Type Distribution of Lymphomas in Lebanon : Five-Year Single Institution Experience

Lymphomas represent the fifth most frequent cancer in Lebanon. Every year, between 600 to 700 new cases of Hodgkin lymphoma and non-Hodgkin lymphoma (NHL) are diagnosed in the country(2004). The last WHO classification of tumors of hematopoietic and lymphoid tissues was adopted in 2008 and distinguishes 5 main subtypes of the lymphoid neoplasms: precursor lymphoid neoplasms, mature B-cell neoplasms, mature Tand NK-cell neoplasms, Hodgkin lymphoma and immunodeficiency-associated lympho-proliferative disorders (Swerdlow et al., 2008). Many epidemiologic studies have been conducted in the Asian continent, to explain different subtype distribution among different countries. The association between lymphomas and viral infections has been discussed, especially regarding Epstein Barr Virus


Introduction
Lymphomas represent the fifth most frequent cancer in Lebanon.Every year, between 600 to 700 new cases of Hodgkin lymphoma and non-Hodgkin lymphoma (NHL) are diagnosed in the country (2004).The last WHO classification of tumors of hematopoietic and lymphoid tissues was adopted in 2008 and distinguishes 5 main subtypes of the lymphoid neoplasms: precursor lymphoid neoplasms, mature B-cell neoplasms, mature T-and NK-cell neoplasms, Hodgkin lymphoma and immunodeficiency-associated lympho-proliferative disorders (Swerdlow et al., 2008).
Many epidemiologic studies have been conducted in the Asian continent, to explain different subtype distribution among different countries.The association between lymphomas and viral infections has been discussed, especially regarding Epstein Barr Virus

Type Distribution of Lymphomas in Lebanon: Five-Year Single Institution Experience
Claude Sader-Ghorra 1 , Marc Rassy 1 , Samah Naderi 1 , Hampig Raphael Kourie 2 *, Joseph Kattan 2 infection in Hodgkin lymphoma patients (Fatima et al., 2011;Li et al., 2012) and Hepatitis B Virus infection in patients diagnosed with any lymphoma (Tang et al., 2013).Patients diagnosed of NHL have been the subject of many more epidemiologic studies.Risk factors has been detected such as a higher consumption of carbohydrate in Oman (Ali et al., 2013) and an increase in pesticides usage in Turkey (Yildirim et al., 2013).The latter has been previously estimated as a 3-fold excess risk in India, among other risk factors: cigarette smoking, consumption of mutton and consumption of milk (Balasubramaniam et al., 2013).On the other hand, a reduced risk of NHL was associated with coffee consumption in India (50% reduction) (Balasubramaniam et al., 2013) and with a higher educational level and a higher intake of vegetables in Oman (Ali et al., 2013).Finally, the gene expression profiling of NHL has been the main interest of recent studies.New differentially expressed genes may be markers for NHL patients and individuals at high risk of cancer development (Zekri et al., 2013).Among NHL subtypes, DLBCL patients have been further studied for epidemiologic characteristics.Indeed, DLBCL has even been reported as the most frequent lympho-proliferative disorder detected in multiple primary cancers (Demirci et al., 2012).A Chinese study identified a direct or indirect protective effect of traditional Chinese medicine against DLBCL.It also revealed a possible predisposition for DLBCL in TB patients and farmers (Fan et al., 2012).
To our knowledge, the literature is poor regarding the distribution of lymphoid neoplasm subtypes in the Lebanese population especially according to the 2008 WHO Classification of tumors of hematopoietic and lymphoid tissues.
The aim of this study is to determine the epidemiologic characteristics of lymphomas in Hôtel-Dieu de France University Hospital, knowing that approximately 20% of all newly Lebanese cancer cases are diagnosed in this tertiary hospital (unpublished data).Moreover, the distribution of these lymphoma cases according to WHO classification of 2008 will be reported.

Materials and Methods
A search for the diagnosis of lymphoid neoplasms in the computerized database of the pathology department of Hôtel-Dieu de France, Saint Joseph University hospital was conducted.From January 2008 to December 2012, 502 patients newly diagnosed with lymphomas at any site were included after eliminating all the duplicated cases.Two different pathologists established the diagnosis.Discordant cases were reviewed by expert hematopathologists.The age, the gender and the lymphoma subtype according to the 2008 WHO Classification of Hematopoietic and Lymphoid Tissues of patients were attributed and analyzed using the SPSS version 20 statistics program.

Results
Of the 502 cases of lymphomas diagnosed during five years in our institution, HL accounted for 119 cases (24% of all lymphomas), NHL for 383 cases (76% of all lymphomas), mature B cell neoplasms for 332 cases (87% of all NHL), mature T cell neoplasms for 34 cases (9% of all NHL) and precursor lymphoid neoplasms for 17 cases (4% of all NHL).
Hodgkin lymphomas (HL) were equally distributed in both sexes with a mean age at diagnosis of 30 years (age ranged from 6 to 75) (Table 1).More than 50% (62 cases) of HL were diagnosed between the ages of 10 to 30.Another peak incidence was detected within the 6th decade of age.
Concerning non-Hodgkin lymphomas (NHL), the mean age of patients was 44 years old (age ranged from 6 to 95).Among those, 44% (169 cases) were women with a mean age of 40 years and 56% (214 cases) were men with a mean age of 48 years (Table 1).60% of patients diagnosed with NHL were aged between 50 and 80 years.
The mean age of patients diagnosed with DLBCL was 57 years (age ranged from 15 to 95); 48% (70 cases) were women and 52% (77 cases) were men.The peak incidence of patients with DLBCL was between 60 and 80 years.The mean age of patients diagnosed with follicular lymphoma was 60 (age ranged from 32 to 89); 43% (27 cases) were women and 57% (38 cases) were men.The peak incidence of these patients was between 50 and 70.The mean age of patients diagnosed with mantle cell lymphoma was 61 years (age ranged from 12 to 86 years); 15% (4 cases) were women with a median age of 70 and 85% (23 cases) were men with a median age of 60 years (Table 1).
Only 9% of NHL (34 cases) were mature T-and NKcell neoplasms with a mean age of 53 years (age ranged from 7 to 77).29% were women with a mean age of 45 years and 71% were men with a mean age of 57 years (Table 1).Approximately 50% of these lymphomas were diagnosed in patients aged more than 60 years.
At last, 4% of NHL (17 cases) were precursor lymphoid neoplasms with a mean age of 25 years (extremes 6 to 65).65% were women with a median age of 22 and 35% were men with a median age of 30 (Table 1).The three quarter of these patients were aged less than 30 years.

Discussion
To our knowledge, this study is the largest in Lebanon analyzing more than 500 cases of lymphomas in a single institution over a five-year period.It describes the epidemiologic characteristics and subtypes of lymphomas according to the WHO classification of 2008.A one-year national study of 227 cases of lymphomas classified according to the 2001 WHO classification of malignant lymphomas has recently been published (Otrock et al., 2013).
HL represents 24% of all lymphomas in our study, a high percentage when compared to the literature.In Asia, HL incidence doesn't exceed the 5% in Korea (Yoon et al., 2010) and in China 13% (Yang et al., 2011).In developed countries, HL represents 9% of all lymphoma cases in the US (Morton et al., 2006), 13% in England (Lowry and Linch, 2013) and 16% in France (Troussard et al., 2009).Our results concerning HL proportion are not far from the results mentioned in the Lebanese cancer registry where the HL represents 22% of all lymphomas(2004).HL constitutes 32% of all lymphoid neoplasm in Saudi Arabia (Akhtar et al., 2009) and 17% in Turkey[10] (Table 2).
In our study, B cell lymphomas represent 87% of all our NHL cases.These results are similar to those found in developed countries (Morton et al., 2006;Troussard et al., 2009;Lowry and Linch, 2013) and discordant with most Far East Asian countries (Sukpanichnant, 2004;Aoki et al., 2008;Yang et al., 2011), where T cell lymphomas are more frequent (Table 2).
When discussing the subtypes of B cell lymphomas, many characteristics are detected.Follicular lymphomas (FL) represent nearly 20% of all NHL in our study.This is a relatively high percentage when compared to the FL percentage in China (9%) (Yang et al., 2011), Korea (3%) (Yoon et al., 2010) and US (10%) (Wu et al., 2009), where FL represents less than 10% of all NHL.Similarly a high proportion of FL is described in the French population (20%) (Troussard et al., 2009) (Table 2).
In conclusion, the distribution of the different lymphoma subtypes in Lebanon is unique when compared to other countries from around the world.Indeed, Hodgkin and follicular lymphomas are more frequent than in most Far Eastern, European and American countries, while T-cell lymphomas and DLBCL are less frequent.

Table 2 . Comparison of Lymphoma Subtypes Frequencies in Different Countries
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