Mucosa-Associated Lymphoid Tissue Lymphoma of the Lung With Cold-reacting Autoantibody-mediated Hemolytic Anemia – Case Report
The primary mucosa-associated lymphoid tissue lymphoma (MALToma) of the lung is a rare low-grade В cell lymphoma arising from bronchus-associated lymphoid tissue which had been regarded as pseudolymphoma. It has characteristic histologic findings with monoclonal В cells of centrocytelike lymphoid cells and a lymphoepithelial lesion. This is a case report of MALToma of the lung and cold-reacting autoantibody-mediated hemolytic anemia. To our knowledge, there is no other report of such an association in the English-language medical literature. A morphologic and immunohistologic analysis of the case demonstrates the variety of distinctive histologic features ascribed to low-grade lymphoma of pulmonary MALT, which is consistent with the histologic details of MALToma arising from a variety of other glandular epithelial tissues.
A 39-year-old Chinese woman was admitted to National Taiwan University Hospital in May 1992 with a 2-year history of chronic productive cough accompanied by yellowish sputum. The chest radiograph showed diffuse alveolar consolidations in both lungs (Fig 1). The patient had received antituberculosis therapy for 1 year without improvement in 1991. She had been hospitalized elsewhere without a definite diagnosis, even by transbronchial lung biopsy, 1 year prior to admission. Dyspnea and intermittent fever gradually developed in addition to the productive cough.
On admission, the woman was pallid and dyspneic, with low-grade fever and peripheral cyanosis. Bronchial sounds and inspiratory crackles were audible in both lower lung fields. There was neither lymphadenopathy nor hepatosplenomegaly. The chest computed tomographic scan revealed extensive peribronchial infiltration along the major branches of the bronchi and alveolar consolidations in the right middle and bilateral lower lobes. The blood clotted easily after it was drawn in the syringe at room temperature. The RBC count was 195X lOVjxl; hemoglobin value, 8.6 g/dl; mean corpuscular volume, 118цЛ reticulocytes, 12.8 percent; WBC count, 8,700/it 1, with 68 percent segmented neutrophils, 6 percent eosinophils, 2 percent basophils, 6 percent monocytes, and 18 percent lymphocytes. The serum lactic dehydrogenase level was 1,150 U/L (normal, less than 460 U/L), bilirubin value, 2.1/0.5 mg/dl; and haptoglobin level, less than 5 mg/dl (normal, 200 to 400 mg/dl). The remaining serum hepatic enzymes, as well as the serum ferritin level, were within normal limits. The Coombs’ test was positive. The titer of cold agglutinin was greater than 1:1,024 at 4°C and negative at 37°C; the serum cryoglobulins and antinuclear antibody titer were normal. Serum immunoelectrophoresis revealed a small spike in the gamma region with increased IgM (734 mg/dl), low IgG (752 mg/dl), and normal IgA (37 mg/dl) levels. Immunofixation electrophoresis demonstrated IgM (\) monoclonal gammopathy. The arterial blood gas analysis showed PaO, to be 50.9 mm Hg, with 5 L/min Ov The patient had become less dvspneic, with the PaO, level increasing to 93.7 mm Hg after administration of prednisolone, 80 mg daily for 3 weeks.
An open-lung biopsy from the right middle lobe was performed on the 28th day of hospitalization. Histologic examination of the lung specimen showed malignant lymphoma composed of small angulated lymphoid cells diffusely infiltrating the lung tissue. The most characteristic finding was the scattered lvmphepithelial lesions, a feature characteristic of the mucosa-associated lymphoid tumor (Fig 2). Immunophenotypic studies performed on freshly frozen tissue revealed that the lymphoid cells were positive for CD19, CD20, and IgM (\[bFig 3]), but negative for CD3, CD4, and CD5, results which w’ere consistent with an immunophenotype of MALToma. Chemotherapy with cyclophosphamide, vincristin, and prednisolone was instituted 10 days after surgery. The general condition improved except for steroid-induced myopathy. The hemoglobin level, serum lactic dehydrogenase, and bilirubin levels returned to normal limits, while the cold agglutinin titer still remained high (1:1,024) in spite of treatment. This patient continues to be well to the present.
Figure 1. Roentgenogram showing diffuse alveolar consolidation in both lung fields.
Figure 2. Low-grade В-cell lymphoma of MALT composed mainly of centrocvte-like cells with irregular nuclei and pale cytoplasm. Clusters of tumor cells are seen between epithelial cells, the so-called lvmphoepithelial lesion (arrowheads) (hematoxylin-eosin, original magnification X 400).
Figure 3. Low-grade В-cell lymphoma of the MALT with positive immunoreaction for \ light chain (brown color in the cytoplasm by immunoperoxidase stain, original magnification X 1,000).