Low Grade B Cell Mucosa Associated Lymphoid Tissue Lymphoma of the Stomach: Clinical and Endoscopic Gut: First Published As 10.1136/Gut.33.12.1621 on 1 December 1992

Gut 1992;33: 1621-1625 1621

Low grade B cell mucosa associated lymphoid tissue lymphoma of the stomach: clinical and endoscopic Gut: first published as 10.1136/gut.33.12.1621 on 1 December 1992. Downloaded from features, treatment, and outcome

M Blazquez, C Haioun, M-T Chaumette, P Gaulard, F Reyes, J-C Soule, J-C Delchier

Abstract commonly used by pathologists in the diagnosis A retrospective study of the clinical and of MALT lymphomas. A large clinicopatho- endoscopic features of low grade gastric logical study based on the review of surgical lymphomas of mucosa associated lymphoid specimens has recently confirmed results from tissue (MALT) in 16 patients together with previous shorter series.""'"' by showing the treatment and outcome was undertaken. good prognosis of small cell gastric lymphomas Immunohistochemical studies of fresh tissue from MALT origin.'7 easily distinguished MALT lymphoma from Details of symptoms and endoscopic aspects benign reactive lymphoid hyperplasia (pseudo- of the stomach in this type of lymphoma, how- lymphoma) and showed that tumour cells had ever, remain scarce in the published reports, and the characteristic phenotype indicative oftheir the best treatment has not yet been established. origin from MALT. Persistant epigastric pain This prompted us to report 16 consecutive cases was the main presenting complaint, and was of low grade gastric MALT lymphomas diag- often associated with acute bleeding, anaemia, nosed in our institution. In this series, the or weight loss. Eight patients had a past history histological diagnosis was based on biopsy speci- of recurrent peptic ulcers or gastritis. The mens, staging procedures systematically endoscopic appearance suggested malignancy included abdominal and chest computed tomo- in only half the cases and was compatible graphy and bone marrow biopsy, and most with gastritis or a benign peptic ulcer in the patients were not operated on but were success- remainder. There was extragastric involve- fully treated with monochemotherapy. ment of other mucosal sites in eight patients (mainly the lung, but also the parotid gland and

small bowel), but rarely was bone marrow and Patients and methods http://gut.bmj.com/ never the spleen or peripheral lymph nodes affected. Conservative treatment with long PATIENTS term cyclophosphamide was effective in both Sixteen patients with low grade gastric MALT stage I and stage IV disease, and all the lymphoma diagnosed in our institution between patients are alive after a median follow up of 1980 and 1990 were reviewed. The patients, nine 4.5 years. These findings confirm that low men and seven women, ranged in age from 25 to

grade gastric MALT lymphomas are usually 70 years, with a mean of 54 years. on September 25, 2021 by guest. Protected copyright. indolent tumours with non-specific endoscopic aspects and show that dissemination to other PROCEDURES mucosal sites was more frequent than DIAGNOSTIC previously reported. Monochemotherapy Fifteen patients were referred to our endoscopic could be an effective alternative treatment to unit for the investigation of epigastric pain, sometimes associated with acute bleeding or surgery. anaemia. Several biopsy specimens (>6) were (Gut 1992; 33: 1621-1625) taken, with forceps in every case. One patient with an established diagnosis was referred for Services d'Hepato- The gastrointestinal tract, particularly the additional treatment after partial gastrectomy. Gastroenterologie et stomach, is the most common primary site of The diagnosis of lymphoma was based on histo- d'Hematologie et logical and immunophenotypic criteria." Laboratoire extranodal lymphomas.' Most gastric lympho- d'Anatomopathologie, mas are large cell lymphomas of B cell lineage.2 3 Centre Hospitalier Primary small cell gastric lymphomas are less Universitaire Henri Tissue specimen preparation Mondor, Creteil, France frequent and are usually localised, solitary M Blazquez lesions that can be completely excised. Because Tissue specimens were processed for routine C Haioun of their favourable prognosis, they were long TABLE I Antibody panel M-T Chaumette known as pseudolymphomas.17 However, P Gaulard Antigen Antibody Pattern ofreactivity F Reyes immunohistochemical methods have now shown J-C Soule that most of these tumours are monoclonal B CD 3 Anti-Leu 4 T lymphocyte J-C Delchier CD 4 Anti-Leu 3a T helper lymphocyte cell proliferations.'" A number of recent patho- CD 5 Anti-Leu 1 T lymphocyte, subset of B-cells Correspondence to: logical studies have emphasised the specificity of CD 8 Anti-Leu 2 Cytotoxic/suppressor T lymphocyte Dr J-C Delchier, Service CD 19 B 4 B lymphocyte d'Hepato-Gastroenterologie, these B cells, suggesting that they originate from CD 22 B lymphocyte Centre Hospitalier tissue 4 Anti-K, y, g,u, 6 Light and heavy chains Universitaire Henri Mondor, mucosa associated lymphoid (MALT).'2 51 avenue du Marechal Indeed, they have the same cytological and The Leu series was obtained from Becton Dickinson & Co, Delattre de Tassigny, 94010 immunophenotypic characteristics as the B cells Mountain View, CA, USA. B4 antibody and Ig chain antibodies Creteil Cedex, France. were obtained from Coulter Immunology, Hialeah, FL, USA. are found around the mantle zone Accepted for publication that normally CD 22 antigen was obtained from Dakopatts AIS, Glostrup, 27 April 1992 of Peyer's patches. These properties are now Denmark. 1622 Blazquez, Haioun, Chaumette, Gaulard, Reyes, Sould, Delchier

histology and immunohistology. In each case, one patient. The patients were staged using the several tissue specimens were fixed with aqueous Ann Arbor system.20

Bouin's solution. Paraffin embedded sections Gut: first published as 10.1136/gut.33.12.1621 on 1 December 1992. Downloaded from were stained for conventional study with haema- toxylin-eosin-safran (HES) and periodic acid TREATMENT Schiff (PAS). In 12 of the 16 cases, fresh tissue In 14 of the 16 patients, initial treatment was an specimens were snap frozen in liquid nitrogen alkylating agent alone (cyclophosphamide 100 after 30 minutes' incubation in gum sucrose for mg/day). This monochemotherapy was con- immunohistological studies. tinued until complete remission was obtained (normal appearance of the gastric mucosa, negative biopsy specimens, and absence of extra- Immunophenotypic studies gastric localisation). One patient with a severe Deparaffinised and cryostat sections of the form of the disease (large tumour, poor general gastric biopsy specimens were evaluated for the condition, and a rapid course) was treated with presence of various antigens using the immuno- an anthracin-containing regimen (cyclophospha- alkaline phosphatase method (APAAP).'9 The mide, adriamycin, vincristine, prednisone) com- monoclonal antibodies used, their specific bined with radiotherapy (25 Grays). Another had immunoreactivities and commercial sources been operated on (partial gastrectomy) before are shown in Table I. Rabbit antimouse referral to our institution and received additional immunoglobulins and alkaline phosphatase- radiation therapy (30 Grays). antiphosphatase complexes were purchased from DAKO (Dakopatts A/S, Glostrup, Denmark). Alkaline phosphatase activity was FOLLOW UP determined after incubation in fast-red TR Endoscopy with biopsies was repeated every (1 mg/ml, Sigma Chemical Company, St Louis, three months in every case. Chest and abdominal MO, USA) and naphthol AS-TR phosphate (0-2 computed tomography was performed every six mg/ml, Sigma) solution, which contained months when lymph node or lung involvement levamisole (0.24 g/ml) to block endogenous was present at the initial staging. Patients who alkaline phosphatase activity. achieved complete remission underwent endoscopy with biopsies every six months. Complete remission was defined as resolution STAGING PROCEDURES of clinical evidence of disease and of endoscopic Staging systematically included a bone marrow lesions, with negative biopsy specimens and biopsy, chest and abdominal computed tomo- absence of extragastric localisation. Partial graphy, oropharyngolarynx examination, and remission was defined as improvement of clinical

liver function tests. A small bowel barium meal symptoms and endoscopic lesions with a http://gut.bmj.com/ and colonoscopy were performed in eight cases decrease in tumoral infiltration. and gastric endosonography was performed in Analysis was performed in November 1991 TABLE II Clinicalfeatures Case Age Presenting symptoms Extent ofdisease Treatment no (yr) Sex (duration) Past history (stage) Endoscopicfindings (duration) Followv up on September 25, 2021 by guest. Protected copyright. 1 52 F Epigastric pain, weight Gastric ulcer, gastric I Thickening of folds and Cyclophosphamide 18 months* loss 10 kg bleeding erosions ofangulus (1 year) 2 58 M Epigastric pain (6 Gastric ulcer, gastric I Suspectt ulcer of the Cyclophosphamide 18 months* months), bleeding bleeding gastric body (9 months) 3 62 F Epigastric pain (5 years), Gastritis, pseudolymphoma I Thickening ofgastric Cyclophosphamide Lost to follow-up weight loss 7 kg (3 years) folds, erosions 4 72 M Epigastric pain (1 year) - I Suspect ulcer of the Surgery, 7 years* antrum+small nodules, radiotherapy thickening offolds 5 50 F Epigastric pain (1 year), - I Small nodules of the Cyclophosphamide Lost to follow-up weight loss 2 kg antrum 6 65 M Epigastric pain (5 years) Gastritis I Thickening ofgastric folds Cyclophosphamide 3 years* in body (1 year) 7 25 F Epigastric pain (1 year), - I Ulcerative mass of angulus Polychemotherapy 4 years* anemia and body, thickening of (CHOP), folds in antrum radiotherapy 8 56 M Gastric bleeding - I Suspect ulcer of the body Cyclophosphamide 1 year* (1 year) 9 55 M Epigastric pain, weight Pseudolymphoma (10 years) IV (regional lymph Thickening ofgastric folds Cyclophosphamide 1 year partial loss 10 kg nodes lung) in body and antrum* (1 year) remission 10 67 M Epigastric pain (2 Bleeding ulcer requiring IV (lung) Small nodules in gastric Cyclophosphamide 1 year* months), weight loss surgery (7 years) stump (6 months) 5 kg 11 53 M Epigastric pain (1 year) - IV (bone marrow) Suspect ulcer of the body Cyclophosphamide 5 years* (1 year) 12 70 F Gastric bleeding Pseudolymphoma oflung IV (lung) Suspect ulcer ofangulus Cyclophosphamide Relapse at 6 years, and parotid glands (2 years) partial remission 7 years 13 57 F Epigastric pain (3 years) Gastric ulcer, gastritis, lung IV (lung, bone Thickening of antrum Cyclophosphamide Relapse at 6 years, lymphoma marrow) (1 year) small bowel, stomach, and lung 14 50 M Epigastric pain, anaemia - IV (lung mediastinal Suspect ulcer of body Cyclophosphamide 6 years* lymph nodes) (1 year) 15 54 F Epigastric pain Recurrent gastric ulcer, IV (lung) Ulcer of body Cyclophosphamide 18 months* gastric bleeding (1 year) 16 42 M Epigastric pain (6 months) Lung lymphoma IV (lung) Diffuse small nodules, Cyclophosphamide Relapse at 7 years, erosions (2 years) partial remission 7-5 years

* = free from disease; t=suspected of malignancy; f=gastric endosonography disclosed massive infiltration of the gastric wall with perigastric lymph node enlargement. LowgradeB cell mucosa associated lymphoid tissue lymphoma ofthe stomach: clinical and enzdoscopicfeatuires, treatmenalt, anid outcome1 1623

providing minimum and median follow up of 1 with a centroblastic aspect were rare. Superficial and 4 5 years respectively. plasma cells infiltrated underlying lymphoid cells. Residual crypts were rare or absent. Characteristic lymphoepithelial lesions Gut: first published as 10.1136/gut.33.12.1621 on 1 December 1992. Downloaded from Results (lymphoid cells invading gastric glands) were found in every case. In half the specimens CLINICAL FEATURES studied these lesions were found only after The main characteristics ofthe patients are given careful examination of numerous sections and in Table II. staining with an anti-cytokeratin antibody. A Persistent epigastric pain lasting from 6 lymphoid follicle was seen in two cases. Erosions months to 5 years was the predominant com- and ulcerations were generally present. plaint, associated with acute gastric bleeding in three patients, anaemia in two (haemoglobin <10 g/dl), and weight loss (>5 kg) in five at the Surgical specimens time of diagnosis. Eight patients had a past Two surgical specimens were examined. In history of recurrent gastric ulcer (n=5), endo- patient 4, who had been operated on before being scopic gastritis (n=3), or gastrointestinal bleed- referred to our institution, neoplastic cells ing (n=4) from 2 to 10 years before diagnosis. including centrocyte like appearance infiltrated One patient had been operated on (partial the mucosa, submucosa, and stomach muscles, gastrectomy) for a bleeding ulcer seven years with sparse extensions into the perigastric con- previously. Two patients had a past history of junctive tissue. Characteristic lymphoepithelial small cell lung lymphoma treated surgically lesions and rare lymphoid follicles were present. (n= 1) or with chemotherapy (n= 1). One of the In patient 10, who had been operated on for a latter patients had previously presented with a bleeding ulcer seven years previously, a gastric parotid gland localisation. lymphoma was diagnosed on the basis of biopsy specimens. A review of the surgical specimen showed that the gastric mucosa contained very ENDOSCOPIC ASPECTS numerous lymphoid follicles with follicular Endoscopic lesions affected the body of the centres suggestive of benign lymphoid infiltra- stomach in seven cases, the antrum in five, and tion. The follicles were surrounded by a popula- both the body and the antrum in four. In eight tion of small round lymphocytes, intermingled cases, the lesion consisted of an irregular and with a few small cleaved cells and centrocyte like large ulcer with raised edges and was highly appearance. A small number of gastric glands suggestive of malignancy. In the other eight exhibited characteristic lympho-epithelial cases endoscopy showed only lesions of a benign lesions. Proliferation was limited to the mucosa gastritis, erosions, small submucosa. These features led to the retro- nature (erythematous and http://gut.bmj.com/ nodules, localised or diffuse thickening ofgastric spective diagnosis of low grade MALT folds). lymphoma.

PATHOLOGICAL STUDY Immunohistochemicalfindings Immunohistochemical findings are given in Table III. lesions were shown

Lymphoepithelial on September 25, 2021 by guest. Protected copyright. Biopsy specimens on deparaffinised sections using anticytokeratin In 15 of 16 patients the diagnosis was based on and antiepithelial membrane antibodies. multiple endoscopic biopsies (>6) showing In the 12 cases in which cryostat sections were invasion of the gastric mucosa by lymphoid studied, tumour cells expressed CD 19 and CD tissue. The infiltrate consisted ofsmall lymphoid 22 B cell antigens, indicating a B cell origin. cells mixed with medium and occasionally large Kappa light chain restriction was present in eight cells. Small cells were lymphocytes with either a cases and lambda light chain restriction in four small round nucleus or an irregular nucleus cases. Tumour cells exhibited the IgM +ve, giving a centrocyte like appearance. Large cells IgD-ve, CD 5-ve phenotype. These histo- pathological results were consistent with the diagnosis of MALT lymphoma. TABLE III Histological and immunohistochemicalfindings Immuno-phenorype Case Lymphoepithelial Centrocyte like Follicular STAGING no lesions cells centres Ig CD 5 IgD The lymphoma was localised within the gastric 1 + + - IgM Kappa - - wall with no evidence of regional lymph node 2 + ++ - ND ND ND 3 + + - IgM Kappa - - involvement (stage I) in eight patients. Eight 4 + + + ND ND ND patients had stage IV disease, because of bone 5 + + + IgM Kappa 6 + + + ND ND ND marrow involvement in two patients and/or lung 7 + + + - IgM Lambda - - involvement in seven. Lung involvement was 8 + + - IgMLambda - 9 + + + + IgM Lambda suspected on the basis of x ray abnormalities and 10 + + + + IgM Kappa - - was confirmed histologically in a surgical biopsy 11 + + - IgM Kappa - 12 + ++ - IgM Kappa - - specimen in three cases and in a transbronchial 13 + ++ - IgM Lambda - biopsy specimen in one. No biopsy was per- 14 + + - IgM Lambda ND ND 15 + ++ - ND ND ND formed in the other cases but the lung opacity on 16 + + + - IgM Kappa the chest x ray or computed tomogram had the ND=Not done. same macroscopic aspect as in the cases ofproved 1624 Blazcquez, Haioun, Chaumctiette, Gaulard, Reves, Sculic, Dclchicri

TABLE IV Macroscopic aspect oflung involvement in seven logical examination showed small and medium patients sized lymphoid cells (centrocyte like cells) Gut: first published as 10.1136/gut.33.12.1621 on 1 December 1992. Downloaded from Case Histological invading gastric glands to form characteristic no Chest radiograph and computed tomogram proof lymphoepithelial lesions. In some cases, the 9 Round opacity of 4 cm in right lung proliferation surrounded and sometimes invaded 10 Round opacity of 2 cm in left lung reactive B cell follicles. Immunohistochemical 12 Bilateral opacities and diffuse shadowing + 13 Round opacity in right lung (1977) studies showed a B cell origin of the lymphoma, Round opacity in left lung (1983) + as well as the IgM+ve, IgD-ve, CD 5-ve 14 2 round opacities of 2 and 5 cm in left lung + 15 Round opacity of 5 cm in left lung phenotype. 16 Bilateral opacities with diffuse shadowing + The clinical presentation of our patients confirmed previous reports of the non-specific nature ofdigestive symptoms, clinical indolence, lung lymphoma and responded to chemotherapy and the slow course in low grade gastric MALT as well as the gastric lesion. The macroscopic lymphoma.'2 '3 All the patients had complained aspect of the lung involvement is described in of chronic epigastric pain for years before diag- Table IV. Gastric endosonography, performed nosis and eight had a past history of recurrent in patient 9, who had thickening of gastric folds gastric ulcer, gastrointestinal bleeding, or gas- in the body and the antrum at endoscopy (Table tritis. The endoscopic aspect of the gastric II), showed massive infiltration of the gastric lesions was clearly suggestive of malignancy in wall together with perigastric lymph node only halfthe patients. In the remaining cases, the enlargement. endoscopist described erythematous gastritis, small nodules or thickening and erosions of gastric folds suggestive of a benign condition. TREATMENT AND OUTCOME This explains how the disease can be misdiag- Fourteen patients were initially treated with nosed over a long period and stresses the need for cyclophosphamide, one with polychemo- biopsy specimens whatever the type of gastric therapy, and one with surgery and irradiation. lesion. In patient 9, endosonography showed Treatment efficacy could be evaluated in 14 of that there was no relationship between the the 16 patients. Two patients (nos 3 and 5) were endoscopic aspect and the locoregional extension lost to follow up. The mean duration offollow up of the lymphoma. Although the endoscopic in the 14 remaining patients was 4X5 years (range: changes were minimal (only mild thickening of 1-7.S years). gastric folds), endosonography disclosed Four of the six evaluable stage I patients were massive infiltration of the gastric wall associated treated with cyclophosphamide. Patient 4 who with an enlargement of regional lymph nodes. had been operated on before referral received This observation illustrates the usefulness of additional radiation therapy. Another patient endosonography in the staging of low grade http://gut.bmj.com/ (no 7), who presented with a bulky tumour ofthe gastric lymphoma.2' gastric body was treated with a polychemo- The chronic nature of the symptoms, the therapy CHOP regimen (cyclophosphamide, benign appearance of the gastric lesions on hydroxyldaunomycin, oncovin, and prednisone) endoscopy, and the equivocal histological aspect +radiation therapy. Complete remission was of the lesions account for the fact that numerous obtained in six patients including four treated MALT lymphomas were considered 'pseudo- with cyclophosphamide, with a follow up lymphomas'47 until the monoclonal nature of the on September 25, 2021 by guest. Protected copyright. ranging from 1 5-7 years. proliferation could be routinely shown by The eight patients with stage IV disease immunochemistry. In our series, two patients received cyclophosphamide. All these patients (nos 3 and 9) were diagnosed as having pseudo- are alive after a follow up ranging from 1 to 7X5 lymphomas 3 and 10 years respectively before years. Four are in a first complete remission and the diagnosis ofMALT lymphoma. In both cases one in partial remission. Three relapsed at 6 a review of previous biopsy specimens showed years (n=2) and 7 years (n= 1). One of these the presence of lympho-epithelial lesions clearly latter patients (no 13) was operated on for an indicative of malignancy."522 This typical lesion obstructive small bowel relapse and in this was also present on the surgical specimen from patient, as in the two others, gastroscopy and patient 10 who had undergone surgery for a chest computed tomography showed both lung 'bleeding ulcer' seven years before the definitive and gastric recurrences. All three patients who diagnosis. relapsed responded again to cyclophosphamide. Our results show that low grade gastric Repeated gastric biopsies did not show progres- MALT lymphoma can be readily diagnosed on sion to a higher grade lymphoma in any of the the basis of biopsy specimens. Lympho- patients. epithelial lesions are observed on fixed tissues Chemotherapy was well tolerated and no cases and immunohistochemical studies of fixed of myelodysplastic syndromes were observed tissues can help to show these lesions with the aid despite follow up exceeding two years in seven of anti-cytokeratin or -epithelial membrane anti- patients treated with alkylating agents. bodies. Finally, immunohistochemical analysis of frozen tissue sections clearly shows the monoclonal nature and B cell phenotype of the pro- Discussion liferation, together with the peculiar IgM+ve, All the patients we studied fulfilled the histo- IgD-ve, CD 5-ve phenotype of the tumoural logical and immunocytological criteria estab- cells, indicative of the MALT origin of the lished by Isaacson et al for the diagnosis of low proliferation. grade B cell lymphoma of MALT.'3'4 Histo- One of the most important findings in our Low gradeB cell mucosa associated lymphoid tissue lymphoma ofthe stomach: clinical and endoscopicfeatures, treatment, and outcome 1625

study was the high frequency of extragastric Cyclophosphamide monochemotherapy pro- locations of MALT lymphomas, present in half cures complete remission, with only slight the patients (8 of 16). Interestingly, they gener- morbidity, and remains effective against Gut: first published as 10.1136/gut.33.12.1621 on 1 December 1992. Downloaded from ally affected other mucosal sites (lung, n=7; relapses. parotid, n=l; small bowel, n=1) and usually spared the peripheral lymph nodes, spleen, and 1 Freeman C, Berg JW, Cutler SJ. Occurrence and prognosis of extranodal lymphomas. Cancer 1972; 29: 252-60. bone marrow. Involvement of other mucosal 2 Lewin KJ, Ranchod M, Dorfman RF. Lymphomas of the sites preceded, coincided with, or followed the gastro-intestinal tract, a study of 117 cases presenting with gastrointestinal disease. Cancer 1978; 42: 693-707. manifestations of the gastric lymphoma. These 3 Grody WW, Weiss LM, Warnke RA, Magidson JG, Hu E, findings were unexpected, as most of previously Lewin JK. Gastrointestinal lymphoma, immunohistochemical studies ofthe cell oforigin. AmJ Surg Pathol 1985; published clinicopathological studies have 9: 328-37. shown that low grade B cell gastric lymphoma is 4 Tokunaga 0, Watanabe T, Morimatsu M. Pseudolymphoma of the stomach: a clinicopathologic study of 15 cases. Cancer a disease process confined to the stomach for 1987; 59: 1320-7.. years.'723 However, recent studies showed that 5 Wolf J, Spjut H. Focal lymphoid hyperplasia of the stomach preceding gastric lymphoma: Case report and review of the malt lymphomas, whatever the organ involved, literature. Cancer 1981; 48: 2518-23. were susceptible to spread to or to recur in other 6 Scoazec JY, Brousse N, Potet F, Jeulain JF. Focal malignant lymphoma in gastric pseudolymphoma: histologic and mucosal sites.'32425 Although the exact fre- immuno-histochemical study of a case. Cancer 1986; 57: quency of extragastric localisation remains to be 1330-6. 7 Brooks J, Enterline H. Gastric pseudolymphoma: its three determined prospectively in a larger series, our subtypes and relation to lymphoma. Cancer 1983; 51: observations suggest that this possibility has to 476-86. 8 Eimoto T, Futami K, Naito H, Takeshita M, Kikuchi M. be taken into account in the choice ofthe staging Gastric pseudolymphoma with monotypic cytoplasmic procedure and therapeutic strategy. immuno-globulin. Cancer 1985; 55: 788-93. 9 Burke J, Sheibani K, Nathwani B, Winberg C, Rappaport H. In previously published studies, most authors Monoclonal small lymphocytic proliferations of the gastro- recommended surgery, arguing that low grade intestinal tract resembling lymphoid hyperplasia: a neo- plasm of uncertain malignant potential. Hum Pathol 1987; gastric MALT lymphomas were localised, 18: 1238-45. solitary lesions that could be excised com- 10 Spencer J, Diss T, Isaacson P. Primary B-cell gastric lymphoma: a genotypic analysis. Am J Pathol 1989; 135: pletely467'324 and that endoscopic biopsy speci- 557-64. mens could miss small foci of high grade, B cell 11 Sigal S, Saul S, Auerbach H, Raffensperger E, Kant J, Brooks J. Gastric small lymphocytic proliferation with immuno- lymphomas.26 However, in our series half the globulin gene rearrangement in pseudolymphoma versus patients had a stage IV lymphoma. Among the lymphoma. Gastroenterology 1989; 97: 195-201. 12 Moore I, Wright D. Primary gastric lymphoma - a tumor of eight with stage I disease, five had tumoural mucosa - associated lymphoid tissue. A histological and involvement of the stomach which would have immunohistochemical study of 36 cases. Histopathology 1984; 8:1025-39. required total gastrectomy, a procedure with a 13 Isaacson P, Spencer J, Finn T. Primary B-cell gastric high morbidity rate and one that is not justified lymphoma. Hum Pathol 1986; 17: 72-82. with a well tolerated, slowly progressing disease. 14 Myrhe M, Isaacson P. Primary B-cell gastric lymphoma. A reassessment of its histogenesis. J Pathol 1987; 152: 1-11. http://gut.bmj.com/ Moreover, in one patient (no 10), the lymphoma 15 Isaacson P, Wright D. Extranodal malignant lymphoma arising from Mucosa-Associated-Lymphoid-Tissue. Cancer relapsed after partial gastrectomy. We therefore 1987; 53: 2515-24. favoured conservative treatment with cyclo- 16 Saraga P, Hurlemann J, Ozzello L. Lymphomas and pseudolymphomas of the alimentary tract. An immunohisto- phosphamide monochemotherapy. chemical study with clinicopathologic correlations. Hum All the patients with stage I disease responded Pathol 1981; 12: 713-23. 17 Cogliatti SB, Schmid U, Schumacher U, Eckert F, Hansmann to therapy, and a complete remission was ML, Hedderich J, et al. Primary B-cell gastric lymphoma: A obtained in those (n=4) treated for at least one clinicopathological study of 145 patients. Gastroenterology 1991; 101: 1159-70. on September 25, 2021 by guest. Protected copyright. year. In the eight stage IV patients in whom the 18 The non-hodgkin's lymphoma pathologic classification follow up was of specially long duration (median project. National Cancer institute sponsored study ofclassi- fications of non hodgkin's lymphomas. Summary and 6 years), a complete remission was initially description ofa working formulation for clinical use. Cancer obtained with cyclophosphamide in every case 1982; 49: 2112-35. 19 Cordell JL, Falini B, Erber WN. Immunoenzymatic labelling and patients whose disease recurred several years of monoclonal antibodies using immune complexes of after the initial treatment remained sensitive to alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP) complexes. J Histochem Cytochem 1984; monochemotherapy. Moreover, in contrast with 32: 219-29. a recent report,25 no cases ofconversion to a high 20 Carbone PP, Kaplan HS, Musshoff K. Report of the commit- tee on Hodgkin's disease staging classification. Cancer Res grade lymphoma were observed. Although 1971;31: 1860-1. cyclophosphamide was well tolerated in our 21 Tio TL, den Hartog Jager FCA, Tytgat GNJ. Endoscopic ultrasonography ofnon Hodgkin lymphoma of the stomach. patients, the risk of developing a myelo- Gastroenterology 1986; 91: 401-8. dysplastic syndrome cannot be excluded. How- 22 Isaacson P, Wright D. Malignant lymphoma of Mucosa- Associated-Lymphoid-Tissue. A distinctive type of B-cell ever, this long term toxicity of alkylating agents lymphoma. Cancer 1983; 52: 1410-6. has been shown to be related to the intensity of 23 Isaacson PG, Spencer J. Malignant lymphoma of mucosa- associated lymphoid tissue. Histopathology 1987; 11: 445-62. therapy given27 and is very unlikely to occur with 24 Addis BJ, Hyiek E, Isaacson P. Primary pulmonary the low doses needed to treat our patients. Thus, lymphoma: a re-appraisal of its histogenesis and its relationship to pseudolymphoma and lymphoid interstitial in our experience, monochemotherapy is appro- pneumonia. Histopathology 1988; 13: 1-17. priate for low grade, gastric MALT lymphomas. 25 Li G, Hansmann L, Zwingers T, Lennert K. Primary lymphomas of the lung: morphological, immunohisto- In conclusion, our findings show that low chemical and clinical features. Histopathology 1990; 16: grade, gastric MALT lymphoma can always be 519-31. 26 Chan JK, Isaacson P. Relationship between high-grade diagnosed on the basis of both fixed and fresh lymphoma and low-grade B-cell Mucosa-Associated endoscopic biopsy specimens. Extragastric Lymphoid Tissue Lymphoma (MALToma) of the stomach. AmJfPathol 1990; 136: 1153-64. involvement seems to be frequent, usually affect- 27 Koeffier HP. Myelodysplastic syndromes. 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