- Email: [email protected]
CLASSIFICATION OF PRIMARY GUT LYMPHOMAS
958 CLASSIFICATION OF PRIMARY GUT LYMPHOMAS
StR,—Primary lymphomas of the gastrointestinal tract have a clinical course unlike that of nodal disease, notably in their tendency to remain localised for a long time.1,2 Many gut lymphomas are also morphologically distinct. 1-3 The conventional lymphoma classifications may thus be inappropriate for gut lymphomas. A major part of our joint experience is from over 250 cases of primary gut lymphoma from the files of St Bartholomew’s and St Mark’s Hospitals, London. Our proposed alternative nomenclature (table) is consistent with current classifications of nodal disease since it incorporates a division into low and high grade, on the basis of tumour cell size (ie, proportion of blast cells) and B and T cell phenotype. Phenotype can now be readily distinguished on conventionally processed histological material.’ We recommend the use of strict criteria5 for designating a gut lymphoma as primary. Most are of B cell phenotype and of low grade. The commonest form is composed of a diffuse infiltrate of a mixed population of small lymphocytes, centrocyte-like cells, lymphoplasmacytoid cells, plasma cells, centroblasts, and immunoblasts in varying proportions. Occasionally a single cell type predominates. We have designated this category of tumour polymorphic B cell lymphoma because of the usual mixed cellular population. A characteristic of these tumours is infiltration and destruction of gut epithelium, or lymphoepithelial lesions.’ Such tumours are assigned to high grade (greater than 20% large, blast type cells) or low grade, a distinction that may have prognostic significance.3 Low-grade forms of this tumour are equivalent to the low-grade tumours of mucosa-associated lymphoid tissue (MALTomas) or tumours of "centrocyte-like cells".1 However, we do not support those terms because, besides being imprecise, "MALToma" implies a biological concept that is as yet unproven, and many of the cells within these tumours are most unlike centrocytes.6 The term "centrocyte" is also used in another form of gut lymphoma (see below). Our own observations and those of IsaacsonI suggest that polymorphic B cell lymphoma represents a spectrum of morphological forms and that transition from low to high grade may occur, usually after a long time. Mixed types do occur but their biological and prognostic significance is unclear. Mediterranean lymphoma (alpha heavy chain disease, immunoproliferative small-intestinal disease) is well documented. Some evidence1,? suggests that it is related to polymorphic B cell lymphoma but in view of its distinctive appearance, epidemiology, and natural history it should for the present be kept distinct. Malignant lymphomatous polyposis (multiple lymphomatous polyposis) has a distinctive macroscopic appearance and is probably always multifocal. The polyps may affect the whole gut or be centred on one area.8 This tumour is composed of centrocytes (small cleaved cells), and mitoses are often prominent. The tumour cells are CD5 positive, in contrast to polymorphic B cell lymphoma. Leukaemic spread is not uncommon in the later stages, and this disease is more aggressive than low-grade polymorphic B cell lymphoma.3 After high grade polymorphic B cell lymphoma the most frequent high grade B cell lymphoma is the Burkitt type (previously called B lymphoblastic lymphoma). This tumour is typically seen in the ileocaecal region in children and it is histologically identical to Burkin-like tumours elsewhere. Plasmacytomas and other B cell tumours that resemble their nodal counterparts may occasionally be observed in the gut. These should be specified as such. We also include an unclassified category. T cell lymphomas are being recognised increasingly often, and a comprehensive scheme of classification of nodal T cell lymphomas has lately been proposed.9.lo We recommend a similar scheme for primary gut lymphomas. The category pleomorphic large T cell lymphoma is equivalent to "medium/large cell lymphoma."9 Pleomorphic refers to the variable morphology of the tumour nuclei. T cell lymphoma in the gut and gluten-sensitive enteropathy are associated." Gastrointestinal lymphoma, particularly in the small bowel, may cause malabsorption. Furthermore, there may be morphological alterations in the gut mucosa in association with lymphoma that mimic gluten-sensitive enteropathy. We therefore
PROPOSED CLASSIFICATION OF PRIMARY GUT LYMPHOMAS
suggest that T cell tumours of the gut are classified by their cellular morphology, but this classification should be qualified by a statement about the presence or absence of an enteropathy and its probable nature. T cell tumours may also be associated with prominent tissue eosinophilia12 and this should be noted. The term "malignant histiocytosis of the intestine" should no longer be used; these tumours are T cell neoplasms.13 True histiocytic lymphomas of the gastrointestinal tract rarely, if ever, occur. As with B cell lymphomas, T cell tumours with morphological appearances similar to those of nodal disease may occasionally be seen, and we recommend that these are so designated. Hodgkin’s disease can affect the gut secondarily; a few cases of primary disease have been reported but we have not seen one that has withstood close scrutiny. The classification we have outlined is compatible with modem notions of lymphoma biology. We hope that it will encourage study of these conditions and exchange of information. This classification will probably be applicable to lymphomas arising in other extranodal sites. Imperial Cancer Research Fund, London WC2A 3PX
PETER A. HALL
University of Auckland, Auckland, New Zealand
JEREMY R. JASS
Guy’s Hospital, London
DAVID A. LEVISON
St Mark’s Hospital and ICRF Histopathology Unit, Royal College of Surgeons, London
BASIL C. MORSON
Gloucestershire
NEIL A. SHEPHERD
Royal Hospital
Armed Forces Institute of Pathology, Washington DC, USA
LESLIE H. SOBIN
St Bartholomew’s Hospital and ICRF Histopathology Unit, Royal College of Surgeons, London
ALFRED G. STANSFELD
PG, Spencer J. Malignant lymphoma of mucosa associated lymphoid tissue Histopathology 1987; 11: 445-62. 2. Filippa DA, Decosse JJ, Lieberman PH, Bretsky SS, Weingrad DN. Primary lymphomas of the gastrointestinal tract: analysis of prognostic factors with emphasis on histologic type. Am J Surg Pathol 1983; 7: 363-72 3. Shepherd NA, Hall PA, Coates PJ, Levison DA. Primary malignant lymphoma of the colon and rectum: a histopathological and immunohistochemical analysis of 45 cases with clinicopathological observations. Histopathology 1988, 12: 235-52. 4. Hall PA, d’Ardenne AJ, Stansfeld AG. Paraffin section immunohistochemistry I. non-Hodgkin’s lymphoma. Histopathology 1988; 13: 149-60. 5. Dawson IMP, Cornes JS, Morson BC. Primary malignant lymphoid tumours of the gastrointestinal tract. Br J Surg 1961; 49: 80-89. 6. Lennert K. Malignant lymphomas other than Hodgkin’s disease. Berlin: SpringerVerlag, 1978. 7 Isaacson PG, Price SK. Light chains in Mediterranean lymphoma. J Clin Pathol 1985, 1. Isaacson
38: 601-07. 8. Isaacson PG, MacLennan KA, Subbuswamy SG. Multiple lymphomatous polyposis of the gastrointestinal tract. Histopathology 1984; 8: 641-56. 9. Suchi T, Lennert K, Tu L-Y, et al Histopathology and immunohistochemistry of penpheral T cell lymphomas. J Clin Pathol 1987; 40: 995-1015. 10. Stansfeld AG, Diebold J, Kapanci Y, et al. Updated Kiel classification for non-Hodgkin’s lymphoma Lancet 1988; i: 292-93 11 Swinson CM, Coles ES, Slavin G, Booth CC. Coeliac disease and malignancy Lancet 1983; li- 111-15. 12. Shepherd NA, Blackshaw AJ, Hall PA, et al. Malignant lymphoma with eosinophilia of the gastrointestinal tract Histopathology 1987; 11: 115-30. 13. Isaacson PG, O’Connor NTJ, Spencer J, et al. Malignant histiocytosis of the intestine a T cell lymphoma. Lancet 1985; ii 688-91.
StR,—Primary lymphomas of the gastrointestinal tract have a clinical course unlike that of nodal disease, notably in their tendency to remain localised for a long time.1,2 Many gut lymphomas are also morphologically distinct. 1-3 The conventional lymphoma classifications may thus be inappropriate for gut lymphomas. A major part of our joint experience is from over 250 cases of primary gut lymphoma from the files of St Bartholomew’s and St Mark’s Hospitals, London. Our proposed alternative nomenclature (table) is consistent with current classifications of nodal disease since it incorporates a division into low and high grade, on the basis of tumour cell size (ie, proportion of blast cells) and B and T cell phenotype. Phenotype can now be readily distinguished on conventionally processed histological material.’ We recommend the use of strict criteria5 for designating a gut lymphoma as primary. Most are of B cell phenotype and of low grade. The commonest form is composed of a diffuse infiltrate of a mixed population of small lymphocytes, centrocyte-like cells, lymphoplasmacytoid cells, plasma cells, centroblasts, and immunoblasts in varying proportions. Occasionally a single cell type predominates. We have designated this category of tumour polymorphic B cell lymphoma because of the usual mixed cellular population. A characteristic of these tumours is infiltration and destruction of gut epithelium, or lymphoepithelial lesions.’ Such tumours are assigned to high grade (greater than 20% large, blast type cells) or low grade, a distinction that may have prognostic significance.3 Low-grade forms of this tumour are equivalent to the low-grade tumours of mucosa-associated lymphoid tissue (MALTomas) or tumours of "centrocyte-like cells".1 However, we do not support those terms because, besides being imprecise, "MALToma" implies a biological concept that is as yet unproven, and many of the cells within these tumours are most unlike centrocytes.6 The term "centrocyte" is also used in another form of gut lymphoma (see below). Our own observations and those of IsaacsonI suggest that polymorphic B cell lymphoma represents a spectrum of morphological forms and that transition from low to high grade may occur, usually after a long time. Mixed types do occur but their biological and prognostic significance is unclear. Mediterranean lymphoma (alpha heavy chain disease, immunoproliferative small-intestinal disease) is well documented. Some evidence1,? suggests that it is related to polymorphic B cell lymphoma but in view of its distinctive appearance, epidemiology, and natural history it should for the present be kept distinct. Malignant lymphomatous polyposis (multiple lymphomatous polyposis) has a distinctive macroscopic appearance and is probably always multifocal. The polyps may affect the whole gut or be centred on one area.8 This tumour is composed of centrocytes (small cleaved cells), and mitoses are often prominent. The tumour cells are CD5 positive, in contrast to polymorphic B cell lymphoma. Leukaemic spread is not uncommon in the later stages, and this disease is more aggressive than low-grade polymorphic B cell lymphoma.3 After high grade polymorphic B cell lymphoma the most frequent high grade B cell lymphoma is the Burkitt type (previously called B lymphoblastic lymphoma). This tumour is typically seen in the ileocaecal region in children and it is histologically identical to Burkin-like tumours elsewhere. Plasmacytomas and other B cell tumours that resemble their nodal counterparts may occasionally be observed in the gut. These should be specified as such. We also include an unclassified category. T cell lymphomas are being recognised increasingly often, and a comprehensive scheme of classification of nodal T cell lymphomas has lately been proposed.9.lo We recommend a similar scheme for primary gut lymphomas. The category pleomorphic large T cell lymphoma is equivalent to "medium/large cell lymphoma."9 Pleomorphic refers to the variable morphology of the tumour nuclei. T cell lymphoma in the gut and gluten-sensitive enteropathy are associated." Gastrointestinal lymphoma, particularly in the small bowel, may cause malabsorption. Furthermore, there may be morphological alterations in the gut mucosa in association with lymphoma that mimic gluten-sensitive enteropathy. We therefore
PROPOSED CLASSIFICATION OF PRIMARY GUT LYMPHOMAS
suggest that T cell tumours of the gut are classified by their cellular morphology, but this classification should be qualified by a statement about the presence or absence of an enteropathy and its probable nature. T cell tumours may also be associated with prominent tissue eosinophilia12 and this should be noted. The term "malignant histiocytosis of the intestine" should no longer be used; these tumours are T cell neoplasms.13 True histiocytic lymphomas of the gastrointestinal tract rarely, if ever, occur. As with B cell lymphomas, T cell tumours with morphological appearances similar to those of nodal disease may occasionally be seen, and we recommend that these are so designated. Hodgkin’s disease can affect the gut secondarily; a few cases of primary disease have been reported but we have not seen one that has withstood close scrutiny. The classification we have outlined is compatible with modem notions of lymphoma biology. We hope that it will encourage study of these conditions and exchange of information. This classification will probably be applicable to lymphomas arising in other extranodal sites. Imperial Cancer Research Fund, London WC2A 3PX
PETER A. HALL
University of Auckland, Auckland, New Zealand
JEREMY R. JASS
Guy’s Hospital, London
DAVID A. LEVISON
St Mark’s Hospital and ICRF Histopathology Unit, Royal College of Surgeons, London
BASIL C. MORSON
Gloucestershire
NEIL A. SHEPHERD
Royal Hospital
Armed Forces Institute of Pathology, Washington DC, USA
LESLIE H. SOBIN
St Bartholomew’s Hospital and ICRF Histopathology Unit, Royal College of Surgeons, London
ALFRED G. STANSFELD
PG, Spencer J. Malignant lymphoma of mucosa associated lymphoid tissue Histopathology 1987; 11: 445-62. 2. Filippa DA, Decosse JJ, Lieberman PH, Bretsky SS, Weingrad DN. Primary lymphomas of the gastrointestinal tract: analysis of prognostic factors with emphasis on histologic type. Am J Surg Pathol 1983; 7: 363-72 3. Shepherd NA, Hall PA, Coates PJ, Levison DA. Primary malignant lymphoma of the colon and rectum: a histopathological and immunohistochemical analysis of 45 cases with clinicopathological observations. Histopathology 1988, 12: 235-52. 4. Hall PA, d’Ardenne AJ, Stansfeld AG. Paraffin section immunohistochemistry I. non-Hodgkin’s lymphoma. Histopathology 1988; 13: 149-60. 5. Dawson IMP, Cornes JS, Morson BC. Primary malignant lymphoid tumours of the gastrointestinal tract. Br J Surg 1961; 49: 80-89. 6. Lennert K. Malignant lymphomas other than Hodgkin’s disease. Berlin: SpringerVerlag, 1978. 7 Isaacson PG, Price SK. Light chains in Mediterranean lymphoma. J Clin Pathol 1985, 1. Isaacson
38: 601-07. 8. Isaacson PG, MacLennan KA, Subbuswamy SG. Multiple lymphomatous polyposis of the gastrointestinal tract. Histopathology 1984; 8: 641-56. 9. Suchi T, Lennert K, Tu L-Y, et al Histopathology and immunohistochemistry of penpheral T cell lymphomas. J Clin Pathol 1987; 40: 995-1015. 10. Stansfeld AG, Diebold J, Kapanci Y, et al. Updated Kiel classification for non-Hodgkin’s lymphoma Lancet 1988; i: 292-93 11 Swinson CM, Coles ES, Slavin G, Booth CC. Coeliac disease and malignancy Lancet 1983; li- 111-15. 12. Shepherd NA, Blackshaw AJ, Hall PA, et al. Malignant lymphoma with eosinophilia of the gastrointestinal tract Histopathology 1987; 11: 115-30. 13. Isaacson PG, O’Connor NTJ, Spencer J, et al. Malignant histiocytosis of the intestine a T cell lymphoma. Lancet 1985; ii 688-91.