Gastrointestinal lymphomas of mucosa associated lymphoid tissue (MALT) - a report of 7 Sri Lankan cases M V D de Silva*, M S Fernando", N Ratnatunga"* Journal of the Ceylon College of Physicians, 1998, 31; 1 & 2, 58-61 Abstract Introduction: Lymphoma of mucosa associated lymphoid tissue (MALT) is a distinct recently described subtype with a good prognosis. It is often confused with other variants of Non Hodgkin's lymphoma (NHL) with a poor prognosis. Objective: 1. To determine the proportion of MALT type lymphoma in gastrointestinal lymphomas previously diagnosed as NHL. 2. To determine if low grade MALT lymphomas are associated with high grade lymphomas. Method: Histology slides of nine NHL of the stomach, ileum and colon, diagnosed between 1987-1995 at the University Department of Pathology, Peradeniya were reviewed for diagnostic criteria of MALT type lymphoma. Results: Seven tumours were subtyped as low grade MALT lymphomas. Four of these showed coexistent high grade large cell lymphoma. Conclusion: 77.7% of gastrointestinal lymp­ homas were of MALT type. The coexistence of high grade lymphoma in 4 cases indicates that MALT lymphomas can transform into large cell lymphomas. Introduction Lymphomas of mucosa associated lymphoid tissue (MALT) were first described by Isaacson and Wright in 19831 as a distinctive type of B-cell Non Hodgkin's Lymphoma (NHL) involving the gastrointestinal tract (GIT). However all GIT lymphomas * Senior Lecturer "Lecturer, Department of Pathology, Faculty of Medicine, Colombo. ""Associate Professor, Department of Pathology, Faculty of Medicine, Peradeniya. This paper was awarded the Daphne Attygalle Award 1997 by Sri Lanka Medical Association. are not of MALT type. They could be large cell or large cell immunoblastic lymphomas, mantle cell lymphomas, small lymphocytic lymphomas or T cell lymphomas2. Recognition of MALT lymphomas as a separate subtype of NHL is important because they remain localized at the site of origin for a long time, tend to relapse in the same or other mucosal sites and if localized may be cured3,4. Most pathologists in Sri Lanka use the international working formulation to classify NHL 5 . In this classification there is no category named MALT lymphoma. Thus the objective of this retrospective study was to determine the proportion of MALT type lymphoma in GIT lymphomas previously diagnosed as other categories of NHL. We also wanted to determine if low grade MALT lymphomas were associated with high grade lymphomas. Method A total of nine gastrointestinal lymphomas had been reported at the Department of Pathology, University of Peradeniya during a 9 year period between 1987-1995. The slides which had been stained with haematoxylin and eosin were reviewed for features of low grade MALT lymphoma. Results Seven tumours were subtyped as low grade MALT lymphomas. Four of these showed coexistent high grade large cell lymphoma. Two cases were high grade NHL without evidence of coexistent MALT lymphoma. The clinical features of the 7 cases of MALT lymphoma are shown in Table 1. Follow up data of patients is not known as this was a retrospective study. All cases showed diagnostic criteria for low grade MALT lymphoma which included the presence of lymphoepithelial lesions (Figure 1), reactive follicles and a mixed diffuse population (Figure 2) of centrocyte like cells, small round lymphocytes, Gastrointestinal lymphomas of mucosa associated lymphoid tissue (MALT) 59 Table 1 Clinical Features of 7 patients with MALT lymphoma Case No: Age (years) Sex Site Mesenteri c nodes Microscopy Depth of penetration 1 56 Female Terminal ileum Enlarged High + low grade MALT lymphoma Confined to bowel wall, 2 57 Female Ascending colon Enlarged High + low grade MALT lymphoma Extended to mesenteric fat 3 55 Male Pylorus of stomach Enlarged High + low grade MALT lymphoma Extended to mesenteric fat 4 33 Male Ileum Not. enlarged High + low grade MALT lymphoma Penetrated the muscularis propria and extended to the serosal surface 5 50 Male Stomach Not enlarged low grade MALT lymphoma Penetrated the muscularis propria and extended to the serosal surface 6 Not known Not known Ileum Not enlarged low grade MALT lymphoma Penetrated the muscularis propria and extended to the serosal surface 7 10 Male Colon Not enlarged low grade MALT lymphoma Confined to bowel wall monocytoid cel ls and p lasma c e l l s 2 , 6 . In the 4 c a s e s where there w a s co-existent high grade lymphoma, the low grade MALT lymphoma component w a s situated at the periphery with the high grade lymphoma occupying the central part of the tumour m a s s or ulcer. There w a s marked destruction of glands in the high grade a r e a s and lymhoepithelial les ions were absent . The high grade component w a s c o m p o s e d of lymphocytes with larger nuclei, c lumped chromatin and frequent mitotic figures (Figure 3) . In all c a s e s where the mesenteric lymph n o d e s were enlarged they were effaced by a high grade large cell lymphoma similar in appearance to that in the GIT. Low grade MALT lymphomas without a high grade component were not assoc ia ted with enlarged mesenteric lymph n o d e s . Figure 1. Lymphoepithelial lesion; infiltration of mucosal glands by lymphocytes (haematoxylin and eosin X 400). Vol. 31, No. 1 & 2, 1998 6 0 Figure 2. L o w grade M A L T lymphoma; diffuse infiltration of mucosa and submucosa by lymphocytes (haematoxylin and eosin X 100). Figure 3. High grade area in M A L T lymphoma (haematoxylin and eosin X 400) . Discussion The clinical, behavioural and pathological features of MALT lymphomas are sufficiently distinctive for them to be considered a s a specific sub type of NHL. The concept of lymphomas of MALT h a s b e e n currently expanded to include several extranodal s i t e s 4 , 7 . Most extranodal MALT lymphomas arise in s i tes without normal MALT such a s the s tomach, salivary g lands and thyroid 6 8 . This is explained by the proposal that they arise in a setting of "acquired MALT". This nonindigenous lymphoid t i ssue is acquired secondary to an infection such a s Helicobacter pylori in the s t o m a c h 9 or an MVDde Silva, M S Fernando, N Ratnatunga Journal of the Ceylon College of Physicians autoimmune d i s e a s e such a s Sjogren's syndrome in salivary glands or Hashimoto's d i s e a s e in the thyroid 6. The growth pattern and immunophenotype of the centrocyte like cells in MALT lymphoma sugges t that they may represent neoplastic marginal z o n e ce l l s 8 . The tendency of MALT lymphomas to evolve slowly, remain localized and to involve other mucosal s i tes when they do spread, may be due to specific homing patterns of MALT derived lymphocytes 4 . MALT lymphomas are consistently CD 10 negative and fail to s h o w rearrangement of the bcl-2 proto-oncogene both of which are characteristic features of follicular center cell lymphomas 3 . Similarly MALT lymphomas are CD 5 negative and fail to show bcl-1 g e n e rearrangement which helps to distinguish them from mantle cell l y m p h o m a s 3 ' 0 . The association of high grade lymphoma and low grade MALT lymphoma a s s e e n in 4 of our c a s e s has been described previously by Chan and co-workers who found 10 c a s e s with this association in a ser ies of 4 8 gastric l y m p h o m a s 1 1 . They s u g g e s t e d that the likelihood of finding this association may increase with the number of sect ions examined. In their series the immunophenotype of the low and high grade components were similar providing strong ev idence that the two components evolve from the s a m e clone. Both high and low grade MALT lymphomas show a favourable behaviour when compared with nodal l y m p h o m a s 8 ' 2 . Early gastric MALT lymphomas are known to regress with treatment for Helicobacter pylori 1 3 . Lcxal surgery has b e e n adopted a s a potentially curative therapeutic modality for MALT lymphoma. However local relapse has been reported often after a long d i s e a s e free interval, even in patients where the initial excision s e e m e d to be comple te ' 4 . Therefor patients should be followed up regularly. References 1 . Isaacson P G , Wright D H . Malignant lymphoma of mucosa-associated lymphoid t issue. A distinctive type of B-cell lymphoma. Cancer 1983; 52: 1410 -1416 . 2. Rosa i J . Ackerman's Surgical Pathology. Volume 1 . 8th edition. S t Lou is : Mosby 1996; 693 -695 . Gastrointestinal lymphomas of mucosa associated lymphoid tissue (MALT) 61 3. Isaacson PG. Lymphomas of mucosa-associated lymphoid tissue (MALT). Histopathology 1990; 16: 617-619. 4. Isaacson PG. Wright DH. Extranodal malignant lymphoma arising from mucosa associated lymphoid tissue. Cancer 1984; 53:2515-2524. 5. Non-Hodgkin's Lymphoma Pathologic Classification Project: National Cancer Institute sponsored study of classification of Non-Hodgkin's lymphoma. Summary and description of a working formulation for clinical usage. Cancer1982; 49:2112-2135. 6. Burke JS. Extranodal lymphomas and lymphoid hyperplasias. In: Jaffa ES, ed. Surgical pathology of the lymph nodes and related organs. 5th edition. Philadelphia: WB Saunders 1995; 479-482. 7. Pelstring RJ, Essell JH, Kurtin PJ, Cohen AR, Banks PM. Diversity of organ site involvement among malignant lymphomas of mucosa-associated tissues. American Journal of Clinical Pathology 1991; 96:738-745. 8. Isaacson PG, Spencer J. Malignant lymphoma of mucosa-associated lymphoid tissue. Histopathology 1987;11:445-462. 9. Wotherspoon AC, Oritz-Hidalgo C, Falzon M, Isaacson PG. Helicobacter pylori associated gastritis and primary B-cell gastric lymphoma. Lancer 1991; 338:1175-1176. 10. Wotherspoon AC, Pan L, Diss TC, Isaacson PG. A genotypic study of tow grade B-cell lymphomas, including lymphomas of mucosa-associated lymphoid tissue (MALT). Journal ot Pathology 1990; 162:135-140. 11. Chan KC, Ng CS, Isaacson PG. Relationship between high grade lymphoma and low grade B-cell mucosa-associated lymphoid tissue lymphoma (MALToma) of the stomach. American Journal of Pathology 1990; 136:1153-1164. 12. Isaacson PG, Spencer J, Wright DH. Classifying primary gut lymphomas. Lancet 1988; 1148-1149. 13. Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, de Boni M, Isaacson PG. Regression of primary low grade B-cell gasric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancef 1993; 1343:575-577. 14. Wotherspoon AC, Doglioni C, Isaacson PG. Low grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT): a mutifocal disease. Histopathology\992; 20:29-34. Vol. 31, No. 1&2, 1998