Clinical manifestations, pathologic features, and diagnosis of enteropathy-associated T cell lymphoma
- Arnold S Freedman, MD
Arnold S Freedman, MD
- Section Editor — Lymphoproliferative Disorders
- Professor of Medicine
- Harvard Medical School
- Jon C Aster, MD
Jon C Aster, MD
- Professor of Pathology
- Harvard Medical School
The peripheral T cell lymphomas (PTCLs) are a heterogeneous group of generally aggressive neoplasms that constitute less than 15 percent of all non-Hodgkin lymphomas (NHLs) in adults. (See "Classification of the hematopoietic neoplasms".)
Among these, in decreasing frequency of occurrence, are [1,2]:
●Peripheral T cell lymphoma, not otherwise specified
●Anaplastic large cell lymphoma, primary systemic type
●Angioimmunoblastic T cell lymphoma
- Swerdlow SH, Campo E, Harris NL, et al. (Eds). World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.
- Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127:2375.
- Isaacson PG, O'Connor NT, Spencer J, et al. Malignant histiocytosis of the intestine: a T-cell lymphoma. Lancet 1985; 2:688.
- Zettl A, deLeeuw R, Haralambieva E, Mueller-Hermelink HK. Enteropathy-type T-cell lymphoma. Am J Clin Pathol 2007; 127:701.
- Cellier C, Delabesse E, Helmer C, et al. Refractory sprue, coeliac disease, and enteropathy-associated T-cell lymphoma. French Coeliac Disease Study Group. Lancet 2000; 356:203.
- Gonzalez CL, Medeiros LJ, Braziel RM, Jaffe ES. T-cell lymphoma involving subcutaneous tissue. A clinicopathologic entity commonly associated with hemophagocytic syndrome. Am J Surg Pathol 1991; 15:17.
- Delabie J, Holte H, Vose JM, et al. Enteropathy-associated T-cell lymphoma: clinical and histological findings from the international peripheral T-cell lymphoma project. Blood 2011; 118:148.
- Deleeuw RJ, Zettl A, Klinker E, et al. Whole-genome analysis and HLA genotyping of enteropathy-type T-cell lymphoma reveals 2 distinct lymphoma subtypes. Gastroenterology 2007; 132:1902.
- Chan JK, Chan AC, Cheuk W, et al. Type II enteropathy-associated T-cell lymphoma: a distinct aggressive lymphoma with frequent γδ T-cell receptor expression. Am J Surg Pathol 2011; 35:1557.
- Ekström Smedby K, Vajdic CM, Falster M, et al. Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. Blood 2008; 111:4029.
- Silano M, Volta U, Vincenzi AD, et al. Effect of a gluten-free diet on the risk of enteropathy-associated T-cell lymphoma in celiac disease. Dig Dis Sci 2008; 53:972.
- Lebwohl B, Granath F, Ekbom A, et al. Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study. Ann Intern Med 2013; 159:169.
- Collin P, Reunala T, Pukkala E, et al. Coeliac disease--associated disorders and survival. Gut 1994; 35:1215.
- Egan LJ, Stevens FM, McCarthy CF. Celiac disease and T-cell lymphoma. N Engl J Med 1996; 335:1611.
- Elfström P, Granath F, Ekström Smedby K, et al. Risk of lymphoproliferative malignancy in relation to small intestinal histopathology among patients with celiac disease. J Natl Cancer Inst 2011; 103:436.
- Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 15-1996. A 79-year-old woman with anorexia, weight loss, and diarrhea after treatment for celiac disease. N Engl J Med 1996; 334:1316.
- Mantovani G, Esu S, Astara G, et al. Primary T cell CD30-positive anaplastic large-cell lymphoma associated with adult-onset celiac disease and presenting with skin lesions. Acta Haematol 1995; 94:48.
- Shiboski CH, Greenspan D, Dodd CL, Daniels TE. Oral T-cell lymphoma associated with celiac sprue. A case report. Oral Surg Oral Med Oral Pathol 1993; 76:54.
- Tse E, Gill H, Loong F, et al. Type II enteropathy-associated T-cell lymphoma: a multicenter analysis from the Asia Lymphoma Study Group. Am J Hematol 2012; 87:663.
- Gale J, Simmonds PD, Mead GM, et al. Enteropathy-type intestinal T-cell lymphoma: clinical features and treatment of 31 patients in a single center. J Clin Oncol 2000; 18:795.
- Ashton-Key M, Diss TC, Pan L, et al. Molecular analysis of T-cell clonality in ulcerative jejunitis and enteropathy-associated T-cell lymphoma. Am J Pathol 1997; 151:493.
- Chott A, Dragosics B, Radaszkiewicz T. Peripheral T-cell lymphomas of the intestine. Am J Pathol 1992; 141:1361.
- Murray A, Cuevas EC, Jones DB, Wright DH. Study of the immunohistochemistry and T cell clonality of enteropathy-associated T cell lymphoma. Am J Pathol 1995; 146:509.
- Spencer J, Cerf-Bensussan N, Jarry A, et al. Enteropathy-associated T cell lymphoma (malignant histiocytosis of the intestine) is recognized by a monoclonal antibody (HML-1) that defines a membrane molecule on human mucosal lymphocytes. Am J Pathol 1988; 132:1.
- Meresse B, Curran SA, Ciszewski C, et al. Reprogramming of CTLs into natural killer-like cells in celiac disease. J Exp Med 2006; 203:1343.
- Tjon JM, Verbeek WH, Kooy-Winkelaar YM, et al. Defective synthesis or association of T-cell receptor chains underlies loss of surface T-cell receptor-CD3 expression in enteropathy-associated T-cell lymphoma. Blood 2008; 112:5103.
- Daum S, Foss HD, Anagnostopoulos I, et al. Expression of cytotoxic molecules in intestinal T-cell lymphomas. The German Study Group on Intestinal Non-Hodgkin Lymphoma. J Pathol 1997; 182:311.
- de Bruin PC, Connolly CE, Oudejans JJ, et al. Enteropathy-associated T-cell lymphomas have a cytotoxic T-cell phenotype. Histopathology 1997; 31:313.
- Verbeek WH, Goerres MS, von Blomberg BM, et al. Flow cytometric determination of aberrant intra-epithelial lymphocytes predicts T-cell lymphoma development more accurately than T-cell clonality analysis in Refractory Celiac Disease. Clin Immunol 2008; 126:48.
- Zettl A, Ott G, Makulik A, et al. Chromosomal gains at 9q characterize enteropathy-type T-cell lymphoma. Am J Pathol 2002; 161:1635.
- Catassi C, Fabiani E, Corrao G, et al. Risk of non-Hodgkin lymphoma in celiac disease. JAMA 2002; 287:1413.
- Howell WM, Leung ST, Jones DB, et al. HLA-DRB, -DQA, and -DQB polymorphism in celiac disease and enteropathy-associated T-cell lymphoma. Common features and additional risk factors for malignancy. Hum Immunol 1995; 43:29.
- Carbonnel F, Grollet-Bioul L, Brouet JC, et al. Are complicated forms of celiac disease cryptic T-cell lymphomas? Blood 1998; 92:3879.
- Hadithi M, Mallant M, Oudejans J, et al. 18F-FDG PET versus CT for the detection of enteropathy-associated T-cell lymphoma in refractory celiac disease. J Nucl Med 2006; 47:1622.
- Mallant M, Hadithi M, Al-Toma AB, et al. Abdominal computed tomography in refractory coeliac disease and enteropathy associated T-cell lymphoma. World J Gastroenterol 2007; 13:1696.
- Daum S, Wahnschaffe U, Glasenapp R, et al. Capsule endoscopy in refractory celiac disease. Endoscopy 2007; 39:455.
- Perry AM, Warnke RA, Hu Q, et al. Indolent T-cell lymphoproliferative disease of the gastrointestinal tract. Blood 2013; 122:3599.
- CLINICAL FEATURES
- - Tumor
- - Adjacent mucosa
- Genetic features
- DIFFERENTIAL DIAGNOSIS
- Refractory celiac disease
- Monomorphic epitheliotropic intestinal T cell lymphoma
- Indolent T cell lymphoproliferative disease
- Extranodal NK/T cell lymphoma
- Gamma-delta T cell lymphoma
- Anaplastic large cell lymphoma
- B cell lymphomas