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Diffuse Lymphomatous Polyposis of the Gastrointestinal Tract
GASTROENTEROLOGY 1985;88:1267-70
Diffuse Lymphomatous Polyposis of the Gastrointestinal Tract A Case Report With Immunohistochemical Studies BERNARD J. FERNANDES, DOMINICK AMATO, and MORRIS GOLDFINGER
Departments of Pathology, Medicine, and Radiology, Mount Sinai Hospital and University of Toronto, Toronto, Canada
A case of diffuse lymphomatous polyposis of the gastrointestinal tract is reported. The patient presented with abdominal pain and weight loss dnd xrays revealed multiple polyps involving the entire gastrointestinal tract. Biopsies confirmed the diagnosis of lymphomatous polyposis. The patient also had involvement of the bone marrow and supraclavicular lymph node. Immunologically this lymphoma was characterized as a monoclonal proliferation of B lymphocytes bearing immunoglobulin M, type K. Diffuse lymphomatous polyposis of the gastrointestinal tract appears to be a generalized malignancy of uncommitted B cells of Peyer's patches. The migratory properties of these cells may account for the tendency to dissemination of lymphomatous polyposis. Diffuse lymphomatous polyposis of the gastrointestinal tract is a distinct entity, separate from the diffuse gastrointestinal lymphoma known as Mediterranean-type lymphoma. The gastrointestinal (GI) tract is the most common she of extranodal malignant lymphomas and accounts for about 30% of these lymphomas (1). Primary GI lymphomas most commonly present as a single lesion (2). However, two varieties of diffuse involvement of the GI tract by malignant lymphoma are recognized. The first, so-called Mediterranean type-lymphoma (MTL), is characterized by a diffuse proliferation of plasma cells in the lamina propria of the small intestine (3-5). The second is lymphomaReceived July 30, 1984. Accepted November 14, 1984. Address requests for reprints to: Dr. B. J. Fernandes, Department of Pathology, Mount Sinai Hospital, 600 University Avenue, Toronto, Canada M5G 1X5. The authors thank Rachel Peters for technical assistance and Marina Prior for manuscript preparation. © 1985 by the American Gastroenterological Association 0016-5085/85/$3.30
to us polyposis (tp) in which multiple polypoid lesions of malignant lymphoma are distributed throughout the GI tract (6). Recently immunoperoxidase techniques have been used to characterize the cells of malignant lymphomas and have offered newer insights into these diseases (7,8). We report a case of LP of the GI tract studied by immunoperoxidase techrtiques and compare the features of this disease with those of MTL. To our knowledge this is the first case of diffuse LP that has been studied by immunologic methods.
Case Report A 67-yr-old man presented with weight loss, anorexia, fatigue, melena, and abdominal pain. Physical examination revealed generalized peripheral lymphadenopathy but was otherwise unremarkable. Laboratory investigations showed a mild normocytic, normochromic anemia and mildly abnormal liver function tests. Serum protein electrophoresis was normal. An air-contrast barium enema revealed a diffuse nodular pattern evenly distributed throughout the colon (Figure 1). The nodules were fairly uniform in size, ranging from 5 to 7 mm. A minute umbilication was seen on the surface of many of the nodules. The duodenal cap and terminal ileum showed similar nodularity and a few nodules were scattered throughout the jejunum. There was no increase in density of the nodules in the terminal ileum. An abdominal computed tomographic scan showed extensive retroperitoneal and mesenteric adenopathy. Biopsies of the jejunum, colon, rectum, lymph node, and bone marrow were performed, and a diagnosis of nodular, poorly differentiated lymphocytic lymphoma was established. Abbreviations used in this paper: LP, lymphomatous polyposis; MTL, Mediterranean-type lymphomas.
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GASTROENTEROLOGY Vol. 88, No.5, Part 1
Results Sections of biopsy specimens from the duodenum, colon, and rectum all showed similar features. There were nodular aggregates of atypical lymphocytes in the lamina propria (Figure 2). These lymphocytes had irregular, cleaved nuclear margins, condensed chromatin, inconspicuous nucleoli, and scanty cytoplasm. The adjacent uninvolved lamina propria showed a normal population of plasma cells and lymphocytes. A diagnosis of poorly differentiated lymphocytic lymphoma was made. The biopsy specimen of the supraclavicular lymph node also showed replacement by nodular, poorly differentiated lymphocytic lymphoma, and the bone marrow specimen demonstrated involvement of that organ. Immunoperoxidqse staining of the duodenal, colonic, and lymph node specimens, showed that the malignant cells were a monoclonal population of B lymphocytes bearing IgM type-K immunoglobulin (Figures 3A, 3B). In the gut, the plasma cells in the uninvolved lamina propria contained both K and A light chains. Figure 1. Air-contrast barium enema of sigmoid colon showing a diffuse nodular pattern of the mucosa. This pattern was also present in the jejunum. ileum, and entire colon.
The patient was treated with chemotherapy (cyclophosphamide, vincristine, and prednisone) but had a poor response to therapy. A subsequent lymph node biopsy showed progression to a diffuse, poorly differentiated lymphocytic lymphoma. Doxorubicin was added to the chemotherapeutic regimen, but with little benefit. The patient died 6 mo after diagnosis. An autopsy was not performed.
Materials and Methods Biopsy specimens were fixed overnight in B5 fixative and embedded in paraffin. Immunoperoxidase staining for immunoglobulins (Ig) G, A, M, and K and A light chains were performed on the paraffin sections. The sections were pretreated with fresh 0.4% trypsin solution in 0.85% hydrochloric acid at 37°C for 30 min. After two 10min washes in phosphate-buffered saline (pH 7.4), the sections were incubated with 10% bovine serum albumin for 30 min. The sections were then incubated with rabbit antihuman serum for 1 h and again washed twice in phosphate-buffered saline (two 10-min washes). Finally, the sections were incubated with peroxidase-conjugated swine antirabbit antiserum for 30 min and washed in phosphate-buffered saline (two 10-min washes). The peroxidase activity was demonstrated using diaminobenzidine tetrahydrochloride. Antibodies were purchased from Dako products (Toronto, Canada) and used at the following dilutions: IgM, 1/600; IgG, 1/1000; IgA, 1/1000; K, 1/1200; A, 1/1200.
Figure 2. A. Biopsy of colon showing a nodular aggregate of monomorphous, small lymphocytes in the lamina propria and adjacent submucosa. (H & E; x 78.) B. Highpower detail of lymphomatous nodule. Note atypical small lymphocytes with condensed chromatin and irregular nuclear margins. (H & E; x 500.)
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May 1985
1269
diagnosis may be suspected on radiologic examination, biopsies are necessary to confirm the diagnosis. These patients frequently develop generalized extraintestinal lymphoma. By the use of immunoperoxidase techniques we were able to demonstrate a monoclonal proliferation of cells and therefore confirm a diagnosis of malignant lymphoma. Lymphomatous polyposis appears to be a B-cell neoplasm. Immunoglobulin M is the most common immunoglobulin type found in malignant lymphomas (8) and appears at an earlier stage of B-cell maturation than IgG or IgA (14). Recently, a second form of diffuse GI lymphoma, MTL, has received increasing attention. It is characterized by diffuse involvement of predominantly the small intestine by an intense proliferation of plasma cells that is initially restricted to the lamina propria (3-5). Eventually it proceeds to an overt malignant lymphoma with the appearance of immature cells, nodular lesions, and extension beyond the lamina propria. Many of these patients have an abnormal paraprotein representing the a-chain fragment of IgA (3).
Figure 3. A. Biopsy of colon stained for IgM by the immunoperoxidase technique. The majority of cells stain positively. (X312.) B. Biopsy of colon stained for K light chains by the immunoperoxidase technique. The majority of cells stain positively. (X312.)
Discussion The GI tract may be involved by malignant lymphoma as a primary tumor or as part of a more widespread disease process. Generally the lymphoma is considered as "primary" in the GI tract when the initial symptoms of the disease are in the abdomen or present as a disturbance of GI function (9). Four types of primary intestinal lymphomas have been described: (a) annular or plaquelike lesions, (b) bulky and protuberant growths, (c) aneurysmal bowel lesions, and (d) multiple lymphomatous polyps spread over long segments of the intestinal tract (10). The final type, multiple LP, which our patient had, is the least common. Comes et al. (6) have described 5 patients with this disease and reviewed a further 22 cases that had been published in the literature. Subsequently, three case reports have appeared (1113) and Lewin et al. (1) found 4 cases of diffuse LP in a review of 117 cases of primary GI tract lymphomas. Our patient shows many features that appear to be characteristic for LP (6), i.e., an elderly patient presenting with nonspecific GI symptoms and absence of a malabsorption syndrome. Although the
There are significant differences between these two types of diffuse GI lymphomas. Lymphomatous polyposis tends to occur in elderly persons and involves the entire GI tract (6). Mediterranean-type lymphoma is more common in younger patients and has a characteristic geographic distribution with a high incidence in the Mediterranean region (3). Lymphomatous polyposis has been reported predominantly in the Western world and no geographic restriction is apparent (15). Mediterranean-type lymphoma is usually associated with a malabsorption syndrome, whereas LP is not. In MTL the entire lamina propria is infiltrated by plasma cells, whereas in LP the uninvolved lamina propria shows a normal population of lymphocytes and plasma cells. The lymphoma associated with MTL is a plasma cell tumor or an immunoblastic sarcoma, whereas the lymphoma in LP includes a spectrum of cytologic types, reflecting those that occur in the peripheral nodes. Mediterranean-type lymphomas rarely spread beyond the abdomen (15), whereas systemic lymphoma is common in LP (6). Mediterranean-type lymphoma is often associated with an a-chain paraprotein (3), but this has not been reported in LP. The occurrence of two distinct types of diffuse GI lymphomas is of interest in the light of present knowledge of gut-associated B lymphocytes (16). It has become apparent that B cells from Peyer's patches are discharged into the intestinal lymph and pass through the mesenteric nodes to the thoracic duct. The lymphocytes are carried in the lymph stream to the blood where the majority demonstrate a selective homing pattern to the gut, where they then extrava-
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sate into the lamina propria and develop into IgAsecreting plasma cells (17). In the Peyer's patches very few B cells contain detectable IgA, whereas the majority of the B cells in the thoracic lymph contain IgA. This suggests that the IgA-containing plasma cells present in the gut mucosa are derived from lymphocytes in the Peyer's patches that mature while migrating to the mesenteric nodes and thoracic duct lymph (18). Thus, two populations of gutassociated B lymphocytes are postulated: a population of uncommitted precursor cells in Peyer's patches that have migratory properties and a population of IgA-secreting plasma cells in the lamina propria that are stationary. As malignant lymphomas are believed to reflect the normal pattern of lymphocyte traffic and homing (19), LP may represent the malignant counterpart of the uncommitted B lymphocytes of Peyer's patches. The presence of IgM in our patient's malignant cells is compatible with an uncommitted B lymphocyte because IgM appears before IgG or IgA on B lymphocytes (14). The tendency to early dissemination in LP suggests the capacity of the malignant lymphocytes for peripheral migration. The widespread distribution of the malignant lymphoid nodules in the intestine at the time of presentation in our patient also supports the notion that they had arisen synchronously from malignant cells in the circulation that had homed to sites in the intestinal mucosa. In contrast, MTL could represent the malignant counterpart of the committed IgAsecreting cells of the lamina propria. The frequent finding of serum a-chain paraproteins (3) is evidence of the capacity, albeit deranged, of these cells to secrete immunoglobulin. The rarity of extraabdomina I disease in MTL (15) is compatible with the stationary properties of plasma cells in the lamina propria (17). Further studies of the immunologic features and migratory properties of malignant cells in LP and MTL are required in order to provide a better understanding of these diseases.
References 1. Lewin KJ, Ranchod M, Dorfman RF. Lymphomas of the
GASTROENTEROLOGY Vol. 88, No.5, Part 1
gastrointestinal tract. A study of 117 cases presenting with gastrointestinal disease. Cancer 1978;42:693-707. 2. Blackledge G, Bush H, Dodge OG, Crowther D. A study of gastrointestinal lymphoma. Clin Oncol 1979;5:209-19. 3. AI-Saleem T, Zardawi 1M. Primary lymphomas of the small intestine in Iraq: a pathological study of 145 cases. Histopathology 1979;3:89-106. 4. Nassar YH, Salem PA, Shahid MJ, et al. "Mediterranean abdominal lymphoma" or immunoproliferative small intestinal disease. Cancer 1978;41:1340-54. 5. Galian A, Locestre M-J, Scotto J, Bognel C, Matruchansky C, Rambaud J-C. Pathological study of alpha-chain disease with special emphasis on evolution. Cancer 1977;39:2081-101. 6. Comes JS. Multiple lymphomatous polyposis of the gastrointestinal tract. Cancer 1961;14:249-57. 7. Taylor CR. An immunohistological study of follicular lymphoma, reticulum cell sarcoma and Hodgkin's disease. Eur J Cancer 1976;12:61-75. 8. Lukes RJ, Taylor CR, Parker JW, Lincoln TL, Pattengale PK, Tindle BM. A morphologic and immunologic surface marker study of 299 cases of non-Hodgkin's lymphomas and related leukemias. Am J Pathol 1978;90:461-86. 9. Gray GM, Rosenberg SA, Cooper AD, Gregory PB, Stein DT, Herzenberg H. Lymphomas involving the gastrointestinal tract. Gastroenterology 1982;82:143-52. 10. Dawson IMP, Comes JS, Morson Be. Primary malignant tumors of the intestinal tract. Br J Surg 1961;49:80-9. 11. Sheahan DG, Martin F, Baginsky S, Mallory GK, Zamchek N. Multiple lymphomatous polyposis of the gastrointestinal tract. Cancer 1971;28:408-25. 12. Harris AR, Hermann RP, Carroll J. Extensive primary lymphoma of the gastrointestinal tract. Aust NZ J Med 1976;6:571-5. 13. Ruppert GB, Smith VM. Multiple lymphomatous polyposis of the gastrointestinal tract. Gastrointest Endosc 1979;25:67-9. 14. Hood L, Campbell JH, Elgin SCR. The organization, expression and evolution of antibody genes and other multigene families. Ann Rev Genet 1975;9:305-53. 15. Lewin KJ, Kahn LB, Novis BH. Primary intestinal lymphoma of "Western" and "Mediterranean" type, alpha-chain disease and massive plasma cell infiltration. Cancer 1976;38:251128. 16. Husband AJ, Monie HJ, Govans JL. The natural history of the cells producing IgA in the gut. In: Immunology of the gut; Ciba Foundation Symposium Series No. 46. New York: Elsevier Science Publishing, 1977:29-42. 17. Hall T. Lymphocyte recirculation and the gut: the cellular basis of humoral immunity in the intestine. Blood Cells 1979;5:479-92. 18. Guy-Grand D, Griscell C, VasalJi P. The gut-associated lymphoid system: nature and properties of the large dividing cells. Eur J ImmunoI1974;4:435-41. 19. Jaffe ES, Braylan RC, Nanba K, Frank MM, Berard CWo Functional markers: a new perspective on malignant lymphoma. Cancer Treat Rep 1977;61:953-62.
Diffuse Lymphomatous Polyposis of the Gastrointestinal Tract A Case Report With Immunohistochemical Studies BERNARD J. FERNANDES, DOMINICK AMATO, and MORRIS GOLDFINGER
Departments of Pathology, Medicine, and Radiology, Mount Sinai Hospital and University of Toronto, Toronto, Canada
A case of diffuse lymphomatous polyposis of the gastrointestinal tract is reported. The patient presented with abdominal pain and weight loss dnd xrays revealed multiple polyps involving the entire gastrointestinal tract. Biopsies confirmed the diagnosis of lymphomatous polyposis. The patient also had involvement of the bone marrow and supraclavicular lymph node. Immunologically this lymphoma was characterized as a monoclonal proliferation of B lymphocytes bearing immunoglobulin M, type K. Diffuse lymphomatous polyposis of the gastrointestinal tract appears to be a generalized malignancy of uncommitted B cells of Peyer's patches. The migratory properties of these cells may account for the tendency to dissemination of lymphomatous polyposis. Diffuse lymphomatous polyposis of the gastrointestinal tract is a distinct entity, separate from the diffuse gastrointestinal lymphoma known as Mediterranean-type lymphoma. The gastrointestinal (GI) tract is the most common she of extranodal malignant lymphomas and accounts for about 30% of these lymphomas (1). Primary GI lymphomas most commonly present as a single lesion (2). However, two varieties of diffuse involvement of the GI tract by malignant lymphoma are recognized. The first, so-called Mediterranean type-lymphoma (MTL), is characterized by a diffuse proliferation of plasma cells in the lamina propria of the small intestine (3-5). The second is lymphomaReceived July 30, 1984. Accepted November 14, 1984. Address requests for reprints to: Dr. B. J. Fernandes, Department of Pathology, Mount Sinai Hospital, 600 University Avenue, Toronto, Canada M5G 1X5. The authors thank Rachel Peters for technical assistance and Marina Prior for manuscript preparation. © 1985 by the American Gastroenterological Association 0016-5085/85/$3.30
to us polyposis (tp) in which multiple polypoid lesions of malignant lymphoma are distributed throughout the GI tract (6). Recently immunoperoxidase techniques have been used to characterize the cells of malignant lymphomas and have offered newer insights into these diseases (7,8). We report a case of LP of the GI tract studied by immunoperoxidase techrtiques and compare the features of this disease with those of MTL. To our knowledge this is the first case of diffuse LP that has been studied by immunologic methods.
Case Report A 67-yr-old man presented with weight loss, anorexia, fatigue, melena, and abdominal pain. Physical examination revealed generalized peripheral lymphadenopathy but was otherwise unremarkable. Laboratory investigations showed a mild normocytic, normochromic anemia and mildly abnormal liver function tests. Serum protein electrophoresis was normal. An air-contrast barium enema revealed a diffuse nodular pattern evenly distributed throughout the colon (Figure 1). The nodules were fairly uniform in size, ranging from 5 to 7 mm. A minute umbilication was seen on the surface of many of the nodules. The duodenal cap and terminal ileum showed similar nodularity and a few nodules were scattered throughout the jejunum. There was no increase in density of the nodules in the terminal ileum. An abdominal computed tomographic scan showed extensive retroperitoneal and mesenteric adenopathy. Biopsies of the jejunum, colon, rectum, lymph node, and bone marrow were performed, and a diagnosis of nodular, poorly differentiated lymphocytic lymphoma was established. Abbreviations used in this paper: LP, lymphomatous polyposis; MTL, Mediterranean-type lymphomas.
1268 FERNANDES ET AL.
GASTROENTEROLOGY Vol. 88, No.5, Part 1
Results Sections of biopsy specimens from the duodenum, colon, and rectum all showed similar features. There were nodular aggregates of atypical lymphocytes in the lamina propria (Figure 2). These lymphocytes had irregular, cleaved nuclear margins, condensed chromatin, inconspicuous nucleoli, and scanty cytoplasm. The adjacent uninvolved lamina propria showed a normal population of plasma cells and lymphocytes. A diagnosis of poorly differentiated lymphocytic lymphoma was made. The biopsy specimen of the supraclavicular lymph node also showed replacement by nodular, poorly differentiated lymphocytic lymphoma, and the bone marrow specimen demonstrated involvement of that organ. Immunoperoxidqse staining of the duodenal, colonic, and lymph node specimens, showed that the malignant cells were a monoclonal population of B lymphocytes bearing IgM type-K immunoglobulin (Figures 3A, 3B). In the gut, the plasma cells in the uninvolved lamina propria contained both K and A light chains. Figure 1. Air-contrast barium enema of sigmoid colon showing a diffuse nodular pattern of the mucosa. This pattern was also present in the jejunum. ileum, and entire colon.
The patient was treated with chemotherapy (cyclophosphamide, vincristine, and prednisone) but had a poor response to therapy. A subsequent lymph node biopsy showed progression to a diffuse, poorly differentiated lymphocytic lymphoma. Doxorubicin was added to the chemotherapeutic regimen, but with little benefit. The patient died 6 mo after diagnosis. An autopsy was not performed.
Materials and Methods Biopsy specimens were fixed overnight in B5 fixative and embedded in paraffin. Immunoperoxidase staining for immunoglobulins (Ig) G, A, M, and K and A light chains were performed on the paraffin sections. The sections were pretreated with fresh 0.4% trypsin solution in 0.85% hydrochloric acid at 37°C for 30 min. After two 10min washes in phosphate-buffered saline (pH 7.4), the sections were incubated with 10% bovine serum albumin for 30 min. The sections were then incubated with rabbit antihuman serum for 1 h and again washed twice in phosphate-buffered saline (two 10-min washes). Finally, the sections were incubated with peroxidase-conjugated swine antirabbit antiserum for 30 min and washed in phosphate-buffered saline (two 10-min washes). The peroxidase activity was demonstrated using diaminobenzidine tetrahydrochloride. Antibodies were purchased from Dako products (Toronto, Canada) and used at the following dilutions: IgM, 1/600; IgG, 1/1000; IgA, 1/1000; K, 1/1200; A, 1/1200.
Figure 2. A. Biopsy of colon showing a nodular aggregate of monomorphous, small lymphocytes in the lamina propria and adjacent submucosa. (H & E; x 78.) B. Highpower detail of lymphomatous nodule. Note atypical small lymphocytes with condensed chromatin and irregular nuclear margins. (H & E; x 500.)
GI LYMPHOMATOUS POLYPOSIS
May 1985
1269
diagnosis may be suspected on radiologic examination, biopsies are necessary to confirm the diagnosis. These patients frequently develop generalized extraintestinal lymphoma. By the use of immunoperoxidase techniques we were able to demonstrate a monoclonal proliferation of cells and therefore confirm a diagnosis of malignant lymphoma. Lymphomatous polyposis appears to be a B-cell neoplasm. Immunoglobulin M is the most common immunoglobulin type found in malignant lymphomas (8) and appears at an earlier stage of B-cell maturation than IgG or IgA (14). Recently, a second form of diffuse GI lymphoma, MTL, has received increasing attention. It is characterized by diffuse involvement of predominantly the small intestine by an intense proliferation of plasma cells that is initially restricted to the lamina propria (3-5). Eventually it proceeds to an overt malignant lymphoma with the appearance of immature cells, nodular lesions, and extension beyond the lamina propria. Many of these patients have an abnormal paraprotein representing the a-chain fragment of IgA (3).
Figure 3. A. Biopsy of colon stained for IgM by the immunoperoxidase technique. The majority of cells stain positively. (X312.) B. Biopsy of colon stained for K light chains by the immunoperoxidase technique. The majority of cells stain positively. (X312.)
Discussion The GI tract may be involved by malignant lymphoma as a primary tumor or as part of a more widespread disease process. Generally the lymphoma is considered as "primary" in the GI tract when the initial symptoms of the disease are in the abdomen or present as a disturbance of GI function (9). Four types of primary intestinal lymphomas have been described: (a) annular or plaquelike lesions, (b) bulky and protuberant growths, (c) aneurysmal bowel lesions, and (d) multiple lymphomatous polyps spread over long segments of the intestinal tract (10). The final type, multiple LP, which our patient had, is the least common. Comes et al. (6) have described 5 patients with this disease and reviewed a further 22 cases that had been published in the literature. Subsequently, three case reports have appeared (1113) and Lewin et al. (1) found 4 cases of diffuse LP in a review of 117 cases of primary GI tract lymphomas. Our patient shows many features that appear to be characteristic for LP (6), i.e., an elderly patient presenting with nonspecific GI symptoms and absence of a malabsorption syndrome. Although the
There are significant differences between these two types of diffuse GI lymphomas. Lymphomatous polyposis tends to occur in elderly persons and involves the entire GI tract (6). Mediterranean-type lymphoma is more common in younger patients and has a characteristic geographic distribution with a high incidence in the Mediterranean region (3). Lymphomatous polyposis has been reported predominantly in the Western world and no geographic restriction is apparent (15). Mediterranean-type lymphoma is usually associated with a malabsorption syndrome, whereas LP is not. In MTL the entire lamina propria is infiltrated by plasma cells, whereas in LP the uninvolved lamina propria shows a normal population of lymphocytes and plasma cells. The lymphoma associated with MTL is a plasma cell tumor or an immunoblastic sarcoma, whereas the lymphoma in LP includes a spectrum of cytologic types, reflecting those that occur in the peripheral nodes. Mediterranean-type lymphomas rarely spread beyond the abdomen (15), whereas systemic lymphoma is common in LP (6). Mediterranean-type lymphoma is often associated with an a-chain paraprotein (3), but this has not been reported in LP. The occurrence of two distinct types of diffuse GI lymphomas is of interest in the light of present knowledge of gut-associated B lymphocytes (16). It has become apparent that B cells from Peyer's patches are discharged into the intestinal lymph and pass through the mesenteric nodes to the thoracic duct. The lymphocytes are carried in the lymph stream to the blood where the majority demonstrate a selective homing pattern to the gut, where they then extrava-
1270
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sate into the lamina propria and develop into IgAsecreting plasma cells (17). In the Peyer's patches very few B cells contain detectable IgA, whereas the majority of the B cells in the thoracic lymph contain IgA. This suggests that the IgA-containing plasma cells present in the gut mucosa are derived from lymphocytes in the Peyer's patches that mature while migrating to the mesenteric nodes and thoracic duct lymph (18). Thus, two populations of gutassociated B lymphocytes are postulated: a population of uncommitted precursor cells in Peyer's patches that have migratory properties and a population of IgA-secreting plasma cells in the lamina propria that are stationary. As malignant lymphomas are believed to reflect the normal pattern of lymphocyte traffic and homing (19), LP may represent the malignant counterpart of the uncommitted B lymphocytes of Peyer's patches. The presence of IgM in our patient's malignant cells is compatible with an uncommitted B lymphocyte because IgM appears before IgG or IgA on B lymphocytes (14). The tendency to early dissemination in LP suggests the capacity of the malignant lymphocytes for peripheral migration. The widespread distribution of the malignant lymphoid nodules in the intestine at the time of presentation in our patient also supports the notion that they had arisen synchronously from malignant cells in the circulation that had homed to sites in the intestinal mucosa. In contrast, MTL could represent the malignant counterpart of the committed IgAsecreting cells of the lamina propria. The frequent finding of serum a-chain paraproteins (3) is evidence of the capacity, albeit deranged, of these cells to secrete immunoglobulin. The rarity of extraabdomina I disease in MTL (15) is compatible with the stationary properties of plasma cells in the lamina propria (17). Further studies of the immunologic features and migratory properties of malignant cells in LP and MTL are required in order to provide a better understanding of these diseases.
References 1. Lewin KJ, Ranchod M, Dorfman RF. Lymphomas of the
GASTROENTEROLOGY Vol. 88, No.5, Part 1
gastrointestinal tract. A study of 117 cases presenting with gastrointestinal disease. Cancer 1978;42:693-707. 2. Blackledge G, Bush H, Dodge OG, Crowther D. A study of gastrointestinal lymphoma. Clin Oncol 1979;5:209-19. 3. AI-Saleem T, Zardawi 1M. Primary lymphomas of the small intestine in Iraq: a pathological study of 145 cases. Histopathology 1979;3:89-106. 4. Nassar YH, Salem PA, Shahid MJ, et al. "Mediterranean abdominal lymphoma" or immunoproliferative small intestinal disease. Cancer 1978;41:1340-54. 5. Galian A, Locestre M-J, Scotto J, Bognel C, Matruchansky C, Rambaud J-C. Pathological study of alpha-chain disease with special emphasis on evolution. Cancer 1977;39:2081-101. 6. Comes JS. Multiple lymphomatous polyposis of the gastrointestinal tract. Cancer 1961;14:249-57. 7. Taylor CR. An immunohistological study of follicular lymphoma, reticulum cell sarcoma and Hodgkin's disease. Eur J Cancer 1976;12:61-75. 8. Lukes RJ, Taylor CR, Parker JW, Lincoln TL, Pattengale PK, Tindle BM. A morphologic and immunologic surface marker study of 299 cases of non-Hodgkin's lymphomas and related leukemias. Am J Pathol 1978;90:461-86. 9. Gray GM, Rosenberg SA, Cooper AD, Gregory PB, Stein DT, Herzenberg H. Lymphomas involving the gastrointestinal tract. Gastroenterology 1982;82:143-52. 10. Dawson IMP, Comes JS, Morson Be. Primary malignant tumors of the intestinal tract. Br J Surg 1961;49:80-9. 11. Sheahan DG, Martin F, Baginsky S, Mallory GK, Zamchek N. Multiple lymphomatous polyposis of the gastrointestinal tract. Cancer 1971;28:408-25. 12. Harris AR, Hermann RP, Carroll J. Extensive primary lymphoma of the gastrointestinal tract. Aust NZ J Med 1976;6:571-5. 13. Ruppert GB, Smith VM. Multiple lymphomatous polyposis of the gastrointestinal tract. Gastrointest Endosc 1979;25:67-9. 14. Hood L, Campbell JH, Elgin SCR. The organization, expression and evolution of antibody genes and other multigene families. Ann Rev Genet 1975;9:305-53. 15. Lewin KJ, Kahn LB, Novis BH. Primary intestinal lymphoma of "Western" and "Mediterranean" type, alpha-chain disease and massive plasma cell infiltration. Cancer 1976;38:251128. 16. Husband AJ, Monie HJ, Govans JL. The natural history of the cells producing IgA in the gut. In: Immunology of the gut; Ciba Foundation Symposium Series No. 46. New York: Elsevier Science Publishing, 1977:29-42. 17. Hall T. Lymphocyte recirculation and the gut: the cellular basis of humoral immunity in the intestine. Blood Cells 1979;5:479-92. 18. Guy-Grand D, Griscell C, VasalJi P. The gut-associated lymphoid system: nature and properties of the large dividing cells. Eur J ImmunoI1974;4:435-41. 19. Jaffe ES, Braylan RC, Nanba K, Frank MM, Berard CWo Functional markers: a new perspective on malignant lymphoma. Cancer Treat Rep 1977;61:953-62.