Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade B-cell neoplasm of the extranodal marginal zone characterized by a lymphoid infiltrate in the mucous layer of hollow organs and glandular tissues[1,2]. The gastrointestinal tract is involved in about 50% of the cases[2,3] with the stomach accounting for 85% of all cases and strongly related to the presence and infection by Helicobacter pylori (H. pylori)[1,4]. Other, less usual regions can also be affected, such as salivary glands, lungs (14%), head and neck (15%), ocular attachments (12%) and skin (11%).
MALT lymphomas in the ileum are extremely rare and few cases have been reported in the literature[5-9]. In these, all patients had already presented with an advanced degree of involvement with notable symptoms and with lesions dispersed throughout the ileocecal region[5,6].
This is the first reported case of a terminal ileum MALT lymphoma in an asymptomatic patient reported in the literature.
History of present illness
A 57-year-old asymptomatic female patient underwent a colonoscopy exam for screening. The examination revealed an ulcer of medium depth with well-defined borders covered by a thin layer of fibrin and a halo of hyperemia in the distal ileum portion (Figure 1). Findings are nonspecific but may signal infections by viruses, protozoa and parasites or inflammatory diseases such as Crohn's disease. Biopsies of the ulcer were taken.
Figure 1 Colonoscopy exam.
A: Ulcer in the terminal ileum; B: Mild ulcer in terminal ileum.
The anatomopathological result revealed an atypical diffuse lymphocytic infiltrate of small cells with a characteristic cytoplasmic halo of marginal zone cells. The infiltrate presented with nodular and poorly delimited areas with dissection of collagen fibers and the muscular layer of the mucosa. There was no clear distinction regarding germinal centers. Signs of cellular atypia were also observed with enlarged nuclei. In the most superficial portion there was focal erosion, epithelial reactivity and eosinophilia (above 15 per high-power field) (Figure 2). No granulomas were found and there were no signs of infection by parasitic agents. An immunohistochemical study was requested to investigate lymphoproliferative disease.
Figure 2 Biopsy of terminal ileum showing.
A: Hematoxylin & eosin-dense lymphocytic infiltrate composed of small cells, with a cytoplasmic halo, characteristic of cells in the marginal zone; B: Cyclin D1-Negative neoplastic infiltrate for protein expression of cyclin D1. Observe the positive control in the glandular epithelium; C: Cytokeratin cocktail AE1/AE3-negative neoplastic infiltrate for protein expression of cytokeratin. Observe the positive control in the glandular epithelium; D: BCL6-Protein label for BCL60. Note the negativity of the neoplastic infiltrate, and the positive internal controls in the germinal center of a reactional follicle.
The immunohistochemical study was performed by the EnVision FLEX Visualization System kit AGILENT (DAKO) method, which the results demonstrated a negative neoplastic infiltrate for the expression of cyclin D1 (Figure 2B) and cytokeratin AE1/AE3 (Figure 2C) and positive for BCL60 in the germinal center (Figure 2D). The test also revealed CD10 positivity in the glandular epithelium and germinal center of a reactive follicle (Figure 3A and B) with dual labeling of CD20 and CD3 demonstrating the B lymphocyte nature of the neoplastic infiltrate (Figure 3C and D). In BCL2 protein labeling, the neoplastic infiltrate is strongly positive with a negative germinal center (Figure 3E and F).
Figure 3 Terminal ileum biopsy showing.
A: Protein labeling for CD10. Note the negativity of the neoplastic infiltrate, and the positive internal controls of the glandular epithelium and germinal center of a reactional follicle; B: Protein labeling for CD10. Note the negativity of the neoplastic infiltrate and the positive internal controls of the glandular epithelium; C and D: Double labeling of CD20 (brown) and CD3 (red) demonstrating the nature of B lymphocytes of the neoplastic infiltrate. Note that T cells border the neoplastic infiltrate and preferably the epithelium, attesting to its reaction nature; E: Protein labeling for BCL2. Note that the neoplastic infiltrate expresses strongly and the internal negative control in the germinal center of a reactional follicle; F: Strong protein labeling of the neoplastic infiltrate for BCL2
Extranodal marginal zone lymphoma (MALT lymphoma) is characterized by the proliferation of small B lymphocytes. The stomach is the most common site of involvement where the main etiology is H. pylori infection. In these cases, the endoscopic findings are varied and involve polyps, ulcerations, erythematous lesions, nodules and other non-specific findings. Extranodal marginal zone lymphomas that affect the ileum region are extremely rare and only a few cases have been reported in the literature[5-9]. None of the previous studies showed H. pylori infections so the etiology of the disease remains unknown.
Endoscopic findings of primary small bowel lymphoma can be classified into 5 patterns: Mucosal fold thickening; nodular pattern, defined by the presence of nodules and micronodules of variable sizes; infiltrative pattern, where the bowel wall is immobile, not distended by insufflation, and firm over forceps; ulcerative pattern with ulcers of variable sizes and depths, and mosaic pattern.
Among the four cases published in the literature on ileum MALT lymphomas, all presented endoscopic findings with multiple protuberances: Two[5,7] cases with ulcerations and two[6,8] cases with smooth mucosa. In one case, the presence of a single mass in the intestine was demonstrated without erosions in the mucosa.
The treatment of MALT lymphoma is initially made with the eradication of H. pylori, in cases with involvement of the bacteria. If there is no concomitant H. pylori infection or no tumor remission after H. pylori treatment, radiotherapy, chemotherapy, or immunotherapy with anti-CD20 monoclonal antibodies should be considered. Radiotherapy has an excellent prognosis when used in cases where the disease is localized. In the presence of disseminated or more advanced disease, the use of radiotherapy or immunotherapy is indicated. Treatment must be individualized according to the stage of the disease and symptoms, as well as the patient's preference. Although MALT lymphoma has a favorable prognosis and is responsive to systematic therapy, especially when identified early, when patients are symptomatic, unfortunately they already have a more advanced degree of involvement.
Terada reported the case of a 34-year-old patient with abdominal pain and melena whose colonoscopy revealed multiple nodules and ulcers scattered throughout the ileum. Endoscopic images were suggestive of ileitis, mesenchymal tumor, or lymphoma.
Hasegawa et al described two cases of oligosymptomatic patients with abdominal pain being a common symptom. Colonoscopy in the first case found multiple whitish nodules in the region close to the ileocecal valve, which had a smooth and polished appearance. In the second case, a colonoscopy revealed an ileocecal valve with an enlarged, soft appearance and areas of enanthema.
Makino et al discussed a case of a patient with initial complaints of postprandial epigastric pain. Colonoscopy examination revealed multiple protruding lesions in the terminal ileum with an erosive surface covered by swollen mucosa.
In the report by Ohashi et al colonoscopy identified multiple polyposis lesions in the terminal ileum with an absence of villi.
In all cases, biopsy with histological evaluation concurrently with immunohistochemical analysis was crucial for the diagnosis of MALT lymphoma.
The uniqueness of the case presented in this study is due to the fact that the patient was asymptomatic and her endoscopic findings had a more discrete and nonspecific pattern compared to other studies which made the diagnosis even more challenging.