Mucosa-associated lymphoid tissue (MALT) lymphomas are the extranodal subset of marginal zone B-cell lymphomas, representing less than 8% of all types of lymphomas and 5% of newly diagnosed non-Hodgkin's lymphoma [1]. MALT lymphomas are generally low grade and follow an indolent course. In the Revised European–American Classification of Lymphoid Neoplasms and World Health Organization classifications, MALT lymphomas are categorized as the most common type of marginal zone B-cell lymphoma. These lymphomas typically arise in locations with limited lymphoid tissue in the setting of chronic inflammation such as Helicobacter pylori–associated chronic gastritis, follicular bronchiectasis in the lung, and Hashimoto thyroiditis. The extranodal sites that are typically affected include the stomach, small bowel, lung, eye, and salivary glands [2–4]. Histologically, MALT lymphoma is characterized by neoplastic marginal cells that display variable-combination colonization of reactive germinal centers, plasmacytic differentiation, and destructive epithelial infiltration that form lymphoepithelial lesions [5].

On low-power microscopy of a histologic specimen, MALT lymphoma is characterized by expansion of the marginal zone with preservation of the lymphoid follicles (Fig. 1A, 1B, 1C, 1D, 1E). At high power, polymorphous infiltrate of small round lymphocytes, monocytoid or plasmacytoid lymphocytes, and lymphoepithelial lesions are typically observed.

Characteristic findings in immunophenotyping are important in differentiating MALT lymphoma from other low-grade non-Hodgkin's lymphoma and include leukocyte common antigen positive (+), CD20⁺, CD79a⁺, CD5^–, CD10^–, and CD23^– (Fig. 1A, 1B, 1C, 1D, 1E) and the presence of λ and κ light-chain restriction. Often, MALT lymphoma is diagnosed by exclusion of other small B-cell lymphomas. For example, follicular lymphoma shows CD10⁺; small lymphocytic lymphoma shows CD5⁺ and CD23⁺ and mantle cell lymphoma shows CD5⁺, CD23⁺ and cyclin D1⁺. Biopsy of the lesion, immunophenotypic analysis, and cytogenetic studies are therefore essential to establish the correct diagnosis [6, 7].

MALT lymphoma usually presents as localized disease but characteristically disseminates either within the same organ or to other extranodal sites in which MALT lymphomas are known to arise [6]. There are two types of MALT lymphomas in disparate organs not corresponding to the peripheral sites of the immune system: One is the native type consisting of lymphoid tissue physiologically present in the gut (e.g., Peyer patches), and the other is acquired MALT lymphoma that develops in sites of chronic inflammation in response to either infectious conditions (e.g., H. pylori gastritis) or autoimmune processes (e.g., Hashimoto thyroiditis). These prolonged lymphoid reactive proliferations lead to the growth of a pathologic clone that progressively replaces the normal lymphoid population, resulting in a MALT lymphoma [5].

Pretreatment evaluation routinely includes endoscopy of the gastrointestinal tract with endoscopic ultrasound for gastrointestinal MALT lymphoma and bronchus-associated lymphoid tissue (BALT) lymphoma, which is frequently associated with gastrointestinal tract involvement, pulmonary function test for BALT lymphoma, or imaging of other relevant anatomic sites. PET/CT has a role in primary staging and posttreatment response assessment of MALT lymphoma, but approximately 35% of MALT lymphomas have no ¹⁸F-fluorodeoxyglucose (FDG) uptake; hence, about a third of MALT lymphomas will not be detected by PET/CT [8].

Gastrointestinal tract–associated lymphomas are the most common extranodal lymphoma, accounting for approximately 50% of all MALT lymphomas. Within the gastrointestinal tract, the stomach is the most common anatomic site. The main presenting symptom is persistent epigastric pain, and associated acute bleeding, anemia, and weight loss are commonly present. Endoscopy typically reveals nonspecific gastritis or peptic ulcer, and mass lesions are unusual. It is uncommon for patients to have elevated lactate dehydrogenase level or β₂-microglobulin level [5, 9]. Gastric lymphoma is strongly associated with H. pylori infection [5] and association with Helicobacter heilmannii is also known [3].

Macroscopically, low-grade MALT lymphoma (Fig. 2A, 2B, 2C, 2D) usually has superficially spreading lesions with mucosal nodularity, whereas high-grade MALT lymphoma exhibits a solitary tumor-forming lesion [10] (Fig. 3A, 3B, 3C). The higher the grade, the larger the tumor.

Staging of gastric MALT lymphoma may be performed using a modification, which was proposed by Mushoff, of the Ann Arbor classification [11]. On barium studies, thickened folds and shallow ulcers/erosions can be seen in low-grade MALT lymphoma, but invasion is confined to the submucosa and mucosa. In contrast, high-grade MALT lymphoma is characterized by highly thickened folds with large and deep ulcers that invade beyond the muscularis propria. On CT, low-grade MALT lymphoma usually shows no abnormality or may show minimal gastric wall thickening of 5–10 mm. Three-dimensional CT shaded-surface display may show small depressed lesions with vague margins (Fig. 2A, 2B, 2C, 2D). Perigastric lymphadenopathy is unlikely to be present.

In high-grade MALT lymphoma, CT shows a diffuse, severely thickened wall (> 10 mm) or a focal well-demarcated mass in the gastric wall, and perigastric lymphadenopathy is more likely to be present. Endoscopic ultrasound shows the depth of tumor invasion, which helps distinguish low-grade from high-grade MALT lymphoma, in which an infiltrative hypoechoic mass within the submucosal layer is observed [2]. However, transformation of gastric MALT lymphoma to diffuse large B-cell lymphoma has been recognized, so some of the previously reported high-grade MALT lymphomas might have been diffuse large B-cell lymphomas. Therefore, one should be aware that prior studies about high-grade gastric MALT lymphomas need to be reviewed with caution [12].

The small bowel is the second most common anatomic location of MALT lymphoma (Figs. 4A, 4B and 5A, 5B). Patients commonly present with pain, nausea, vomiting, anemia, weight loss, and fever. There may be a palpable mass, but small-bowel obstruction is uncommon [12]. Association with Crohn's disease and celiac sprue is common, but a precise pathogen has not yet been identified [2]. MALT lymphoma of the colon (Fig. 6A, 6B) is infrequently seen and the presenting symptoms are nonspecific. Polypoid lesions are the most common form, but CT and contrast enema may reveal other forms of lesion including infiltrative, endoexoenteric, and mesenteric invasive forms [12]. Biliary duct involvement (Fig. 7A, 7B, 7C, 7D, 7E, 7F) is also known but is rare [5].

Tables 1 and 2 summarize the CT features of gastrointestinal MALT lymphoma compared with other types of lymphomas and teaching points for the imaging diagnosis of gastrointestinal MALT lymphoma [8, 12, 13].

MALT lymphoma of the lung, also called bronchus-associated lymphoid tissue (BALT) lymphoma, represents 10% of MALT lymphomas and 60% of primary pulmonary lymphomas and is associated with follicular bronchiectasis of the lung. The patient can be asymptomatic or may present with recurrent respiratory infections.

The radiologic features of BALT lymphomas do not differ from those of other pulmonary lymphomas. Most commonly, lesions consist of masses (Fig. 8A, 8B, 8C), masslike areas of consolidation, or pulmonary nodules (Fig. 9). On PET/CT, BALT lymphomas may or may not show increased uptake of FDG [14]. Air bronchograms and enhancing vessels through the masses can be observed. Pleural effusion and thickening, cavitation, and hilar and mediastinal lymphadenopathy are not commonly seen.

Conjunctival and orbital MALT lymphomas mainly involve the eyeball tunicae (30%) and the lacrimal glands (30%) [2]. MALT lymphomas are the most common type of ocular adnexal lymphomas, accounting for up to 80%. Patients typically present with a periorbital swelling or a mass causing insidious, progressive proptosis that is occasionally associated with periorbital edema, decreased visual acuity, motility disturbances, and diplopia. It is commonly associated with a reactive or inflammatory orbital lesion [15]. Radiologically, the most common pattern observed on CT is a uni- or bilateral enhancing mass of the lacrimal glands or other orbital adnexa without bony erosion. On MRI, the lesion typically shows hypointensity on T1-weighted images and slight hyperintensity on T2-weighted images (Fig. 10A, 10B).

MALT lymphoma represents only up to 3.6% of lymphomas arising in the Waldeyer ring [16]. Sites of involvement include the palatine and lingual tonsils, nasopharynx, paranasal sinuses, and base of the tongue. On imaging, the lesion is depicted as asymmetric thickening of the pharyngeal mucosa or a solitary mass [2] (Fig. 11A, 11B).

Other extranodal sites involved in MALT lymphoma include the thyroid, salivary glands, kidney (Fig. 12A, 12B), urogenital tract, liver, pancreas, gallbladder, breast, skin, and intracranial dura [5, 17]. The radiologic features of these lesions are nonspecific, but a mass or nodule is the most common form of presentation.

MALT lymphoma rarely invades adjacent organs, but dissemination to other foci within the original organ and to other MALT-containing organs does occur (Fig. 13A, 13B, 13C, 13D). Disseminated disease appears to be more common in nongastrointestinal MALT lymphomas. This dissemination may be due to the expression of specific homing receptors or to adhesion on the surface of the B cells of MALT [5].

MALT lymphoma is most commonly seen in the stomach, but nongastric MALT lymphoma can occur at various extranodal sites. In patients with known MALT lymphoma, associated lesions in other possible sites should be explored. The radiologist should be aware of this disease entity and add it to the list of differential diagnoses when suggestive lesions are detected on a routine CT examination. It is exceedingly important to differentiate MALT lymphoma from other types of lymphomas because of differences in clinical behavior and management. Radiologic investigation together with histopathologic analysis must be taken into account before making a diagnosis and treatment plan.

We thank Françoise Heran, Paris, France, for providing images for this pictorial essay.

A. Guermazi receives grant support from GE Healthcare and the National Institutes of Health. He is the president of BICL, LLC; a stockholder of Synark; and a consultant to MerckSerono, Facet Solutions Genzyme, and Stryker.

Address correspondence to D. Hayashi ([email protected]).

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