Mucosa-Associated Lymphoid Tissue Lymphoma of the Lung With Cold-reacting Autoantibody-mediated Hemolytic Anemia – Discussion
The concept of MALToma was first described bv Isaacson and Wright2 in a patient suffering from immunoproliferative intestinal disease and low-grade primary В cell lymphoma of the stomach in 1983. The distinct clinicopathologic entity was later extended to include low-grade В cell lymphoma arising from other mucosal organs including the bronchus, salivary gland, thyroid gland, thymus, orbital organs, bladder, and female genital tract. Pulmonary MALToma is very rare and often difficult to diagnose. It may have a mixed population of small lymphocytes and plasma cell infiltration at the submucosal area, even associated with germinal center formation. Usually it is misdiagnosed as a pseudolymphoma. However, demonstration of typical angulated centrocyte-like lymphoid cells and lymphoepithelial lesions would be characteristic for histologic diagnosis of a MALToma. The dominant component is a diffuse infiltrate of small-to-intermediate-sized В lymphoid cells with irregular nuclei and pale to clear cvtoplasma, which are called “centrocytelike cells” or “monocytoid В cells.” Lymphoid follicles are scattered throughout the infiltrate, which may be distorted or even overrun by the surrounding centrocyte-like cells. Immunohistochemical staining establishes the presence of \ or к light chain restriction within the infiltrate of mono-typic В cells.
Li et al reviewed 62 cases of primary lymphoma of the lung in 1990. There were 38 patients with primary pulmonary MALToma. Most of the patients with MALToma of the lung are asymptomatic (21 of 38), and others present with a long and indolent course characterized by fatigue, body weight loss, night sweats, dyspnea, cough, or pleuritic pain. The roentgenograms were nonspecific: solitary or multiple nodules, or multiple infiltrates with poorly defined borders. In this patient, the roentgenogram showed diffuse alveolar consolidation.
Autoimmune hemolytic anemia of the cold antibody is a well-known, though rare, complication of non-Hodgkin’s lymphoma. Among 78 patients with persistent abnormal cold agglutinin levels, 31 had В cell lymphoma. The histologic type of these lymphomas was reported in 18 patients: diffuse lymphocytic, poorly or well differentiated in 9; histiocytic lymphoma in 7; and nodular lymphocytic in 2 patients. To our knowledge, there have been no reports of MALToma associated with autoimmune hemolytic anemia in the English-language medical literature.
The cold autoantibodies responsible for hemolysis, as a rule of monoclonal IgM, are directed against antigens of the li system, although an anti-P specificity also has been reported. The light chains may be of the к or X type. In our case, the specificity of the cold agglutinins was anti-I type. Immunohistochemical staining also established the presence of X light chain restriction within the infiltrate of monotypic В cells.
The mechanism of high titer of cold agglutinin in a low-grade В cell MALT lymphoma has not been established, and it is uncertain whether the cold agglutinin is secreted from there. However, in this patient, a X light chain restriction was observed in the tumor cells and IgM (X) monoclonal gammopathy in serum immunoelectrophoresis. The monoclonal gammopathy and hemolytic anemia responded to steroid treatment, suggesting that these autoantibodies were possibly released from these low-grade В cell MALTomas.
The MALTomas usually are localized at presentation and show an indolent clinical course with a relatively favorable prognosis. They often respond well to local therapy, such as surgery, radiation therapy, or systemic chemotherapy with steroids and cytoxic agents.