В статье приведено описание редкого диагноза мономорфной эпителиотропной интестинальной Т-клеточной лимфомы (MEITL) ввиду завуалированности ее рядом «масок» энтеропатий. Детальный анализ всех клинико-морфологических и иммуногистохимических данных позволил установить правильный диагноз. Выявленная патология относится к крайне редко встречающейся в практике даже у специалистов гематологов/онкогематологов. В статье продемонстрированы как основные этапы сложной диагностики, так и попытка терапии этой агрессивной формы кишечной лимфомы.
The article describes a rare diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), due to its veiled by a number of so-called “masks” of enteropathies. A detailed analysis of all clinical, morphological and immunohistochemical data made it possible to establish the correct diagnosis. The revealed pathology is extremely rare in practice, even among specialists in hematology. The article demonstrates the main stages of both a complex diagnosis and an attempt at therapy for this aggressive form of intestinal lymphoma.
Keywords: T- and NK-cell lymphoproliferative disorders of the gastrointestinal tract, enteropathy associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma
1. Chan JKC, Fukuyama M. Haematolymphoidtumours of the digestive system. In: WHO Classification of Tumours Editorial Board. WHO classification of tumours of the digestive system. 5th ed. Vol 1. Lyon: IARC, 2019.
2. van Vliet С, Spagnolo DV. T- and NK-cell lymphoproliferative disorders of the gastrointestinal tract: review and update. Pathology. 2020;52(1):128-41. DOI:10.1016/j.pathol.2019.10.001
3. 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;118:148-55. DOI:10.1182/blood-2011-02-335216
4. Jaffe ES, Chott A, Ott G, et al. Intestinal T-cell lymphoma. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Ed. SH Swerdlow, E Campo, NL Harris, et al. Revised. 4th ed. Lyon: IARC, 2017.
5. Mansoor A, Pittaluga S, Beck PL, et al. NK-cell enteropathy: a benign NK-cell lymphoproliferative disease mimicking intestinal lymphoma: clinicopathologic features and follow-up in a unique case series. Blood. 2011;117:1447-52. DOI:10.1182/blood-2010-08-302737
6. Xiao W, Gupta GK, Yao J, et al. Recurrent somatic JAK3 mutations in NK-cell enteropathy. Blood. 2019;134:986-91. DOI:10.1182/blood.2019001443
7. Takeuchi K, Yokoyama M, Ishizawa S, et al. Lymphomatoid gastropathy: a distinct clinicopathologic entity of self-limited pseudomalignant NK-cell proliferation. Blood. 2010;116:5631-7. DOI:10.1182/blood-2010-06-290650
8. 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;18:795-803. DOI:10.1200/JCO.2000.18.4.795
9. 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;87:663-8. DOI:10.1002/ajh.23213
10. Tan SY, Chuang SS, Tang T, et al. Type II EATL (epitheliotropic intestinal T-cell lymphoma): a neoplasm of intra-epithelial T-cells with predominant CD8αα phenotype. Leukemia. 2013;27:1688-96. DOI:10.1038/leu.2013.41
11. Sieniawski M, Angamuthu N, Boyd K, et al. Evaluation of enteropathy-associated T-cell lymphoma comparing standard therapies with a novel regimen including autologous stem cell transplantation. Blood. 2010;115:3664-70. DOI:10.1182/blood-2009-07-231324
12. Silano M, Volta U, De Vincenzi A, Dessi MDM. Effect of a gluten-free diet on the risk of enteropathy-associated T-cell lymphoma in celiac disease. Dig Dis Sci. 2008;53:972-6. DOI:10.1007/s10620-007-9952-8
13. Lebwohl B, Granath F, Ekbom A, et al. Mucosal healing and risk for lymphoproliferative malignancy in celiac disease. Ann Intern Med. 2013;159:169-75.
DOI:10.7326/0003-4819-159-3-201308060-00006
14. Foukas PG, de Leval L. Recent advances in intestinal lymphomas. Histopathology. 2015;66:112-36. DOI:10.1111/his.12596
15. Arps DP, Smith LB. Classic versus type II enteropathy-associated T-cell lymphoma: diagnostic considerations. Arch Pathol Lab Med. 2013;137:1227-31.
DOI:10.5858/arpa.2013-0242-CR
16. Malamut G, Chandesris O, Verkarre V, et al. Enteropathy associated T cell lymphoma in celiac disease: a large retrospective study. Dig Liver Dis. 2013;45:377-84. DOI:10.1016/j.dld.2012.12.001
17. Ondrejka S, Jagadeesh D. Enteropathy-associated T-cell lymphoma. Curr Hematol Malig R. 2016;11:504-13. DOI:10.1007/s11899-016-0357-7
18. Nicolae A, Xi L, Pham TH, et al. Mutations in the JAK/STAT and RAS signaling pathways are common in intestinal T-cell lymphomas. Leukemia. 2016;30:2245-7. DOI:10.1038/leu.2016.178
19. Attygalle AD, Cabeçadas J, Gaulard P, et al. Peripheral T-cell and NKcell lymphomas and their mimics; taking a step forward – report on the lymphoma workshop of the XVIth meeting of the European Association for Haematopathology and the Society for Hematopathology. Histopathology. 2014;64:171-99. DOI:10.1111/his.12251
20. Kikuma K, Yamada K, Nakamura S, et al. Detailed clinicopathological characteristics and possible lymphomagenesis of type II intestinal enteropathy-associated T-cell lymphoma in Japan. Hum Pathol. 2014;45:1276-84. DOI:10.1016/j.humpath.2013.10.038
21. 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;35:1557-69. DOI:10.1097/PAS.0b013e318222dfcd
22. Ko YH, Karnan S, Kim KM, et al. Enteropathy-associated T-cell lymphoma – a clinicopathologic and array comparative genomic hybridization study. Hum Pathol. 2010;41:1231-7. DOI:10.1016/j.humpath.2009.11.020
23. Tomita S, Kikuti YY, Carreras J, et al. Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan. Mod Pathol. 2015;28:1286-96. DOI:10.1038/modpathol.2015.85
24. Isaacson PGT, Bhagat G. Enteropathy-associated T-cell lymphoma and other primary intestinal T-cell lymphomas. In: Jaffe ES, Arber DA, Campo E, et al., ed. Hematopathology. 2nd ed. Philadelphia: Elsevier, 2017.
25. Chott A, Haedicke W, Mosberger I, et al. Most CD56+ intestinal lymphomas are CD8+CD5-T-cell lymphomas of monomorphic small to medium size histology. Am J Pathol. 1998;153:1483-90. DOI:10.1016/S0002-9440(10)65736-7
26. Moffitt AB, Ondrejka SL, McKinney M, et al. Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2. J Exp Med. 2017;214:1371-86. DOI:10.1084/jem.20160894
27. Roberti A, Dobay MP, Bisig B, et al. Type II enteropathy-associated Tcell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations. Nat Commun. 2016;7:12602. DOI:10.1038/ncomms12602
28. Lamure S, Duléry R, Di Blasi R, et al. Determinants of outcome in Covid-19 hospitalized patients with lymphoma: A retrospective multicentric cohort study. E Clinical Medicine. 2020;27:100549.
29. Challenor S, Tucker D. SARS-CoV-2-induced remission of Hodgkin lymphoma. Br J Haematol. 2021;192:415. DOI:10.1111/bjh.17116
30. de la Cruz-Benito B, Lázaro-Del Campo P, Ramírez-López A, et al. Managing the front-line treatment for diffuse large B cell lymphoma and high-grade B cell lymphoma during the COVID-19 outbreak. Br J Haematol. 2020;191:386-9. DOI:10.1111/bjh.17066
31. Lang N, Kuruvilla J. Evolving management strategies for lymphomas during the COVID-19 pandemic. Leuk Lymphoma. 2020:1-19. DOI:10.1080/10428194.2020
32. Perini GF, Fischer T, Gaiolla RD, et al. Hemoterapia e TerapiaCelular (ABHH) How to manage lymphoid malignancies during novel 2019 coronavirus (CoVid-19) outbreak: a Brazilian task force recommendation. Hematol Transfus Cell Ther. 2020;42:103-10. DOI:10.1016/j.htct.2020.04.002
33. Betrains A, Godinas L, Woei-A-Jin FJSH, et al. Convalescent plasma treatment of persistent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in patients with lymphoma with impaired humoral immunity and lack of neutralising antibodies. Br J Haematol. 2021;192:1100-5. DOI:10.1111/bjh.17266
________________________________________________
1. Chan JKC, Fukuyama M. Haematolymphoidtumours of the digestive system. In: WHO Classification of Tumours Editorial Board. WHO classification of tumours of the digestive system. 5th ed. Vol 1. Lyon: IARC, 2019.
2. van Vliet С, Spagnolo DV. T- and NK-cell lymphoproliferative disorders of the gastrointestinal tract: review and update. Pathology. 2020;52(1):128-41. DOI:10.1016/j.pathol.2019.10.001
3. 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;118:148-55. DOI:10.1182/blood-2011-02-335216
4. Jaffe ES, Chott A, Ott G, et al. Intestinal T-cell lymphoma. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Ed. SH Swerdlow, E Campo, NL Harris, et al. Revised. 4th ed. Lyon: IARC, 2017.
5. Mansoor A, Pittaluga S, Beck PL, et al. NK-cell enteropathy: a benign NK-cell lymphoproliferative disease mimicking intestinal lymphoma: clinicopathologic features and follow-up in a unique case series. Blood. 2011;117:1447-52. DOI:10.1182/blood-2010-08-302737
6. Xiao W, Gupta GK, Yao J, et al. Recurrent somatic JAK3 mutations in NK-cell enteropathy. Blood. 2019;134:986-91. DOI:10.1182/blood.2019001443
7. Takeuchi K, Yokoyama M, Ishizawa S, et al. Lymphomatoid gastropathy: a distinct clinicopathologic entity of self-limited pseudomalignant NK-cell proliferation. Blood. 2010;116:5631-7. DOI:10.1182/blood-2010-06-290650
8. 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;18:795-803. DOI:10.1200/JCO.2000.18.4.795
9. 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;87:663-8. DOI:10.1002/ajh.23213
10. Tan SY, Chuang SS, Tang T, et al. Type II EATL (epitheliotropic intestinal T-cell lymphoma): a neoplasm of intra-epithelial T-cells with predominant CD8αα phenotype. Leukemia. 2013;27:1688-96. DOI:10.1038/leu.2013.41
11. Sieniawski M, Angamuthu N, Boyd K, et al. Evaluation of enteropathy-associated T-cell lymphoma comparing standard therapies with a novel regimen including autologous stem cell transplantation. Blood. 2010;115:3664-70. DOI:10.1182/blood-2009-07-231324
12. Silano M, Volta U, De Vincenzi A, Dessi MDM. Effect of a gluten-free diet on the risk of enteropathy-associated T-cell lymphoma in celiac disease. Dig Dis Sci. 2008;53:972-6. DOI:10.1007/s10620-007-9952-8
13. Lebwohl B, Granath F, Ekbom A, et al. Mucosal healing and risk for lymphoproliferative malignancy in celiac disease. Ann Intern Med. 2013;159:169-75.
DOI:10.7326/0003-4819-159-3-201308060-00006
14. Foukas PG, de Leval L. Recent advances in intestinal lymphomas. Histopathology. 2015;66:112-36. DOI:10.1111/his.12596
15. Arps DP, Smith LB. Classic versus type II enteropathy-associated T-cell lymphoma: diagnostic considerations. Arch Pathol Lab Med. 2013;137:1227-31.
DOI:10.5858/arpa.2013-0242-CR
16. Malamut G, Chandesris O, Verkarre V, et al. Enteropathy associated T cell lymphoma in celiac disease: a large retrospective study. Dig Liver Dis. 2013;45:377-84. DOI:10.1016/j.dld.2012.12.001
17. Ondrejka S, Jagadeesh D. Enteropathy-associated T-cell lymphoma. Curr Hematol Malig R. 2016;11:504-13. DOI:10.1007/s11899-016-0357-7
18. Nicolae A, Xi L, Pham TH, et al. Mutations in the JAK/STAT and RAS signaling pathways are common in intestinal T-cell lymphomas. Leukemia. 2016;30:2245-7. DOI:10.1038/leu.2016.178
19. Attygalle AD, Cabeçadas J, Gaulard P, et al. Peripheral T-cell and NKcell lymphomas and their mimics; taking a step forward – report on the lymphoma workshop of the XVIth meeting of the European Association for Haematopathology and the Society for Hematopathology. Histopathology. 2014;64:171-99. DOI:10.1111/his.12251
20. Kikuma K, Yamada K, Nakamura S, et al. Detailed clinicopathological characteristics and possible lymphomagenesis of type II intestinal enteropathy-associated T-cell lymphoma in Japan. Hum Pathol. 2014;45:1276-84. DOI:10.1016/j.humpath.2013.10.038
21. 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;35:1557-69. DOI:10.1097/PAS.0b013e318222dfcd
22. Ko YH, Karnan S, Kim KM, et al. Enteropathy-associated T-cell lymphoma – a clinicopathologic and array comparative genomic hybridization study. Hum Pathol. 2010;41:1231-7. DOI:10.1016/j.humpath.2009.11.020
23. Tomita S, Kikuti YY, Carreras J, et al. Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan. Mod Pathol. 2015;28:1286-96. DOI:10.1038/modpathol.2015.85
24. Isaacson PGT, Bhagat G. Enteropathy-associated T-cell lymphoma and other primary intestinal T-cell lymphomas. In: Jaffe ES, Arber DA, Campo E, et al., ed. Hematopathology. 2nd ed. Philadelphia: Elsevier, 2017.
25. Chott A, Haedicke W, Mosberger I, et al. Most CD56+ intestinal lymphomas are CD8+CD5-T-cell lymphomas of monomorphic small to medium size histology. Am J Pathol. 1998;153:1483-90. DOI:10.1016/S0002-9440(10)65736-7
26. Moffitt AB, Ondrejka SL, McKinney M, et al. Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2. J Exp Med. 2017;214:1371-86. DOI:10.1084/jem.20160894
27. Roberti A, Dobay MP, Bisig B, et al. Type II enteropathy-associated Tcell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations. Nat Commun. 2016;7:12602. DOI:10.1038/ncomms12602
28. Lamure S, Duléry R, Di Blasi R, et al. Determinants of outcome in Covid-19 hospitalized patients with lymphoma: A retrospective multicentric cohort study. E Clinical Medicine. 2020;27:100549.
29. Challenor S, Tucker D. SARS-CoV-2-induced remission of Hodgkin lymphoma. Br J Haematol. 2021;192:415. DOI:10.1111/bjh.17116
30. de la Cruz-Benito B, Lázaro-Del Campo P, Ramírez-López A, et al. Managing the front-line treatment for diffuse large B cell lymphoma and high-grade B cell lymphoma during the COVID-19 outbreak. Br J Haematol. 2020;191:386-9. DOI:10.1111/bjh.17066
31. Lang N, Kuruvilla J. Evolving management strategies for lymphomas during the COVID-19 pandemic. Leuk Lymphoma. 2020:1-19. DOI:10.1080/10428194.2020
32. Perini GF, Fischer T, Gaiolla RD, et al. Hemoterapia e TerapiaCelular (ABHH) How to manage lymphoid malignancies during novel 2019 coronavirus (CoVid-19) outbreak: a Brazilian task force recommendation. Hematol Transfus Cell Ther. 2020;42:103-10. DOI:10.1016/j.htct.2020.04.002
33. Betrains A, Godinas L, Woei-A-Jin FJSH, et al. Convalescent plasma treatment of persistent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in patients with lymphoma with impaired humoral immunity and lack of neutralising antibodies. Br J Haematol. 2021;192:1100-5. DOI:10.1111/bjh.17266
1 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
2 ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России, Москва, Россия
*doktor-gai@yandex.ru
________________________________________________
Igor Yu. Gadaev*1, Vladimir I. Ershov1, Alla М. Kovrigina2, Irina Ya. Sokolova1, Olga V. Tashyan1, Marat A. Mingalimov1, Olga N. Antyufeeva1, Darya A. Budanova1, Marina G. Mnatsakanyan1, Olga V. Bochkarnikova1, Daria S. Nagornaia1
1 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
2 National Medical Research Center for Hematology, Moscow, Russia
*doktor-gai@yandex.ru