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ISSN 1007-9327 CN 14-1219/R  World J Gastroenterol  2007 March 7;13(9): 1453-1457

A case of mucosa-associated lymphoid tissue lymphoma forming multiple lymphomatous polyposis in the small
intestine


Naoto Hirata, Kazunari Tominaga, Kensuke Ohta, Kaori Kadouchi, Hirotoshi Okazaki, Tetsuya Tanigawa, Masatsugu Shiba, Toshio Watanabe, Yasuhiro Fujiwara, Shiro Nakamura, Nobuhide Oshitani, Kazuhide Higuchi, Tetsuo Arakawa

 

 


 


 

Naoto Hirata, Kazunari Tominaga, Kensuke Ohta, Hirotoshi Okazaki, Tetsuya Tanigawa, Masatsugu Shiba, Toshio Watanabe, Yasuhiro Fujiwara, Shiro Nakamura, Kazuhide Higuchi, Tetsuo Arakawa, Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan

Kaori Kadouchi, Department of Hematology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan

Nobuhide Oshitani, Department of Gastroenterology, Rinku General Medical Center, 2-3 Rinkuouraikita, Izumisano, Osaka 598-0048, Japan

Supported in part by a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Science and Culture in Japan

Correspondence to: Kazunari Tominaga, Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. tomy@med.osaka-cu.ac.jp

Telephone: +81-6-66453811  Fax: +81-6-66453813

Received: 2006-12-16           Accepted: 2007-03-03

  

Abstract

A 50-year old woman suffering from diabetes had a CT scan that revealed a diffuse thickening of small intestinal wall and swollen paraaortic lymph nodes. An esophagogastroduodenoscopy (EGD) confirmed multiple polypoid lesions in the duodenum and small intestine, and conventional histological testing revealed non-specific inflammatory changes. Further examinations including the immunohistochemical profiles of the biopsied specimens led us to diagnose the lesion as a marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type, forming multiple lymphomatous polyposis sequentially spreading from duodenal bulb to terminal ileum. According to Lugano’s classification, its staging was clinically diagnosed as stage . Two courses of a standard CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and predonisolone) regimen with rituximab reduced the lesion and the patient had a almost complete response. A 5-year follow-up EGD and histological examinations detected no recurrence of the disease.

 

© 2007 The WJG Press. All rights reserved.

 

Key words: Intestinal lymphoma; Mucosa-associated lymphoid tissue lymphoma; Multiple lymphomatous polyposis

 

Hirata N, Tominaga K, Ohta K, Kadouchi K, Okazaki H, Tanigawa T, Shiba M, Watanabe T, Fujiwara Y, Nakamura S, Oshitani N, Higuchi K, Arakawa T. A case of mucosa-associated lymphoid tissue lymphoma forming multiple lymphomatous polyposis in the small intestine. World J Gastroenterol 2007; 13(9): 1453-1457

 

 http://www.wjgnet.com/1007-9327/13/1453.asp

  

INTRODUCTION

Lymphomas in the gastrointestinal (GI) tract may be ulcerative, superficial, polypoid, or diffuse, and may also have other less common characteristics[1]. Multiple lymphomatous polyposis (MLP) is characterized by the formation of multiple mucosal polyps[2]. Polypoid lesions of MLP are usually widely spread to several regions of the GI tract including the esophagus, stomach, duodenum, and intestine. Histological findings tend to lead to the classification of most MLPs as mantle cell lymphomas[3-5]. Therefore, MLP may be one of the poor prognostic lymphomas in the GI tract, even though several regimens of systemic chemotherapy have been adapted for its treatment.

We report a rare and interesting case of MLP whose histology was a marginal zone B-cell mucosa-associated lymphoid tissue (MALT) lymphoma. A range of polypoid lesions was observed from duodenal bulb to the terminal ileum by various image examinations. The present case failed to respond to treatment to eradicate H pylori, but was successfully managed using a CHOP regimen combined with rituximab.

 

CASE REPORT

A 50-year old woman underwent an abdominal CT scan during an educational admission for diabetes mellitus at another hospital. CT scan revealed a diffuse thickening of small intestinal wall and swollen paraaortic lymph nodes, but no abnormal mass in her pancreas. Gallium citrate scintigraphy showed abnormal accumulation in the small intestine. Esophagogastroduodenoscopy (EGD) showed multiple polypoid lesions in the duodenum, and histological finding revealed non-specific inflammatory changes including infiltration of lymphoid cells. All these findings indicated a lymphatic proliferative disease. To obtain a differential diagnosis, she underwent endoscopic partial mucosal resection to perform the Southern blot analysis for immunoglobulin (Ig) genes but results were negative for changes in Ig-heavy chain JH. Then the patient was admitted to our hospital for further examination and treatment.

On admission, she had no clinical symptoms. Physical examinations revealed no superficial lymphadenopathy and no abnormal abdominal mass. Laboratory findings showed only mild liver dysfunction, mild elevation of lactate dehydrogenase and total cholesterol. No atypical lymphocytes were seen in peripheral blood, and the serum soluble interleukin-2 level was within normal limits. EGD showed multiple yellowish granular polypoid lesions sequentially spreading from the bulb to the distal tract over descending portion of the duodenum (Figure 1A and B). On the other hand, such polypoid lesions were not detected in the stomach except for atrophic mucosa. Cultures were positive for H pylori. Endoscopic ultrasonography revealed hypoechoic thickening from the first to the second sonographic layer, indicating that it was almost confined to the mucosal layer (Figure 1C). Fluoroscopic examination of the small intestine aiming to estimate the extent of lesion showed many round defects from the duodenal bulb to the end of jejunum (Figure 2), suggesting that the lesion was extending from the duodenum to the jejunum and ileum. Lower endoscopic findings showed whitish small polypoid lesions in the terminal ileum, but no obvious lesion in the colon and rectum (Figure 1D). Abdominal CT scan showed thickening of the duodenal and small intestinal walls. Abdominal MRI images also showed swollen paraaortic lymph nodes (approximately 1 cm in diameter) and an abnormal mass at the left side of supra-mesenteric artery (7 cm × 3 cm) which was probably composed of swollen mesenteric lymph nodes.

Histological findings of the specimens obtained from the lesions of duodenum and ileum showed follicular colonization dominantly composed of many small lymphocytes and a few large lymphocytes (Figure 3A), as well as a lymphoepithelial lesion, one of the typical features of mucosa-associated lymphoid tissue (MALT) lymphoma (Figure 3B). Immunohistochemical examinations showed that a large number of lymphoma cells were positively stained for bcl-2 and CD20 (the B-cell marker), but negative for UCHL-1 (T-cell marker). On the other hand, the tumor cells were negatively stained for CD5, CD10, and Cyclin D1 (Figure 4). All these findings including the immunohistochemical profiles led us to diagnose this lesion as a marginal zone B-cell lymphoma of the MALT type according to the WHO classification[6] but not as a mantle cell lymphoma, forming MLP sequentially spreading from the duodenal bulb to the terminal ileum. According to Lugano’s classification[7], its staging was clinically diagnosed as stage .

Eradication therapy was selected as the first treatment modality for H pylori infection (lansoprazole 60 mg/d, clarithromycin 800 mg/d, and amoxicillin 1500 mg/d, for one week), since it was less invasive for the patient. Follow-up EGD findings after H pylori eradication showed no improvement of these lesions. We selected the systemic chemotherapy as the second treatment modality for H pylori infection because the lymphoma may spread to the duodenum and other areas, even though the histopathological findings did not reveal a high potential for it to become malignant. The patient then received a standard CHOP (cyclophosphamide: 750 mg/m2, doxorubicin hydrochloride: 50 mg/m2, vincristine sulfate: 1.4 mg/m2, and predonisolone: 100 mg) regimen in combination with rituximab: 375 mg/m2 regimen, followed by a further CHOP treatment at their half dose. Ten days after the first therapeutic course, EGD findings showed that each polypoid lesion of the duodenum became smaller, and their tops collapsed and showed evidence for erosion. Following 2 courses of CHOP plus rituximab regimen, the lesions and abdominal lymph nodes almost completely resolved (Figure 5). A 5-year follow-up with EGD and histological examination showed no recurrence of the disease.

 

DISCUSSION

The present case of lymphatic proliferative disease in the GI tract was diagnosed by endoscopy, radiographic imaging, and genetic profiling. The clinical features indicated a MLP type of lymphoma in the duodenum and small intestine. Actually, many reports have demonstrated the consensus that the majority of MLPs are histologically mantle cell type lymphomas, and a few cases of follicular lymphoma or T-cell lymphoma have been reported[8-12]. In the present case, however, histological examination showed characteristic findings such as lymphoepithelial lesions and immunohistological profiles (positive CD20 and bcl-2; negative UCHL-1, CD5, CD10, and CyclinD1). These findings motivated us to diagnose the case as a B-cell MALT lymphoma, which was discriminated from a mantle cell or follicular type lymphoma. On the other hand, the differential diagnosis was considered as an immunoproliferative small intestinal disease (IPSID), a subtype of MALT lymphoma[13]. However, this case was clinically different from the typical features of IPSID, because the dominant region for IPSID is duodenum and upper jejunum and it usually causes malabsorption syndrome or protein-losing gastroenteropathy. Thus, the present case was more consistent with a MALT lymphoma forming MLP rather than IPSID. To our knowledge, only 4 cases of MALT lymphoma forming MLP have been reported[14-16], indicating that our present case is actually rare. In regard to the origin of this lymphoma, we could not completely deny the suspicion that a lymph node might be the origin of the disease because of the swollen mesenteric lymph nodes. However, the involvement of other lymph nodes was unremarkable although the polypoid lesions were widely distributed in the GI tract. Furthermore, no atypical lymphocytes were shown in peripheral blood, and this case was compatible with the definition about primary GI tract lymphoma described by Lewin and Herrmann[17,18]. Thus, it was more likely that the primary lesion of the present lymphoma was in the GI tract.

Recently, treatment to eradicate H pylori has become a standard management for primary gastric MALT lymphoma[19-21]. Certainly, there are various reports showing that eradication of H pylori is effective for duodenal MALT lymphoma[22,23]. Nakamura et al[24] reported that primary duodenal lymphoma might have different characteristics between locations at the bulb and descending portion. Lymphomas originating from duodenal bulb might have similar characteristics with gastric MALT lymphomas, suggesting that H pylori eradication therapy is often effective. Unfortunately, the lesions observed over the descending portion might be less associated with H pylori infection, indicating that H pylori eradication therapy cannot be expected to be totally effective. On the other hand, the efficacy of H pylori eradication therapy for the small intestine or colorectal lymphoma is not known, though a few responsive cases have been reported[25,26]. Since H pylori eradication therapy was ineffective in the present case, we used a more potent therapy due to the potential of the lymphoma to spread more extensively and its possible transformation of MALT lymphoma cells into diffuse large B cell lymphoma cells in the presence of a few large cells in the specimens. In general, surgical resection, systemic chemotherapy, and radiation therapy are performed in the treatment of malignant lymphoma in the GI tract[27]. Since curative surgical resection or radiation therapy was not suitable in our case because the lesion was already diffuse and widespread, we selected a systemic chemotherapy as a second line treatment. Combination therapy of a CHOP regimen, the most common regimen in combination with rituximab (a molecular targeting agent for this particular follicular type lymphoma), has been recently used in the treatment of GI tract lymphoma[28,29]. This combination therapy contributed to a significant improvement in the present case. We performed careful follow-up examinations such as laboratory analyses, EGD examination, and various abdominal images at every six months interval. EGD examination revealed no obvious recurrence of MLP and there was no evidence for recurrent lesions or clinical symptoms during the 5-year follow-up.

In conclusion, we reported a rare case of MALT lymphoma in the small intestine which was histologically diagnosed as a marginal zone B-cell MALT lymphoma. CHOP regimen in combination with rituximab is an effective therapy for MALT lymphomas in the GI tract.

 

REFERENCES

1      Nakamura S, Matsumoto T, Iida M, Yao T, Tsuneyoshi M. Primary gastrointestinal lymphoma in Japan: a
  clinicopathologic analysis of 455 patients with special reference to its time trends. Cancer 2003; 97: 2462-2473
  PubMed

2      Cornes JS. Multiple lymphomatous polyposis of the gastrointestinal tract. Cancer 1961; 14: 249-257   PubMed

3      Isaacson PG, MacLennan KA, Subbuswamy SG. Multiple lymphomatous polyposis of the gastrointestinal tract.
  Histopathology
1984; 8: 641-656   PubMed

4      Ruskone-Fourmestraux A, Delmer A, Lavergne A, Molina T, Brousse N, Audouin J, Rambaud JC. Multiple
  lymphomatous polyposis of the gastrointestinal tract: prospective clinicopathologic study of 31 cases. Groupe D'etude des
  Lymphomes Digestifs. Gastroenterology 1997; 112: 7-16   PubMed

5      Lavergne A, Brouland JP, Launay E, Nemeth J, Ruskone-Fourmestraux A, Galian A. Multiple lymphomatous polyposis of
  the gastrointestinal tract. An extensive histopathologic and immunohistochemical study of 12 cases. Cancer 1994; 74:
  3042-3050   PubMed

6      Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD. The World Health
  Organization classification of neoplasms of the hematopoietic and lymphoid tissues: report of the Clinical Advisory
  Committee meeting--Airlie House, Virginia, November, 1997. Hematol J 2000; 1: 53-66   PubMed

7      Rohatiner A, d'Amore F, Coiffier B, Crowther D, Gospodarowicz M, Isaacson P, Lister TA, Norton A, Salem P, Shipp M.
  Report on a workshop convened to discuss the pathological and staging classifications of gastrointestinal tract
  lymphoma. Ann Oncol 1994; 5: 397-400   PubMed

8      Tomita S, Kojima M, Imura J, Hori H, Ueda Y, Koitabashi A, Suzuki Y, Nakamura T, Nakamura Y, Mitani K, Terano A,
  Ohkura Y, Kawamata H, Fujimori T. Extranodal diffuse follicular center lymphoma mimicking mantle cell lymphoma of the
  intestine. Am J Hematol 2003; 74: 287-289   PubMed

9      Sakata Y, Iwakiri R, Sakata H, Fujisaki J, Mizuguchi M, Fukushima N, Fujimoto K. Primary gastrointestinal follicular
  center lymphoma resembling multiple lymphomatous polyposis. Dig Dis Sci 2001; 46: 567-570   PubMed

10    Yoshino T, Miyake K, Ichimura K, Mannami T, Ohara N, Hamazaki S, Akagi T. Increased incidence of follicular lymphoma
  in the duodenum. Am J Surg Pathol 2000; 24: 688-693   PubMed

11    Isomoto H, Maeda T, Akashi T, Tsuchiya T, Kawaguchi Y, Sawayama Y, Koida S, Ohnita K, Kohno S, Tomonaga M.
  Multiple lymphomatous polyposis of the colon originating from T-cells: a case report. Dig Liver Dis 2004; 36: 218-221
  PubMed

12    Hirakawa K, Fuchigami T, Nakamura S, Daimaru Y, Ohshima K, Sakai Y, Ichimaru T. Primary gastrointestinal T-cell
  lymphoma resembling multiple lymphomatous polyposis. Gastroenterology 1996; 111: 778-782   PubMed

13    Isaacson PG, Norton AJ. Extranodal Lymphomas. Edinburgh: Churchill Livingstone, 1994: 1-65

14    Saito T, Toyoda H, Yamaguchi M, Nakamura T, Nakamura S, Mukai K, Fuke H, Wakita Y, Iwata M, Adachi Y, Shiku H.
  Ileocolonic lymphomas: a series of 16 cases. Endoscopy 2005; 37: 466-469   PubMed

15    Breslin NP, Urbanski SJ, Shaffer EA. Mucosa-associated lymphoid tissue (MALT) lymphoma manifesting as multiple
  lymphomatosis polyposis of the gastrointestinal tract. Am J Gastroenterol 1999; 94: 2540-2545   PubMed

16    Yatabe Y, Nakamura S, Nakamura T, Seto M, Ogura M, Kimura M, Kuhara H, Kobayashi T, Taniwaki M, Morishima Y,
  Koshikawa T, Suchi T. Multiple polypoid lesions of primary mucosa-associated lymphoid-tissue lymphoma of colon.
  Histopathology
1998; 32: 116-125   PubMed

17    Herrmann R, Panahon AM, Barcos MP, Walsh D, Stutzman L. Gastrointestinal involvement in non-Hodgkin's lymphoma.
  Cancer
1980; 46: 215-222   PubMed

18    Lewin KJ, Ranchod M, Dorfman RF. Lymphomas of the gastrointestinal tract: a study of 117 cases presenting with
  gastrointestinal disease. Cancer 1978; 42: 693-707   PubMed

19    Boot H, de Jong D. Gastric lymphoma: the revolution of the past decade. Scand J Gastroenterol Suppl 2002; 27-36 
  PubMed

20    Ahmad A, Govil Y, Frank BB. Gastric mucosa-associated lymphoid tissue lymphoma. Am J Gastroenterol 2003; 98: 975-
  986
   PubMed

21    Stolte M, Bayerdorffer E, Morgner A, Alpen B, Wundisch T, Thiede C, Neubauer A. Helicobacter and gastric MALT
  lymphoma. Gut 2002; 50 Suppl 3: III19-III24   PubMed

22    Nagashima R, Takeda H, Maeda K, Ohno S, Takahashi T. Regression of duodenal mucosa-associated lymphoid tissue
  lymphoma after eradication of Helicobacter pylori. Gastroenterology 1996; 111: 1674-1678   PubMed

23    Toyoda H, Yamaguchi M, Nakamura S, Nakamura T, Kimura M, Suzuki H, Mukai K, Sawa H, Kawamura K, Shiku H.
  Regression of primary lymphoma of the ampulla of Vater after eradication of Helicobacter pylori. Gastrointest Endosc
  2001; 54: 92-96
   PubMed

24    Nakamura T, Suzuki T, Matsuura A, Ohashi K, Yokoi T, Nakamura H. Clinocopathological features of MALT lymphoma
  and follicular lymphoma of the duodenum. Stom
Intest 2001; 36: 1529-1540  

25    Nakamura S, Matsumoto T, Takeshita M, Kurahara K, Yao T, Tsuneyoshi M, Iida M, Fujishima M. A clinicopathologic
  study of primary small intestine lymphoma: prognostic significance of mucosa-associated lymphoid tissue-derived
  lymphoma. Cancer 2000; 88: 286-294   PubMed

26    Raderer M, Pfeffel F, Pohl G, Mannhalter C, Valencak J, Chott A. Regression of colonic low grade B cell lymphoma of the
  mucosa associated lymphoid tissue type after eradication of Helicobacter pylori. Gut 2000; 46: 133-135   PubMed

27    Al-Shemmari SH, Sajnani KP, Ameen RM, Ragheb AM. Primary gastrointestinal non-Hodgkin's lymphoma: treatment
  outcome. Clin Lymphoma 2003; 4: 99-103   PubMed

28    Wohrer S, Puspok A, Drach J, Hejna M, Chott A, Raderer M. Rituximab, cyclophosphamide, doxorubicin, vincristine and
  prednisone (R-CHOP) for treatment of early-stage gastric diffuse large B-cell lymphoma. Ann Oncol 2004; 15: 1086-
  1090   PubMed

29    Al-Salman J, Salib H, Boonswang P. Successful treatment of gastrointestinal follicular lymphoma with rituxan and
  combination chemotherapy. Med Oncol 2001; 18: 277-283   PubMed

 

                  S- Editor  Liu Y    L- Editor  Wang XL    E- Editor  Zhou T

 

 


 

 

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