Sinonasal lymphomas in Indonesia: immunophenotype and Epstein-Barr virus association

Abstract

AbstrakLimfoma sinonasal merupakan kelainan yang jarang dijumpai yang mencakup jenis sel NK/T atau sel B. Penelitian2 terdahulu menunjukkan adanya perbedaan angka kejadian limfoma NK/T (LNKT) yang sesuai daerah geografis serta kaitan yang sangat tinggi dengan infeksi virus Epstein Barr. Penelitian yang dilakukan terhadap 4l kasus penyakit limfoproliferatif sinonasal yang tersimpan di arsip Bagian Patologi Anatomik Fakultas Kedokteran Universitas Indonesia dalam kurun waktu 1994-2002 menunjukkan 35 kasus merupakan limfoma sinonasal. Pulasan imunohistokimia membuktikan 20 kasus (57%) sebagai LNKT dan 15 kasus (43%) limfoma sel B jenis sel besar. LNKT menunjukkan laki2 lebih banyak dari wanita (L:W=4:1) serta usia yng lebih muda (median 37 tahun); sedangkan limfoma sel B lebih banyak pada wanita (1:1.5) serta usia yang lebih tua (median 49 tahun). Hasil pemeriksaan genom virus Epstein Barr dengan cara hibridisasi in situ menggunakan pelacak EBER-1 menunjukkan 90% LNKT positif dan negatif pada semua limfoma sel B. Tulisan ini merupakan laporan limfoma sinonasal yang pertama dari Indonesia yang menunjukkan predominasi relatif limfoma sel B dibandingkan dengan beberapa negara Asia lainnya. Tidak adanya kaitan dengan virus Epstein Barr pada limfoma sel B juga berbeda dengan penemuan di negara Asia lain (positivitas 25-4l%) . Predominasi limfoma sel B tanpa kaitan dengan virus Epstein Barr mengarah pada kemungkinan adanya faktor etiologik yang spesifik untuk Indonesia. Abstract Sinonasal lymphoma is a rare disease with NK/T-cell (NKTC) or B-cell immunophenotype. Previous study revealed the geographic difference in frequency of NKTC lymphoma (NKTCL) and almost constant association with Epstein-Barr virus (EBV) infection.Through review of 41 cases with sinonasal lymphoproliferative diseases registered in the Department of Anatomical Pathology, University of Indonesia during the period 1994 to 2002, thirty-five were accepted as sinonasal lymphoma. Immunohistochemistry revealed that 20 cases (57%) were NK/T-cell type and 15 (43%) B-cell type with large cell morphology, i.e.,diffuse large B-cell lymphoma. NKTCL showed a marked male preponderance (M/F= 4:1) and younger onset of disease (median age, 37 years), and Bcell lymphoma showed a relative female preponderance (1:1.5) and older disease onset (median age, 49 years). In situ hybridization using EBER-1 probe revealed that 90 % of NKTCL were EBV-positive, but none of B-cell lymphoma were EBV-positive. This is the first report on sinonasal lymphoma in Indonesia showing relative predominance of B-cell lymphoma compared to other Asian countries and Peru (14-24 %). Lack of EBV-association in Indonesian sinonasal B-cell lymphoma showed a marked contrast to that in other Asian countries (EBV positive rate,(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). Predominance of sinonasal B-cell lymphoma without EBV genome might suggest presence of specific etiologic factors in Indonesia. (Med J Indones 2004; 13: 71-6)

Nasal NK/T-cell lymphoma: epidemiology and pathogenesis

“…The disease is rare in the USA [64] and Europe [65]. The patients with NKTCL seem to be clustered also in Latin American countries and Indonesia [66, 67]. Information from other parts of the world such as Africa, the Middle and Near East, and Rusia is helpful to elucidate the etiology of this disease.…”

“…Subsequent study revealed the constant association of NKTCL with EBV in the world (Fig. 2 ) (Table 1 ) [ 18 – 23 ]. Sino-nasal lymphomas are immunophenotypically classified into NK/T-(CD56 + ), T-, and B-cell type with distinctive clinical features [ 24 ].…”

Gene mutation analysis of sinonasal lymphomas in Indonesia

“…Information for age and gender were not available in 5 cases. Histologic and immunohistochemical findings together with the brief clinical findings of a part of these cases were reported previously (22). Briefly, there was a marked male preponderance in NKTCL type as compared to B-cell type: 2.8 to 1 and 1 to 1.6, respectively.…”

“…In conclusion, the frequency of mutations was higher in p53, c-kit, and bak genes examined in the B-cell than in NKTCL cases, with almost statistically significant level in bak gene. This contrast the higher frequency of EBV positive rate in NKTCL cases but none of B-cell cases were EBV positive among Indonesian sinonasal lymphomas (22). Taken together, gene mutations might be the driving-force for development of B-cell lymphoma, whereas combined EBV infection and gene mutations might contribute to NKTCL development in Indonesian sinonasal lymphomas.…”

Prevalence of Epstein–Barr virus associated with nasal lymphoma in patients attending the regional hospital of Valdivia, Chile, between 1987 and 2005

“…The prevalence of NK/T cell lymphoma, nasal type, is known to be higher in Asian (7-8%) than Western countries (<1%), and it is associated with a high incidence of EBV infection, as are some peripheral T-cell lymphomas [Anderson et al, 1998;Chang et al, 2004;Hardjolukito et al, 2004]. In a 2004 study including North American institution, the nasopharyngeal NK/T-cell lymphoma was seen at higher frequency (3%) than prior North American reports, most likely due to the high proportion of Asians included in that study [Savage et al, 2004].…”