40% of non-Hodgkin lymphomas occur in extranodal sites. Of these, the majority are diffuse large B-cell lymphomas. Of the small B-cell non-Hodgkin lymphomas, the majority are extranodal marginal zone B-cell lymphomas of mucosa associated lymphoid tissue (MALT lymphomas) (6). 50% of MALT lymphomas are located in the gastrointestinal tract, and 85% of the GI MALT lymphomas are found in the stomach. Both lung and salivary gland are sites of involvement in approximately 14% of cases. Ocular adnexa (12%) and skin (11%) are also common sites. Thyroid and breast are affected in 4%. Most cases occur in older adults, with an average age of 61, and a slight female predominance (3).
MALT lymphomas arise in locations typically devoid of lymphoid tissue. In the case of gastric lymphoma, Helicobacter pylori infection may stimulate lymphoid proliferation in which lymphoma subsequently develops. In the skin, an association between MALT lymphoma and Borrelia burgdorferi infection has been reported. In thyroid and salivary gland MALT lymphomas, autoimmune disease is common. Patients with Sjogren syndrome or lymphoepithelial sialadenitis have a 44-fold increased risk of developing lymphoma, and 94% of thyroid lymphomas show evidence of thyroiditis in the adjacent gland (3).
Immunophenotypically, the classic MALT lymphoma is positive for B-cell markers CD20 and CD79a and negative for BCL-6 and CD10. CD43 may be positive or negative, but if positive, aberrant expression is useful in distinguishing a neoplastic from a reactive process. All but rare cases are negative for CD5, and in the rare positive cases, negative cyclin D1 allows distinction from mantle zone lymphoma. Light chain restriction is demonstrated which is most commonly IgM and less often IgA or IgG (3).
The most common chromosomal abnormality observed in MALT lymphoma is trisomy 3 which is reported in 30 - 60% of cases (5). t(11;18)(q21;q21) is seen in 25-50% of cases of gastric and pulmonary MALT lymphomas, and less frequently when other sites are involved. t(11;18)(q21;q21) involves the apoptosis regulator gene API2 and MALT1, a paracaspase. The API2-MALT1 fusion product activates a transcription factor involved in lymphocyte activation and survival. In gastric MALT lymphoma, H. pylori eradication leads to regression of MALT lymphoma in over 50% of cases, however, the presence of t(11;18)(q21;q21) is associated with failure to respond to H. pylori eradication and disease progression.
MALT lymphomas are generally indolent tumors, and bone marrow involvement and disseminated disease are rare. In a study of 159 patients with MALT lymphoma, 31 (20%) had bone marrow involvement, 19 (12%) had spread to another extranodal site, and 12 (7.5%) had distal nodal involvement. Furthermore, the authors observed that dissemination of disease did not alter clinical outcome (5). Surgical resection is often the treatment of choice, however microscopic multifocal mucosal disease may be present. Therefore, patients must be closely monitored for both local and distant recurrence. In ocular MALT lymphoma, radiotherapy is generally considered the treatment of choice (5).
Our case is an extremely rare example of a primary esophageal MALT lymphoma. Primary lymphoma of the esophagus, of any type, accounted for only 3 of 1467 cases of extranodal lymphomas reported by Freeman and colleagues in a large study published in Cancer in 1972 (6). A search of the recent literature yields only four case reports. The first case involved a 74 year-old man with a connective tissue disorder who had a submucosal MALT lymphoma discovered by EGD. He was H. pylori negative and achieved complete remission with radiation therapy (4). In the second case, an 83 year-old woman underwent endoscopy for heartburn, and two asymptomatic submucosal tumors were discovered and subsequently diagnosed as MALT lymphoma. She underwent endoscopic resection and was disease free after 22 months. She was also H. pylori negative (2). The third case involved a 61 year-old H. pylori positive man with autoimmune thyroiditis who was incidentally discovered to have a MALT lymphoma involving the submucosa and lamina propria of the esophagus. Surgical resection was performed, but no follow-up provided (1). The most recently published case involved an asymptomatic 49 year-old man with a bulbous mass discovered at endoscopy that was later resected and diagnosed as a MALT lymphoma (7). As for our patient, with the exception of periodic dilatations for stricture, she continues to do well more than a year after esophagectomy. Biopsies of the anastomosis site and fundus showed no evidence of lymphoma.
Contributed by Amy Davis, MD and Fiona Craig, MD