Hematopathology Case Studies


CASE 8: MALToma


Clinical History:

A 60-year-old woman has had worsening nausea and vague epigastric abdominal pain for the past 6 months. She has tried taking calcium containing antacids without relief. She does not report hematemesis. On physical examination there are no abnormal findings. Laboratory studies show Hgb 13.5 g/dL, Hct 43.7%, MCV 87 fL, platelet count 303,600/microliter, and WBC count 8050/microliter. An upper GI endoscopy is performed and there is diffuse erythema of the gastric mucosa along with a 3 x 4 cm area of nodular, raised antral mucosa that lacks rugal folds and has focal erosions. Biopsies are taken. A CT scan of the chest and abdomen shows focal antral thickening, but no lymphadenopathy, hepatomegaly, or splenomegaly. A bone marrow biopsy is unremarkable. She has a positive urea breath test.
  1. What is the organism identified in adjacent gastric mucosa?

    2. The short, curved rods in the gastric mucus are Helicobacter pylori organisms. This organism produces urease, and this accounts for the positive urea breath test.

  2. What is the diagnosis?

    3. This is a variant of a marginal zone lymphoma known as a mucosa-associated lymphoid tissue (MALT) tumor, or MALToma. They are CD19 and CD20 positive, typical for B cell proliferations, but they are CD5 and CD10 negative. The tumor cell infiltrates are heterogenous and can resemble follicular center cells, small lymphocytes, or monocytoid cells. Scattered lymphoblasts are common. The tumor cells often invade into gastric glands. A local immune response is suggested by the presence of scattered blasts and plasma cells.

  3. How does this lesion arise?

    4. MALTomas arise in places where there has been chronic inflammation with either autoimmune or infectious processes. The process begins as a polyclonal immune response. Within this setting a monoclonal proliferation can arise, but it may still require CD4 cell stimulation from inflammation to continue. Late in the course, the lesion may transform to a more aggressive B cell neoplasm. Thus, chronic gastritis from H. pylori infection drives MALToma of the stomach. Some gastric MALTomas have t(11;18) which fuses the inhibitor of apoptosis (API2) gene to the MALT 1 (MLT) gene and generates a chimeric fusion protein that increases nuclear factor-kB (NF-kB) activation.

    Other examples include Hashimoto thyroiditis, which may give rise to B cell proliferation in the thyroid. A MALToma may arise in a salivary or lacrimal gland involved with Sjogren syndrome.

  4. How could her illness be treated?

    5. Treating the H.pylori infection can take away the stimulus for B cell proliferation, and the lesion may regress. However, MALTomas with t(11;18) are less likely to respond to H. pylori eradication therapy, are more likely to present with advanced stage disease, but are unlikely to develop secondary chromosomal abnormalities and transform into diffuse large cell lymphoma. A standard choice for H. pylori eradication therapy includes a combination of omeprazole, amoxicillin, and clarithromycin for 10 to 14 days.