Synchronous Mucosa-Associated Lymphoid Tissue Lymphoma and Gastrointestinal Stromal Tumor of the Stomach Presenting With Gastric Bleeding
By Yamaguchi, Tetsuya Takahashi, Hiroshi; Kagawa, Ryuzaburo; Takeda, Ryoji; Sakata, Shingo; Yamamoto, Michihiro; Nishizaki, Daisuke; Yasui, Hiroshi
We report an extraordinarily rare case of synchronous mucosa- associated lymphoid tissue lymphoma and gastrointestinal stromal tumor of the stomach. An 80-year-old man presented with gastric bleeding. Gastroscopy showed an ulcerative lesion and a submucosal tumor at the upper corpus of the stomach. The ulcerative lesion was proven by biopsy to be mucosa-associated lymphoid tissue lymphoma, but the submucosal tumor could not be diagnosed. Due to the repeating episodes of massive gastric bleeding, a total gastrectomy with lymphadenectomy was performed. After the operation, the submucosal tumor was pathologically proven to be a gastro- intestinal stromal tumor. In this case, synchronous occurrence of mucosa-associated lymphoid tissue lymphoma and gastrointestinal stromal tumor seems to be coincidental rather than related with the same pathogenic triggering. Surgical resection of the stomach provided an accurate diagnosis and an effective treatment. PRIMARY GASTRIC LYMPHOMA is a rare entity, accounting for one to five per cent of all primary gastric neoplasms.1 B-cell lymphoma of mucosaassociated lymphoid tissue (MALT lymphoma) is the most common type of gastric lymphomas.2 It accounts for approximately 40 per cent to 50 per cent of all gastric lymphomas.3 Gastrointestinal stromal tumors (GISTs) are also rare, but are the most common mesenchymal tumors to arise in the gastrointestinal tract.4 Synchronous MALT lymphoma and GIST of the stomach is extraordinarily rare. To our knowledge, it has been reported only twice.5,6 In this report, we present a case of synchronous MALT lymphoma and GIST of the stomach treated successfully by surgical resection.
Case Report
An 80-year-old man presented with hematemesis, tarry stool, and general fatigue of several months duration. His past history was unremarkable. He had no family history of gastrointestinal disease. Laboratory investigations showed a hemoglobin count of 6.1 g/dL. Abdominal CT scan showed a heterogeneous mass of 3.6 cm in diameter at the anterior wall of the upper corpus of the stomach (Fig. 1). Gastroscopy showed a submucosal tumor with a depression of its top at the anterior wall of the corpus. At its opposite site (posterior wall of the corpus), an ulcerative lesion with bleeding was also observed. Several biopsies were performed from these two lesions. Pathologic examinations of the ulcerative lesion showed infiltrating atypical lymphoid cells, characteristic of lymphoepithelial lesions consistent with the diagnosis of low-grade B-cell lymphoma of the MALT type (Fig. 2). At the same time, numerous Helicobacter organisms were observed. However, the diagnosis of the submucosal tumor could not be determined pathologically. Due to the repeating episodes of massive gastric bleeding, an operative therapy was selected. In January 2006, a total gastrectomy with lymphadenectomy was performed. The submucosal tumor was 4.0 cm in diameter. Pathologically, it was monomorphic, composed of spindle shaped cells (Fig. 3), and immunohistochemical examination revealed that it was positive for c-kit and CD34, and to the contrary, negative for smooth-muscle actin and S-100. These findings were consistent with a diagnosis of GIST. The ulcerative lesion was again pathologically confirmed to be low-grade B-cell lymphoma of the MALT type. There was no nodal involvement. Immunohistochemically, this lesion was positive for CD20, but negative for CD3, CD5, and CDlO. His postoperative course was uneventful. One year after the surgery, he is doing well and reveals no signs of recurrence.
FIG. 1. Abdominal CT scan showed a heterogeneous mass of 3.6 cm in diameter at the anterior wall of upper corpus of the stomach. The white arrow shows a mass.
Discussion
Gastric mucosa ordinarily lacks lymphoid tissue. However, it may acquire MALT in close association with chronic inflammation as Helicobacter pylori infection.2,7 In 1983, Isaacson and Wright2 classified primary gastric lymphomas as a distinct entity from previously classified nodal lymphomas. A benign reactive process in response to an antigen leads to the formation of lymphoid follicles. At this stage, the tissue may be referred to as reactive lymphoid hyperplasia. As progression continues, there is formation of a diffuse cellular infiltrate of small centrocyte-like cells that arise from the marginal zone of the lymphoid follicle and invade the epithelial lining, forming classic lymphoepithelial lesions.8 These cells stimulate a monoclonal population of B cells that is still dependent on the antigen, a characteristic shared by low grade lymphomas at a wide variety of extranodal sites, and is collectively referred to as MALT lymphoma.9 MALT lymphoma is often preceded by chronic Helicobacter pylori infection in the stomach. In primary gastric lymphomas, the initiating antigen is mainly thought to be Helicobacter pylori, which provokes the host’s immune system. An etiological link between gastric MALT lymphoma and lymphoid reaction to Helicobacter pylori infection has been demonstrated.10 Therefore, eradication of Helicobacter pylori has been shown to result in regression of the tumor in many cases. Treatment with an anti- Helicobacter pylori regimen at this point is accepted to aid in the regression of the tumor. Thus, this stomach-conserving approach is now considered to be the first line therapeutic option to gastric MALT lymphoma.11 However, some patients present with high-grade primary gastric lymphomas. These tumors produce a monoclonal B cell clone that may not be dependent on the antigenic stimuli that triggered the initial chain of events.8 Despite the initiation of tumor formation by Helicobacter pylori, the autonomous nature of high grade primary gastric lymphoma makes it highly unresponsive to Helicobacter pylori therapy. In those cases, thus, the other therapeutic modalities should be considered, such as chemotherapy, radiotherapy, and surgical therapy. Debate continues as to the treatment of these patients.
FIG. 2. H.E. x 200. A diffuse cellular infiltrate of centrocytelike cells forming classic lymphoepithelial lesions is seen in the gastric mucosa.
FIG. 3. H.E. times;100. Spindle-shaped cells formed bundles. Neither mitosis nor atypical cells were seen.
The need for operation in the management of gastric MALT lymphoma has decreased and a stomachconserving approach of antibiotic therapy, radiotherapy, or chemotherapy alone or in various combinations is favored. However, in this case, repeating gastric massive bleeding episodes occurred from MALT lymphoma. Due to those episodes, a stomachconserving approach of antibiotic therapy could not be adopted. Furthermore, all the pathological examinations of the submucosal tumor failed. Consequently, we performed a total gastrectomy with lymphadenectomy. Even in low-grade disease of gastric MALT lymphoma, lymph node involvement is reported to be seen in 36 per cent.12 This lymph node involvement rate is too high to be neglected. Therefore, an additional lymphadenectomy is thought to be beneficial in cases of gastric MALT lymphoma, because limited nodal involvements in gastric MALT lymphoma can be completely controlled by the additional lymphadenectomy.13
GISTs reveal a wide clinical spectrum from benign to malignant.14 The first line treatment of GISTs is now surgical resection of the tumor.14 However, recent studies have shown that cells in GISTs express a growth factor receptor with tyrosine kinase activity termed c-kit. This receptor, the product of the protooncogene c- kit, seems to be the most specific diagnostic criterion for the diagnosis of GIST.15 Mutations of c-kit that cause constitutive activation of the tyrosine kinase function of c-kit are thought to play a central part in the pathogenesis of GISTs.16 These mutations result in uncontrolled cell proliferation and stimulation of down- stream signaling pathways. Molecular targeting of this critical mechanism with imanitib mesylate, which is an inhibitor of the tyrosine kinase activity of c-kit, is particularly encouraging. Imanitib mesylate has been shown to have potent activity even against metastatic GIST.17 It is now widely used in cases of GISTs with metastases or advanced diseases.18
As for synchronous MALT lymphoma and adenocarcinoma of the stomach, those tumors can occur because Helicobacter pylori infection plays an early role in the generation of both types of neoplasms.19 However, the pathogenic link of GIST with Helicobacter pylori infection has never been clarified. Thus, in this case, synchronous occurrence of MALT lymphoma and GIST seems to be coincidental rather than related with the same pathogenic triggering.
To control massive bleeding from the MALT lymphoma and diagnose the submucosal tumor, we had no choice other than surgery. In this case, surgical resection of the stomach provided an accurate diagnosis and an effective treatment.
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TETSUYA YAMAGUCHI, M.D.,* HIROSHI TAKAHASHI, M.D.,* RYUZABURO KAGAWA, M.D.,* RYO)I TAKEDA, M.D.,* SHINGO SAKATA, M.D.,* MICHIHIRO YAMAMOTO, M.D.,* DAISUKE NISHIZAKI, M.D.,* HIROSHI YASUI, M.D.[dagger]
From the Departments of *Surgery and [dagger]Pathology, Rakuwakai- Otowa Hospital, Kyoto, Japan
Address correspondence and reprint requests to Tetsuya Yamaguchi, M.D., Department of Surgery, Rakuwakai-Otowa Hospital, 2 Otowachinjicho, Yamashina-ku, Kyoto 607-8062, Japan. E-mail: rakuwadr011@rakuwadr.com .
Copyright Southeastern Surgical Congress Mar 2008
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