Histopathological subtypes of pediatric lymphomas and relation to Ebstein-Barr virus: an immunohistochemical and in situ hybridization study
Öz
Aim: Lymphomas are the second most common malignant disease after leukemia
and brain tumors in developing
contries. Ebstein-Barr virus has a
initiator role in the development of lymphoma,
but it is known that socioeconomic conditions, genetic features and the immune
supressive factors is also important. We aimed to explore the histopathologic
subtypes of pediatric lymphomas and their relation with Ebstein-Barr virüs infection
in our region.
Material
and Methods: In this
retrospective study, 87 children
including 36 cases with hodgkin lymphoma and 51 cases with non-hodgkin lymphoma
were included in the study. The pathologic slides were used to investigate immunohistochemical staining with Ebstein-Barr
virüs latent membrane protein-1 and in-situ hybridization.
Results: The most common histopathological subtype in hodgkin lymphoma cases were mixed cellular classical Hodgkin lymphoma
(55.6%) followed by nodular sclerosis classical hodgkin lymphoma (16.6%). The most common histopathological subtype in non-Hodgkin
lymphoma cases was Burkitt lymphoma
(51.0%) followed by precursor T-cell lymphoblastic leukemia/lymphoma (13.7%). Ebstein-Barr
virüs latent membrane protein-1 was positive in 29 Hodgkin lymphoma. All non-Hodgkin lymphoma cases were
stained negative with ımmunohistochemical. The positive staining rate of Hodgkin lymphoma cases with in-situ hybridization
was 83.3% and this rate was
27.5% in non-Hodgkin lymphoma cases. The differences between groups for both
staining methods were statistically significant (p<0.001)
Conclusion: The results of this study show that the distribution of histopatholojik
subtypes of pediatric lymphomas similar to in developing countries. And we have
observed that in-situ hybridization is
more specific than immunohistochemistry because Ebstein-Barr virus positivity is more detected in in-situ hybridization.
Anahtar Kelimeler
Ebstein-Barr virüs Hodgkin Lymphoma; Immunohistochemistry; In situ hybridization pediatric Non-Hodgkin Lymphoma
Kaynakça
- 1 Ozoya OO, Sokol L, Dalia S. EBV-Related Malignancies, Outcomes and Novel Prevention Strategies. Infect disord drug targets 2016;16:4-21.
- 2 Anagnostopoulos I, Hummel M. Epstein-Barr virus in tumours. Histopathology 1996;29:297-315.
- 3. Pasman PC, Tiebosch A, Erdkamp FL, Vrints LW, Breed WP, Schouten HC. P53 as a marker of the malignant cell in Hodgkin's disease. Ann oncol. 1994;5 Suppl 1:89-91.
- 4. Jarrett RF, MacKenzie J. Epstein-Barr virus and other candidate viruses in the pathogenesis of Hodgkin's disease. Semin Hematol 1999;36:260-269.
- 5. Yilmaz F, Uzunlar AK, Sogutcu N, Ozaydin M. Hodgkin's disease and association with Epstein-Barr virus in children in Southeast Turkey. Saudi Med. J. 2005;26:571-575.
- 6. Cavdar AO, Tacoy A, Babacan E, Gozdasoglu S, Arcasoy A, Topuz U. Hodgkin's disease in Turkish children: A clinical and histopathologic analysis. J Natl Cancer Inst. 1977;58:479-481.
- 7. Tinguely M, Brundler MA, Gogos S, Kerl K, Borisch B. Epstein-Barr virus association in pediatric abdominal non-Hodgkin-lymphomas from Turkey. Arch Immunol Ther Exp (Warsz) 2000;48:317-322.
- 8. Durmaz R, Aydin A, Koroglu M, et al. Detection and genotyping of Epstein-Barr virus by polymerase chain reaction in tissues obtained from cases with Hodgkin's disease in Turkey. Acta Virol 1998;42:375-381.
- 9. Tacyildiz N, Cavdar AO, Ertem U, et al. Unusually high frequency of a 69-bp deletion within the carboxy terminus of the LMP-1 oncogene of Epstein-Barr virus detected in Burkitt's lymphoma of Turkish children. Leukemia 1998;12:1796-1805.
- 10. Ertem U, Duru F, Pamir A, Tacyildiz N, Dagdemir A, Akcayoz A. Burkitt's lymphoma in 63 Turkish children diagnosed over a 10 year period. Pediatr Hematol Oncol. 1996;13:123-134.
- 11. Cavdar AO, Yavuz G, Babacan E, Gozdasoglu S, Unal E, Ertem U. Burkitt's lymphoma in Turkish children: Clinical, viral [EBV] and molecular studies. Leuk Lymphoma 1994;14:323-330.
- 12. Cavdar AO, Gozdasoglu S, Yavuz G, Babacan E, Unal E, Uluoglu O. Burkitt's lymphoma between African and American types in Turkish children: Clinical, viral (EBV), and molecular studies. Med Pediatr Oncol 1993;21:36-42.
- 13. Ataoglu O, Fen T, Suer O, Dagl M, Ak Z, Yamac K. Epstein-Barr Virus latent membrane protein 1 (LMP-1) in Hodgkin's lymphoma patients in Turkey. Turk J Haematol 2001;18:123-126.
- 14. Aktas S, Kargi A, Olgun N, Diniz G, Erbay A, Vergin C. Prognostic significance of cell proliferation and apoptosis-regulating proteins in Epstein-Barr virus positive and negative pediatric Hodgkin lymphoma. Lymphat Res Biol 2007;5:175-182.
- 15. Tanyildiz HG, Yildiz I, Bassullu N, et al. The Role of Epstein-Barr Virus LMP-1 Immunohistochemical Staining in Childhood Hodgkin Lymphoma. Iran J Pediatr. 2015;25:e2359.
- 16. Zeytinoglu A, Hekimgil M, Erensoy S, Aydemir S, Berber S, Cagirgan S. [Investigation of Epstein-Barr virus DNA and RNA in tissues of patients with lymphoma]. Mikrobiyol Bul 2005;39:473-481.
- 17. Weinreb M, Day PJ, Niggli F, et al. The role of Epstein-Barr virus in Hodgkin's disease from different geographical areas. Arch Dis. Chil. 1996;74:27-31.
- 18. Armstrong AA, Alexander FE, Paes RP, et al. Association of Epstein-Barr virus with pediatric Hodgkin's disease. Am J Pathol 1993;142:1683-1688.
- 19. Araujo I, Foss HD, Bittencourt A, et al. Expression of Epstein-Barr virus-gene products in Burkitt's lymphoma in Northeast Brazil. Blood 1996;87:5279-5286.
- 20. Philip Lanzkowsky, Jeffrey M. Lipton and Jonathan D. Fish. Non-Hodgkin's Lymphoma in Manual Pediatric Hematology and Oncology. London, Academic Press 6th ed. 2016, 442-452.
- 21. Reiter A. Non-Hodgkin lymphoma in children and adolescents. Klin Padiatr 2013;225:87-93.
- 22. Capone G, Fasano C, Lucchese G, Calabro M, Kanduc D. EBV-Associated Cancer and Autoimmunity: Searching for Therapies. Vaccines (Basel) 2015;3:74-89.
- 23. Pollock BH, Jenson HB, Leach CT, McClain KL, Hutchison RE, Garzarella L. Risk factors for pediatric human immunodeficiency virus-related malignancy. JAMA 2003;289:2393-2399.
- 24. Epstein MA, Achong BG, Barr YM. Virus particles in cultered lymphoblasts from Burkitt's lymphoma. Lancet 1964;1:702-703.
- 25. Anwar N, Kingma D, Boch AR. The investigation of Ebstein-Barr viral sequences in 41 cases of Burkitt's lymphoma from Egypt. Cancer 1995;76:1245-1252.
- 26. Peylan-Ramu N, Diment J, Krichevsky S, Ben-Yehuda D, Bhatia K, Magrath IT. Expression of EBV encoded nuclear small non-polyadenylated RNA (EBER) molecules in 32 cases of childhood Burkitt's lymphoma from Israel. Leuk Lymphoma 2001;40:405-411.
- 27. Klumb CE, Hassan R, De Oliveira DE, De Resende LM, Carrico MK, De Almeida Dobbin J. Geographic variation in Epstein-Barr virus-associated Burkitt's lymphoma in children from Brazil. Int J Cancer 2004;108:66-70.
- 28. Mansoor A, Stevenson MS, Li RZ, Frekko K, Weiss W, Ahmad M. Prevalence of Epstein-Barr viral sequences and EBV LMP1 oncogene deletions in Burkitt's lymphoma from Pakistan: Epidemiological correlations. Hum. Pathol. 1997;28:283-288.
- 29. Whittle HC, Brown J, Marsh K, Blackman M, Jobe O, Shenton F. The effects of Plasmodium falciparum malaria on immune control of B lymphocytes in Gambian children. Clin Exp Immunol. 1990;80:213-218.
- 30. Pinkus GS, Said JW. Hodgkin's disease, lymphocyte predominance type, nodular--a distinct entity? Unique staining profile for L&H variants of Reed-Sternberg cells defined by monoclonal antibodies to leukocyte common antigen, granulocyte-specific antigen, and B-cell-specific antigen. Am J Pathol 1985;118:1-6.
Pediatrik lenfomalarda histopatolojik subtip ve Ebstein-Barr virus ilişkisi: immünohistokimyasal ve in situ hibridizasyon çalışması
Öz
Amaç: Bu çalışmanın amacı bölgemizdeki pediatrik lenfomaların histopatolojik alt tiplerinin oranını ve bunların Ebstein-Barr virüs enfeksiyonu ile olan ilişkisini incelemektir.
Gereç ve Yöntem: Hodgkin lenfoma tanısı alan 36 olgu ve non-hodgkin lenfoma tanısı alan 51 olgu retrospektif arşiv taraması yapılarak çalışmaya dahil edildi. Olgulara immünohistokimyasal olarak Ebstein-Barr virüs latent membran proteini-1 ve in-situ hibridizasyon uygulandı.
Bulgular: Hodgkin lenfoma olgularında; en sık rastlanan histopatolojik alt tipler sırası ile mikst sellüler klasik hodgkin lenfoma (%55,6) idi. Non-Hodgkin lenfoma olgularında en sık rastlanan histopatolojik alt tip Burkitt lenfoma (%51) idi. Ebstein-Barr virüs latent membran proteini-1 ile 29 hodgkin lenfoma olgusunda pozitif iken non-hodgkin lenfoma olgularında immünohistokimya ile pozitif boyanma saptanmadı. Hodgkin lenfoma olgularında in situ hibridizasyon ile boyanma oranı % 83.,3 iken non-Hodgkin lenfoma olgularında bu oran % 27.5 idi.. Her iki boyama yöntemi için gruplar arasındaki fark istatistiksel olarak anlamlıydı.
Sonuç: Bu çalışmada, olgularımızın histopatolojik dağılımlarının gelişmekte olan ülkelerdeki pediatrik lenfoma olguları ile benzer olduğunu göstermektedir. Aynı zamanda in situ hibridizasyon’da Ebstein-Barr virüs pozitifliği daha fazla olması nedeniyle in situ hibridizasyonun ebstein barr virüs tespitinde immünohistokimyadan daha spesifik olduğunu düşünmekteyiz.
Anahtar Kelimeler
Ebstein Barr virüs Hodgkin lenfoma İmmünohistokimya İn situ hibridizasyon Non-Hodgkin lenfoma pediatrik
Kaynakça
- 1 Ozoya OO, Sokol L, Dalia S. EBV-Related Malignancies, Outcomes and Novel Prevention Strategies. Infect disord drug targets 2016;16:4-21.
- 2 Anagnostopoulos I, Hummel M. Epstein-Barr virus in tumours. Histopathology 1996;29:297-315.
- 3. Pasman PC, Tiebosch A, Erdkamp FL, Vrints LW, Breed WP, Schouten HC. P53 as a marker of the malignant cell in Hodgkin's disease. Ann oncol. 1994;5 Suppl 1:89-91.
- 4. Jarrett RF, MacKenzie J. Epstein-Barr virus and other candidate viruses in the pathogenesis of Hodgkin's disease. Semin Hematol 1999;36:260-269.
- 5. Yilmaz F, Uzunlar AK, Sogutcu N, Ozaydin M. Hodgkin's disease and association with Epstein-Barr virus in children in Southeast Turkey. Saudi Med. J. 2005;26:571-575.
- 6. Cavdar AO, Tacoy A, Babacan E, Gozdasoglu S, Arcasoy A, Topuz U. Hodgkin's disease in Turkish children: A clinical and histopathologic analysis. J Natl Cancer Inst. 1977;58:479-481.
- 7. Tinguely M, Brundler MA, Gogos S, Kerl K, Borisch B. Epstein-Barr virus association in pediatric abdominal non-Hodgkin-lymphomas from Turkey. Arch Immunol Ther Exp (Warsz) 2000;48:317-322.
- 8. Durmaz R, Aydin A, Koroglu M, et al. Detection and genotyping of Epstein-Barr virus by polymerase chain reaction in tissues obtained from cases with Hodgkin's disease in Turkey. Acta Virol 1998;42:375-381.
- 9. Tacyildiz N, Cavdar AO, Ertem U, et al. Unusually high frequency of a 69-bp deletion within the carboxy terminus of the LMP-1 oncogene of Epstein-Barr virus detected in Burkitt's lymphoma of Turkish children. Leukemia 1998;12:1796-1805.
- 10. Ertem U, Duru F, Pamir A, Tacyildiz N, Dagdemir A, Akcayoz A. Burkitt's lymphoma in 63 Turkish children diagnosed over a 10 year period. Pediatr Hematol Oncol. 1996;13:123-134.
- 11. Cavdar AO, Yavuz G, Babacan E, Gozdasoglu S, Unal E, Ertem U. Burkitt's lymphoma in Turkish children: Clinical, viral [EBV] and molecular studies. Leuk Lymphoma 1994;14:323-330.
- 12. Cavdar AO, Gozdasoglu S, Yavuz G, Babacan E, Unal E, Uluoglu O. Burkitt's lymphoma between African and American types in Turkish children: Clinical, viral (EBV), and molecular studies. Med Pediatr Oncol 1993;21:36-42.
- 13. Ataoglu O, Fen T, Suer O, Dagl M, Ak Z, Yamac K. Epstein-Barr Virus latent membrane protein 1 (LMP-1) in Hodgkin's lymphoma patients in Turkey. Turk J Haematol 2001;18:123-126.
- 14. Aktas S, Kargi A, Olgun N, Diniz G, Erbay A, Vergin C. Prognostic significance of cell proliferation and apoptosis-regulating proteins in Epstein-Barr virus positive and negative pediatric Hodgkin lymphoma. Lymphat Res Biol 2007;5:175-182.
- 15. Tanyildiz HG, Yildiz I, Bassullu N, et al. The Role of Epstein-Barr Virus LMP-1 Immunohistochemical Staining in Childhood Hodgkin Lymphoma. Iran J Pediatr. 2015;25:e2359.
- 16. Zeytinoglu A, Hekimgil M, Erensoy S, Aydemir S, Berber S, Cagirgan S. [Investigation of Epstein-Barr virus DNA and RNA in tissues of patients with lymphoma]. Mikrobiyol Bul 2005;39:473-481.
- 17. Weinreb M, Day PJ, Niggli F, et al. The role of Epstein-Barr virus in Hodgkin's disease from different geographical areas. Arch Dis. Chil. 1996;74:27-31.
- 18. Armstrong AA, Alexander FE, Paes RP, et al. Association of Epstein-Barr virus with pediatric Hodgkin's disease. Am J Pathol 1993;142:1683-1688.
- 19. Araujo I, Foss HD, Bittencourt A, et al. Expression of Epstein-Barr virus-gene products in Burkitt's lymphoma in Northeast Brazil. Blood 1996;87:5279-5286.
- 20. Philip Lanzkowsky, Jeffrey M. Lipton and Jonathan D. Fish. Non-Hodgkin's Lymphoma in Manual Pediatric Hematology and Oncology. London, Academic Press 6th ed. 2016, 442-452.
- 21. Reiter A. Non-Hodgkin lymphoma in children and adolescents. Klin Padiatr 2013;225:87-93.
- 22. Capone G, Fasano C, Lucchese G, Calabro M, Kanduc D. EBV-Associated Cancer and Autoimmunity: Searching for Therapies. Vaccines (Basel) 2015;3:74-89.
- 23. Pollock BH, Jenson HB, Leach CT, McClain KL, Hutchison RE, Garzarella L. Risk factors for pediatric human immunodeficiency virus-related malignancy. JAMA 2003;289:2393-2399.
- 24. Epstein MA, Achong BG, Barr YM. Virus particles in cultered lymphoblasts from Burkitt's lymphoma. Lancet 1964;1:702-703.
- 25. Anwar N, Kingma D, Boch AR. The investigation of Ebstein-Barr viral sequences in 41 cases of Burkitt's lymphoma from Egypt. Cancer 1995;76:1245-1252.
- 26. Peylan-Ramu N, Diment J, Krichevsky S, Ben-Yehuda D, Bhatia K, Magrath IT. Expression of EBV encoded nuclear small non-polyadenylated RNA (EBER) molecules in 32 cases of childhood Burkitt's lymphoma from Israel. Leuk Lymphoma 2001;40:405-411.
- 27. Klumb CE, Hassan R, De Oliveira DE, De Resende LM, Carrico MK, De Almeida Dobbin J. Geographic variation in Epstein-Barr virus-associated Burkitt's lymphoma in children from Brazil. Int J Cancer 2004;108:66-70.
- 28. Mansoor A, Stevenson MS, Li RZ, Frekko K, Weiss W, Ahmad M. Prevalence of Epstein-Barr viral sequences and EBV LMP1 oncogene deletions in Burkitt's lymphoma from Pakistan: Epidemiological correlations. Hum. Pathol. 1997;28:283-288.
- 29. Whittle HC, Brown J, Marsh K, Blackman M, Jobe O, Shenton F. The effects of Plasmodium falciparum malaria on immune control of B lymphocytes in Gambian children. Clin Exp Immunol. 1990;80:213-218.
- 30. Pinkus GS, Said JW. Hodgkin's disease, lymphocyte predominance type, nodular--a distinct entity? Unique staining profile for L&H variants of Reed-Sternberg cells defined by monoclonal antibodies to leukocyte common antigen, granulocyte-specific antigen, and B-cell-specific antigen. Am J Pathol 1985;118:1-6.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Araştırma |
| Yazarlar | |
| Yayımlanma Tarihi | 29 Aralık 2018 |
| Kabul Tarihi | 11 Şubat 2018 |
| Yayımlandığı Sayı | Yıl 2018 Cilt: 43 Sayı: 4 |
