Nasal NK/T-Cell Lymphoma. A Comparative Analysis of a Mexican Population with the Other Populations of Latin-America
Oncology Research Unit. Oncology Hospital National Medical Center, IMSS, México DF, Mexico.
Received: August 4, 2015
Accepted: August 24, 2015
Mediterr J Hematol Infect Dis 2015, 7(1): e2015052, DOI 10.4084/MJHID.2015.052
This article is available on PDF format at:
| This is an Open Access article distributed
under the terms of the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Nasal natural killer/T-cell lymphoma (nasal NKTCL), is a rare presentation of extranodal lymphoma in North-America and Europe, but in some countries, as China and Korea, nasal NKTCL occurred in 20 to 46 % of T-cell lymphomas. Some studies, analyzing the incidence in Latin-America, observed some differences between the various populations. However, this comparison included Argentina and Chile, Peru, and other Latin-America but not the Mexico. Thus, we performed a retrospective analysis of the patients diagnosed and treated as nasal, NKTCL, in our institution that is an academic tertiary national reference hospital of Mexico.
From 1988 to 2014, we diagnosed and treated 14,816 cases of non-Hodgkin’s lymphoma, 10,957 (73%) were of B-cell histology and 3822 (26%) were of T-cell histology. Nasal, NKTCL, was the most frequent of the T-cell histology: 40%. We compared our results with those of other countries and observed that nasal, NKTCL have a small number of cases in North-America, and in some countries of Latin-America, as Argentina, Brazil, and Chile. However, the number of NKTCL cases found in Mexico was similar to that found in Guatemala and Peru, and also in China and Korea. Our study suggests that this neoplasm could have a racial basis, but environmental factors should also be considered.
Nasal NK/T-cell lymphoma (NKTCL), is a rare presentation
of malignant lymphoma with protean clinical features,
characterized by destruction of the upper
respiratory tract, in particular of the nasal cavity,
nasal and paranasal sinuses, and hard palate.
It is more common in Asia, and in some countries of Latin America, as Guatemala and Peru than in Western countries.
Mexico is a country that geographically and politically is part of North-America, but with racial differences, that can reflect the differences in some neoplasm, specifically NK/TCL. Although some environmental factors have to be considered as part of these differences, until now, the racial differences appear mostly to be the cause of the high proportion of these special setting of patients in Mexico.
Thus, we performed a retrospective analysis of patients with NK/TCL, which were diagnosed and treated at our Hospital. The Oncology Hospital at National Medical, is a tertiary national reference center for patients with cancer, in the Mexican Institute of Social Security. Although our institution has a national coverage with 53,000,000 of people; we cannot considered these study as a national study. Subsequently, we searched for reports of NKTCL, in other countries. Some of these patients have been previously reported.[2-7]
Patients and Methods
We, while searching clinical records of the patients from 1988 to
2014 with a diagnosis of Non-Hodgkin lymphoma, separated patients with
a confirmed diagnosis, according to the criteria of the
World Health Organization. From 2009 to 2012, our Pathology
Department performed a revision of all T-cell lymphomas, which were
reclassified according to the World Health Organization.
Entry criteria were as follow: age >18 years without upper limit; no gender differences; at the immunohistochemical studies, all lymphomas were CD2+, cytoplasm CD3epsilon+, CD56+, and expressing perforin enzyme B, TIA. Evidence of Epstein-Barr virus was shown by in situ hybridization. Prognostic factors were evaluated according to the International Prognostic Index (IPI) and the Korean proposal. Staging studies were performed as previously mentioned; positive emission tomography (PET) was added since available in our institution (2008).
Treatment was made as previously reported, and was based on the administration of combined therapy, chemotherapy and radiotherapy, most cases as the “sandwich“ technique, that at present is considered the treatment of choice in our institution.
From 1988 to 2014, we diagnosed 14,816 cases of non-Hodgkin
lymphoma, 10958 (73%) were of B-cell histology; and 3822 (26%) were of
T-cell histology. In 36 cases, the type of cell was not identified,
because the slides were not available for revision, and these cases
were not included in this paper.
Table 1, shown the histopathology of the T-cell lymphoma, most cases (40%), were NKTCL, followed by peripheral T-cell non-specified, other T-cell lymphomas were rare.
Table 2 shows the clinical and laboratory characteristics of the NKTCL patients. According the stage, the early stages were more frequent. Also according the clinical risk, the low and intermediate forms evaluated by IPI, and the groups 0 and 1, by Korean prognostic model for nasal NK/T-cell lymphoma were more frequently found.
As expected, patients with advanced stages: III and IV, had poorer prognosis factors, a clinical high risk in both systems and a poor performance status. Curiously, of the advanced stages, only 21 patients (2.7%) were at stage III.
Table 3 shows that, in early stages, radiotherapy attained a complete response (RT) of 73%, of patients, but the relapse, especially outside the radiation site, was frequent. Salvage chemotherapy rescued more patients, but the overall survival (OS) was low when compared to combined therapy. We did not treat advanced stages with radiotherapy alone. The best results were achieved with the use of combined therapy; “sandwich technique” is considered the best combination. Taking into consideration the poor results with chemotherapy alone in early and advanced stages, we did not recommend chemotherapy alone in this type of lymphoma.
Table 4 shows a comparative analysis of patients from different countries.[8-18] NKTCL, nasal type, is a rare disease in Europe and North-America, also in the Latin-American countries, with a high proportion of European-migration, as Chile and Argentina.
|Table 1. T-cell lymphoma. Mexican Population.|
|Table 2. Nasal NK/T-cell lymphoma. Mexican population.|
|Table 3. The outcome from Nasal NK/T-cell lymphoma in the Mexican population.|
|Table 4. Frequency of T-cell lymphoma and NNK subtype by country and region|
In Mexico, NKTCLs represent the 40% of all T-cell lymphomas, and 10%
of all malignant lymphomas, diagnosed in our hospital. The
International T-cell Project was the first attempt to explore the
geographic variations about the T-cell lymphomas; and specifically of
NKTCL. These results showed that the NKTCLs represent about 10% of the
total of T-cell lymphomas found in North America, Europe, and Asia.
The percentage ranged from 4.3% in Europe to “2.4% in Asia. In the USA,
the percentage was 5.1%. Some years, ago, the study was
repeated in another countries, with small variations In a
subsequent study, also made in the USA, Bellesi et al.
reported that the NKTCLs were the 13% of all 737
cases of T-cell lymphomas, with a percentage ranging from 6% in
Europe and 31% in the Middle/Far East. In the USA, the percentage was
the 9%. Recently Dubal et al., performed a retrospective analysis
of cancer of head and neck in the USA, and found 1382 cases of
sino-nasal lymphomas, but only 328 (23%) were considered that were
NKTCL. Moreover, the analysis for a general population showed that
NKTCLs in the USA represent only 0.032/100,00 habitants. The T-cell Project report that the frequency in European countries, the presence of NKCTLs is rare, 4.3 % of 1314 cases, and subsequently 6.0% of 737 patients. Isolated reports from some European countries has been published: Italy: 26 cases; Portugal: 12 patients, which were analyzed the molecular changes found in these patients.
Marcos-Gragera in a retrospective survival analysis of a different form
of lymphoid neoplasms in European Countries reported that NKTCLs were
Laurini et al. have presented the incidence of NKTCL in Central and South America in the confrontation with the USA. In this report these neoplasm represent 0% in the USA and the 23 % of all T-cell lymphoma (27 cases in 118 cases of T-cell lymphoma) in Central/South America, respectively 13 %(4/31 cases) in Peru, 4.5% (1/22 cases) in Argentina, 9% (2/18 cases) in Brazil, 22 % (5/22 cases) in Chile, 66% (15/25) in Guatemala, 13% (4/31) in Perù.
Bellesi et al. reported 9 cases (11%) in Chile, and 8 cases Brazil (15%) among 152 cases found in South America. Gualco et al. reported 122 Brazilian patients, but they only analyzed the presence of the subtypes of EBV virus in patients with NKTCL. However, these differences could be considered to because they were performed in different populations.
The high rate of frequency of NKTCL in Guatemala, Central America, is also confirmed by the report of Van der Rijn et al.. In the analysis of neoplasms of head and neck, these authors found that 17 cases (88%) were NKTCL, this search was also able to detect that many patients were positive for EBV. Although, nasal NK/T-cell lymphoma shown a higher prevalence of EBV seropositive, the role in the pathogenesis of nasal NKTCL not has been defined. Other forms of the chronic EBV-associated disease are not common in the Mexico. Ortega et al.. reported a Mexican study, analyzed 264 cases of non-Hodgkin’s lymphoma with the nodal and extranodal presentation. In the extranodal presentation, 55 cases, 16 patients were considered lymphoma of the midline or centrofacial with angiocentricity. Thus, we considered that were NKTCLs, even if the molecular profile was the most important task of this research. Perry et al. in another report from Guatemala, analyzed 226 patients with non-Hodgkin’s lymphoma, 25 cases were of T-cell origin, and 18 (7.9 % of the total of cases) were NKTCL, no other dates were included.
The number of NKTCL cases found in Mexico was similar to that
found in Guatemala and Peru, and also in China and Korea. Our
study suggests that this neoplasm could have a racial basis, but
environmental factors also had to be considered.
According our experience and of others concomitant/sequential chemotherapy and radiotherapy is the standard treatment. Radiotherapy alone, also for the first stages, is inadequate because of high systemic failure rate.
- William BM, Armitage JO.: International analysis of the frequency and outcome of NK/T-cell lymphoma. Best Pract Res Clin Haematol. 2013;20:23-32. http://dx.doi.org/10.1016/j.beha.2013.04.003 PMid:23768638
- Avilès A, Rodriguez L, Guzman R, Talavera A, García EL, Diaz-Maqueo JC.: Angiocentric T-cell lymphoma of the nose, paranasal sinuses and hard palate. Hematol Oncol 1992;10:141-147. http://dx.doi.org/10.1002/hon.2900100303 PMid:1398510
- Avilés A, Diaz N, Neri N, Cleto S, Talavera A.: Angiocentric nasal T/natural killer cell lymphoma.A single center study of prognostic factors in 108 patients. Clin Lab Haematol 2000;22:215-220. http://dx.doi.org/10.1046/j.1365-2257.2000.00307.x PMid:11012633
- Avilés A, Neri N, Fernandez R, Calva A, Huerta-Guzmán J, Nambo MJ.: Nasal NK/T-cell lymphoma with disseminated disease treated with aggressive combined therapy. Med Oncol 2003;20:13-17. http://dx.doi.org/10.1385/MO:20:1:13 PMid:25805960
- Avilés A.: T-cell lymphoma. Standard treatment :The Mexican Experience. Haematol Rep 2006;2:22-24.
- Avilés A, Cleto S, Casta-eda C, Namba MJ.: CMED in the treatment of nasal natural killer cell lymphoma with distant metastased. Hematology 2007; 12:241-244. http://dx.doi.org/10.1080/10245330701214327 PMid:17558700
- Aviles A, Neri N, Fernandez R, Huerta-Guzman J, Nambo MJ.: Combined therapy in untreated patients with NK/T-cell lymphoma. Results of a clinical trial. Med Oncol 2013;30:637. http://dx.doi.org/10.1007/s12032-013-0637-1 PMid:23797771
- Vose J, Armitage J, Weisenburger D; International T-Cell Lymphoma Project. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008 Sep 1;26(25):4124-30. http://dx.doi.org/10.1200/JCO.2008.16.4558
- Bellei M, Chiattono ES, Luminari S, Pesce EA, Cabrera MC, DeSousa A, et al.: T-cell lymphoma in South America and Europe. Rev Bras Hematol Hemorr, 2012;34:42-7. http://dx.doi.org/10.5581/1516-8484.20120013 PMid:23049383 PMCid:PMC3459617
- Dubal PM, Dutta R, Vasquez A, Patel D, Baredes S, Eloy JA.: A comparative population based analysis of sinonasal diffuse large B-cell lymphoma and extranodal NK/T-cell lymphoma. Laryngoscope, 2015;125:1077-1083. http://dx.doi.org/10.1002/lary.25111 PMid:25546466
- Laurini JA, Perry AM, Boilesen E, Diebold J, Maclennan KA, Müller-Hermelink HK, Nathwani BN, Armitage JO, Weisenburger DD. Classification of non-Hodgkin lymphoma in Central and South America: a review of 1028 cases. Blood. 2012 Dec 6;120(24):4795-801. http://dx.doi.org/10.1182/blood-2012-07-440073
- Pagano L, Gallamini A, Trapé G, Fianchi L, Mattei D, Todeshi G; et al.: NK/T-cell lymphoma "nasal" type. An Italian Multicentric retrospective survey. Ann Oncol 2006;17:794-800. http://dx.doi.org/10.1093/annonc/mdl015 PMid:16497823
- Lima M, Spinoza S, Santos AH, Rodriguez J, Oliveira L, Queiroz ML, et al.: Aggressive mature natural killer-cell neoplasm. Report of a series of 12 patients with emphasis on flow cytometry based immunophenotype and DNA content iof neoplastic natural killer-cells.- Leuk Lymphoma 2015;56:103-112. http://dx.doi.org/10.3109/10428194.2014.905772 PMid:24669939
- Marcos–Gragera R, Allemani C, Tereral C, DeAngelis R, Capocaleta R, Mayradic M, et al.: Survival of European patients diagnosed with lymphoid neoplasm in 2000-2002. Haematologica 2011;96:720-727. http://dx.doi.org/10.3324/haematol.2010.034264 PMid:21330324 PMCid:PMC3084919
- Van der Rijn M, Bhargava N, Molina-Kirsh H, Carlos-Bragni R, Warnike RA, Cleary ML, et al.: Extranodal head and neck lymphoma s in Guatemala. Hum Pathol 1997;28:834-839. http://dx.doi.org/10.1016/S0046-8177(97)90158-1
- Ortega V, Verastegui E, Flores G, Meneses A, Ocadiz R, Alfaro G.: Non-Hodgkin’s lymphoma in México. A clínico-pathological and molecular analysis. Leuk Lymphoma 1998;31:572-582.
- Perry AM, Molina-Kirsh H, Natwani N, Diebold J, MacLennan K, Muller-Hemelink K, et al.: Classification of non-Hodgkin's lymphomas in Guatemala according to the World Health Organization system. Leuk Lymphoma 2011;52:1681-1689. http://dx.doi.org/10.3109/10428194.2011.584254 PMid:21635203
- Gualco G, Dowery-Duarte P, Lucimaro C., Chiato H, Clinico-pathological and molecular profiles of 122 Brazilian cases of nodal and extranodal NK/T-cell lymphoma, nasal type, with EBV subtype analysis. Am J Surg Pathol 2011;35:1195-1200. http://dx.doi.org/10.1097/PAS.0b013e31821ec4b5 PMid:21716086
- Au WY, Weisenburguer DD, intragumtornchai T, Nakamura S, Kim WS, Snq I, et al.: Clinical differences between nasal and extranasal natural killer/T-cell lymphoma. Blood 2009;113:3931-3937. http://dx.doi.org/10.1182/blood-2008-10-185256 PMid:19029440
- Tse E, Kwong YL.: How I treat NK/T-cell lymphoma. Blood 2013;121:4997-5005. http://dx.doi.org/10.1182/blood-2013-01-453233 PMid:23652805
Metrics powered by PLOS ALM
Copyright (c) 2016 Mediterranean Journal of Hematology and Infectious Diseases
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.