without cavitation, calcification, or pleural involvement, but no malignant change occurred during this period. Currently, clinical application of genetic engineering is attracting attention. Gene analysis has been suggested as a valuable means of differentiating tumor-related lymphocyte proliferation from reactive proliferation. This also has a role in defining whether proliferating cells are from T or B cells. Patients with pseudolymphoma show rearranged bands for the H-chain.8
From a clinical viewpoint, it is more important to determine the extent of involvement by the disease. Patients with lymphoma involving the lung only and pseudolymphoma, have good long-term prognosis (as in the present case), although the possibility of recurrence or the development of additional lymphoproliferative disorder cannot be ruled out. There is certainly no merit in giving chemotherapy or radiotherapy to patients undergoing lung resection for localized lymph nodules involving the lung, as initial treatment to prevent recurrence.
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REFERENCES
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Saltztein SL. Pulmonary malignant lymphomas and pseudolymphomas: classification, therapy and prognosis. Cancer
1963;16:928–55.
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Isaacson PG, Spencer J. Malignant lymphoma of mucosa-associated lymphoid tissue. Histopathology
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Itoyama T, Sadamori N, Ichimaru M, Senju R, Hirota M, Yoshida T, et al. Evidence for neoplasia in "pseudolymphoma" of lung. Lancet
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Jelsrud RR, Li BCY, Rosenow EC, Crowe JK. Pulmonary process of mature appearing lymphocytes. Pseudolymphoma, well-differentiated lymphocytic lymphoma and lymphocytic interstitial pneumonia. Radiology
1978;127:289–96.[Abstract]
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Marchevsky A, Padilla M, Kaneko M, Kleinerman J. Localised lymphoid nodules of lung. Cancer
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Koss MN, Hochhozer L, Nicholas PW, Wehunt WD, Lazarus AA. Primary non-Hodgkin's lymphoma and pseudolymphoma of lung: a study of 161 patients. Hum Pathol
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Holland EA, Ghahremani GG, Fry WA, Victor TA. Evolution of pulmonary pseudolymphomas: clinical and radiologic manifestations. J Thorac Imaging
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Shiota T, Chiba W, Ikeda S, Nobuhiro I. Gene analysis of pulmonary pseudolymphoma. Chest
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ABSTRACT
INTRODUCTION
