Medical Oncology

, 30:502

Secondary mucosa-associated lymphoid tissue (MALT) lymphoma of the colon

Authors

  • Shagufta Shaheen
    • Department of Internal Medicine, Harvard Medical School, Massachusetts General HospitalHarvard University
    • Department of Internal Medicine, Harvard Medical School, Massachusetts General HospitalHarvard University
Short Communication

DOI: 10.1007/s12032-013-0502-2

Cite this article as:
Shaheen, S. & Guddati, A.K. Med Oncol (2013) 30: 502. doi:10.1007/s12032-013-0502-2

Abstract

Mucosa-associated lymphoid tissue (MALT)-type lymphomas most commonly occur in the stomach and have been associated with Helicobacter pylori infection. However, MALT-type lymphoma of the colon is a rare entity. It commonly manifests with symptoms of weight loss, low-grade fever, constipation, melena, and hematochezia. Unlike gastric lymphoma, it is difficult to detect MALT-type lymphoma of the colon by imaging. Colonoscopy may reveal lesions whose biopsy most commonly shows abundant B lymphocytes. There is no universal immunohistochemistry profile for MALT-type lymphoma but CD 20 staining is commonly seen. Trisomies and translocations have been described and their presence has been correlated with treatment response. Due to the rarity of colonic MALT-type lymphoma, no standard guidelines are available for its management. It often occurs individually and rarely occurs simultaneously with concurrent colon adenocarcinoma. This case report describes the presentation and clinical course of a secondary MALT-type lymphoma in a patient who underwent colectomy for a prior colon adenocarcinoma.

Keywords

MALTSecondaryColonAdenocarcinomaLymphoma

Introduction

Mucosa-associated lymphoid tissue is found in the gastrointestinal tract and is involved in immune surveillance [1]. It occurs as isolated lymphoid follicles composed of mostly B lymphocytes. Tissues with similar function have been observed in the bronchial tree [bronchial-associated lymphoid tissue (BALT)], nose [nose-associated lymphoid tissue (NALT)], and vagina [vulvo-vaginal-associated lymphoid tissue (VALT)]. Specialized cells called M cells in the mucosal epithelium absorb, process, and present antigens to the subepithelial lymphocytes. These lymphocytes consisting of B cells, T cells, and dendritic follicular cells are collectively responsible for the effector mechanisms involving IgA and IgM immunoglobulins [2]. Mucosa-associated lymphoid tissue lymphoma (MALT) was first described by Isaacson and Wright as a distinct type of lymphoma [3]. The most common sites of occurrence of MALT-type lymphomas are the stomach, small intestine, and the colon [4]. Notably, more than 90 % of MALT-type lymphomas of the stomach are associated with Helicobacter pylori infections [5]. Autoimmune diseases like Sjogren’s syndrome and celiac disease have been proposed to play an etiological role in the development of MALT-type lymphoma. The clinical presentation is varied and may mimic symptoms of peptic ulcer disease. It may also present with generalized symptoms of weight loss, chronic fatigue, nausea, and anemia. The prognosis, especially for gastric MALT-type lymphomas, is stage dependent. Antibiotic therapy against H. pylori often results in an excellent remission in patients with gastric MALT-type lymphomas but also predisposes them to higher rate of gastric cancer and non-Hodgkin’s lymphoma [6]. The therapeutic modality for MALT-type lymphoma of the colon is dependent on the presentation with surgical intervention being used for solitary lesions and chemotherapy being used for diffuse disease [7]. MALT-type lymphoma of the colon may present as abdominal pain, constipation, melena, and hematochezia. It often occurs individually and has rarely been seen to occur simultaneously with concurrent colon adenocarcinoma. The detection of MALT-type lymphoma in patients with concurrent colon adenocarcinoma has been coincidental and has been a result of careful examination of colectomy specimens. The case described here involves the detection of a secondary MALT-type lymphoma in a patient who underwent colectomy for a prior colon adenocarcinoma.

Case summary

The patient is a 79-year-old gentleman with a past medical history significant for right-sided colon adenocarcinoma treated with right hemicolectomy without chemotherapy, diabetes mellitus, hypertension, coronary artery disease treated with coronary artery bypass graft, and cholecystectomy who presented with a history of painless bright red blood per rectum and black tarry stools for 3 days. He denied any dizziness, abdominal pain, fever, chills, night sweats, and recent weight loss. He was a smoker but quit 35 years ago and had never consumed alcohol. There was no family history of malignancy. Physical examination revealed a moderately built elderly African American male in no acute distress. No pallor, icterus, clubbing or thrush was noted. No cervical or supraclavicular lymph-adenopathy was noticed but bilateral axillary lymph-nodes measuring 1 cm each were palpated. Abdominal examination was benign except from old surgical scars. The patient’s hemoglobin was 12.2 g/dL and hematocrit was 36.3 % on admission. Stool cultures, ova, parasites, and Clostridium difficile toxin assay were all negative. MRI/MRA of the abdomen ruled out ischemic bowel disease. A colonoscopy was performed which revealed multiple large heaped-up ulcers throughout the entire length of the colon and up to 5-mm colon polyps were observed at the anastomotic site, transverse colon, and rectum along with internal hemorrhoids (Fig. 1, Panels a, b). The polyps and ulcerated masses at the rectum, sigmoid colon, transverse colon, and the anastomotic site were biopsied which revealed markedly atypical proliferation of large atypical lymphoid cells effacing the architecture. CD 20 and leukocyte common antigen (LCA) stains were positive and CD 3 and cytokeratin AE1/AE3 were negative consistent with MALT-type lymphoma (Fig. 2, Panels a, b). The CT scan of the chest revealed bilateral axillary lymphadenopathy with no hilar or mediastinal adenopathy. The CT scan of abdomen and pelvis did not reveal any hepatomegaly or liver metastasis but two small low-density nodules were noticed within the spleen. A HIV test was negative. A PET scan was done to stage the disease, and multiple focal areas of increased fluorodeoxyglucose uptake were noted in the head and neck, bilateral axillary and right peri-tracheal region, extra-hepatic abdomen, lumbar spine and inguinal regions bilaterally indicating diffuse neoplastic process. In order to quantitate cardiac function prior to starting anthracycline therapy, a MUGA scan was obtained which revealed cardiac ejection fraction of 54 %. The patient was given four cycles of CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) and Rituximab chemotherapy. Follow-up colonoscopy after 6 months revealed a 3-mm polyp at the transverse colon and a nodular appearance in the rectosigmoid area biopsies of which revealed hyperplastic polyps and mild chronic inflammation. Serial PET scans at one- and 2-year intervals showed no evidence of active neoplastic disease or metastasis.
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Fig. 1

Panels a, b. Ulcers with heaped-up margins are seen in several locations in the colon

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Fig. 2

Panel a. Hematoxylin and Eosin stain showing large neoplastic cells with prominent nucleoli and irregularly shaped nuclei. Panel b. Immunohistochemistry showing the surface expression of CD 20

Discussion

Adenocarcinoma of the colon is the third most commonly diagnosed malignancy in the world [8]. However, primary large bowel lymphomas constitute approximately 0.2 % of all large bowel malignancies. A male predominance of 1.5: 1 was noted on gastric MALT-type lymphomas but no such predominance was found in colonic MALT-type lymphomas [9, 10]. The etiology of MALT-type lymphoma in the stomach has been attributed to chronic infection, especially by H pylori [5]. Specifically, H pylori strains expressing cytotoxin-associated gene A (CagA) have been shown to promote preneoplasia [11]. However, the correlation between H pylori infection with colonic MALT-type lymphoma has not been proven conclusively. There have been conflicting reports that elimination of H pylori infection leads to resolution [12], regression of MALT-type lymphoma in spite of persistence of H pylori infection [13], and spontaneous regression of MALT-type lymphoma [14]. This is especially true for patients with nodal disease who have been observed not to attain complete response with H pylori eradication [1517]. Genetic abnormalities involving trisomies of chromosomes 3, 12, and 18 and translocations of t[11, 18][q21;q21], t[14, 18][q32;q21], t[1, 14][p22;q32], and t[3, 14][p14;q32] have also been observed. In the context of sustained antigenic stimulation, some of these abnormalities have been shown to activate the nuclear factor B (NF-B) oncogenic pathway [18].

Histological examination of MALT-type lymphomas often reveals lymphoepithelial lesions with irregular nuclei and hyperchromasia. Similar formations involving reactive lymphoid infiltrates may also appear in benign conditions involving inflammation. Lymphoid cells may expand in the lamina propria and occasionally infiltrate the muscularis mucosa. Infiltration through the muscularis propria may be manifested as mucosal ulcers. The case described here manifested in a similar manner. MALT-type lymphoma is notable for a preponderance of B cells which can be detected by CD 20 staining. These cells are negative for CD10, CD 23, and cyclin D1, and cells with plasmacytic differentiation may stain strongly for kappa and lambda chains [19]. Due to the rarity of colonic MALT-type lymphoma, no standard guidelines are available for its management. Besides surgery and chemotherapy, radiotherapy has also been used to treat MALT-type lymphoma of the colon [20, 21]. Simultaneous occurrence of MALT lymphoma and adenocarcinoma is rare with only a few cases reported so far in the medical literature [22, 23]. The patient described in this case report had right-sided hemicolectomy, and it is possible that the decreased length of the colon may have enhanced the immunologic reaction to an unknown antigen and precipitated MALT-type lymphoma. It is rare to detect a secondary MALT-type lymphoma after successful resection of the primary adenocarcinoma of the colon. This case illustrates the need for heightened awareness of the possibility of development of secondary malignancies, especially MALT-type lymphoma after hemicolectomy.

Conflict of interest

None.

Copyright information

© Springer Science+Business Media New York 2013