Non-Hodgkin Lymphoma (NHL) is the most prevalent hematopoietic neoplasm globally, and represents 4% of all cancer diagnoses. In the Middle East, NHL constitutes 60-75% of all cases of lymphomas as suggested by several series.
As the name suggests, NHL is a cancer of lymphoid tissue. Unlike other cancers that originate in other tissues and spread to the lymphatic system, lymphomas like NHL originate within the lymphoid tissue, and metastasize through the lymphatic vessels to the tonsils, adenoids, spleen, thymus, and bone marrow. There are more than 30 different subtypes of NHL. For convenience, however, they are all grouped into three categories, based on the aggressiveness of the cancer. These are - indolent or low-grade, aggressive or intermediate-grade, and highly aggressive or high-grade. NHL symptoms are similar to other lymphomas and leukemias and include fever, fatigue, unintentional weight loss, loss of appetite, abdominal pain, night sweats, and severe itchiness.
Physical examination of lymph nodes to detect any swellings is the first step towards diagnosis of NHL. Blood and urine tests are also employed to rule out the possibility of any infectious disease. This is usually followed by the use of imaging techniques, such as X-ray, CT scan, and PET imaging. The most definitive diagnosis, however, comes with the lymph node, and bone marrow biopsy. Indolent NHL is usually not treated immediately, but observed over a period of time. Aggressive NHL needs to be managed immediately, either through radiation and/or combination chemotherapy. Prognosis also depends upon the stage of the cancer.
Many genes and chromosomal loci have been identified in the familial and sporadic cases of NHL. These include Caspase 10, del (7q22-23), Ataxia-Telangiectasia Mutated Gene (ATM), RAD54L, V-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF), and Perforin 1 (PRF1). In addition, a few chromosomal translocations have also been implicated in the pathogenesis of NHL. These include t(14;18)(q32;21), which juxtaposes the BCL2 oncogene to the IgG locus, t(11;14)(q13:q32), which causes over-expression of bcl1, translocation of 8q24, which causes dysregulation of c-myc, and t(2;5)(p23;q35), which causes fusion of the Neucleophosmin (NPM) and Anaplastic Lymphoma Kinase (ALK1) genes.
Shome et al. (2004) conducted a retrospective hospital-based study to determine the clinicopathologic features of malignant lymphomas in Bahraini patients during the period from January 1996 to December 2001. Seventy-two cases met the inclusion criteria. This included 24 (33.3%) cases of Hodgkin's disease (HD) and 48 (66.7%) cases of Non-Hodgkin lymphomas (NHL). The majority of NHL showed diffuse high or intermediate grade lesions. A high number of primary extra nodal neoplasms (41.7% of NHL) and frequent involvement of the gastrointestinal tract with Helicobacter pylori-associated gastric lymphomas were notable features among NHL cases. Immunohistochemical staining in 30 cases showed 26 cases (86.7%) of B cell and 4 cases of T cell origin.
Naresh et al. (2004) provided a summary report of the International Network of Cancer Treatment and Research (INCTR), focused on the pathology of NHLs in children and adults in various countries. Interestingly, follicular lymphoma accounted for less than 5% of NHL cases in Egypt, which was significantly lower than those reported in Western countries. Kuwait also showed a low percentage of follicular lymphoma cases (11%). On the other hand, frequencies of Burkitt Lymphoma were relatively high in Egypt (7%).
[See also: Jordan > Amr et al., 1986].
[See: Jordan > Amr et al., 1986].
Amr et al. (1986) reported 373 children with malignant disease through the period of five years (1975-79). The most frequent tumors experienced were found to be lymphomas comprising 28.7%, preceded by 19.6% leukemias, and 16.1% brain tumors. The cohort was divided into three thirds comprising Hodgkin's disease, Burkitt's lymphoma, and lymphocytic lymphoma. Patients with non-Hodgkin's lymphoma experienced frequent abdominal involvement. Amr et al. (1986) stated gaining similar results to those described from neighboring countries including Kuwait, Iraq, Saudi Arabia, and Egypt, while contradicting the results obtained from developed countries were leukemias and brain tumors were found to be more frequent than lymphomas.
[See also: Kuwait > Temim et al., 2003].
Alwan et al. (1990) carried out a retrospective analysis of 35 patients (29 males) with primary NHL of the gastrointestinal tract. Majority of tumors had high grade histology. All tumors selected were in stage I and II; majority being in IIA. All patients, except one, underwent resection of the tumor, followed either by combined chemotherapy (25) or chemotherapy followed by radiotherapy (3). Surival rates were better in patients with low stage and low grade tumors, with overall 5-year survival being 38%.
Al-Bahar et al. (1996) studied all cases of non-Hodgkin's lymphoma reported in the Kuwait Cancer Registry between 1980 and 1989, and compared the age-specific and age standardized incidence rates for the two periods 1980-1985 and 1985-1989. There were a total of 325 and 338 cases of Hodgkin's disease in the two periods, indicating a significant decrease in the annual NHL incidence. The incidence of low and intermediate grade NHL was observed to decline significantly, while the incidence of high grade NHL increased with time, although the increase was not significant. Al-Bahar et al. (1996) suggested that this increase in high-grade lymphomas might be related to the population structure in Kuwait.
Temmim et al. (2003) described the epidemiology and pathoclinical features of extranodal NHL in all 935 patients (821 adults) diagnosed between 1985 and 2000 in Kuwait. Of these patients, 317 were Kuwaitis, while of the 504 non-Kuwaitis, 428 were of Arabic origin. The extra-nodal localization was most commonly found in the digestive tract and the skin. Bulky disease was found to be common, especially in the children. Therapy involved chemotherapy, radiation therapy, or a combination of both. Complete remission was seen in 71.4% of the adults and 63.2% of the children. Eight adults (six Kuwaitis and two Jordanians) showed a positive family history. In six of these, the affected members were direct relatives, while in two they were cousins. The study consolidated earlier ones from the region highlighting the high incidence of extranodal lymphomas in the Arabian Gulf region.
[See also: Egypt > Naresh et al., 2004; Jordan > Amr et al., 1986].
Al-Kuraya et al. (2005) conducted a retrospective cohort study based on 100 Diffuse Large B Lymphoma (DLBCL) tumor samples collected between 1990 and 2000 in Saudi Arabia. MGMT hypermethylation was found in 71% of the samples, and was found to be associated with absent MGMT protein expression. MGMT methylation status was also found to be strongly associated with overall survival, with increasing survival among patients with samples with increased methylation. Similar results were found by the study of Al-Kuraya et al. (2006), which included samples from 190 Arabian patients with DLBCL. MGMT hypermethylation was found to be strongly associated with prolonged survival. In addition, multivariate analysis, including immunophenotype and MGMT methylation revealed an independent prognostic significance for MGMT methylation.
Siraj et al. (2007) conducted a study among Saudi diffuse large B lymphoma (DLBCL) patients. The study included 160 DLBCL patients (107 men and 53 women, with a median age of 49 years) and 511 Saudi controls. All samples were analyzed for MTHFR C677T and A1298C functional polymorphisms using restriction fragment length polymorphism in association with MGMT and FHIT genes promoter hypermethylation. It was found that Saudi individuals who carry MTHFR 1298CC and the 1298C allele had 4.23 and 1.73-fold higher risk of developing DLBCL, respectively. In addition, the CCC genotype was associated with 3.489, and CTCC was related to 9.515-fold higher risk, compared with full MTHFR enzyme activity. The results suggested an association between MTHFR polymorphisms and increased susceptibility to develop DLBCL among Saudi population. No association was found between the MTHFR variants and MGMT or FHIT hypermethylation in DLBCL.
The Centre for Arab Genomic Studies Work Group (2004) conducted a retrospective study for cancers described at AlQassimi Hospital in Sharjah from years 2002-2004. Only one case of non-Hodgkin's lymphoma was described in 35-year-old male in year 2004. No further details could be obtained.
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