Primary Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma in a Patient With Acquired Immune Deficiency Syndrome

Discussion

MALT lymphoma was first described by Issacson and Wright in 1983, in the gastrointestinal tract. In the latest World Health Organization classification,⁵ MALT lymphoma belongs to the marginal-zone lymphomas but is distinguished from the nodal and splenic forms by its different clinical behavior and cytogenetic characteristics. These tumors occur most commonly in the gastrointestinal tract, but they have been reported in other organs, including the salivary gland, head and neck, ocular adnexa, skin, thyroid, and breast.⁶ There are only a few case reports of pulmonary MALT lymphoma. Its pathogenesis is unclear, but chronic antigenic stimulation, as in autoimmune diseases, smoking, and infection, has been hypothesized as a trigger,⁷ which suggests that dysregulation of T cell function may be involved.

Similar mechanisms may be in play in HIV-positive patients who develop MALT lymphomas. In HIV-positive patients, some case reports and small series have reported MALT lymphomas at various sites, including the stomach, intestine, and thyroid gland, with secondary involvement of the lungs,⁸ but there are only rare reports of primary MALT of the lung in immunocompromised patients with AIDS.⁹

MALT lymphoma of the lung is most commonly diagnosed around age 60, possibly due to its slow growth and occult behavior, but there have been a few cases reported in the young. Our patient presented at age 51, which might be due to his altered immunity from HIV infection. Pulmonary MALT lymphoma patients are usually asymptomatic or have non-specific complaints, and the disease is often detected on routine chest radiograph. Symptomatic patients can present with cough, sputum, hemoptysis, chest pain, and/or moderate fever. Our patient had similar symptoms and physical signs, which contributed little to the diagnosis. The appearance of MALT lymphoma on plain chest radiograph is highly heterogeneous, but characterized by consolidation and well defined mass or reticulonodular pattern.² Computed tomogram usually shows findings that are parenchymal, peripheral, predominantly in the lower zones, and bilateral/multiple.¹⁰ Pulmonary masses or consolidation or nodules, peribronchial or bronchovascular distribution, air bronchograms, dilated airways within the consolidated lung mistaken for cavitation, and pleural effusion have been described. Hilar or mediastinal lymphadenopathy is less common and suggests disseminated disease.^9,10 Our patient had bilateral lower lobe involvement with consolidation and subpleural/interseptal thickening.

Bronchoalveolar lavage fluid (BALF) shows predominance of lymphocytes, and flow cytometric analysis helps differentiate it from reactive lymphocytic proliferation. Screening for monoclonal IgG in BALF supernatant (via immunoelectrophoresis) and restricted membranous or intracytoplasmic Ig light-chain expression (via slide immunohistochemistry) may be useful for diagnosis.¹¹ The absence of a dominant B-cell clone in BALF could help dismiss invasive investigations of pulmonary lesions. In our patient, BALF was inconclusive. Histology of surgical biopsy is diagnostic in most cases. The biopsy can usually be via percutaneous transthoracic needle, but occasionally video-assisted thoracoscopic or open-lung biopsy is needed, as in our patient. The lymphoma cells are small to medium size, with irregular nuclear membranes, inconspicuous nucleoli, and moderate amounts of pale cytoplasm admixed with plasma cells, which predominantly infiltrate the marginal zone. In glandular tissues, the epithelium is often invaded by aggregates of lymphoma cells, resulting in lymphoepithelial lesion. These clonal cells express B-cell markers (CD20 and CD79a) with light-chain restriction, but are negative for T cell markers, CD5, CD10, CD23, and cyclin D1. The tumor cells usually show immunoglobulin heavy-chain rearrangement, via molecular studies.^3,11

Localized MALT lymphoma has a good prognosis; the 5-year survival rate is > 80%. There is no consensus on treatment. There is no identified culprit antigen in the lung, contrary to the stomach (Helicobacter pylori), so antibiotics effective on low-grade localized gastric lymphoma are inappropriate. The treatment options are surgery, chemotherapy, and radiotherapy. Owing to a lack of comparative series, some authors have proposed watchful waiting, as we did in our patient.¹² Occasionally, transformation to high-grade primary pulmonary lymphoma has been reported.

Surgical resection is preferred for localized tumors.¹³ Chemotherapy is generally used for patients with bilateral or extrapulmonary involvement, relapse, or progression. Combination regimens, such as cyclophosphamide, adriamycin, oncovin, and prednisone (CHOP), have not shown higher response rates than single-agent regimens with chloraminophene, cyclophosphamide, Azathioprine, or steroid.^12,13 Radiotherapy is rarely used. The effect of anti-retroviral therapy on MALT lymphoma in patients with coexisting AIDS is not known.

With aggressive support and highly active anti-retroviral therapy for AIDS, HIV-positive patients are living longer, so it is likely that more cases of MALT and low-grade lymphoma will occur in these patients. Our case suggests that primary MALT lymphoma can be an early manifestation of AIDS or possibly that a latent primary pulmonary lymphoma can be unmasked by HIV infection. Thus, it is important to be sensitized to rare diagnoses such as these, because with time the biologic behavior of these lesions may become evident. The possibility of low-grade and MALT types of lymphoma should be considered when biopsy shows a dense small lymphocytic infiltrate in an HIV-positive patient. Immunologic and molecular analysis of tissue has a critical role in establishing the diagnosis.